There is growing evidence that bisphenol A (BPA), a molecule largely released in the environment, has detrimental effects on ecosystems and on human health. It acts as an endocrine disruptor targeting steroid hormone receptors, such as the estrogen receptor (ER), estrogen-related receptor (ERR) and androgen receptor (AR). BPA-derived molecules have recently been shown to interact with the AR N-terminal domain (AR-NTD), which is known to be largely intrinsically disordered. This N-terminal domain contains an 11 residue conserved domain that forms amyloid fibers upon oxidative dimerisation through its strictly conserved Cys240 residue. We investigate here the interaction of BPA, and other potential endocrine disruptors, with AR-NTD amyloid fibers using the WaterLOGSY NMR experiment. We observed a selective binding of these compounds to the amyloid fibers formed by the AR-NTD conserved region and glutamine homopolymers. This observation suggests that the high potency of endocrine disruptors may result, in part, from their ability to bind amyloid forms of nuclear receptors in addition to their cognate binding sites. This property may be exploited to design future therapeutic strategies targeting AR related diseases such as the spinal bulbar muscular atrophy or prostate cancer. The ability of NMR WaterLOGSY experiments to detect weak interactions between small ligands and amyloid fibers may prove to be of particular interest for identifying promising hit molecules. Bisphenol A (BPA) is a chemical additive that was widely used in the plastics industry, until growing evidence of its detrimental effect on human health was revealed. Long-term exposure to low-doses of BPA is responsible for developmental defects of the reproductive system, as well as metabolic and neurologic disorders. Higher doses of BPA display oxidative toxicity and carcinogenesis effects . MultiplN of glutamines in the sequence. All variants can form amyloids ).6 at 100 mM. All NMR experiments were performed in 3 mm tubes using 180 μl of H2O containing 10% DMSO-d6 and 10% D2O v/v at final pH = 7.0. The final concentrations of the molecules were set to 1 mM for both the peptide and the ligand.Stock solutions of the ligand molecules were stored in DMSO-d6 and 10% D2O incubated for 24 h at 37°C. Then, the fiber suspension was diluted to different extents  maintaining the concentration of both DMSO-d6 and D2O to 10% v/v.Fibers were prepared as described in Asencio-Hernández et al  from 1 m® .All NMR studies were performed at 25°C on a Bruker Avance III 700 MHz spectrometer equipped with a Z-gradient cryoprobe. The spectra were processed and analyzed using NMR-notebook1H spectra were recorded using a 1 s presaturation pulse with a B1 power of 200 Hz.1D 1 power of 60 Hz. The mixing time was set to 1.2 s and the relaxation time was set to 6 s.  were performed using the ePHOGSY experiment from Dalvit et al. 2001 . Selecti° pulse was between 9 and 11 μs.Experiments were acquired with 256 scans for a total duration of 36 min. For all experiments, the 90P11 were performed for all screened molecules. All control experiments displayed a negative WL signal for the ligand resonances ..P11 pept ligands , neverth ligands . For thiThe presence of large positive signals for proton resonances of the BPA molecule in the WL spectrum indicates that water magnetization was transferred to BPA while bound to a large molecular object. The residual protonated DMSO peak displays a negative intensity, indicative of a direct magnetization transfer between water and DMSO only, providing us with a negative control .P11 fibrils were responsible for the magnetization transfer from water to BPA, we performed the same measurement after two steps of sample centrifugation by sedimentation to remove high molecular weight species from the solution  or, less specifically, from a particular geometric organization of the peptide backbone, arguably within the fiber. In order to distinguish between these two hypotheses, we tested whether WL signal can be observed using fibers formed by homopolymers of glutamines (polyQ). We used fibers formed by Q41 peptides whose amyloid forming property is responsible for spinal and bulbar muscular atrophy [The interaction between BPA and  atrophy , 22.P11 fibers is shown in P11 fibers, we measured a strong positive WL signal, showing that both fibers promote strong ligand-water magnetization transfer through the weak ligand-fiber interaction. This is an indication that the recognition is mediated by molecular features that are specific to the amyloid state but independent of the peptide primary structure.The comparison of WL signal obtained from experiments performed with peptides and BPA concentrations similar to those used for the P11 peptide fibers using WL experiments. EPI–001 is a non-steroidal antagonist of AR derived from BPA, which binds covalently to the AR-NTD [We then investigated whether other molecules known to interact with AR or with other intrinsically disordered domains display some affinity for e AR-NTD . EPI–001e AR-NTD –26. Chlo6 and their interactions with P11 peptide fibers were tested with WL experiments performed at concentrations of 1 mM for the ligand and 200 μM for P11. The results are summarized in Stock solutions of these compounds were prepared in DMSO-dRemarkably, all the tested compounds present a positive WL signal, indicative of a weak interaction with the fibers, with the exception of chloramphenicol. This observation suggests that amyloid fibers have the ability to bind a wide range of ligands presenting different chemical features.Nevertheless, the apparent scarcity of non-binding examples (n = 1) limits our ability to discern any salient features of a structure-activity relationship.P11 peptide, a conserved sequence motif found in the AR-NTD. This interaction seems to be related to specific properties conferred to the oligomerized peptide by the amyloid structure rather than to a binding pocket formed by specific amino-acid side-chains, as indicated by the binding observed between BPA and glutamine homopolymer fibers. The ability of BPA to bind P11 peptide amyloid fibers is shared by a number of other molecules including some members of the polyphenol family, such as the resveratrol and epigallocatechin gallate. The lack of interaction observed for chloramphenicol suggests that this ability requires specific molecular features that remain to be defined using high-throughput screening. The interaction between BPA and P11 fibers was evidenced by the WaterLOGSY experiment, an NMR method designed to detect transient binding between a ligand and a large molecular target using water mediated magnetization transfer. In the case of BPA binding to P11 or polyQ amyloid fibers, this experiment provided us with a strikingly large effect, while other NMR experiments used to evidence transient interactions, such as saturation transfer difference spectroscopy [This study shows that BPA, a molecule which is known to be an endocrine disruptor, displays a weak affinity for amyloid fibers formed by the troscopy  led to utroscopy . Furthertroscopy . Our resP11 region, AR-NTD contains a number of homopolymer sequences that are potentially involved in the supra-molecular organization of AR, such as a polyQ tract [The design of ligands able to specifically target the NTD of AR is a subject of intensive research, as this domain is involved in the constitutive and unfaithful induction of the gene expression in the case of castration-resistant prostate cancer . The maiyQ tract . FurtheryQ tract , suggestA similar route could be followed to design potent molecules targeting AR. The EPI–001 molecule and its derivatives have been described as potential new drugs promoting the regression of prostate cancer , 23. TheNon-specific molecular interactions mediated at the surface of amyloid fibers emerge as novel protein-ligand interactions potentially involved in the mechanisms leading to to amyloid diseases. In the case of androgen receptor, amyloid fibers play an important, albeit enigmatic, role in pathologies such as spinal bulbar muscular atrophy and prostate cancer , 11, andS1 Spectra1H NMR spectra from of the different molecules used in this study: regular 1D spectra; WaterLOGSY (WL) spectra in presence of the P11 peptide; control WL spectra in absence of peptide.This Supporting Information presents various (PDF)Click here for additional data file.S1 NMRData(ZIP)Click here for additional data file.


To identify the rate and predictors of utilization of rehabilitation services among people with psychotic disorders in rural communities of Guangxi.A cross-sectional survey was conducted among individuals with schizophrenia or other psychoses , aged over 15 years, and their care-givers in Guangxi, China. Trained village doctors located individuals known to them and suspected as having schizophrenia or other psychoses within the target areas and recruited them into the study. Data on demographic characteristics, clinical symptoms and functions, treatment history, and reasons, if any, for non-utilization of mental health service were collected. Logistic regression was used to determine associated factors for utilization of mental health services.A total of 424 individuals experiencing psychosis  and 319 caregivers (mean age 55.3 ± 14.2 years) were interviewed. The median duration of disease was 13.4 years. 83.0% of patients had never used rehabilitation services. Greater use of rehabilitation was associated with having a non-organic disorder  and living with a caregivers . The top three reasons for not using rehabilitation services were lack of awareness (57.1%), lack of money (14.2%) and lack of belief in the service (12.8%).These findings indicate a high unmet need for psychiatric rehabilitation services among people with psychotic disorders in rural areas of Guangxi. Strategies such as outreach programme and collaborative and partnership network with the local community are needed to encourage people with psychotic disorders in rural communities to increase their utilization of rehabilitation services. Mental disorders occur at high rates in every country, and have already become a global challenge, especially in fast-growing developing countries such as China , 2. The Psychiatric rehabilitation is an important part of a mental health service. It promotes recovery, community integration, and improves quality of life for patients who have been diagnosed with any mental health condition that seriously impairs their ability to lead meaningful lives. If the patients received rehabilitation their social function will be improved which in turn will decrease the burden of caregivers . PsychiaThe practice of psychiatric rehabilitation over the last few decades has undergone gradual refinement and sophistication, which has resulted in a multitude of intervention programmes in the United States, Canada and the United Kingdom –12. HoweLack of utilization of mental health services can lead to irreversible conditions. However, mental health services in China are mostly provided by psychiatric specialists in large hospitals. In addition, most psychiatrists and psychiatric specialist hospitals are located in cities. Guangxi is located in southern China. Very few mental health services exist in this relatively underdeveloped province, especially in rural areas. The prevalence of schizophrenia in rural Guangxi was 9.2% , 21. UtiWHO stated there remains a group of patients with psychotic disorders who do not recover adequately to be discharged home following efficient psychiatric services . Lack ofVery few surveys have been conducted attempting to understand the situation of psychiatric rehabilitation service utilization , 20–27, Over half of the people with schizophrenia are not receiving proper care . AbsenceAccording to the current status of psychiatric rehabilitation research , 33, 34,A cross-sectional survey was conducted to investigate the utilization of psychiatric rehabilitation among individuals aged over 15 years with severe mental disorders and their caregivers during June to September, 2016. The survey employed a multistage stratified, clustered sampling scheme to select 118 villages from nine towns in three counties of Guangxi Autonomous Region, China. Altogether, 12 psychiatrists, 36 township hospital nurses or doctors, 118 village doctors and 20 research assistants were trained and participated in the survey. Liujiang county, Liucheng county and Xiangzhou county were selected as sample counties. Three townships were selected from each county based on the distance and population size. Four most populous administrative villages were chosen from each township . All the natural villages of the administrative village were included in the sample. Finally 118 villages from three counties were included in this study, including 36 villages from Lijiang county, 41 villages from Liucheng county and 40 villages from Xiangzhou county with 47,929 residents altogether. All individuals suspected as having schizophrenia or other psychoses within the target area reported by the village doctors were screened by the township nurses and diagnosed by the psychiatrists. A total of 424 severe mental disorder patients were diagnosed and interviewed, including 185 patients from Liujiang county, 115 patients from Liucheng county and 124 patients from Xiangzhou county.An indigenous field worker sampling method was employed in which village doctors were trained to recruit participants. These village doctors located individuals known to them and suspected as having schizophrenia or other psychoses within the target area and recruit them into the study. Multiple sites and recruitment networks were chosen to ensure a wide coverage of the target population and to reduce volunteer bias.Individuals aged 15 years or over, residing in the study area for at least 6 months prior to the study period were eligible. In this study, severe mental disorders included schizophrenia, schizotypal, and delusional disorders  codes F20–F29) and other psychoses (e.g. organic psychoses) which are consistent with the “Severe mental illness treatment and management specification” launched by the Chinese Government. All patients were assessed for a definitive diagnosis by qualified psychiatrists.After providing written informed consent, each participant met in person with a research staff for an interview that lasted approximately half an hour. Data on demographic characteristics, clinical symptoms, treatment history, use of psychiatric rehabilitation services and, if appropriate, reasons for not utilizing the service were elicited. Psychiatrists conducted clinical interviews to evaluate the severity of a patient’s condition using the positive and negative syndrome scale (PANSS) . Scores Utilization of psychiatric rehabilitation services was defined as any use of psychiatric rehabilitation programmes by the patients within 12 months prior to the survey. This included social skills training, cognitive/cognitive-behavioral therapy, family psycho education and vocational rehabilitation. In this study, the utilization of psychiatric rehabilitation services included both inpatient and community-based services.The study was approved by the Ethics Committee for Research in Human Subjects, Faculty of Medicine, Prince of Songkla University. All participants provided written informed consent to participate in the study. Data collection was conducted in private and participants were assured that any information disclosed would be treated in strict confidence. All data on patients were saved and analyzed anonymously. The China Medical Board approved the study.p value ≤ 0.20 in the univariate analyses were included in the initial model. To identify predictive factors influencing the utilization of psychiatric rehabilitation services, multivariate logistic regression models were then used to calculate adjusted odd ratios (OR) and 95% confidence intervals (CI). The significance level was set at p < 0.05. All data were analyzed using R version 3.3.2.Descriptive statistics were used to summarize the demographic data of the participants and their caregivers. Pearson’s Chi square test was used to compare differences in socio-demographic variables, cause of illness and disease duration between those utilizing and not utilizing psychiatric rehabilitation services while Student’s independent t-test was used to compare differences in positive, negative and general symptom scores. Based on some previous studies, patients’ characteristics, including demographics, course of illness, type of symptoms (positive or negative) and type of psychotic disorders as well as caregivers’ characteristics were associated with the use of treatment and rehabilitation services , we therA total of 424 severe mental disorder patients  aged over 15 years and 319 caregivers were interviewed. The mean age of the patients was 41.4 ± 13.0 years and the caregiver was 55.3 ± 14.2 years. Most (72.4%) patients were Zhuang ethnicity, completed elementary (38.4%) or junior high school (37.7%) and 49.5% were single. 63.4% were engaged in agricultural work while 30.0% were not currently employed and 44.8% had a low per-capita annual family income level (< 981 USD). The median duration of illness was 13.4 (Interquartile range (IQR): 6.45–67) years. Median scores of positive, negative and general symptoms of the PANSS were 12, 15 and 25, respectively. The utilization rate for any rehabilitation service was 17.0%. Demographic variables are summarized in Table There were no significant differences between those who ever utilized and those who had never utilized any rehabilitation service in terms of gender, ethnicity, age group, marital status, occupation, annual family income, disease duration and caregiver’s gender. However, statistically significant differences were found in educational level, type of psychoses, having a caregiver and PANSS scores in the univariate analyses as shown in Table From the results of the multivariate logistic regression model shown in Table As shown in Table This study describes the utilization of psychiatric rehabilitation services and associated factors among people with severe mental disorder in Guangxi rural communities. The utilization rate was very low, only 17.0%, which is consistent with previous studies in China and in other developing countries (1–40%) –27, 36. Compared with previous studies in China , 25–27, This study found that patients with organic psychoses were less likely to use psychiatric rehabilitation services. It is likely that this group of patients is lack of the ability to express their needs adequately or their caregivers did not believe the psychiatric rehabilitation service could work on the patients, thus did not seek psychiatric rehabilitation services . SeveralPatients with caregivers were more likely to utilize rehabilitation services compared to those without. Caregivers constitute the major support system bearing the responsibility for patient care  and inflThis study found that participants who did not utilize psychiatric rehabilitation services had higher scores for negative symptoms, higher scores for positive symptoms and higher scores for general psychopathology compared to those who did not utilize these services. Psychiatric rehabilitation service users often have prominent ‘negative’ symptoms that may impair their motivation and organizational skills to manage daily activities. This places them at risk of self-neglect. Many also have on-going ‘positive’ symptoms which have not responded fully to medication and can make communication and engagement difficult. They are lack of the ability to express their needs thus their caregiver and family members are required to help them to access the psychiatric rehabilitation service. However, for some reasons such as the low education level or lack of the awareness, patients and their family can’t express their needs adequately. However, those differences were not shown in the multivariate analysis, indicating that the severity of the illness was not associated with utilization after adjusting for cause of disease and presence of a caregiver. This finding was consistent with the study in China reported by Li . SeveralThe top three reasons for not utilizing psychiatric rehabilitation services were lack of awareness (57%), lack of money (14%) and lack of belief in the service (13%). It seems that the patients and their family members may not be aware of the importance of the psychiatric rehabilitation services available to them, and this represents a significant barrier for patients and their families. This lack of awareness and belief in the importance of psychiatric rehabilitation services more likely led to the low utilization rate found in this study. More efforts are needed to make mentally ill patients more aware of the importance of psychiatric rehabilitation services for their long-term recovery. Regarding the cost of treatment, psychiatric rehabilitation services are not covered by the current medical insurance system , which mResults of this study should be interpreted with the following three main limitations in mind. First, since the sample was selected from only three counties, the results may be not representative of the general situation in Guangxi. Second, an indigenous field worker sampling method was employed, thus we may have missed some less severe mental disorder patients. Since the study was a community-based survey, homeless or some institutionalized patients may have been inadvertently missed. Hence, caution should be made when generalizing these findings in formulating suggestions for mental health services or policies in Guangxi. Finally, we did not evaluate the perspective of the service providers, such as their resources and skills. Further studies exploring the effect of service providers on psychiatric rehabilitation utilization are recommended.The findings of this study highlight a low utilization of psychiatric rehabilitation services in Guangxi. It is important that the government formulate relevant mental health policies and incorporate them into public health and social policy that suits the needs of severe mental disorder patients and their families. Psychiatric rehabilitation service operates as a whole system which includes many other institutions and organizations. Therefore, the collaborative and partnership network should be developed and the links with local community resource to facilitate services should be strengthened. Psychiatric rehabilitation service worker training programs and psychiatric rehabilitation intervention programs as done in other developed countries such as US, Canada, UK and Australia  should b


While children that present with pertussis have a characteristic whooping cough, adults can simply have a persistent, nonspecific cough and remain undiagnosed. Macrolide antibiotics, such as azithromycin, are the currently recommended treatment for pertussis. Solithromycin is a new macrolide and the first fluoroketolide with broad activity against a wide spectrum of bacterial pathogens and has completed clinical development for community-acquired bacterial pneumonia. This study reports the potent  Bordetella pertussis endotoxin in addition to detoxified diphtheria and tetanus toxin was replaced in the 1990s with an acellular pertussis antigen  trials  trials , 10.The following drugs were tested: amoxicillin-clavulanate , azithromycin , cefdinir , cefpodoxime , clarithromycin , doxycycline , penicillin , solithromycin , and trimethoprim-sulfamethoxazole . The drugs were dissolved and diluted for testing in accordance with the recommendations of Clinical and Laboratory Standards Institute (CLSI) document M100-S25 .B. pertussis were cultured from patient specimens submitted to the clinical laboratories at the University of Rochester Medical Center, Rochester, NY. The MICs of solithromycin (CEM-101) and comparator drugs were determined for 34 clinical strains cultured from nasopharyngeal specimens collected from 2010 to 2014.Strains of B. pertussis was subcultured onto Mueller-Hinton agar (MHA) supplemented with 5% sheep blood for 48 h at 36°C in ambient air supplemented with 5% CO2. The MICs of solithromycin and comparator drugs were determined by agar dilution methodology as described by CLSI document M7-A9  and equipment and of test personnel was monitored using quality control organisms as recommended by the CLSI. The MICs of all drugs for quality control organisms tested in parallel with test organisms were within acceptable ranges, as recommended by the CLSI , and waning immunity from vaccines. Prior to the introduction of the pertussis vaccine in the 1940s, more than 200,000 cases of pertussis were reported annually and, in the last century, pertussis was one of the most common childhood diseases and a major cause of childhood mortality in the United States (B. pertussis is difficult to culture and testing for B. pertussis by any method must be specifically requested, therapy for severe respiratory illness is empirical. Solithromycin has been shown to be active against a wide variety of respiratory pathogens, including azithromycin-resistant pneumococcus (B. pertussis in this study were 0.03 μg/ml in media with sheep blood and 0.06 μg/ml in media with horse blood, and solithromycin was the most potent of the nine antibiotics tested. Solithromycin was 2- to 4-fold more active than azithromycin and clarithromycin against these strains. Solithromycin is active against a broad spectrum of respiratory pathogens and has been successfully tested in monotherapy for moderate to moderately severe CABP in two phase 3 clinical trials. The results from the present study show that solithromycin could provide coverage against pertussis when treating severe respiratory tract infections.Since mococcus . Unlike mococcus . The MIC


Androgen receptor (AR) and PI3K/AKT/mTORC1 are major survival signals that drive prostate cancer to a lethal disease. Reciprocal activation of these oncogenic pathways from negative cross talks contributes to low/limited success of pathway-selective inhibitors in curbing prostate cancer progression. We report that the antibiotic salinomycin, a cancer stem cell blocker, is a dual-acting AR and mTORC1 inhibitor, inhibiting PTEN-deficient castration-sensitive and castration-resistant prostate cancer in culture and xenograft tumors. AR expression, its transcriptional activity, and androgen biosynthesis regulating enzymes CYP17A1, HSD3β1 were reduced by sub-micro molar salinomycin. Estrogen receptor-α expression was unchanged. Loss of phosphorylated AR at serine-81, which is an index for nuclear AR activity, preceded total AR reduction. Rapamycin enhanced the AR protein level without altering phosphoAR-Ser81 and CYP17A1. Inactivation of mTORC1, evident from reduced phosphorylation of mTOR and downstream effectors, as well as AMPK activation led to robust autophagy induction. Apoptosis increased modestly, albeit significantly, by sub-micro molar salinomycin. Enhanced stimulatory TSC2 phosphorylation at Ser-1387 by AMPK, and reduced inhibitory TSC2 phosphorylation at Ser-939/Thr-1462 catalyzed by AKT augmented TSC2/TSC1 activity, which led to mTORC1 inhibition. AMPK-mediated raptor phosphorylation further reduced mTOR's kinase function and mTORC1 activity. Our novel finding on dual inhibition of AR and mTORC1 suggests that salinomycin is potentially active as monotherapy against advanced prostate cancer. Mechanistic Target of Rapamycin Complex-1 (mTORC1) activities are two key drivers of prostate cancer. Apoptosis of castration-sensitive prostate cancer cells in response to androgen deprivation therapy (ADT) causes initial regression of the disseminated disease, although recurrence to a castration-resistant lethal phenotype is inevitable, and for ~70% post-ADT patients cancer progresses within 20 months [Androgen receptor (AR) and 0 months , 4. Inhi0 months –8. Synth0 months .Ras Homolog Enriched in Brain), which is a positive regulator of mTORC1. The mTORC1 complex is a hub for signal convergence from numerous positive and negative regulatory cascades. TSC2/TSC1 inhibition due to AKT-mediated TSC2 phosphorylation at serine-939 and threonine-1462 leads to mTORC1 activation, whereas mTORC1 inhibition and consequent cell growth arrest in response to nutrient deprivation or oxidative stress is caused by activation of AMP-activated kinase (AMPK) and a phosphorylation-dependent cascade that ensues. TSC2 phosphorylation at serine-1387 by AMPK stimulates TSC2/TSC1 activity, thus inhibiting mTORC1. Raptor phosphorylation at serine-722 and Ser-792 by AMPK also inactivates mTORC1 [The PI3-kinase/AKT/mTORC1 oncogenic axis is activated in ~40% primary prostate cancer and ~70% mCRPC, ascertained on the basis of whole-genome exome profiling of tumor samples from several hundred patients . The serActivation of the PI3-kinase (PI3K) axis from PTEN deficiency suppressed AR transcriptional output in murine models of prostate cancer , 16. Howin vitro and inhibition of prostate tumor growth in vivo in xenograft tumor models. Loss of serine-81 AR phosphorylation preceded total AR reduction in salinomycin-treated cells. Inhibition of mTORC1 was associated with enhancement of AMPK-mediated phosphorylation of TSC2 and raptor, as well as reduction of TSC2 phosphorylation by AKT. Our results suggest that salinomycin may be clinically active as monotherapy against advanced prostate cancer.Herein we provide the first evidence that salinomycin, a potassium ionophore and a human cancer stem cell inhibitor, can lower AR expression and activity, reduce protein levels of CYP17A1 and HSD3β1, the critical regulators of the androgen biosynthesis pathway, and block mTORC1 activity in PTEN-deficient prostate cancer cells. These molecular changes are associated with reduced proliferation of castration-sensitive and castration-resistant prostate cancer cells Salinomycin inhibited cell proliferation for AR-expressing LNCaP (castration-sensitive) and C4-2B (castration-resistant) human prostate cancer cells Figure . InhibitAnnexinV+PI− cells, indicating early apoptosis, increased significantly after cells were treated with the drug for 3 days Figure . The modAutophagy induction by salinomycin was revealed from elevated LC3B levels in LNCaP-II (an LNCaP variant) and C4-2B cells Figure . Autophaversus salinomycin-treated RWPE-1 cells  and the downstream effector ribosomal protein S6 (RPS), which is an S6K substrate Figures . Marked s Figure . The enhs Figure  is consis Figure . P-RPS ds Figure . P-RPS ws Figure . P-RPS rs Figure . Other is Figure . Reductis Figure . Decreass Figure .Salinomycin reduced AR mRNA and protein levels in LNCaP and C4-2B cells Figures  & 4B. ReAR phosphorylation at serine-81, a metric of its nuclear activity, was inhibited by salinomycin -- the inhibition preceding total AR reduction Figure . In C4-2CYP17A1 (cytochrome P450 lyase/hydroxylase) and HSD3β1 (hydroxysteroid dehydrogenase-3β1) are key regulators of the androgen biosynthesis pathway and thus, the intratumoral androgen level. Reduced expression of both enzymes in C4-2 cells was observed upon 20hr incubation with salinomycin. No change in CYP17A1 and HSD3β1 was detected at 6 hour Figure . GAPDH . The mRN3. For LNCaP-II xenografts, intraperitoneal (i.p.) injections of salinomycin (5 mg/Kg body weight) or vehicle (DMSO) were administered every 3rd day till day-16, after which tumors were harvested. Tumor growth rate declined significantly for the salinomycin group after 6 injections compared to the vehicle control p<0.04, n=5  and prostate histology  levels were elevated by salinomycin in prostate cancer cells . Since oReduced TSC2 phosphorylation at Ser-939 and Thr-1462 (two AKT-targeted sites) within 6hr drug treatment Figure  also conin vitro and in tumor xenografts, and prevented a compensatory negative crosstalk between AR and mTORC1, which otherwise would have led to reciprocal activation of the two oncogenic pathways, causing activation of one when the other is blocked. This compensatory interplay is believed to have contributed to the low activity of a combined regimen of everolimus (mTORC1 inhibitor) and bicalutamide (AR antagonist) against metastatic prostate cancer in a phase II trial [The present study identified salinomycin as the first example of a dual-acting inhibitor of AR and mTORC1. Salinomycin, a polyether antibiotic, inhibited PTEN-null castration-sensitive and castration-resistant prostate cancer cells for expansion II trial . This clII trial , 17, 33.Figure Increased RPS phosphorylation by the synthetic androgen R1881 is consistent with previous reports that androgen stimulated mTORC1 in LNCaP cells due to induction of nutrient transporters, which would increase nutrient availability , 22. RobImpaired AR signaling by salinomycin due to interference with AR's Ser-81 phosphorylation, AR mRNA and protein reduction and inhibition of AR transcriptional readout – all of which are novel findings in the present study- contrasts rapamycin-mediated increase in the AR level and activity, which likely contributed to the clinical failure of everolimus against castration-resistant prostate cancer , 43. CYPERK1/2 Map kinase was activated by salinomycin and rapamycin , which iAMPK activation by salinomycin Figure  is in kein vitro and in xenograft models. The drug did not cause overt toxicity, since tumor growth inhibition was not associated with changes in prostate histology ; rapamycin, LC Laboratories ; DPT, T0901317 ; EB1089 . LNCaP, RWPE-1 and PC-3 are from American Type Culture Collection ; LNCaP-II, C4-2, C4-2B, ViroMed Laboratories Inc. . RWPE-1 cells were cultured in keratinocyte medium plus 5% fetal bovine serum (FBS), supplemented with penicillin and streptomycin. Other cell lines were in RPMI 1640 with 5% FBS plus penicillin/ streptomycin6cells/well (6-well dishes) were treated with vehicle or salinomycin at 48-hour post-seeding. Each point is average of three biological replicates. Annexin V-and propidium iodine(PI)-stained cells were analyzed by flow cytometry. Cells were stained using Annexin V Apoptosis Detection Kit APC . Samples were acquired on LSRII  within 30 minutes of conclusion of Annexin V staining. The Diva  or FlowJo  software was used for analysis.Viable cells (Trypan blue excluded) were counted in an automated cell counter . Cell number for each experiment was average from duplicate wells. Cells seeded at 10Cell Signaling Technology  was the source for antibodies to mTOR/ phospho-mTOR, Ser2448(D9C2); AKT1/phospho-AKT1, Thr308(#9275); Tuberin (TSC2)/phospho-Tuberin (TSC2), Thr1462(5B12); p70S6Kinase/phospho-p70S6 Kinase, Thr389 (#9205); GSK3α/β- phospho-GSK3β, Ser9 (#9322); S6 Ribosomal Protein/phospho-S6 Ribosomal Protein, Ser235/ 236(#2211); 4E-BP/phospho-4E-BP, Thr37/46(#9459); AMPKα/phospho-AMPKα, Thr172(40H9); Raptor/phospho-Raptor, Ser792 (#2083); PRAS40/phospho-PRAS40, Thr246(D4D2); ERK1/2/phospho-ERK1/2, Thr202/Tyr204 (D13.14.4E); Rheb (E1G1R); LC3B (D11). Antibodies to AR(N-20), FKBP12(N-19), GAPDH, β-actin and cofilin (FL-166: sc-33779) from Santa Cruz Biotech ; Antibody to phospho-AR, Ser-81(#07-1375) from EMD-Millipore . Antibodies to: CYP17A1 (EPR 6293) from GeneTex ; HSD3β1 (ARP 41821-P050) from Aviva Systems Biology  and p16  from Abcam .5′AAGA-CGCTTCTACCAGCTCACCAA-sens.e, 5′TCCC AGAAAGGATCTTGGGCACT-antisense; PSA: 5′TG ACCAAGTTCATGCTGTGT-sense, 5′GTCATTTCCAAGG TTCCAAG-antisense; NKX3.1: 5′AC-TTGGGGTCTTATC-sense, 5′CTTCTGCGGCTGCTTAGGG-antisense; CYP17A 1: 5′ACCTGGAGG TGCCAGATGAT-sense, 5′GGCG CACCTTGATCTTCACT-antisense; GAPDH internal control: 5′GA-CAGGATGCAGAAGGAGAT-sense, 5′TT GCTGATCCACATCTGCTG-antisense. A validated primer set, Bio-Rad (Cat#10025636) was used for qPCR of HSD3β1 cDNAs. QPCR was performed using CFX384 Real Time PCR machine .Total cell RNAs were isolated using TRIZOL® and converted to cDNAs for QRT-PCR analysis using previous conditions . PCR PriFor protein analysis, harvested cells were taken up in RIPA buffer  containing protease inhibitors . For phospho-protein analysis, protein phosphatase inhibitor  was added to RIPA buffer containing protease inhibitors. Cells were sonicated  using Sonic Dismembrator, setting 5 . Supernatants of lysed cells were analyzed by Western blotting after 10% SDS-PAGE . Two seg6 cells, mixed 1:1 (v/v) with matrigel . Treatment started at ~200-250 mm3 of palpable tumor. Tumor volume=½(length × width2); length=maximum longitudinal diameter and width=maximum transverse diameter, measured with a caliper. Tumors with an adjacently placed ruler were photographed for record keeping. Mice received salinomycin  and vehicle  by i.p. injections (LNCaP-II xenografts) or oral gavage (C4-2 xenografts). Tumor lysates were prepared in RIPA buffer. Protocol approved by the Institutional Animal Care and Use Committee was used.Tumor xenografts were produced subcutaneously at the right flank of athymic nude mice  with cells at 3 × 10Data were analyzed using SPSS 15 software. Student's t-test was used; data presented as mean ± SEM; p < 0.05 is significant.


The present article investigates explanations for gendered trends in Physics and Engineering access, reporting findings from a large-scale study funded by the UK Economic and Social Research Council and drawing primarily on data from interviews with 132 15–16 year-old adolescents and their parents. Survey results in our study and elsewhere show strong gender disparities in anticipated pursuit of Physics after completion of compulsory education. In order to explore the constructions of gender and Physics underlying these trends, we focus on qualitative interview data, applying Foucaultian analysis of discourse to investigate gendered narratives underpinning adolescents’ and their parents’ articulations. This analysis reveals three key discourses at work on the topic of women’s access to Physics: (a) equality of opportunity, (b) continued gender discrimination in and around Physics, and (c) Physics as quintessentially masculine. We additionally identify five distinct narratives supporting the discourse of physics as masculine. These various discourses and narratives are interrogated, and their implications explored. We conclude that it is only by disrupting prevalent constructions of the Physical sciences as a masculine and “hard” domain will we increase the presence of women in the sector. Working with young people to analyse and deconstruct the discursive assumptions made in relation to gender and Physics, as well as further work to increase accessibility and broaden representation in Physics, may be fruitful ways to challenge these longstanding associations between Physics and masculinity. The situation is especially acute for Physics  continue to preoccupy policymakers, scholarly institutions, and employers  also tend to articulate less confidence in their own abilities and are less likely to identify themselves as being “good” at science and/or mathematics, irrespective of their actual abilities and attainment , as well as what might help to reverse this pattern. Research has established that STEM subjects, and Physics in particular, continue to be constructed as masculine, precipitating various practices that deter girls from pursuing these subjects for higher study. However, there has been less attention to how individuals explain these trends or the discourses underpinning such explanations.binarised . This dualistic construction is maintained by gender discourses , at the micro level there is plasticity, contradiction, and resistance, that is, heteroglossia. Francis  project. The longitudinal study, and its predecessor “ASPIRES” study, have been tracking and exploring children’s science and career aspirations from ages 10–19. Methods include a quantitative online survey of the cohort and repeated interviews with a sub-sample of students and their parents. In the present project phase, these methods have been applied when students are age 15/16 years-old (Year 11). Our paper draws primarily on the qualitative interview data generated from the interviews with young people and their parents in the present project phase. The present study subscribes to the ethical standards of the British Educational Research Association, and it has been appraised and approved by the ethics committee of King’s College London.The present paper reports only briefly on elements of the quantitative survey findings. Nevertheless, given that some findings from the survey are alluded to and precipitate the qualitative investigation, we briefly outline the survey method here. The survey collected a range of demographic data, and it covered topics such as aspirations (including a focus on science); subject preferences; science participation in and outside school; self concept in relation to, and perceptions of, Physics, Biology, and Chemistry; parental and peer attitudes; and careers education. All items were validated  were male and 7155 (53.3 %) were female; 6561 (49 %) were categorised as social class 1 , 3764 (28 %) as social class 2 , 1498 (11 %) as social class 3 , 761 (6 %) as social class 4 , and 819 (6 %) were uncategorised. We gathered data on our survey relating to parental occupation, which was used in analyses as a proxy for socio-economic classification . Pupils were asked about their mother’s and father’s (or caregiver’s) occupations, and categorisations were assigned based on the highest recorded occupation. Due to the complexities of asking children about their parents’ occupations, a simplified categorisation task was developed and used . Respondents self-reported as White , Asian , Middle Eastern , Black , Chinese/East Asian , Mixed/Other , and 456 (3.4 %) of students preferred not to answer.The present article primarily draws on qualitative data from 132 interviews (in the current project phase) with 70 15/16 year-old students  and 66 of their parents . All these respondents had been previously tracked since students were aged 10/11. The recruited interview respondents came from a broad range of socioeconomic classes and ethnic backgrounds: White British (15 boys and 26 girls), White European , British Asian , Asian  and Black African/Caribbean (3 boys and 3 girls), Mixed . When drawing data for our article, we recorded each respondent’s pseudonym (which they chose themselves when first interviewed at age 10/11), gender, ethnic heritage, and social class category. The latter categorisation is based on information gained from interviews such as parental occupations (using the NS-SEC categorisations), housing tenure, and parental educational backgrounds. Categorisations run from 1 to 4, where 1 represents professional and/or highly educated parental backgrounds and 4 represents minimally educated/manual unskilled parental occupations.Interview participants were originally recruited from 11 schools in England . These schools were sampled from the 279 schools that responded to the Phase 1 survey as part of the wider study  are White middle-class women , and one (LY) is a White woman Ph.D. student of working class heritage. We see the interview encounter as contextually situated and are interested in the discourses precipitated therein  planned to pursue Physics at A Level. This is a significantly higher proportion than is reflected in national statistics for the proportion of students pursuing Physics A Level (8 %: see Questions for Governors n = 756) were female . Furthermore, students from certain minority ethnic groups (notably South Asian) are disproportionately represented . These different variables clearly intersect with gender in access to Physics. The relationship between gender and social class concerning identification with Physics (or otherwise) is explored further in Archer et al.  This diversity is illustrated by the quotes from the qualitative data we cite.n = 7 of 30) felt there might be things that put women off pursuing careers in Physics, with more male adolescents (n = 12) either simply answering “no there isn’t,” or offering equal opportunities and individual meritocracy discourses to argue that there is nothing deterring women. This was in comparison to more than half of young women (n = 22 of 40) who felt there were things that put women off—with gender discrimination and stereotyping as notable explanations among these accounts. Only 10 girls said there was nothing deterring women from pursuing Physics careers .In contrast, some gendered trends in responses were evident. Asked “Do you think there is anything that is putting women off pursuing careers in Physics?,” it was interesting to see a gender discrepancy in interview responses: less than a quarter of young men (n = 3) said that there is nothing putting women off pursuing engineering careers, and 12 said there were (various) reasons, with four additional young men providing ambiguous answers or “don’t know” responses. Sixteen young women agreed that there are barriers to women pursuing engineering careers, with only three saying there is nothing deterring women (a further three young women either did not know or provided ambiguous responses). These responses appear to chime with the particularly gendered profile of engineering  students and 12 (18 %) parents who claimed there is nothing deterring women from careers in Physics, those who elaborated their response tended to draw on narratives of individualism and meritocracy identified as highly prevalent in other studies  neoliberal individual agency Um, to be honest at the moment no, because like girl power has got really strong recently and I think it’s more girls and women are trying to put their names and faces into things that predominantly men are meant to like be good at, so I think it’s actually more of like a willpower to go into things like that I think it’s just themselves and the confidence to be honest—I think it’s all to do with confidence. I don’t believe that it’s a man’s world and all that nonsense anymore, I think that’s well and truly died out—women are more than capable to learn what they want to learn. As Francis et al.  argue, iHence respondents’ rejection of the idea that women are deterred from pursuit of Physics tended to rest on discourses of equality of opportunity and meritocracy. These discourses reject and deny gender discrimination, with the potential effect of positioning women as individually responsible for their lack of access to Physics.However, as we observed previously, a third of young men and nearly two-thirds of young women asserted that there are impediments to women’s pursuit of Physics careers . These respondents provided a variety of explanations, drawing on two key discourses (and a variety of narratives articulating these): (a) continuing gender discrimination in and around Physics and (b) Physics (and Engineering) as quintessentially masculine. An additional recurrent theme was the disproportionate representation and domination of Physics by men as an explanation for women’s lack of participation. We explore each, with additional attention to this latter theme of lack of women’s representation in Physics: this theme could express both discourses, but it was largely articulated in critiques of sexism and discrimination and was notably recurrent in participants’ responses (it was used by 61 of the 132 respondents).Really?Like today in Chemistry … we have a different teacher to normal because the other one’s off … and my friend said that she wanted to do higher level Maths. And apparently that is really really hard to get a 7 in . And the teacher said, (she’s a girl), she said “Oh I think you have to have a boy brain to do that” … What?” (laughs) “You don’t say that at this school.” And like my friend now really just wants to do it because … to prove her wrong. We don’t really understand what she was saying by a “boy brain,” She said “Oh you get boys that tend to be really geeky and good at Maths” but we were like “Well you get girls like that too.” She’s a Chemistry teacher!The whole class was like “As Table She went … I’ve forgotten what company it was … but in the interview they asked her how will you cope as a woman in this male company. And she was just like “What?” And then they pretended that they hadn’t asked her like such a sexist question.Indeed, several respondents had cautionary tales of sexism that female novices had experienced in seeking to access Physics and Engineering. For example, referring to the “great shame” that women are under-represented in Physics careers, Harris  recounts that one of his daughter’s friends “had a really rough time doing the Sciences (inaudible) at a good university and really struggled—she was the only girl on the course.” Likewise, Kate  explains that her brother’s girlfriend is studying Engineering at university and needed to undertake a year’s study in industry as part of the course:stops you doing anything – I think it just puts pressure on you not to. I think there’s probably any job you could do in Engineering as a girl, but you’re less likely to probably.So I think you would face issues, but probably [...] So I don’t think it Kate’s conclusion illustrates the discursive impact of such ongoing discriminatory practices on other potential female applicants:These “cautionary tales” of sexism from teachers and gatekeepers are especially worrying given the findings about the strong impact of teacher and other “expert” expectations and their communication on young women’ self-confidence and pursuit or otherwise of Physics ; and “Yeah all those stereotypes and that, that it should be men who do that kind of thing” .J: Well there’s a whole bunch of reasons really that I talked about in my essay sort of—stereotyping, women not being given jobs just because of being women [...] got some stuff about that in there. Toys can sometimes put women off science because … or particularly Physics … because boys’ toys tend to encourage more spatial awareness than girls’ toys do. There’s stereotype threat – I don’t know if you’ve heard of that.Interviewer: MmJ: And there’s –I: What, sorry, “stereotype threat”J: It’s when you feel that you’re covered by a negative stereotype in a situation where you may exemplify that stereotype, you will put extra pressure on yourself to try and defy it, and in the end choke and just end up exemplifying it in the end anyway. So a lot of women suffer from that, as well “imposter syndrome” where women feel like they’ve got where they are by luck.These social science constructs were used to explain how gender-distinct behaviours originate with, and are perpetuated by, society, supporting social rather than gender essentialist accounts for the lack of women in Physics. Joanne  provides an especially developed illustration of the application of explanatory social science constructs:Hence in contrast to the elevation of agency and the relegation of structural accounts of inequality to the past produced by equal opportunities/individual choice discourses, the discourses mobilised in these accounts positioned gender dualist and discriminatory practices as ongoing and as impinging on and/or determining women’s behaviour.The discourse of continued gender discrimination and lack of equality of opportunity in relation to Physics was also expressed within an especially frequent explanation for why women are deterred from pursuing Physics careers—a theme concerning the numerical dominance of Physics by men and the consequent lack of representation of women. It was notable that the concept of “role models” was mentioned by only a few of respondents . However the issue of numerical domination by men, as well as the discouraging messages this conveys to women, was an extremely strong theme in our data.There were a range of different versions of this explanation. Some young women presented the numerical domination by men as itself off-putting and intimidating: “Um … well I mean at the moment it’s mostly boys, so they probably get put off being like ‘Well I’m going to be in a class full of boys, so they don’t want to do it’” ; and “Um … I don’t know, it is definitely like a male job. Like I was looking about [college] like I told you, and my brother was like ‘Well if you’re going to do Physics you will be the only girl in the class’” .because like in class yeah there’s all the boys who do Physics and like if you’re a girl and you’re good at it, it would be like it just seems a bit weird [...]. I think people just see it as a bit weird. [...] Like I think the boys just like … and because like a lot of boys do it as well, so I think it would just, it’s just like uncomfortable if you’re a woman and you try and go there and I think like the boys in my class they don’t really expect girls to be that smart, so like if you do it [...] you know. Whereas these statements evoke isolation, and almost a fear of obliteration as “the only girl,” others highlighted the potential stigmatisation of being “odd” or “weird” as a minority: “people might you know think a woman doing a, you know a stereotypical man’s job like a builder they might find it strange or something […] that’s probably quite a big factor rather than like a small one, so…” ; andKelsey’s words evoke the common association between Physics, masculinity and “cleverness” to which we shall return later in our article. But her words also suggest visceral discomfort and vulnerability at “standing out.”But I could imagine that there is still a bit of a kind of “Physics is a man thing.” Cos like for example if you take The Big Bang Theory [a television program] right, like if you think about … obviously well there’s Penny, who’s not even a scientist, but the two girls who are scientists—they’re both biologists. And then all the guys are Physics. So like there is kind of this underlying sort of thing where you’re a bit like “Mm, why is Physics not a girl thing?” Cos Amy Farrar Fowler could easily be a physicist right, and then like you know … for example, I don’t know, like Leonard could probably be a biologist, but they’ve just made it so that all the guys are physicists or engineers, and then the girls … so I guess there is kind of still a little bit of a kind of gender roles sort of deal going on. The lack of representation of women in science was also presented directly as excluding/precluding women’s participation: “Um, yeah there’s been sort of like a stigma with I don’t know. It [women in Physics] doesn’t seem like it’s as prevalent. You don’t see any female scientists being advertised in the same way that like you’ve got male scientists” ; andThese statements clearly suggest that the lack of women in Physics  sends a message about what is (in)appropriate for women. Here the theme of gender representation overlapped with the afore-mentioned concepts of gender stereotyping in young people’s accounts.um, like have you ever seen Big Bang Theory? [...] It’s four physicists and they’re all men and people don’t really think of that as being sexist, but it is because the female character Penny is like the one that isn’t smart, because she’s a girl and she’s interested in girl things and that’s a whole like running joke on the show, but it’s just sexist. It’s not funny. The frequency of references to the TV show “The Big Bang Theory,” especially from young women, to exemplify the gender stereotyping of Physics was highly notable.The prevalence of the trope of the male scientist in the popular imagination was frequently blamed on the media, and was presented as perpetuating perceptions of science as “for males”: “I don’t really know, it’s probably just … I don’t actually know where my view of that’s come from, but it could be from like movies, the media. Like if you have a mad scientist – it’s always male, it’s never female. It’s just stuff like that I guess” ; and “I think it’s more because like in the news you’ve got like mainly the people that do are seen as like physicists like Stephen Hawking and people like that. They’re all male overall. You don’t really see many female ones anywhere” . Such statements are supported by research analysis showing the associations between science competence and men/masculinity in the media  also illustrate how this lack of representation can also be interpreted or conveyed as presenting a “natural” order wherein men are simply better at Physics:I don’t see any reason why women should be put off Physics and you know there is no reason, but in a way … like in the same way that people view intelligence as an interest in Science, people view you know Science as all the men at NASA working at their computers with the men landing on the moon and you know people forget that you know there are several prominent women [..]. Other students critiqued such narratives, maintaining that women’s presence in science has been actively masked:The importance of representation of women in Physics for “evidencing” the possibility and hence facilitating equity discourses  was clear from many responses. For example, Mienie  supports her claim that women can be successful Physicists by highlighting: “because there’s. .. you know there’s a lot of female physicists out there, so—.” Yet equally, it was also noticeable how, rather than necessarily disrupting the monoglossic account of science as a naturally and wholly male terrain, the few heteroglossic cases of women scientists that are publically recognised or included in the curriculum could apparently be easily discounted or ignored, failing to disrupt the monoglossic facade: “Cos like when you see most like discoveries. .. they might just take credit, but like most of them you see them as male. There’s only a few like female scientists like we’ve heard of in science” .Um, yeah I like I see it as more of a like guy thing. I don’t know why. I just like when I hear Physics I think of like the three nerdy, well I suppose nerdy boys in my year, but they’re really good at it, which is why I think of them, so I don’t really think of girls like because they’re all into beauty and that in my school. Hence our data highlight the importance of representation in terms of “im/possibilising” imagined science futures for young women: their lack of representation in media and ‘real life’ science discursively positions  men as ‘naturally’ inhabiting the science terrain, and any women as interlopers, oddities or ‘impossible subjects’ Butler . In answHence, the issue of representation is shown to remain key in young people’s constructions of gender and science and in the im/possibilisation of Physics trajectories for girls and women. The relentless repetition of images that present male bodies in association with Physics, and hence work to embody Physics as male in the public psyche, may be identified and critiqued by respondents, but are nevertheless hard to resist—and impact material practices by constituting and reinforcing Physics as masculine. Our data illustrate the symbolic violence and impact of the repetitive motif of the male Physics body on young women’ perceptions of Physics as an inhospitable, “unnatural,” and potentially isolating route Although a few students remarked on the construction of Physics as masculine without attributing a reason for this labelling, some drew on the concept of gender stereotyping to position this as an invalid socially perpetuated association. Others drew on the narrative of men and women as naturally different and drawn to different subjects to explain the dearth of women physicists as due to natural phenomena :Biology could be classed a bit. .. not saying it’s more feminine, but women. .. or maybe the females would know more about biology, a) with what we all go through. .. not saying men don’t go through it, but you know we learn a bit more about our bodies and why are bodies are doing things from a lot earlier age with like periods and stuff—we get involved a little bit more about biology earlier on. And we could maybe go more into the medical profession or the caring profession—that side of things. So Biology maybe is a little bit easier or we understand. .. not understand it more, but we can get involved in it easier. It was interesting to see which subjects were considered appropriate for each gender here. Supporting previous findings, “caring” and “creative” subjects and occupations tended to be seen as appropriate for females Francis , in compAs Sally Ann’s response illustrates, often when probed for rationales for these different gender “dispositions” for different subjects, respondents talked in rather vague terms about different gendered interests in relation to potential subject content in different disciplines. Interestingly, “circuits” were mentioned on numerous occasions as an exemplification of an element of Physics that might deter young women’ interest, either as reported by young women as a topic they didn’t like or as a topic which young men and young women suggested would not appeal to young women. Luna’s  response is indicative here: “Cos I don’t think that electrical circuits really … for a lot of young women might not stand out to them and make them want to do it at A Level … which might be a reason why they don’t continue it.”Hence, the narratives presented thus far interpolated males and females as different, as well as Physics as more appealing to males, whether due to (spurious) gender socialisation, or to “natural” inherent differences between males and females which render particular subjects more appropriate to one or the other gender. However, the power hierarchy at the heart of the monoglossic, binarised account of gender produced in the discourse of Physics (and Engineering) as masculine emerged more clearly in the three further, inter-related narratives articulated: Femininity is antithetical to (masculine) manual work; femininity as superficial; and cleverness as masculine (and Physics is a clever subject). As we reported previously, many students, especially young men, denied that there was anything deterring women from Physics, but reversed this view in the case of Engineering. For a few, this was about lack of representation. But for the majority, this was due to the association of Engineering with manual work, and manual work with masculinity: “Like isn’t that [Engineering] more manual? So there’d probably be more men in there just for the sake if it being manual labour” .I don’t have a clear idea on that one, but I think people tend to associate Physics, well no not people, I’m not sure about the general view, but I associate Physics with Engineering and I’ve sort of got a view on Engineering as them building. I see it as a more practical subject with wires and rusty equipment and stuff like that. [...] It’s sort of in the same area in my mind as being a mechanic and stuff like that, so it’s different to Biology which you can see is a very clean and hygienic subject. What was intriguing, though, was that none of the accounts positioned physiological differences  as underpinning this envisaged deterrent of manual elements for women. Rather, overwhelmingly, respondents positioned the “problem” as being feminine avoidance of “dirt” or mess: “I was going to say they [women] don’t really like getting dirty and building stuff” ; andI do think there’s still a you know a lot of girls that want to do girl things. [...] you’ve still got that type of girl that think they should only do girl things and oh well I don’t want to do that, because that will be, you know they don’t do sport and they don’t do Sciences and they don’t do Maths and stuff like that, because “ooh no what do I want to do that for? I want to go and file my nails and you know do hairdressing and stuff like that.”  ; “I think that’s why a lot more like men are mechanics and things because it’s hands on. Women don’t want to break their nails do they?” ; andWhat these extracts produce, especially via the vivid misogynist trope of the obsession with “broken nails” and the mimicking of voices, is a denigration of femininity as superficial. As many feminist researchers have recorded, this construction of femininity remains prevalent in educational environments ; andMm, why do they do that? Uh … probably because they’re sitting near young men. well like some young women in my year they act stupid. Like I don’t think they are stupid, but I think they act it. [...] So they think ‘Oh I can’t do it, cos I’m stupid’ – but they’re not at all. The narrative of “Physics as ‘clever’ and masculine” was reported and/or articulated by some respondents, as an explanation as to why fewer women pursue Physics: “I think young men are just thought of to be the smart gender” ;Clearly, in each case these young women are reporting what they see as stereotypes, but Hannah’s words especially evoke the ways in which for young women to invest in “masculine/clever” subjects, and/or to actively position themselves as clever, involves a negation of the feminine which may be experienced as untenable  equality of opportunity, (b) continuing gender discrimination in and around Physics, and (c) Physics as quintessentially masculine. Clearly, each of these discourses is in direct tension with the other, hence providing discursive tension and heteroglossic shifts and contradiction within responses when different discourses are drawn upon by respondents to make particular points.The primary contribution of our findings and analysis has been to identify three key discourses operating within young people’s and their parents’ responses on gender and access to Physics: that of equality of opportunity, that of continuing gender discrimination in and around Physics, and that of Physics as quintessentially masculine. And we have identified how the latter discourse is articulated via five different narratives: (a) Certain subjects are stereotyped as being masculine or feminine (and hence as appropriate for different genders), (b) Men and women are naturally different and drawn to different subjects accordingly, (c) Femininity is antithetical to (masculine) manual work, (d) Femininity as superficial, and (e) Cleverness is masculine and Physics is a clever/difficult subject.We have illustrated the ways in which these three discourses and five narratives emerged in our respondents’ talk, and we analysed how they positioned gendered subjects and the disciplines of Physics and Engineering in particular ways. Especially, we have shown how the narratives connected to the “opportunities as equal,” meritocratic discourse risk positioning women as responsible for their lack of pursuit of Physics and the continued prevalence of the discourse of Physics as quintessentially masculine. This latter finding supports prior research concerning the longstanding association between masculinity and the Physical Sciences  representation in Physics which was frequently used by respondents to explain women’s lower pursuit of Physics, especially by those articulating the discourse of continuing gender discrimination in and around Physics. We have elaborated the apparent effects of this narrative of women’s lack of representation in perpetuating the construction of Physics as an inhospitable domain for women.In addition to our discourse analytic approach, our approach was novel in directly asking respondents their views on gender and access to the Physical sciences. Our thematic analysis has shown that young women were more likely than young men to say that women are impeded from accessing Physics and were also more likely to explain this view via an account of gender discrimination and/or social stereotyping. A further finding from our quantitative data supports the existing literature in showing that young women are significantly less likely than are young men to anticipate pursuing the study of Physics after the end of compulsory schooling.Although the research presented here offers several contributions to knowledge, a number of limitations need to be addressed. For example, the results presented in the present study relating to our survey data do not escape the limitations of similar self-report measures . However, through conducting repeated in-depth interviews alongside the survey, our work covers both the breadth and depth of participants’ aspirations and constructions of identity, thus reducing any of these threats to validity.In addition to issues relating to internal validity, several issues regarding the external validity of the research presented in our paper also need to be addressed. Although the results presented can arguably be generalised to secondary school students in England , wider cultural comparisons need to be made cautiously. Further research replicating these results in other countries would help to build confidence in the generalisability of our findings.Another issue relating to external validity that should be discussed at this point is the choice of students to be included as respondents to the surveys. Although schools were encouraged to invite a spread of top, middle, and bottom sets, or entire cohorts, to participate, it is possible that teachers self-selected certain classes and students  to be involved. This likely bias is indicated by the relatively high proportion of students from professional backgrounds included in our sample.Testing these points, especially generalisability to contexts outside England, comprise possible areas for future research. Additionally, identification and exploration of the specific discourses and narratives underpinning respondents’ discussion of gender and science access provides an important first step in understanding what is necessary to change and confront if access patterns are to alter. However, how this is done, and what strategies might prove most effective in disrupting and challenging these particular narratives, remains unanswered. Hence exploring and trialling such initiatives comprises an important area for future research.inequality in relation to the pursuit of Physics, if to reflect on and confront the remaining binary and discriminatory discursive constructions which we have shown to remain prevalent in their talk. One way to approach this may be for those working with young people to use some of the quotes from the data in the present article to provoke discussion . This approach of analysing and “deconstructing” illustrative texts on gender construction in reflective group discussion has been shown to be an effective one in both primary and secondary schools . As we have said, it is important not to disparage young people’s frequent faith in the attainment of equality of opportunity and meritocracy. Nevertheless, they need to be aware of the overwhelming evidence on continued Second, our findings have illustrated the importance of representation, and the negative impact of the lack of women in Physics  on perceptions of Physics as a field, and consequently for women’s access to it . The lack of representation of women in Physics triggers and legitimates a range of narratives, including cyclical assumptions that women’s inability and/or lack of suitability explains their absence. But additionally, our data shows the visceral concerns at minoritisation and/or isolation for young women—whether for being numerically engulfed or for being stigmatised as “weird.” These concerns are not unreasonable, especially when accompanied with a ready store of cautionary tales of discrimination and humiliation that women have endured in entering the Physics and/or engineering fields.Hence we need to continue work to ensure that women are represented in the Physical sciences: in higher study, in careers, and in educational and media vehicles and materials. Many Physics and STEM associations and Societies are increasingly paying conscious attention to equity in visual representations of the subject. However, it would appear from our findings that these are not yet having sufficient traction or disruptive impact on continued wider representations. Educators and activists continue to have an important role in encouraging media, employers, and educational institutions to recruit and present women in Physics. We need to encourage organisations to take a determined approach to ensuring the appointment and representation of women in key positions and to campaign to persuade the media to adopt a more socially responsible attitude to representation. Findings from Seymour and Hewitt  and otheThis leads to the third issue we wish to highlight: The construction of Physics as a “hard” subject . Some notable exemplar organisations have already acknowledged and embraced this agenda. For example, the UK’s Institute of Physics is leading the way in its attention to gender and its recent agenda to present Physics as an accessible and welcoming subject, rather than a hard one. Drawing on such exemplars, those working with young people in teaching or activist capacities are well-placed to alert young people to the daily relevance of science, as we are demanding accessible and illustrative learning materials that engage rather than deter students. We can also challenge the myth that science is “hard” and difficult, whenever raised by students, colleagues, by our institutional practices or in the media. Only by disrupting the symbolic hegemony which perpetuates the Physical sciences as a masculine and “hard” domain will we increase the presence of women in the sector.International research has shown the social and economic benefits of widening participation in STEM. Representation of women has been shown to be especially problematic in the Physical sciences. Having shown that our wider cohort study’s findings support prior research evidence that young women are less likely than are young men to pursue Physics, the present paper explored respondents’ explanations for such patterns. We have drawn on interviews that asked students and parents directly about gender and access to Physics to identify the various discourses and narratives at play in respondents’ talk. These discourses and narratives are frequently contradictory, and a discourse of continuing gender discrimination in the Physical sciences was used by some respondents to contest discourses that position the underrepresentation of women in Physics as “natural” and/or their own fault. However, these latter discourses were very powerful, respectively evoking opportunities as equal or of Physics as quintessentially masculine to produce women as deficient. It is argued that we need to find ways to work with young people to unpack these discourses in order to reflect critically on the status quo. Presentations of STEM as “hard” and difficult need to be challenged to encourage identification and participation from non-traditional STEM students, and diversity of representation in the Physical sciences needs to be taken seriously to the same end. In these ways we may support greater equality of access to the Physical science, benefitting individuals and society.


The atoms remain in the cages upon heating to 400 K. The trapping and release of Ar is studied combining surface science methods and density functional theory calculations. While the frameworks stay intact with the inclusion of Ar atoms, the permeability of gasses  through them is significantly affected, making these structures also interesting candidates for tunable atomic and molecular sieves. These findings enable the study of individually confined noble gas atoms using surface science methods, opening up new opportunities for fundamental research.The confinement of noble gases on nanostructured surfaces, in contrast to bulk materials, at non-cryogenic temperatures represents a formidable challenge. In this work, individual Ar atoms are trapped at 300 K in nano-cages consisting of silicate hexagonal prisms forming a two-dimensional array on a planar surface. The trapping of Ar atoms is detected  While noble gases can be trapped in 3D porous structures, immobilizing them on 2D surfaces represents a formidable challenge. Here, the authors cage individual argon atoms in 2D model zeolite frameworks at room temperature, providing exciting opportunities for the fundamental study of isolated noble gas atoms using surface science methods. Immobilizing single atoms of noble gases at room temperature within a two-dimensional 2D) array of nano-sized cages is both fundamentally interesting and technologically relevant. This could allow the vast artillery of surface science tools to study with exquisite level of detail the behaviour of individual unreactive atoms and molecules in nano-confinement, as well as the mechanism by which they enter and exit the cages. In addition, the knowledge gained using this approach could provide guidelines for the design, selection and improvement of adsorbent materials and membranes for gas separation1D array o3Excellent candidates for these cages are found in 2D silicate bilayer frameworks, consisting of an array of polygonal prisms forming a 2D self-containing structure, that interacts weakly with a single crystal metal substrate onto which is grown56913142, CO and O2  and aluminosilicate (Al0.16Si0.84O2) frameworks were grown on a Ruthenium(0001) surface, as described in detail elsewhere5in situ by Ambient Pressure X-ray Photoelectron Spectroscopy (AP-XPS). The 2D framework is first exposed to 0.5 mbar Ar. The AP-XPS spectrum in 3/2 peak at 243.55 eV (P1) and a weak Ar 2p3/2 peak at 241.85 eV (P2). As the Ar pressure is lowered, the P1 peak gradually decreases and eventually disappears, while the P2 peak still remains even after evacuating the gas. P1 can then be assigned to gas phase Ar. Reference experiments carried out on a clean Ru(0001) surface show the gas phase Ar peaks only  when compared to spectra taken at θ=20°. This indicates that the shoulder corresponds to Ar atoms at a deeper location and are assigned to the interface between the silica framework and the Ru(0001) surface (Arinter) (cage). The peak assignment is confirmed by DFT calculations at Θ=0.25 , where the Ar 2p3/2 binding energy (EBE) of Arcage is 1.12 eV higher than that of the Arinter (see Well-ordered 2D silica (SiOaks only  and no eArinter) , while tΘ=0.15. Note that the potential existence of larger polygonal prisms, in addition to the hexagonal prisms cages, may result in underestimating the coverage as the total density of hexagonal prism cages may be smaller2727By comparing the ratio of peak areas between the Ar 2p and Si 2p , the totinter/Arcage ratio is reduced from 0.24 to 0.11, suggesting that the Ar atoms trapped at the interface are less stable than those in the nano-cages. It is worth noting that the inclusion of Ar atoms in silica bilayer films does not change the characteristic phonon vibration frequency of the framework associated with the Si–O–Si linkage perpendicular to the surface plane at 1,296 cm−1, as shown in IRRA spectra in Upon annealing the sample to 400 K , the are0.16Si0.84O2) (ref. x<0.25)  ref. . The topO2) ref. . The surO2) ref. , corresp25) ref. , as evid0.2Si0.8O2) bilayer film at room temperature. The spectra as a function of time are shown in rTo further examine the kinetics of desorption of Ar atoms from the nano-cages, time dependent XPS was carried out for an aluminosilicate . It should be noted that the exponential pre-factor and desorption energy may depend on the coverage of trapped Ar even for this simple system. The frequency factor used in this assumption is the one commonly chosen, when using the Redhead equationwhere p(2 × 1)−O/Ru(0001) (2)8/4O/Ru(0001)) with two Ar concentrations were modelled 16/8O/Ru(0001) in Θ=0.25 and Ar-(SiO2)8/4O/Ru(0001) in Θ=0.50). The structural changes of the silica film upon Ar trapping are quantified by following three different parameters: the changes in the thickness of the silica film (dz(Ot−Ob)) defined by the distance between O atoms in the top and bottom layers of the silica film; the interlayer distance (dz(Ru−Ob)) defined by the distance between the top layer of Ru(0001) and the bottom layer of Ob atoms in the silica film; and the size of the cages characterized by the distance between atoms at opposite sides of the six-membered rings within the five different atomic planes in the silica film: that is, the average nearest neighbour Si–Si distance in the top layer (d(Sit−Sit)) and bottom layer (d(Sib−Sib)), the average O–O distance in the top layer (d(Ot−Ot)), the middle layer (d(Om−Om)) and the bottom layer (d(Ob−Ob)). Trapped Ar atoms in the nano-cages of the silica film (Arcage) cause expansions at the Om layer, where d(Om−Om) increased by 0.08 Å at −1, as direction of the expansion is orthogonal to the Si–O–Si linkage perpendicular to the surface plane, which is responsible for the aforementioned vibrational mode. On the other hand, trapped Ar atoms at the interface (Arinter) push the silica film away from the Ru substrate, where the inter-space dz(Ru-Ob) increased by 0.41 Å at To explore the Ar trapping mechanism, DFT calculations were carried out for the case of silica bilayer. Silica bilayer films on at =0.25  and by 05 , SiO2/O/Ru(0001) and Ar, respectively. All energies refer to the optimized structures of the systems and subsystems. The calculated ΔEtrap (cage) is −34 meV at Etrap (inter) is 331 meV at where Etrap (cage) and ΔEtrap (inter) exhibit opposite trends with respect to Θ. ΔEtrap (cage) at d(Om–Om) increases from 6.28 to 6.31 Å, resulting in a release of the stress caused by Ar trapping. In contrast, ΔEtrap (inter) at inter−silica/O/Ru(0001) and silica−O/Ru(0001) in the surface normal direction, which is discussed in more details by the analysis using interaction energies Moreover, Δd(Sit−Sit) increases from 6.23 to 6.26 Å, and d(Ot–Ot) increases from 5.39 to 5.55 Å. The calculated The activation energy for Ar adsorption , which is within tunnelling range, given the ∼10 eV energy gain resulting from the difference between the first ionization energy of Ar (15.76 eV) and the O-Ru(0001) work function (∼6 eV)2, O2 and CO1920−1  below the silica bilayer21−1 once CO is evacuated  to trap the Ar atoms. These trapped Ar atoms are removed from the cages upon heating to 450 K. Note that higher pressures, above 2 mbar, are needed in IRRAS experiments, showing that the presence of X-rays in XPS experiments aid in trapping the Ar atoms. The desorption activation energy was determined to be ∼1.08±0.18 eV from time-dependent XPS, in agreement with DFT calculations carried out as part of this work. While noble gases have been trapped before in three-dimensional porous materials, this is, to the best of our knowledge, the first report of a noble gas trapped in cages on a two-dimensional porous material. This is of major importance for fundamental studies as it allows the use of surface science techniques for the study of individual inert atoms in confinement, opening exciting opportunities in the field.We report the room-temperature trapping of individual Ar atoms within hexagonal prism silicate nano-cages forming a two-dimensional framework on a flat Ru(0001) surface. The trapping is confirmed In addition to the possibility of using these cages for trapping small atoms and molecules and study them in confinement, the presence of Ar atoms within the cages affects the passage of small molecules through the 0.5 nm thick two-dimensional framework, allowing the reversible tuning of the permeability of the smallest molecular sieve ever reported.+ sputtering and annealing at 1,400 K. It was then exposed to 3 × 10−6 mabr O2 at 1,200 K in order to form a chemisorbed 3O-(2 × 2)-Ru(0001) overlayer. The silica and aluminosilicate bilayers were grown on the oxygen pre-covered ruthenium surface. Briefly, Si (and Al) was thermally evaporated onto the 3O-(2 × 2)-Ru(0001) surface at room temperature under 2 × 10−7 mbar of O2, followed by oxidation at 1,200 K in 3 × 10−6 mbar O2 for 10 min and slowly cooled down in O2 environment.The Ru(0001) single-crystal surface was cleaned with cycles of Ar−9 mbar) of the end-station was equipped with a differently pumped hemispherical analyser (Specs Phoibos 150 NAP), which was offset by 70° from the incident synchrotron light. Unless otherwise stated, the sample surface normal is 20° off the axis of the electron analyser. The Ar gas was introduced into the main chamber through precision variable leak valves for the trapping studies. Note that the spectra in AP-XPS measurements were carried out at the beamline X1A1 of the National Synchrotron Light Source (NSLS) and the Coherent Soft X-ray Scattering and Spectroscopy beamline (CSX-2) of the National Synchrotron Light Source II (NSLS-II). The main chamber (base pressure 2 × 10−10 mbar). IRRA spectra were collected at 4 cm−1 resolution using a grazing angle of 85° to the surface normal. High purity CO and Ar exposure was carried out in a separate cell sealed from the UHV chamber by a Viton O-ring.The IRRAS measurements were performed in a separate UHV system (base pressure 5 × 102) physisorbed on O/Ru(0001) with the unit cell size defined by a=5.392 Å and b=9.339 Å. Si atoms in the bilayer were chosen to sit on hollow sites of Ru(0001). The number of chemisorbed oxygen atoms on Ru(0001) corresponds to the coverage of p(2 × 1)-O/Ru(0001)2)8/4O/Ru(0001), the unit cell was used with 50% of the nano-cages of silica films or the corresponding inter-space filled with Ar atoms (Θ=0.50). In Ar-(SiO2)16/8O/Ru(0001), a 2 × 1 supercell was used with a 25% filling (Θ=0.25). In the surface normal direction, c=27 Å was chosen to ensure the vacuum region to be at least 10 Å thick, except for nudged elastic band calculation where the minimum of vacuum region was 7.5 Å in the initial state.DFT calculations were performed using plane-wave basis set and the projector augmented wave formalism implemented in the Vienna Ab initio simulation package (VASP)34362)8/4O/Ru(0001) and Ar-(SiO2)16/8O/Ru(0001), respectively. Ar atoms, silica films and top two layers of the Ru substrate were allowed to relax during the structure optimization until forces were smaller than 0.01 eV Å−1. The dipole correction methodEBE) were calculated using the transition state modelEBE values of Ar 2p were given relative to that of Ar 2p at the interface.A kinetic energy cutoff of 800 eV was used to meet the required numerical convergence for vdW-DF-cx with hard pseudopotentialsAll data that support the findings of this study are available from the authors on request.How to cite this article: Zhong, J.-Q. et al. Immobilization of single argon atoms in nano-cages of two-dimensional zeolite model systems. Nat. Commun.8, 16118 doi: 10.1038/ncomms16118 (2017).Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


Sodium silicate and sodium hydroxide (NaOH) solution were used as alkaline activator with a NaOH concentration of 14 M. The geopolymer samples were prepared with different S/L ratios  and Na2SiO3/NaOH ratios . The main evaluation techniques in this study were compressive strength, X-Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), and Scanning Electron Microscope (SEM). The results showed that the maximum compressive strength (11.9 MPa) was obtained at a S/L ratio and Na2SiO3/NaOH ratio of 1.5 and 2.5 at seven days of testing.This paper investigates the effect of the solids-to-liquids (S/L) and Na The study of alkali-activated binder was started by Purdon in the 1940s in which blast furnace slag was activated with sodium hydroxide (NaOH) solution . BesidesGeopolymer systems can be divided into two types of binding system which are silica-aluminum (Si + Al) with medium to high alkaline solution and silica-calcium (Si + Ca) with a mild alkaline solution . For the2SiO3) leads to higher geopolymerisation rates compared to hydroxide alone [2SiO3 solution acts as binder [For the alkaline activator solution, the combination of NaOH and sodium silicate solution  ratio which is important in developing the mechanical strength of the geopolymer [The mix design for geopolymers can be divided into solids/liquid (S/L) and sodium silicate/NaOH  in natural zeolite based geopolymers showed that increasing the Na2SiO3/NaOH ratio up to 1.5 increased the compressive strength, but beyond that the strength was decreased [2SiO3/NaOH ratio to produce high strength geopolymer is in the range 0.67–1.00 [ et al. [2SiO3/NaOH ratios (0.4 and 2.5) on the performance of fly ash based geopolymer. They found that when the ratio increased the strength of geopolymer also increased.The influence of the Naecreased . This maecreased . Researc.67–1.00 . Meanwhi2SiO3/NaOH) and curing temperature on geopolymer paste. The results of the geopolymer paste are evaluated in terms of compressive strength, X-Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), and Scanning Electron Microscope (SEM).Malaysia is one of the world’s largest producers of palm oil products and as such the waste material from this industry is also widely available and estimated to be about 44.9 million tonnes. The solid wastes are burned in the boiler to generate electricity at the palm oil mill and the palm oil boiler ash (POBA) or bottom ash is obtained at the lower compartment of the boiler. Generally, palm oil fuel ash (POFA) is used as a cement replacement in concrete as POBA contains coarse particles. As such this study investigates the utilization of POBA in geopolymers and the effect of solids-to-liquids ratio (S/L), alkaline activator ratio  was achieved at S/L and Na2SiO3/NaOH ratio of 1.5 and 2.5. Furthermore, at S/L ratio 1.0, 1.25 and 1.5 the maximum compressive strength was obtained at a Na2SiO3/NaOH ratio of 2.5. The compressive strength of geopolymer paste increased when the amount of Na2SiO3 increased. Moreover, the use of Na2SiO3 helps to improve the geopolymerisation process by accelerating the dissolution of source material [2SiO3/NaOH ratio increased the geopolymerisation rate. Conversely, when the Na2SiO3/NaOH ratio was more than 3.0 the compressive strength tended to decrease for all S/L ratios. This may be due to excessive alkali content which retards the geopolymerisation process. It occurs when Al-Si phase precipitation prevents interaction between reacting material and alkaline activator thus reducing the activator concentration [The strength of the geopolymer paste with different solid/liquid (S/L) and Namaterial . It was material  that incntration .2SiO3/NaOH ratios 2.5 and 3.0 the geopolymer paste was unable to mix due to lower workability. As such, geopolymer strength was unable to be acquired. This condition showed that the Na2SiO3/NaOH ratio was correlated to the workability and compressive strength of the geopolymer paste. For this S/L ratio, the maximum strength (11.5 MPa) was contributed by a geopolymer sample with a Na2SiO3/NaOH ratio 1.5.However, at S/L ratio 1.75 with Na− that was left in the system, thus weakening the geopolymer structure [2SiO3/NaOH ratios did influence the compressive strength and the workability of geopolymers. The optimum mix design for POBA geopolymer paste was obtained at S/L and Na2SiO3/NaOH ratios of 1.5 and 2.5, respectively.Meanwhile, for S/L ratio 1.0 and 1.25 contributed a low strength of geopolymer paste and can be due to a high content of alkaline activator. The high content of alkaline activator produced excessive OHtructure . From th et al. [ et al.  also men et al. ,18,19,20 et al. [ et al. [Geopolymer samples exhibited slightly reduced compressive strength after curing at temperature 90 °C. Bakharev  found th et al.  conclude et al. . Additio[ et al.  stated tThe X-Ray Diffraction (XRD) analysis for S/L of 1.0, 1.25, 1.5, and 1.75 with maximum compressive strength is presented in The peaks of cristobalite and quartz at 2θ = 21° and 2θ = 22° in POBA still exists in geopolymer paste. Besides that, the geopolymer paste with the different mix design also demonstrated an amorphous to semi crystalline phase which is the same as with POBA. Since the crystalline peaks were detected more with a S/L ratio of 1.5, it can be concluded that the existence of these peaks helps to increase the strength of the geopolymer paste .−1 were due to stretching vibrations OH and HOH. In addition, the bending vibration of HOH was detected at 1651–1655 cm−1. The existence of these bondings was related to entrapped water molecules in the geopolymeric network.−1[2 from the atmosphere [The stretching vibration of O-C-O was still detected in each of the geopolymer samples at 1411–1412 cm−1 which wamosphere .−1 indicated the formation of aluminosilicate gel [−1. At 583–721 cm−1, symmetric stretching vibrations of Si-O-Si and Al-O-Si were identified. In the meantime, the bending vibrations of Si-O-Si and O-Si-O were found at area 467–479 cm−1.The band attributed to asymmetric stretching vibration of Si-O-Si and Al-O-Si around area 1011–1027 cmcate gel . Besides−1 indicating the presence of stretching vibrations OH and HOH as in −1 where all these bondings represent water molecule. The band at 1412–1432 cm−1 represents the stretching vibration of O-C-O. The aluminosilicate gel (asymmetric stretching vibrations Si-O-Si and Al-O-Si) were detected at 1011–1023 cm−1. When the curing temperature increased, the asymmetric stretching vibrations Si-O-Si and Al-O-Si also shift to lower frequency. Besides that, the symmetric stretching vibration Si-O-Si was found at 776–794 cm−1.The broad band appeared in all IR spectra in the region 2287–3435 cm−1. However, at 467–476 cm−1, bending vibrations Si-O-Si and O-Si-O were identified which represents quartz, thus indicating that quartz which originally exists in POBA did not fully react with the alkaline activator solution which correlates with the finding in XRD analysis.In addition, the symmetric stretching vibrations Si-O-Si and Al-O-Si were located at 621–721 cm2SiO3/NaOH 2.5 are shown in For each S/L ratio  the samples that contributed the maximum compressive strength are displayed in 2SiO3/NaOH 2.5 demonstrated a denser geopolymer matrix compared to previous figures. Therefore, the quantity of alkaline activator affects the saturation rate of the geopolymerisation process and the strength of geopolymer. In this sample, microcrack was detected and may be due to the sample preparation for the SEM analysis.Besides that, 2SiO3/NaOH 2.5 as in Geopolymer samples with ratio S/L 1.25 and Na2SiO3/NaOH 1.5 and the maximum compressive strength (11.5 MPa) was obtained. For this mix design with Na2SiO3/NaOH more than 2.0, the geopolymer samples were unable to be prepared due to low workability. As such, from the figure it shows incomplete geopolymerisation due to less alkaline activator available to react with POBA.The morphology of geopolymer samples with different curing temperature is displayed in  et al. [In the meantime, a geopolymer sample cured at 40 °C showed less incomplete geopolymerisation and a dense matrix was formed. At this temperature, the geopolymerisation process starts only slowly to form the geopolymer matrix. A dense gel-like matrix imbedded with POBA particles is seen in  et al.  mentioneAt a curing temperature of 60 °C d, a densThe POBA was obtained from United Palm Oil Mill in Penang, Malaysia where it contained large particles which included unburned nutshells, fibers, and kernels as in 2SiO3) solution were used as alkaline activator to synthesize POBA. NaOH pellets with 99% purity brand name of Formosoda-P, from the Formosa Plastic Corporation, Taiwan were used to produce the NaOH solution. The NaOH solution with 14 M concentration was prepared by diluting NaOH pellets with distilled water. Sodium silicate (Na2SiO3) solution was obtained from South Pacific Chemical Industries Sdn. Bhd. (SPCI), Malaysia.NaOH solution and sodium silicate (Na2SiO3/NaOH ratio), six solutions were prepared according to the ratio 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 [2SiO3/ NaOH ratios. All the samples were cured at 80 °C for 24 h and left at room temperature for 7 days for compressive strength testing.The fine POBA was mixed with an alkaline activator with four different S/L  ratios such as 1.0, 1.25, 1.5, and 1.75. Meanwhile, for alkaline activator solution , 40 °C, 50 °C, 60 °C, 70 °C, 80 °C, and 90 °C for 24 h [After the optimum S/L ratio and Nafor 24 h . Then, a2SiO3 solution until a homogeneous solution was achieved. Then, the alkaline activator was mixed with POBA in the mechanical mixer for about 5 min approximately. The geopolymer paste was placed in a mould (50 × 50 × 50 mm) and then placed in a vibrating table for 10 s to remove entrapped air. The geopolymer samples that underwent heat curing were covered with a plastic sheet to avoid moisture loss.The alkaline activator solution was prepared by mixing NaOH solution with NaThe strength of geopolymer pastes was measured using compressive strength testing based on American Society for Testing and Materials (ASTM C109). The testing was carried out using an Instron machine series 5569 Mechanical Tester  with maximum loading 50 KN and speed rate 50 mm/min. Three samples were used for each mix design to determine the optimum compressive strength.The phase of geopolymer paste that leads to maximum compressive strength was determined using XRD. The geopolymer paste was crushed into powder and tested using a XRD-6000, Shimadzu X-ray diffractometer using Cu-Kα radiation generated at 30 Ma and 40 kV. The samples were tested in powder form starting from 10° to 90° (2θ) at 0.04° steps with step time 1.0 s.−1 to 4000 cm−1.The FTIR analysis was conducted using a Perkin Elmer FTIR Spectrum RX1 Spectrometer. The samples of geopolymer paste were prepared in powder form where they were mixed with potassium bromide (KBr), then a cold press machine was used with a 4 ton loading for 2 min. All the samples used wavelengths from 450 cmThe microstructure of POBA geopolymer paste was observed using Scanning Electron Microscope (SEM). The geopolymer paste samples were cut into small pieces and coated with platinum by using an Auto Fine Coater. A JSM-6460LA model Scanning Electron Microscope  was used in this analysis.(a)2SiO3/NaOH = 2.5 with maximum compressive strength 11.9 MPa. During XRD analysis, the existence of albite which is due to the formation of an aluminosilicate gel was detected in the optimum mix design. The ratio of Na2SiO3/NaOH also plays an important role in the mix design of the geopolymer paste. When the ratio of Na2SiO3/NaOH is more than 2.5, the compressive strength for S/L  tends to decrease due to excessive alkali content that retards the geopolymerisation process.The optimum mix design for geopolymer paste using POBA is S/L = 1.5 and Na(b)The optimum curing temperature for POBA in this study was 80 °C which led to maximum compressive strength (11.5 MPa) at 24 h curing period. Thus, heat curing for geopolymer is needed in order to obtain sufficient strength and with heat curing, the geopolymerisation becomes more rapid. The presence of albite during XRD analysis was also detected in the geopolymer sample cured at 80 °C. The morphology of the geopolymer samples showed changes in the matrix when the curing temperature was increased.From this study the results led to the conclusions below: