During conversations participants alternate smoothly between speaker and hearer roles with only brief pauses and overlaps. There are two competing types of accounts about how conversationalists accomplish this: (a) the signaling approach and (b) the anticipatory (‘projection’) approach. We wanted to investigate, first, the relative merits of these two accounts, and second, the relative contribution of semantic and syntactic information to the timing of next turn initiation. We performed three button-press experiments using turn fragments taken from natural conversations to address the following questions: (a) Is turn-taking predominantly based on anticipation or on reaction, and (b) what is the relative contribution of semantic and syntactic information to accurate turn-taking. In our first experiment we gradually manipulated the information available for anticipation of the turn end (providing information about the turn end in advance to completely removing linguistic information). The results of our first experiment show that the distribution of the participants’ estimation of turn-endings for natural turns is very similar to the distribution for pure anticipation. We conclude that listeners are indeed able to anticipate a turn-end and that this strategy is predominantly used in turn-taking. In Experiment 2 we collected purely reacted responses. We used the distributions from Experiments 1 and 2 together to estimate a new dependent variable called Reaction Anticipation Proportion. We used this variable in our third experiment where we manipulated the presence vs. absence of semantic and syntactic information by low-pass filtering open-class and closed class words in the turn. The results suggest that for turn-end anticipation, both semantic and syntactic information are needed, but that the semantic information is a more important anticipation cue than syntactic information. Participants in a conversation have a number of tasks that they have to perform simultaneously. They have to comprehend the speaker’s utterance while at the same time they need to prepare their response to that utterance, preferably before the current speaker ends their turn. Despite the complexity of these processes the alternation between the speaker and the hearer roles is generally timed with only short pauses and overlaps . This coanticipatory approach, in which it is assumed that participants are able to predict the end of a turn in advance, and the signaling approach, which assumes that listeners perceive specific signals to detect the end of a turn.There are two competing main approaches providing an explanation for the turn-taking organization: the The aim of this study was first to determine the relative contribution of these two proposed mechanisms to turn-taking and second, to investigate which linguistic information sources listeners predominantly use for end-of-turn anticipation. To this end, we conducted a series of button-press experiments with turns from natural conversations while manipulating both the respective critical information sources and the task.The anticipatory approach argues that the precise timing in conversations can only be explained by the listeners’ ability to make accurate predictions about the end of the speaker’s utterances. Depending on the assumed anticipatory model listeners use various kinds of information to anticipate. The first to claim that listeners are able to anticipate a turn ending were anticipate these signals but react to them after having perceived them. Influential proponents of the signaling approach who did numerous studies on finding explicit turn taking signals are In contrast, the signaling approach assumes that turn transitions are regulated by an exchange of conventional vocal or gestural signals e.g., . So in tThe standard argument against the signaling approach is that the relevant cues occur too late in the speaker’s turn to enable timely speaker changes. As a counter-argument, We want to suggest that the presence of gaps longer than 200 ms does not necessarily mean that the turn before the gap was reacted to. Speakers often intentionally delay the production of so-called ‘dispreferred’ responses, which leads to longer pauses .The stimulus collection procedure is the same as the one described in For the audio recordings we put the participants in two separate rooms and required them to wear closed headphones. Directional microphones were placed on a table in front of them. We established a telephone-like connection between them, such that both participants could hear both themselves and their interlocutor. The speech of each of the two participants was recorded separately on the two channels of a stereo recording device. This way, we avoided cross talk between the participants in our recordings. The participants rapidly got used to the recording situation and the resulting conversations appeared natural and lively.Figure 1 shows the distribution of the FTO values.After recording the corpus, the conversations were transcribed, registering overlaps, pauses, laughter, turn beginnings and endings, assessments , and conTable 1) 1.Although the general shape of the FTO distribution resulting from the German telephone corpus looks similar to the Dutch FTO distribution from Table 2 presents some descriptive statistics of the target turns.From this corpus we randomly selected 100 target turns and an additional 16 turns for practice purposes. We took care that the turns contained at least five words so that the participants in the planned button-press experiments obtained enough information content to potentially base their reaction on. Furthermore, we made sure that the random selection reflected the distribution of pauses and overlaps of the natural conversations. Furthermore we balanced the sex of the speaker in the target turns . The total number of different speakers in our target stimuli was 16. After selecting the target turns, we extracted them into individual sound files using Praat  and creaNatural-Turn. The target turn was presented as it occurred in the natural conversations. In this condition the participants had access to all potentially relevant information to base their anticipation orreaction on.Advance-Knowledge. The participants could first read the content  of the turn before they heard the target stimulus. Because the participants knew in advance how the turn was going to end, they were, in principle, maximally capable to anticipate the turn end. In this condition the response distribution of anticipated responses was measured.Scrambled-Word-Order. We randomly changed the order of the words within the target turn using Praat. The pauses between the words in the original were assigned to the subsequent word. The resulting stimuli therefore had the same duration as the Natural-Turn stimuli. In this condition there was no sequential word-order information to base the anticipation on, but there were still words present. Thus, the predictability of a word on the basis of its preceding words is switched off, i.e., the cloze probability  each containing 25 target turns. Within each block there were four practice trials followed by the 25 target turns. We created eight different experimental lists. In the first four lists we permutated the block order according to a Latin-square design. The remaining four lists were the same as the first four lists with the block order as well as the presentation order of the stimuli reversed. Each of the target turns appeared in all four conditions across the lists but none appeared twice within the same experimental list.The participants received a written instruction that they had to listen to short audio fragments, taken from real conversations, and to press a button as soon as they thought the speaker in the fragments would finish speaking. They were informed that they would be presented with four different blocks, and that in one of these blocks they had to first read the content of the fragment before they heard the corresponding audio fragment. Furthermore, they were informed that in two blocks the stimuli were manipulated acoustically. The stimuli were presented to them via closed headphones. We randomly assigned the participants to one of the eight experimental lists (10 per list).The participants were presented first with the four practice trials and after that with the corresponding trial block. After each practice block the participants got the chance to ask the experimenter questions. Each experimental block contained a visual countdown from 3 to 1 followed by the auditory presentation of the stimuli. As soon as the participants pressed the button the sound was immediately cut off. In this way we made sure that the participants got no feedback about their performance. The trial block Advance-Knowledge differed from the other trial blocks because after the visual countdown the participants were presented with a written sentence, representing the content of the turn. After pressing the button the sentence disappeared and the acoustic presentation of the stimulus started.For the presentation of the stimuli we used the E-Prime software package ,b, whichFigure 2 shows the BIAS distributions for the four different conditions. Figure 3 shows an overview of the average BIAS per condition. The average BIAS is negative in all conditions, which gives a first hint that participants tried to anticipate the turn ending, rather than wait until the turn fragment was over.We first calculated the BIAS, which is defined as response time minus the duration of the target turn. F1 = 23.259, p < 0.001; by items: F2 = 18.82, p < 0.001). Bonferroni-corrected paired t-tests, pairing over identical turn fragments from the two conditions under comparison, revealed that the Natural turn condition led to significantly more negative BIAS than the Noise and the Scrambled-Word-Order condition. The latter condition led to significantly more negative BIAS than the Noise condition. Whereas the BIAS in the Advance-Knowledge and the Natural turn condition did not differ significantly from each other.An ANOVA for the dependent variable BIAS showed a significant effect for presentation condition . This provides “strong” evidence for the null hypothesis.The Bayesian paired t-test resulted in “substantial” evidence (BF = 0.1) for the null hypothesis. This analysis allows us to conclude that there is no statistically reliable difference between the BIAS in the Advanced-Knowledge and the Natural Turn condition. So the participants’ button press accuracy with the natural turns was just as good as when they had advance information about the content of the turn. This finding suggests that participants are indeed able to anticipate a turn ending, and that they are using this strategy to predict when a turn is going to end.Comparing the subject means of the BIAS variable with the Bayesian paired The significant difference between Scrambled-Word-Order and Noise condition indicates that having access to words (even though they were in the wrong order) still allowed them to anticipate better than chance.response consistency. To investigate the response consistency over conditions we computed the Entropy for every stimulus/condition pair  = 62.5, p < 0.001). Bonferroni-corrected paired t-tests revealed that all differences between individual conditions were significant (p < 0.001), the exception being the difference between Advance-Knowledge and Natural-Turn.As in the BIAS analysis, an ANOVA of the Entropy showed a main effect for condition t-test. The analysis (BF = 0.2) provided “substantial” evidence for the null hypothesis .Again we compared the Entropy values in the Advance-Knowledge and Natural-Turn condition using a Bayesian paired The analysis of the participants’ button press consistency supports the interpretation of the BIAS results. The results showed that the Entropy in the Natural-Turn condition and the Advance-Knowledge condition was comparable. Thus, in the Natural-Turn condition the participants were able to consistently and accurately anticipate the turn-end and consequently used anticipation as a strategy to tell when a turn was over.In contrast, in the Scrambled-Word and the Noise condition the Entropy values were significantly higher than in the other two conditions. This suggests that the participants tried to anticipate the turn-end rather than just waited for the end of the fragment, which lead to significantly broader distributed responses. In addition, the average Entropy in the Scrambled-Word order condition was significantly lower than in the Noise condition. This corresponds to the BIAS analysis above where participants in the Scrambled-Words condition were significantly more accurate in detecting the turn end. Hence, the participants are more consistent and accurate in the end-of-turn projection when they have access to words compared to when they only hear noise. One explanation of this finding could be that even with the scrambled word order listeners are able to recognize the basic meaning of the turn, enabling them to roughly guess when the turn finishes. Additionally, it is possible that once the participants “gambled” that a certain word was the last word, they could anticipate the end of that word, as suggested by research on auditory word recognitions .We showed in Experiment 1 that listeners in dialog are indeed able to anticipate the end of the speaker’s turn and that they consistently use this ability to predict when a turn is going to end. When listening to the natural turns the participants showed the same response accuracy and consistency as when they knew the end of the turn in advance. Our results are in line with earlier findings that listeners anticipate turn endings and that natural language is predictable to a certain degree . Hence, We now have an empirically derived distribution of anticipation times, from a task in which the participants were asked to anticipate turn-ends, and had the information to do so. To find out about the distributional properties of the reaction process, which we assume also plays a role, we need to study the reaction time distribution of participants that had no information to anticipate (as in the Noise condition of Experiment 1) but in addition, were not instructed to anticipate, but rather to respond to the end of the stimulus. To this end, we conducted Experiment 2.An empirically estimated anticipation distribution is provided by the Advanced-Knowledge condition of Experiment 1. In Experiment 2 we want to find the other distribution based on pure reaction time. To this end, we used the Noise stimuli from Experiment 1, but now explicitly instructed the participants to respond only after they perceived the end of the fragment.Twenty native speakers of German participated in the second experiment . None of the participants in Experiment 2 had taken part in Experiment 1.Each participant was presented with all of the 100 noise target stimuli created in Experiment 1. In addition we took four stimuli from the practice block for practice purpose. There were two experimental lists, whereas in the second list the presentation order of the stimuli  was reversed.The participants received a written instruction that they had to listen to noise fragments and press a button as soon as the noise stopped.Within the experiment the participants were presented first with the four practice trials followed by the 100 target stimuli. After the practice trials the participants got the opportunity to ask questions. After the presentation of the first 50 target stimuli there was a break. The participants had to start the presentation of the remaining 50 stimuli by pressing a button, so that they could determine the length of the break by themselves. The participants were randomly assigned to one of the two experimental lists (10 per list).Figure 5. As expected, the reaction time distribution shows a pronounced sharp peak at a positive FTO  whereas the anticipation distribution is broader and extends into the negative FTO range. In addition, the mode of the anticipation distribution is at a negative FTO value. The intersection of the two distributions characterizing the response time at which anticipation and reaction are equally probable is in good agreement with the 200 ms cut-off value proposed by The reaction time distribution obtained in this experiment is presented together with the anticipation distribution from Experiment 1 in relative probability of anticipation and reaction. The so-called Reaction Anticipation Proportion (RAP) value is defined as the natural logarithm of the ratio of anticipation and reaction probability.This is why we define a new measure designed to capture the Ant(t) and reaction probabilities PReac(t) at time t.Equation 1: Definition of the RAP value as logarithmized ratio of the anticipation PAnt(t)P and Reac(t)P denote the probability that a response at time t was an anticipation or reaction, respectively. These probabilities were computed in R  ted in R  using thFigure 6. The RAP is positive for a broad FTO interval ranging from about -750–200 ms and negative for FTO values in the interval from about 200–550 ms. Hence, reaction is more probable only in a relatively brief time interval. In addition, the influence of the pronounced sharp peak of the reaction distribution on the RAP value is weakened by the non-vanishing anticipation probability in the corresponding FTO range.The RAP as a function of FTO is presented in To demonstrate and validate the use of the RAP measure we applied it to the data analysis of the Natural turn and Noise conditions of the first experiment. The mean RAP value of the Natural turn condition was 0.60 and of the Noise condition -0.53. This supports our interpretation of the results of Experiment 1 that in the Natural turn condition the participants anticipated the end of the turn. In contrast, the responses in the Noise condition were predominantly based on reaction. It is noteworthy that the absolute value of the mean RAP of the two conditions are comparable, indicating that anticipation and reaction are about equally probable in the correspondingconditions.We used the RAP measure to study the relative contribution of semantic and syntactic information in end of turn anticipation in Experiment 3.In Experiment 3 we investigated the relative role of syntax and semantics as a cue for end-of-turn anticipation. Experimental as well as corpus-based studies  suggest 2.To tease apart semantic and syntactic information in natural communication we used the widely used distinction between open and closed class words in linguistics and psycholinguistics. Open class words in German contain nouns, verbs, adjectives, adverbs, and proper names. The open class words are “rich in referential meaning” , p. 539 Therefore, in this experiment, we operationalized semantic information as open class words, and syntactic information as closed class words. To address the question which information source listeners use for anticipation, we conducted a similar reaction time experiment as in Experiment 1. We manipulated the presence of semantic and syntactic information in the turn fragments from Experiment 1 by acoustically manipulating the recognizability of open- and closed class words. To evaluate the influence of these manipulations on the anticipation and reaction probability we used the RAP measure introduced before.If only syntax is used for end-of-turn prediction, then the absence of closed class words should result in a decrease in anticipated and an increase of reacted responses. On the other hand, if semantic information is used for the anticipation of a turn ending, we expect a deteriorated anticipation performance in absence of open class words. However, if both semantic and syntactic information are used to the same extent, then the effect should be similar in absence of content as well as closed class words.Eighty native speakers of German who neither participated in Experiment 1 nor in Experiment 2 participated in Experiment 3 .Table 4 for an example of one experimental stimuli in all conditions). Natural Turn: the target turn was presented as it occurred in the natural conversation. Closed-Class-Words-Removed: the closed class words were “removed” by low-pass filtering (at 500 Hz Hanning Window). Open-Class-Words-Removed: by low-pass filtering we “removed” the open class words (at 500 Hz Hanning Window). Intonation-Only: the whole turn was low-pass filtered (at 500 Hz Hanning Window) so that no words could be recognized, but intonation remained intact. This condition served as a comparative baseline since neither syntactic nor semantic information were left in the turn fragment.The same 100 target and 16 practice turns as in Experiment 1 were used. We created four different versions of each turn fragment  Natural-Turn, (2) Intonation-Only, (3) The stimuli from the Closed-Class-Words-Removed and Open-Class-Words-Removed condition. The latter were presented within one block. The blocks Natural-Turn and Intonation-Only contained 25 and the combined block Closed-Class-Words-Removed and Open-Class-Words-Removed 50 target turns (25 stimuli from Closed-Class-Words-Removed and 25 stimuli from Open-Class-Words-Removed). Within each block there were four practice trials followed by 25 and 50 target turns, respectively. We created eight experimental lists. As in Experiment 1, we permutated the block order in four of these lists according to a Latin-square design. The remaining four lists were the same as the first four lists with the presentation order of the target stimuli and the practice trials reversed. As in Experiment 1 the lists were constructed so that all of the 100 target stimuli appeared in all four conditions across the lists but none appeared twice within the same experimental list.We used the same procedure as in Experiment 1.Figure 7 shows the response distributions for the four different conditions. Figure 8 shows the average RAP values for the different conditions. The average positive RAP values in the Natural-Turn and the Closed-Class-Words-Removed condition indicate that the participants anticipated more frequently than reacted to the end of the turn in these conditions. In the Open-Class-Words-Removed and the Intonation-Only condition the participants reacted more often to the end of the turn.F1 = 47.85, p < 0.001, by items: F2 = 74.11, p < 0.001). Bonferroni-corrected paired t-tests revealed that all differences between individual conditions were significant (p < 0.001).An ANOVA on the RAP values showed a significant effect for presentation condition  they reacted significantly more frequently to the turn end than when only open class words were identifiably.The results suggest that semantic information is more important than syntactic information for end-of-turn anticipation. If no semantic information is available, it is less likely for the listeners to anticipate the turn ending. This also means that only knowing the syntactic frame and number of slots is not sufficient to estimate the timing of the turn. Nevertheless, the anticipation performance increased significantly when both open class words as well as closed class words were available. This could be explained by the fact that by removing closed class words the prediction of the content of the turn is also hampered. So for maximal anticipation performance listeners need semantic as well as syntactic information, probably because they need to be able to project the content of the turn. These results support the findings of Another interesting finding is that participants’ anticipation performance was significantly higher when they got only closed class words compared to when only intonational and rhythmical information was available. This indicates that on top of the prosodic properties the syntactic structure provides additional anticipation cues.Taken together these results suggest that semantic information is the most essential cue for anticipation. But to be maximally capable to anticipate a turn ending listeners need both semantic and syntactic information, since only the combination of both information sources allows for a correct projection of the content of the turn.In this study we addressed three different questions. First we investigated whether the observed accuracy in natural turn-taking was primarily due to anticipation or reaction to signals. Second, we wanted to quantitatively estimate the relative contribution of anticipation and reaction processes to the observed distribution of floor transfer timings. Finally, we studied the relative contribution of semantic and syntax in the timing of turn transitions.In Experiment 1 we conducted a button press experiment in which we manipulated the information necessary for anticipation. The results showed that the listeners’ response accuracy and consistency are similar when they (a) heard the natural turn and (b) when they are maximally able to anticipate the turn end by having advance information about the turn content. We conclude that listeners are indeed able to anticipate a turn ending andthat they use this strategy consistently to tell when a turn is going to end. Thus, our findings support the functioning of the turn-taking mechanism proposed by The data collected in Experiment 1 allowed us to estimate an empirical distribution for pure anticipation, sowe proceeded to assess the counterpart distribution for pure reaction in Experiment 2 by explicitly instructingparticipants to react to the end of noise signals. We combined the two distributions to estimate the RAP, whichrepresents the relative probability for a turn transition to have been guided by anticipation or reaction. By instructing the participants to react to the offset of a noise signal we estimated the ‘other extreme’ of anticipation, namely responding to the very end of a stimulus. We assume that a reaction to the offset of noise and a reaction to possible signals occurring at the very end of the turns  are comparable from a reaction time point of view. It should bepointed out that it is also possible that conversationalists react to signals that occur before the very end ofthe turn. Because in our approach we assessed only the extreme opposites of pure  anticipation and reaction, our data do not allow for an estimation of the possible contribution of such responses to the relative proportion of anticipation and reaction.In Experiment 3 we investigated the effect of the presence or absence of semantic and syntactic information on the anticipation and reaction probability using the RAP measure. The results showed that the participants werestill able to anticipate the end of the turn when they got access to semantic information. With only syntactic information available, the participants started to rely more on reaction. However, we found that to be maximallyable to anticipate, listeners need syntactic information as well as semantic information. The absence of syntactic information hampers the projection of the content of the turn. We concluded that for anticipation both semantic and syntactic information are needed. Nevertheless, it appears that semantic information is a more important cue than syntactic information.stochastic view of the turn taking process. By empirically estimating, for the first time, separate probability distributions for anticipation and reaction processes in end-of-turn detection, we were able to estimate the relative probability for a turn transition to be caused by anticipation or reaction at a given FTO value. This differs from the approach by The RAP measure introduced in Experiment 2 is not only an analysis tool for the characterization of turn transitions but implies an inherently Despite the mentioned advantages of the RAP measure over the strict threshold value suggested by We showed in Experiment 3 that semantic information is a more important cue for anticipation than syntax. This finding contradicts former studies  which asAnother explanation for the importance of semantic information in turn-taking could be that in naturalistic contexts, the semantics may provide stricter constraints on the turn construction than syntax does. Syntax theoretically allows for an infinite extension of a turn by the addition of new constituents. Furthermore, non-sense sentences like the famous “Colorless beautiful green ideas sleep furiously” , p. 15 aBy presenting isolated turns from natural conversations and letting the participants respond to the end of the turn by a button press we could both keep the characteristics of natural speech and at the same time systematically manipulate the turn fragments in order to test our specific hypotheses. Nevertheless, by isolating the turns we are not able to consider the impact of dialog context on anticipation. The discourse context could add information about the speaker’s illocutionary intentions in the turn that is being produced, which in turn could help the listener anticipate its content. It is an interesting issue for future research whether, and if so, how, the discourse context can improve the anticipation of a turn ending.The authors contributed to the following activities. Carina Riest and Jan P. de Ruiter designed the studies. Carina Riest and Annett B. Jorschick collected the data. Carina Riest, Annett B. Jorschick, and Jan P. de Ruiter analyzed the data. The paper was drafted by Carina Riest and revised by Annett B. Jorschick and Jan P. de Ruiter. All authors approved the final version of the manuscript and agreed to be accountable for all aspects of the work.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The demonstrated novel and simple scheme for obtaining graphene p-n junctions can be used for other optoelectronic devices such as solar cells and be applied to other two dimensional materials based devices.Graphene has been considered as an attractive material for optoelectronic applications such as photodetectors owing to its extraordinary properties, e.g. broadband absorption and ultrahigh mobility. However, challenges still remain in fundamental and practical aspects of the conventional graphene photodetectors which normally rely on the photoconductive mode of operation which has the drawback of e.g. high dark current. Here, we demonstrated the photovoltaic mode operation in graphene p-n junctions fabricated by a simple but effective electron irradiation method that induces n-type doping in intrinsic p-type graphene. The physical mechanism of the junction formation is owing to the substrate gating effect caused by electron irradiation. Photoresponse was obtained for this type of photodetector because the photoexcited electron-hole pairs can be separated in the graphene p-n junction by the built-in potential. The fabricated graphene p-n junction photodetectors exhibit a high detectivity up to ~3 × 10 Graphene, a single layer of carbon atoms arranged in a honeycomb lattice with broadband light absorption spectrum57et al.1213151720Pioneering works have already been reported on building asymmetric potential in graphene sheet, attempting to obtain graphene p-n junctions where the photoexcited electron-hole pairs can be intrinsically separated. For instance, Mueller 2 interface in the substrate which induces a gating effect on the irradiated graphene. Using this novel but simple strategy, we obtained graphene photodetectors in a field effect transistor (FET) structure with high detectivity and fast response time which were found to be strongly dependent on the electron irradiation. The methodology demonstrated here enables us to modify the transport properties of graphene by electron irradiation, thus paving the way to fabricating graphene homo-junctions controllably and benefiting the future electronic and photonic applications of graphene and other two dimensional (2D) materials based electronic and optoelectronic devices.In this study, we partially irradiated the graphene sheet to obtain an n-type graphene region which is originally p-doped, thus forming a lateral graphene p-n junction. The physical mechanism behind it is due to the interaction of the electron beam with the Si/SiO2/Si wafer and then verified by Raman spectroscopy (see Methods). We next fabricated single layer graphene FETs with the heavily doped silicon substrate as a backgate electrode by standard photolithography and e-beam evaporation. After that, the FETs were placed in a scanning electron microscope (SEM) under high vacuum and selected area was exposed to the electron beam with controlled low-energy electron beam irradiation (see Methods). The electron beam irradiates part of the graphene sheet and modifies the properties of graphene and the SiO2/Si substrateSingle layer graphene samples were fabricated by mechanical exfoliation of highly ordered pyrolytic graphite (HOPG) on SiOds/dVb × L/(W × (ε0εr/d) × Vds), where L, W and d are the channel length, width and the thickness of SiO2 layer (285 nm in our devices), Vds, Ids and Vb are source-drain bias, current and bottom gate voltage, ε0 and εr are the vacuum dielectric constant and the dielectric constant of SiO2 (εr = 3.9), respectively. The mobility of the n-type region (~1500 cm2 V−1s−1) is several times lower than that of pristine graphene (~5500 cm2 V−1s−1), which might be caused by the change of carrier density and the shift of Fermi level in the graphene channel after the electron irradiation2223Electrical transport measurements were employed to investigate the effect of electron beam irradiation on the electronic properties of graphene FETs. As shown in Fermi level of graphene can be characterized and qualified by the G peak position of graphene. As shown in The doping effect of electron irradiation on graphene as demonstrated by the G peak shift as shown in D2> is the deformation potential of the E2g mode, M is the atomic weight of carbon, ω0 is the frequency of the G-band in perfect graphene, υF is the Fermi velocity of graphene, and ΔEF is the shift of the Fermi level. The blue shift of G peak indicates n-type doping resulting from the charge transfer from the treatment or the substrate to grapheneG peak. Similarly we can plot the Fermi level shifts of the samples with different irradiated times from 10 s to 50 s in where <D, D’ and D + G bands at ~1350 cm−1, 1630 cm−1 and 2930 cm−1, and their intensities increase with irradiation dosage that controlled by the irradiation time. On the other hand, these three bands are absent in the pristine graphene sample as shown in 2D band at ~2700 cm−1 remains symmetric, although the intensity decreases slowly with the irradiation dosage, which indicates the decrease of the quality of graphene under the electron irradiation. The decrease of I2D/IG with the irradiation time longer than 50s indicates the amorphization of graphene from sp2 to sp3 carbonThere are two mechanisms that may contribute to the shift of the Fermi level of graphene from negative (p-doped) to positive (n-doped): defect effectD) induced by electron irradiation can be calculated fromL (2.33 eV) is the laser excitation energy, I(D) and I(G) are the intensities of the D band and G band as shown in 13 cm−2). This low defect effect here cannot cause the opening of bandgap of graphene, which is consistent with the density function theory (DFT) calculations in previous worksHowever, we note that a relatively large Fermi level shift of ~0.3 eV for the sample after 50 second electron irradiation cannot be totally contributed to the generation of defects in which the excess electrons are localized according to density function theory (DFT) predication and experimental demonstration292/Si interface because of the mismatch of the workfunction of silicon and p-doped silica where the conduction and valence bands in Silicon bend downward at the interface2 interface2/Si interfaceThe main physical mechanism changing the p-doped graphene to n-doped under electron beam irradiation is shown in IPC = CPγ (C is a constant and P is the illumination power) as shown in 34533The potential barrier built here is the force driving the separation and transportation of photo-excited electron-hole pairs and facilitates the optoelectronic applications of graphene. 10 Jones (cm Hz1/2 W−1) for both 633 nm and 532 nm laser illuminations (see methods), which is in the same level as these for conventional semiconductor phototransistors.Another key figure of merit for a photodetector is the detectivity, which is defined as the ability to distinguish photoresponse signal from noise. In our devices, all the photoresponse measurements are conducted without source-drain bias as the photoexcited carriers can be separated by the built-in potential in the p-n junction, resulting in an extremely low dark current and invoking a high detectivity in the range of 3 × 10To summarize, we investigated the electron irradiation effect on graphene FETs and its optoelectronic application as a photodetector. The energetic electron collision induces defects on graphene sheet and modifies the substrate band bending, resulting in localized n-type doping of graphene. A potential barrier is built between the un-irradiated and irradiated regimes efficiently separating the photo-excited electron-hole pairs. On the other hand, the energetic electron/graphene collision reduces the carrier mobility and photoresponse speed of graphene based photodetectors. This work highlights the importance of the irradiation created potential barrier for graphene photodetectors and opens new venues for exploring graphene based optoelectronic devices.2 layer. The silicon substrate was heavily doped p-type silicon which was employed as a back gate electrode. The location and quality of graphene was identified by optical contrast using an optical microscope and Raman spectroscopymW to avoid the laser induced damage of the graphene sample.Single layer graphene flakes were mechanically exfoliated from a crystal of highly oriented pyrolytic graphite (HOPG) using adhesive 3M-tape and deposited on a silicon wafer with a 285 nm thermalized SiO−6 Torr) under a voltage of 20 kV. The emission current was kept at 10 μA, which corresponded to a ~10 pA beam current under our experimental condition. The SEM images were taken under a low voltage (~1 kV) to reduce the irradiation effect. Soon after the location of the sample, the irradiation process was carried out with a selected area of 20 × 20 μm2 focused by the electron gun and covered part of the FET channel. The electron irradiation dosage (DOS) was controlled by the exposing time as the electron flux was kept constant during all experiments. The dose density for our device was ~n × 40 e/nm2 after n times of scans (every scan lasts 10 s). AFM  was used to image the un-exposed and exposed graphene samples in taping mode in air by measuring the surface morphology and height profiles. The electrical characteristics were examined by a semiconductor analyzer . The photoresponsivity measurement was performed in a digital deep level transient spectroscopy (BIORAD) system with different lasers to illuminate the whole devices. The gain and detectivity are calculated as followingElectron beam irradiation was conducted with a JEOL field-emission SEM system under high vacuum .


The prelimbic (PL) cortex allows rodents to adapt their responding under changing experimental circumstances. In line with this, the PL cortex has been implicated in strategy set shifting, attentional set shifting, the resolution of response conflict, and the modulation of attention towards predictive stimuli. One interpretation of this research is that the PL cortex is involved in using information garnered from higher-order cues in the environment to modulate how an animal responds to environmental stimuli. However, data supporting this view of PL function in the aversive domain are lacking. In the following experiments, we attempted to answer two questions. Firstly, we wanted to investigate whether the role of the PL cortex in using higher-order cues to influence responding generalizes across appetitive and aversive domains. Secondly, as much of the research has focused on a role for the PL cortex in performance, we wanted to assess whether this region is also involved in the acquisition of hierarchal associations which facilitate an ability to use higher-order cues to modulate responding. In order to answer these questions, we assessed the impact of PL inactivation during both the acquisition and expression of a contextual bi-conditional discrimination. A contextual bi-conditional discrimination involves presenting two stimuli. In one context, one stimulus is paired with shock while the other is presented without shock. In another context, these contingencies are reversed. Thus, animals have to use the present contextual cues to disambiguate the significance of the stimulus and respond appropriately. We found that PL inactivation disrupted both the encoding and expression of these context-dependent associations. This supports a role for the PL cortex in allowing higher-order cues to modulate both learning about, and responding towards, different cues. We discuss these findings in the broader context of functioning in the medial prefrontal cortex (PFC). Previous research has demonstrated that the prelimbic (PL) cortex facilitates the ability of animals to respond adaptively under changing circumstances. For example, function in the PL cortex is necessary to allow animals to exhibit an instrumental response which is reflective of the current value of a goal, a switch between response and strategy sets, the use of contextual cues to resolve response conflict, and a change in the degree of attention directed towards a stimulus on the basis of how well it predicts a motivationally-significant outcome . In one context (context A), one CS (CS1) would be paired with shock, and the other CS (CS2) would be presented in the absence of shock. In the other context (context B), these contingencies are reversed so that CS1 would now be presented in the absence of shock, and CS2 would be paired with shock in this context. In a subsequent test session, rats will be presented with both CSs in both contexts under extinction to assess whether their behavior towards the CSs is reflective of the contexts in which they were trained. The nature of this procedure, where the CSs are predictive of shock in one context and not in another, likely necessitates that the animals use the context  to inform the animal of the status of the CS in that context. This would allow the context to exert top-down modulation over responding to the CS. Thus, investigating the role of the PL cortex in this task will bring insight into whether this region is involved in using contextual cues to modulate responding towards a CS in an aversive procedure.We investigated the role of the PL cortex in the contextual bi-conditional discrimination at two time points. More specifically, Experiment 1 investigated the impact of PL inactivation during the extinction test session, where animals had to express the associations formed during acquisition of the contextual bi-conditional discrimination. On the basis of the research in the appetitive domain, we anticipated that animals without PL function would be unable to use the contextual cues present at test to modulate responding towards the CSs. In Experiment 2, we investigated the impact of PL inactivation during acquisition of the discrimination. If the PL cortex is involved in the development of a conditional association where the context comes to modulate the expression of a response, inactivation during acquisition will disrupt the subsequent expression of the contextually-dependent response at test.Subjects were experimentally-naïve male albino Wistar rats , weighing between 350 and 450 g at the start of the experiment. All animals were housed 4 rats per cage in a temperature- and humidity-controlled (22°C) environment in a 12 h light/dark cycle (lights on at 7:00 am). Rats were between 10–14 weeks at the commencement of the experiment. All behavioral and surgical procedures took place during the light cycle. Rats were handled 3 days prior to surgical procedures.All animal procedures, both experimental and routine care, were carried out in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals  and were approved by the University of New South Wales Animals Care and Ethics Committee (ACE: 13/102A).Prior to any training, surgery was conducted under complete anesthesia induced by inhalation of isoflurane in oxygen carrier . Following the onset of anesthesia, rats were placed in a stereotaxic frame . An incision was made into the scalp, and the skin was retracted to expose the skull. For each rat, the incisor bar was adjusted such that bregma and lambda were level. Small holes above the intended lesion site were made with a high-speed dental drill, and the dura mater was severed to reveal the cortical parenchyma. Bilateral stainless steel guide cannulae  were lowered 0.5 mm dorsal to the infusion site . Cannulae were held in place by dental cement and anchored to the skull with four fixing screws located on different bone plates. Removable dummy cannulae were inserted into the guide cannulae to prevent the cannulae from blocking.A agonist; 5-aminomethyl-3-hydroxyisoxazole; Sigma- Aldrich, Australia) was dissolved in nonpyrogenic saline (0.9% w/v) to obtain a final concentration of 0.5μg/μl and was infused bilaterally into the PL cortex by inserting a 33 gauge internal cannula into the guide cannula. The internal cannula was connected to a 25 μl glass syringe  attached to an infusion pump (World Precision Instruments Inc.) and projected an additional 0.5 mm from the tip of the guide cannula. A total volume of 0.5 μl was infused bilaterally at a rate of 0.5 μl/min. This amount was in line with those used in appetitive experiments demonstrating effects selective to the PL cortex  and one in the afternoon (PM) separated by at least 3 h.Training and testing took place in 8 operant chambers  which were individually housed in light- and sound-attenuating compartments. Boxes were 30 cm wide × 24 cm deep × 21 cm high and consisted of two aluminium walls and an aluminium ceiling, and two Perspex side walls. The chamber floors were constructed of 19 stainless steel rods . Each chamber was equipped with a pellet dispenser that delivered one 45-mg pellet into a recessed magazine when activated. Two levers could be extended to the left and right of the recessed magazine. Two panel lights (2 cm in diameter), were located on the right hand wall of the chamber above the magazine. A 3 W house light was located on the upper left hand wall of the chambers. The chambers contained a white noise and a heavy duty relay that delivered a 5 kHz clicker stimulus. A computer equipped with MED-PC software (Med Associates) controlled the equipment and recorded the responses.Different wallpapers, scents, and lighting were used to create two contexts that were used for the duration of the experiments. Four of the chambers were designated as contexts A (CXT A) and fitted out with laminated spotted wallpapers on three of the four walls. During sessions in these boxes, the house light and both panel lights were illuminated and diluted peppermint essence (10% solution) was dropped in four corners of the bedding below the steel rod flooring to create a strong scent within these compartments. The remaining four boxes served as context B and were fitted out with sandpaper on three of the four walls, and only the house light was illuminated during sessions in this context. Further, diluted rose essence (10% solution) was used as the defining scent for this context. Half the rats in each experiment received AM training sessions in context A and PM training sessions in context B, while the other half received AM training in context B and PM training sessions in context A.The CSs used were 30-s presentations of a clicker stimulus and a white noise. The unconditioned stimulus (US) used for fear conditioning was a 1-s 0.8 mA shock delivered through the stainless steel rods on the floor of the operant chambers connected to a scrambled shock generator . The design for Experiments 1 and 2 is represented in Table In Experiment 1 and 2, rats each received lever training in both CXT A and CXT B prior to conditioning. During conditioning sessions in CXT A, rats received pairings of CS1 with shock, while CS2 was presented without shock. In CXT B rats received pairings of CS2 with shock, while CS1 was paired without shock. Rats were then tested for levels of responding to both CSs in both CXT A and CXT B. CS1 and CS2 were either a clicker or a white noise stimulus, counterbalanced across rats. + denotes delivery of a 0.8 mA shock. Bold characters indicate infusion of either muscimol or saline.All rats received 2 30-min sessions of magazine training, one in each context, where a 45 mg grain pellet  was delivered according to a 60-s variable time schedule. Following magazine training, rats received 6 lever-training sessions, three in each context. In context A, the right lever was made available whereas in context B the left lever was made available. In the first two lever-training sessions, each lever press was reinforced with delivery of a pellet  and ended once rats had received forty rewards. Rats then progressed onto a 30-s variable interval schedule where a reward became available on average once every 30 s and the next lever-press response led to the delivery of this reward. In the final two lever-training sessions, this schedule was reduced further and the reward became available on average once every 60 s. Following instrumental training, rats progressed to conditioning phase of the experiment. During all training and testing sessions, the lever was extended and reinforcement available according to a 60-s variable interval schedule as per the last sessions of training.Rats each received 7 conditioning sessions. Two CSs were used, a clicker and a white noise. If the stimulus was followed by the shock US, the shock was presented at the offset of the stimulus. For half the rats in each experiment, context A signaled that the clicker would lead to shock and the noise did not, whereas context B signaled that the noise would be followed by shock and the clicker would not. This contingency was reversed for the other half of the rats in each experiment. Each conditioning session comprised 6 CS presentations, 3 of each stimulus, with an ITI varying around a 7-min mean. This yielded sessions of approximately around 55 min long. In Experiment 1, rats received mock infusions 10 min prior to the conditioning session, where dummy cannulae were removed and the infusion needle was lowered into the PL cortex without the administration of any substance. In Experiment 2, rats received infusions of muscimol or saline into the PL cortex 10 min prior to the start of the session.Twenty four hours following the final conditioning session, rats received two extinction test sessions, one in each context. The extinction test sessions were the same as the conditioning sessions with the exception that no CS was followed by delivery of shock. In Experiment 1, rats received infusions of muscimol or saline into the PL cortex 10 min prior to the start of the extinction test session. In Experiment 2, rats received mock infusions 10 min prior to the extinction test session, where dummy cannulae were removed and the infusion needle was lowered into the PL cortex without the administration of any substance.Suppression of lever pressing was used to assess fear to the CS , where A is the period during CS presentation and B is the 30 s pre-CS period). Thus, a suppression ratio below 0.5 indicates a suppression of lever pressing during CS presentation, where lower number indicates greater suppression .All the end of all experiments, rats were killed with an overdose of sodium pentobarbitone  and decapitated. Brains were removed, immediately placed on a Peltier element of a cryostat  and frozen overnight. 40 μm coronal sections were cut through the region of the PL cortex and mounted onto glass slides. Tissue was stained using 1% cresyl violet nissl stain and subsequently assessed for the placement of cannulae microscopically by a trained observer. The PL region was defined by the boundaries specified in the atlas of Paxinos and Watson . Rats win = 9, muscimol-infused animals n = 12.Figure F < 1). It is worth noting here that this is a relatively low rate of responding. It is possible that the presence of the cannulae on the heads of the animals make magazine entries slightly more arduous and therefore lever pressing is reduced as it take longer for animals to retrieve reward or check whether reward has been delivered in the magazine. This would be particularly the case early on in instrumental training when magazine entries are the dominant response. In line with this, our pilot studies have indicated that animals perform at a slightly higher rate without the presence of cannulae.All rats acquired the lever-press response within the first two CRF sessions, each receiving 40 pellets in each context. Further, all animals maintained a stable rate of responding across instrumental sessions with the leaner reinforcement schedule with a one-way ANOVA of the average number of lever presses made per minute during these sessions revealing no differences in baseline rates between the intended groups (mean (±SEM): saline 3.57 (0.49); muscimol 3.50 (0.23), F = 4.03, p > 0.05) and no interaction between the intended groups (F < 1). Further, this analysis also demonstrated that there was no overall differences between levels of suppression between the intended groups (F < 1). A one-way ANOVA also revealed that there was no difference between the intended groups in the number of lever-press responses made during the 30-s pre-CS period (mean (SEM): to-be saline 2.19 (0.37); to-be muscimol 2.72 (0.52); F < 1).Figure F = 4.01, p = 0.06), however, there was a significant interaction between CS and group  = 7.17, p < 0.05). This analysis also revealed that there was no overall difference in levels of suppression between groups (F < 1). Follow-up analyses of simple main effects demonstrated that the source of this interaction was due to rats in the saline-infused group exhibiting a significant difference in levels of fear exhibited towards the CS trained in the test context relative to the CS that did not predict shock in that context  = 9.58, p < 0.05). Rats infused with muscimol during the test session failed to demonstrate this difference (F < 1). There was no difference between groups in levels of responding to the non-reinforced cues  = 1.91, p > 0.05), or the reinforced cues (F < 1). There was also no difference in average levels of pre-CS responding across these sessions (mean (±SEM): saline 3.78 (0.33); muscimol 3.63 (0.48), F < 1).Figure n = 6, muscimol-infused animals n = 7.Figure F < 1).All rats acquired both left and right lever-press responses within the first two CRF sessions, each receiving 40 pellets in each context. All animals maintained a stable rate of responding across instrumental sessions with the lean reinforcement schedule with a one-way ANOVA of the average number of lever presses made per minute during the final session demonstrating that there was no differences in lever-pressing rates between the intended groups (mean (±SEM): saline 4.52 (0.68); muscimol 4.94 (0.71), Fs < 1). Further, there was no difference in average number of lever presses made during the 30-s pre-CS period across conditioning sessions (mean (±SEM): saline 2.50 (0.56); muscimol 3.07(0.29); F = 1.41, p > 0.05).Figure F = 5.68, p < 0.05). This analysis also demonstrated that there was no significant between-group differences in overall levels of suppression (F < 1). Follow-up analysis of simple main effects demonstrated that the source of the interaction was due to a significant difference in responding to the non-reinforced and reinforced cues in the saline-infused animals  = 7.02, p < 0.05), but no such difference in the muscimol-infused animals (F < 1). There was no significant simple main effect for responding to cues non-reinforced in the test context  = 2.68, p > 0.05), or in responding to the cues non-reinforced in the test context (F < 1). Further, there were no differences in levels of lever pressing during the pre-CS period (mean (±SEM): saline 4.07 (1.52); muscimol 3.33 (0.29), F < 1).Figure The present experiments aimed to address two questions. Firstly, we wanted to investigate whether a role for the PL cortex in using contextual cues to modulate responding could be generalized to the aversive domain. Secondly, we wanted to examine whether the PL cortex may also be involved in the acquisition of an hierarchal association which subsequently allows an animal to use contextual cues to modulate responding. In Experiment 1 we found that animals without PL function during the extinction test session failed to use the present contextual cues to modulate responding to the CSs. Further, Experiment 2 demonstrated that the PL cortex is also involved in the acquisition of the contextual bi-conditional discrimination. That is, we found that animals without PL function during the conditioning phase failed to express context-specific responding towards the CSs when tested drug free. Taken together, these data demonstrate that the PL cortex is necessary to allow animals to modulate their response towards a stimulus. In addition, these studies show for the first time that the PL cortex also contributes to the ability of animals to form context-specific associations that allows them to use conditional cues to modulate responding towards CSs in the future.There are many forms that the contextually-mediated associations developed in the contextual bi-conditional association may take. For example, Bouton’s , 1994 inIn contrast to a role of context in exerting control over Pavlovian associations, other researchers have argued that the association that is formed when the CS is not reinforced involves a stimulus-response (S-R) association , rather, the IL cortex is argued to be involved in the promotion of S-R pathways independently of contextual cues, whether the associations between the stimulus and response is inhibitory or excitatory. For example, in the case of extinction these S-R pathways may involve inhibitory associations (Delamater, In line with the framework discussed above, these data can be interpreted as a role for the IL cortex in opposing the process whereby the PL cortex exert top-down control to bias activation of the S-R pathway appropriate to current circumstance. Rather, the IL cortex appears to promote the performance of the response at the terminal end of the stronger S-R pathway. This results in behavior becoming impervious to the influence of contextual cues following extended training, where the strong S-R pathway becomes capable of dominating behavior. It is unclear whether the IL cortex directly opposes the influence of the PL locally, or whether the IL cortex promotes the activation of the stronger S-R pathway at a broader, circuit level. Given the lack of projections of the IL cortex to other regions involved in promoting habitual performance (i.e., the dorsolateral striatum, DLS; but see a role for the central nucleus of the amygdala, Lingawi and Balleine, The present experiments have demonstrated that the PL cortex is involved in facilitating the use of contextual cues to modulate responding towards a CS in the aversive domain. Further, we have found for the first time that this region is involved in the formation of the context-specific associations. In doing so, we have found evidence to support for a framework whereby the PL cortex exerts top-down control over S-R pathways according to present contextual cues, to influence both the acquisition and expression of conditioned fear. This is consistent with the functional role of the PL cortex in appetitive procedures. In contrast, previous research has suggested that the IL cortex opposes the role of the PL cortex in facilitating context-specific responding to promote execution of the well-trained, context-independent response across both aversive and appetitive procedure. Taken together, these data suggest that the PL and IL cortices act in a manner to establish a trade-off between using contextual cues to change responding when appropriate and performing a well-trained response independently of contextual cues.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Transposable elements (TEs) are notable drivers of genetic innovation. Over evolutionary time, TE insertions can supply new promoter, enhancer, and insulator elements to protein-coding genes and establish novel, species-specific gene regulatory networks. Conversely, ongoing TE-driven insertional mutagenesis, nonhomologous recombination, and other potentially deleterious processes can cause sporadic disease by disrupting genome integrity or inducing abrupt gene expression changes. Here, we discuss recent evidence suggesting that TEs may contribute regulatory innovation to mammalian embryonic and pluripotent states as a means to ward off complete repression by their host genome. Mammalian embryonic development is governed by a complex set of genetic and epigenetic instructions. This genomic blueprint undergoes evolutionary selection and, as such, the fundamental order of development is well conserved among mammals. At fertilization, sperm and egg unite to form the zygote, which undergoes successive cleavage divisions, yielding two-, four-, and eight-cell embryonic stages , 2. InitPluripotent states arising embryonically in vivo, or achieved in vitro by cellular reprogramming, are associated with epigenetic derepression and transcriptional activation of transposable elements (TEs) –6. TheseAll retrotransposons mobilize via a “copy-and-paste” mechanism involving a transcribed RNA intermediate that is reverse transcribed and integrated as a nascent cDNA into genomic DNA. However, there are essential differences in the retrotransposition mechanisms used by LTR and non-LTR retrotransposons Fig. . L1 mRNARecent studies have revealed a complex and somewhat paradoxical interplay between retrotransposons and their host genome in pluripotent cells. On one hand, retrotransposons have long been regarded as fundamentally selfish genetic elements  that, toHere, we review the restraint and activity of TEs in embryonic cells and later in development, as well as the unexpected promotion of pluripotent states by ERVs. We further appraise the convergent contributions to embryogenesis made by ERVs in distinct mammalian clades as evidence of an evolved strategy to avoid, or at least delay, host genome repression.Although there are spectacular examples of TE proteins underpinning functional innovation, such as in the placenta , regulatERV transcription independent of protein-coding genes has also been linked to pluripotency. Despite an apparent lack of retrotransposition activity, specific HERVs are actively transcribed in hESCs and are thought to influence pluripotency maintenance –32, 47. Human oocytes and zygotes (to the cell–cell stage) contain the highest percentages of HERV transcripts observed during development; these are almost certainly deposited maternally prior to embryonic genome activation . Abundanenv gene and is responsible for nuclear export and translation of viral RNAs , 4226, 4ral RNAs . Rec canral RNAs , 52. Conral RNAs  suggestev region , 54. Intv region . It is tv region , that hEHERV-H is another primate-specific retrotransposon  with a pXist, a prototypical lncRNA involved in X chromosome inactivation, TEs are a core component of lncRNA biogenesis [Xist, and a few additional examples, lncRNAs have proven difficult to evaluate functionally because, as well as containing TEs, lncRNAs are often expressed at very low levels [Long noncoding RNAs (lncRNAs) are RNA transcripts greater than 200 nucleotides long that possess no, or very little, protein-coding potential –60. Mostogenesis . Other tw levels . Howeverw levels , 63. Intw levels  reportedw levels , and in w levels , 44, 47.w levels .Alu element. HPAT5 is thus an unusual, and yet fascinating, example of retrotransposon-driven regulatory innovation.One particularly interesting lincRNA, HPAT5, is hypothesized to be involved in post-transcriptional gene regulation: HPAT5 binds AGO2, a core protein catalyzing microRNA (miRNA) processing , and thelincRNA-RoR, with its TSS located in a HERV-H element, represents an excellent example of a primate-specific TE found to modulate pluripotency [lincRNA-RoR is expressed more highly in iPSCs than in ESCs and can promote iPSC reprogramming [ESRG, which uses a domesticated HERV-H promoter, plays a role unique to human pluripotency [ESRG encodes an intact open reading frame (ORF) in humans, but possibly not in other primates, and is expressed exclusively in the human ICM and cultured pluripotent cells [ESRG knockdown compromises stem cell self-renewal and promotes differentiation, while ESRG overexpression aids reprogramming [More broadly, HERV-driven transcripts contributing to pluripotency networks unique to humans or primates are of particular interest. ipotency . Notablygramming , perhapsgramming . In anotipotency . Unusualnt cells . ESRG kngramming . These cTo discover new lncRNAs regulating pluripotency, Fort et al.  surveyedDomesticated TEs clearly play important functional roles in stem cell biology. However, TE repression can shift as cells transition through pluripotent states, as encountered during reprogramming. As a result, opportunistic TEs may mobilize, cause insertional mutagenesis and, potentially, compromise the integrity of reprogrammed cells , 48, 71.TE repression is dynamic during reprogramming. In a high-resolution analysis of mouse and human iPSC lines, Friedli et al.  found thThe machineries responsible for ERV regulation in ESCs are evidence of the complex relationships that can form between TEs and their host genome. Broadly speaking, to reduce the probability of retrotransposon-derived mutagenesis, mammalian genomes target ERVs with DNA methylation, heterochromatin-forming factors, transcriptional repressor complexes, proviral silencing factors, and post-transcriptional arrest or degradation of viral RNAs Table  19, 20,,20, 72. Even ERVs in accessible chromatin can be decisively silenced by DNA methylation. In mice, de novo DNA methylation is regulated by the canonical Zfp/Trim28/Eset machinery . KrüppelIt follows that models explaining ERV silencing are typically complex, which, at times, can lead to differing conclusions. For instance, the SNF2-type chromatin remodeler Atrx is another crucial component for IAP silencing that renders Eset-dependent heterochromatin less accessible  and is lAlu and SINE–VNTR–Alu (SVA) elements have also been reported by Klawitter et al. [Alu insertion in a cultured hESC line. L1 may, therefore, trans mobilize Alu and other SINEs during development, an important finding due to the high potential of SINEs to impact gene regulation [The early embryo is a viable niche for the generation of potentially heritable retrotransposon insertions. In particular, L1 mobilization in human and rodent embryos may drive somatic and germline mosaicism –101 and,r et al.  in severgulation , 104. Klgulation .Although both L1 and ERV retrotransposons are active in the mouse germline , 106, thSomatic L1 retrotransposition can also occur later in development. Over the past decade, it has become accepted that the mammalian brain, particularly cells of the neuronal lineage, accommodate mobilization of engineered and endogenous L1 elements –37, 108.Neuronal L1 insertions impart no obvious evolutionary benefit as they cannot be transmitted to subsequent generations. Thus, it is tempting to speculate that L1 activity is derepressed during neuronal commitment to serve a biological purpose for the host organism, analogous to the potential exaptation of ERV transcription for pluripotency maintenance and following the example of the vertebrate adaptive immune system, where domesticated TEs mediate V(D)J recombination and functional diversification through genomic mosaicism . SimilarThe mammalian genome clearly strives to limit TE activity in pluripotent cells. The silencing mechanisms involved are collectively complex and broadly potent and yet are also capable of great specificity and dynamism in targeting individual TE copies . In thisWhy are TEs active, and apparently essential, in the embryo? The relationship between TEs and the host genome is often referred to as an evolutionary arms race , 124. A Although not rejecting models based on serendipity or conflict, we highlight that ERVs and other successful TE families commonly arise as low copy number families and then rapidly expand over generations. This scenario could lead to TEs acquiring traits of early pioneers in a potentially hostile genomic landscape. Two not necessarily exclusive strategies can aid TE survival in this environment. One is stealth. For example, adaptation of the L1 5′ promoter (Box 2) enables evasion of host genome surveillance, leading to continuing L1 retrotransposition during development. That most new L1 copies are 5′ truncated, and lack the canonical promoter, also reduces their visibility to surveillance. Although this self-limits the capacity of new L1 insertions to retrotranspose, it also reduces pressure on the host genome to clamp down on L1 activity. The other strategy is gaining acceptance by being useful. ERV promoters are repeatedly found in pluripotency regulatory networks and may, therefore, be intrinsic to the pluripotent state. In this setting, efforts by the host genome to limit ERV activity could be detrimental to pluripotency. As such, ERVs may be able to propagate for longer than would be possible should the host engage in resolute inhibition. Importantly, these strategies are predicated on embryonic retrotransposition having potential for germline transmission, i.e., carrying risk for host genome integrity, as many studies have now found. Even after ERV families are no longer capable of mobilization, their inherent capacity for regulation, especially by solo LTRs, is retained and provides a long-term evolutionary incentive for the host genome to maintain at least one active TE family, as almost all mammals do. As such, rather than an arms race, conflict, or even symbiotic relationship, we would propose that pioneer ERVs adopt peaceful survival strategies and that intricate mechanisms for TE repression have evolved to allow the host genome to harness those strategies over time, allowing some ERV families to expand and, as witnessed in the embryo, securely embed themselves by becoming indispensable. In advocating this model, we emphasize that indispensability of ERV-mediated regulatory effects in natural pluripotency and embryogenesis in vivo is still an open question. While difficult to pursue in humans, genetic knockout or deletion of individual mouse ERVs or ERV families implicated in pluripotency is possible  and, indMyc using retroviral vectors [Programmed shifts in transcriptional and epigenetic states during embryogenesis have been studied primarily using in vitro systems. Embryonic stem cells (ESCs) are pluripotent cells derived from the blastocyst inner cell mass. Cultured ESCs are intensively used to study pluripotency, particularly in humans. Over the past decade, a core regulatory circuit incorporating the transcription factors Oct4 , Sox2, and Nanog –128 has  vectors , 132. Nu vectors . As for  vectors , 132Alu and SINE–VNTR–Alu (SVA) elements in trans [F, GF, and A) that are autonomous, as well as nonautonomous short interspersed elements (SINEs) retrotransposed by L1 [cis to form a cytoplasmic ribonucleoprotein particle (RNP) [The non-long terminal repeat retrotransposon long interspersed element-1 (L1) is the only autonomous, mobile human transposable element , 134. L1in trans , 136. Mied by L1 . L1 accoed by L1 . A full-ed by L1 , 137–139ed by L1  can alsoed by L1 . This aned by L1 , 140. L1ed by L1  and reveed by L1  activitile (RNP) . The RNPle (RNP)   are derived from exogenous retroviruses that, at some point, infected an individual organism’s germ cells, integrated into their genome, and were subsequently inherited by their offspring. ERVs are divided into class I, class II, and class III elements, based on the exogenous virus class that they are most similar to . Full-leansposon , 148. ERansposon   comprise about 8 % of the human genome . All HER


Thin-film elastomers (elastic polymers) have a number of technologically significant applications ranging from sportswear to medical devices. In this work, we demonstrate that graphene can be used to reinforce 20 micron thin elastomer films, resulting in over 50% increase in elastic modulus at a very low loading of 0.1 wt%, while also increasing the elongation to failure. This loading is below the percolation threshold for electrical conductivity. We demonstrate composites with both graphene oxide and reduced graphene oxide, the reduction being undertaken in-situ or ex-situ using a biocompatible reducing agent in ascorbic acid. The ultrathin films were cast by dip moulding. The transparency of the elastomer films allows us to use optical microscopy image and confirm the uniform distribution as well as the conformation of the graphene flakes within the composite. Rubber is most commonly processed in the form of a latex, a stable dispersion (emulsion) of polymer microparticles in an aqueous medium Elastomers are viscoelastic polymers with weak inter-molecular forces that exist in an amorphous state above their glass transition temperature. Elastomers can be classified as thermosets or thermoplastics; thermosets such as various rubbers require cross-linking by a curing process such as vulcanisation, whereas thermoplastics such as polystyrene are not cross-linked Elastomer products can be formed by a variety of techniques such as injection moulding, dip moulding, blow moulding, compression moulding, etc. There are a wide range of elastomer products which are produced worldwide predominantly by dip-moulding method. Such applications include gloves, plastic bags, condoms, coatings on metallic objects for corrosion protection, rubber grip coatings, etc. Dip-coating is used because it can form a thin, conformal coating over a range of arbitrary and complex shapes; this is not achieved by other moulding or coating methods. The coatings may either be left on the object (e.g. for corrosion or damage protection) or removed and utilised as a thin-film such as gloves and condoms.For thin-film applications such as condoms and gloves, where the elastomers are formed to thicknesses of less than 100 microns, traditional fillers with particle sizes in the micro-scale or larger are unsuitable. Nano-scale fillers such as graphene 22.12.1.1GO was produced by oxidising graphite according to a modified Hummers method 2.1.2® DLN-SD (Covestro AG). The NRL used in this work was Revultex® HR 8/012  SDN BHD). wPU at 40% solids or NRL at 60% solids content was blended with graphene oxide at 2.5 mg/ml using a magnetic stirrer at room temperature to obtain a homogenous blend to obtain the GO/wPU or GO/NRL blends. To obtain rGO, 1 M ascorbic acid The wPU used in this work was Impranil2.1.3wPU films were dipped on 32 mm OD smooth glass mandrels and NRL films were dipped on 22 mm OD smooth glass mandrels without any release agents or other processing aids, as shown in 2.1.4b/2Ax, where: T = tensile strength, Fb = breaking force , and Ax is the cross-section area of the ring. The formula used for elongation at break is: E = 100((2D + G−C)/C), where: E = elongation at break, %, D = distance between centres of rollers at break, G = circumference of one roller, C = circumference of the specimen.Tensile testing of graphene/wPU composite was performed followed the procedures in ASTM Standard D3492 – 97 3We used two ‘grades’ of GO, with flake size distribution of <1 μm , and 3–30 μm (large). 2 surface layer. Additional magnifications and images are shown in online supporting information. GO, on the other hand, did not offer sufficient optical contrast to be imaged optically in the NRL matrix. Excellent uniform dispersion of individual graphene flakes could be observed in the NRL matrix for rGO for small and large flakes. The NRL appears to stabilise the dispersion of the graphene effectively and prevent aggregation prior to or during the dip moulding process. The small rGO flakes were general flat, but occurring in small clusters. Large rGO flakes were generally individually dispersed, but not flat. This morphology of the different rGO flake sizes could correlate to the resulting mechanical properties described subsequently. This also confirms that the general assumption of graphene as a flat sheet Due to the good transparency of NRL thin-films, the distribution of rGO flakes inside the NRL matrix could be imaged by optical microscopy in reflectance mode . In ordeSince the wPU used here is an anionic aliphatic polyester and GO is also anionic This could be attributed to the morphology of the small and large graphene flakes within the elastomer matrix. The built-in undulations in the large graphene flakes compared to the flat small graphene flakes is attributed to the higher ultimate elongation whereas the same morphology combined with the clustering of small graphene flakes is attributed to the lower ultimate elongation. There are two major contributing factors to the different aggregation rates of small and large rGO flakes. Rheology measurements on similar concentration dispersions of small and large GO flakes have shown that larger flake dispersions have higher viscosities, especially at low shear rate and amplitudes, both in the GO dispersion The above results, taken together, demonstrates that the addition of a small amount of optimum graphene filler to NRL and wPU significantly improves the mechanical properties of these elastomers in their thin-film form.One of the various ways to test the integrity of elastomer thin-film products, such as gloves and condoms, is electrical conductance test. This is the only standard non-destructive test that is integrated into the production flow, where electrical conductivity across the elastomer thin-film is interpreted as a flaw such as a pin-hole leading to product rejection. To avoid invalidating this unique industrial standard test, it is essential that the addition of a conductive filler such as graphene should not introduce electrical conductivity to the thin-film product. Owing to the low graphene loading in the composites studied here, which is well below the percolation threshold, no electrical conductivity is observed in the thin-film composite samples tested here.4In conclusion, we have developed two varieties of water-based graphene/elastomer composite thin-films, which are 10s of microns thick. In the case of wPU, the graphene was incorporated as GO followed by in-situ reduction by ascorbic acid, whereas in the case of NRL, the graphene was first reduced to rGO and then added to the NRL so as to not disturb the stability of the latex emulsion. The graphene was well-dispersed as monolayers within the composites. In both composites, the elastic modulus was improved by 50% by the addition of just 0.1 wt % of large rGO flakes, while the elongation to failure was either maintained or improved. This is critical; as summarised in Ref.


The STOPAH trial was a double-blind, 2x2 factorial, phase III randomised clinical trial assessing the treatment of prednisolone and pentoxifylline in patients with severe alcoholic hepatitis; a study that aimed to evaluate 28-day mortality .At the time of trial development, the benefits/harms of pentoxifylline in this patient population were unknown. Prednisolone had a significant though uncertain evidence base. No treatment interaction was assumed yet there was uncertainty about its effect. Therefore, pre-specified stopping rules to assist decision making in stopping treatment arms were required.There was no published methodology on stopping rules for factorial trials, so a design based on the Peto-Haybittle  rule wasAn independent data monitoring committee assessed these stopping rules after 200, 400 and 800 patients had reached the primary endpoint. The stopping rules were not met at any of the three interim looks. The results of the STOPAH trial have recently been published .


Deoxyribonucleic acid or DNA based sensors, especially as humidity and alpha particle sensors have become quite popular in recent times due to flexible and highly optimizable nature of this fundamental biomaterial. Application of DNA electronics allow for more sensitive, accurate and effective sensors to be developed and fabricated. In this work, we examined the effect of different humidity conditions on the capacitive and resistive response of Aluminum (Al)/DNA/Al Schottky barrier structure when bombarded by time-dependent dosages of alpha particles. Based on current-voltage profiles, which demonstrated rectifying behaviours, Schottky diode parameters such as ideality factor, barrier height and series resistance was calculated. Results observed generally pointed towards a decrease in the resistance value from the pristine to the radiated structures. It was also demonstrated that under the effect of humidity, the capacitance of the DNA thin film increased from 0.05894 to 92.736 nF, with rising relative humidity level. We also observed the occurrence of the hypersensitivity phenomena after alpha irradiation between 2 to 4 min by observing a drop in the series resistance, crucial in the study of DNA damage and repair mechanisms. These observations may also suggest the exciting possibility of utilizing Al/DNA/Al Schottky diodes as potentially sensitive humidity sensors. The quantity of water vapor in the atmosphere is called humidity, which affects all environmental biological and chemical processes. Humidity also negatively affects various industrial-manufacturing methods if proper steps are not taken. As such, humidity level in terms of relative humidity (RH) are closely monitored to reveal fluctuations in situations ranging from high to low temperatures or in mixtures with other gasesFlexible, chipless and wireless humidity sensors are built based on the difference in dielectric constant (capacitive), proton/ionic conduction (resistive), refractive index , frequency (impedance) or mass of the active material against humidity level68910et al. and Otsuka et al. observed the RH value effect on the conductance of samples involving various DNA molecules. They reported that poly(dC)-poly(dG) sample demonstrated a higher sensitivity to RH13et al.et al. observed that the conductivity of DNA of length 140 nm demonstrated insulating behaviors when placed in dry environment (about 30% RH). This was in contrast to improved conductivity under moist environment (80–90% RH)et al. and Yamahata et al. observed and reported that the conductivity followed the increase in humidity level exponentially in dsDNA and single-strand DNA (ssDNA) due to the absorption of water molecules to the nanostructured film surface17+2 and Ni+2 mixed with DNA. A color transition from blue to red with change in the UV absorption due to the humidity effect was observed. This type of sensors are flexible, non-hazardous and cheap to fabricateet al. used DNA functionalized carbon nanotube (DFC) networks to develop a field effect transistor (FET)-based humidity sensor. They reported that the charge transfer mechanism between the DNA and the water molecules caused the exponential variation of conductance of the DFC network with RHHan et al. observed that the ionic conduction through water layers under atmospheric conditions was the dominant conduction mechanism by using the frequency (100-1 KHz). Utilizing micro- and nanoelectrodes of DNA film, they observed that the semicircle becomes smaller in the high frequency range at high humidityet al. demonstrated that the sensitivity of Graphene Oxide (GO) at 1 KHz was higher than that at 100 Hz and 10 KHz of frequencieset al. meanwhile found that for carbon film, the capacitive response at 1 kHz was over 200% for RH shifting from 11 to 95%, compared with other frequenciesStructures of DNA are strongly influenced by the environmental conditions due to their polymorphic nature212527Generally, the experiments involved measuring various diode parameters against bombardment of alpha particles under various humidity conditions. As such, the data provides information of humidity dependent electronic parameters of sensitive DNA sensing material. The results, as clearly observed shows a distinct behavior specific to the humidity level used. These features, we believe, provides an effective avenue towards accurately and effectively sensing humidity fluctuations using the DNA molecules, which are totally biodegradable and abundant in nature besides having a high degree of flexibility. It is also very well known that humidity highly influences the semiconducting behavior of DNA, forming a solid reason behind the motivation into utilizing DNAs as a humidity sensing organic material. The experiments conducted in these studies have also brought to light the possibility of interrogating various important DNA related processes especially damage and repair mechanisms based on the occurrence of the interesting effect of hypersensitivity.In this current study, we developed and utilized for the first time, a novel Al/DNA/Al surface-type Schottky diode as the humidity sensor. The fabricated Schottky diodes are further studied by investigating the fundamental changes induced by different time-dependent dosages of alpha particle irradiation on the DNA molecules. This was achieved by measuring its electrical characteristics under controlled chamber humidity to establish its humidity sensing potentials.293018At high humidity levels, water molecules play an important role towards improvement in conductivity in which case, the increase in electron transfer along the dsDNA helix may lead to the improvement in charge conduction. The charge transfer phenomena may therefore play an important role in the sensing mechanism, which could have primarily lead to the insignificant base-line shift and faster recovery time. This change in the electrical properties of the Al/DNA/Al structure due to the change in RH may therefore be generally attributed to the absorption of water molecules and the increase of the number of holes due to tracks made by the alpha particles upon bombardment.In is known that alpha particles lead to primary and secondary ionizations in atoms upon interaction. These processes in turn produce several types of ions and excited molecules in cells ultimately causing intermolecular bond biomolecule cleavage. Cleavage occurs within the cytoplasm and other intracellular components besides the cell nucleus. As such, DNA molecule being double stranded exhibits cleavage in one or both the strands. The DNA molecule has characteristic capability to repair single-strand damage; but a scission in double-stranded DNA repair to its original form is not trivial. However repair of double-stranded scission of the DNA molecule may cause gene mutations as a result of the exposure to radiationThe relationship between humidity and the resistance within the range from 20 to 99.9% RH is demonstrated in 2O molecule concentration and displacement currents, and the concentration of charge carriers doped by water moleculeset al., who in their work indicated that the reason for the low output signal current from the networks may be due to it being unsuitable for use in low RH sensors. Since the output signal current of the detector rises exponentially with increase in RH, the device display elevated sensitivity especially at higher RHAs discussed, the resistance in general decreased exponentially , while tThe resistance meanwhile decreased exponentially and was attributed to adsorption of water molecules by the DNA. This change is explained as follows; DNA consists of three portions; bases, sugars, and phosphoric acids. The hydrophilic phosphoric acid around the base pairs of DNA caused the water molecules to be easily absorbed and form hydrogen bonds between the phosphoric acid and the water molecule. Resistance values quickly decline as the RH increases and tend to saturate for humidity above 99.9%. These phenomena agree with ionic conduction at higher humidity scaleet al. studied the humidity influence on the electrical conductivity of DNA thin film1 and OH− species produced by water adsorption. The ions separate and recombine according to the Grotthus mechanism, which describes the passing of protons through the cooperation of neighboring water moleculesOtsuka 1039o is the initial capacitance, ε represents the relative dielectric constant, εo the absolute permittivity, A is equal to the area of the surface and d the distance between the electrodes. where C1 and m2 are the constants. In the case of relative capacitance, where H is the relative humidity level and mFrom et al.4243Sensitivity is calculated using the following relation;Sensitivity = Capacitance at high humidity (99.9%) − Capacitance at low humidity (20%)/(high humidity - low humidity) as shown in The dielectric constant from the fits made from 3445The surface morphology of the Al/DNA/Al thin films was examined using Atomic Force Microscope (AFM)  and shown in 1030The profiles in The electrical characteristics of the Schottky barrier height connections are very sensitive to the features of the metal-semiconductor (MS) interface. As such, the I–V characteristics of the connection are suitable displays of the interface features. For a Schottky barrier diode, the thermionic emission theory predicts that the I–V characteristics at forward bias V are given by* = 120 Am−2K−2 is the effective Richardson constant for Alb is the barrier height (in eV). For values of V > 3 KT/q, the ideality factor can be obtained from where Aet al. obtained under different humidity conditions. The highly rectifying curve and inverted S shape in this work at high relative humidity are clearly attributed to water molecules adsorbed by the DNA. Dielectric constant increase lead to the increase of the ionic conduction+ and OH− and the different mobility between H+ and OHThe ideality factor determined from the slope of the linear region of the forward bias (ln (I)–V) characteristic through the relation in 52S = S) versus voltage of the surface type Schottky diode is demonstrated in S values were the highest for 8, 2 and 6 min, respectively in reducing order, followed by the sample radiated for 4 min and non-radiated at 76% RH. At 99.9% RH meanwhile, the series resistance values were the highest for 8 min, non-radiated and 2 min in reducing order followed by the sample radiated for 4 and 6 min. However above 2.0 V, the series resistance values become insignificant.The values of series resistance are calculated from the junction resistance formula R2O molecules  and intermolecular features under humidity effectAccording to Ha 59S) were extracted. The results generally indicate an increase in the ideality factor with increasing humidity, while the series resistance and the barrier height values register attenuations with increase in the humidity. The influence of RH on capacitance and resistance of the sensor was studied in the humidity range of 20 to 99.9% RH. The sensors fabricated in this work demonstrated higher sensitivity across all the humidity range tested. Results also indicated that with the rise in humidity, capacitance increases while the device resistance dropped. Resistance and capacitance-humidity relationships recorded significant variations in the range of 50–99.9% and 45–75% RH. The resistance of the film generally reduced from a high of 1678 to a low of 6.523 KΩ and 1512 to 1.801 KΩ for the non-radiated and 2 min of alpha irradiation, respectively. The series resistance value increased after the irradiation for 2 min, followed by a decrease at 4 min (≈53.0755 KΩ) for characteristic to the hypersensitivity phenomena, which may correspond directly to the damage and repair mechanism in DNA, It was also shown that under the effect of increasing humidity, the capacitance of DNA thin film increased from 0.05894 to 92.736 nF for both the non-radiated and irradiated samples. These observations show the exciting possibility of utilizing Al/DNA/Al Schottky barriers as potentially sensitive humidity sensors and may even provide a platform to allow the study of charge transfer mechanism in DNA damage and repair processes.Humidity sensing properties of the DNA films deposited by drop casting method were investigated. Electrical characterization studies were carried-out using I–V profiles under humidity fluctuations and Schottky diode parameters such as ideality factor (n), barrier height (ф) and series resistance  amplification. The procedure starts with the collection of minute quantities of mycelium (0.1–1.0 g) from a colony of the fruiting body (Stipe) of a mushroom species using a sterilized tweezer. Standard procedures according to Hibbett −5 mbar, whereas the deposition rate was maintained at 0.1 nm/s and the gap length and width of gaps (between the electrodes) was 25 mm and 400 μm, respectively. After which, formation of the organic DNA layer was carried-out by using a micro-syringe  containing the pre-prepared DNA solution (concentration of 1.80 ng/μl). The fabricated device was then kept in a 1 K Cleanroom to allow self-assembly overnight. Sample irradiation by alpha particles was achieved using a 241Am source with an activity of 150 nCurie and t1/2 of 457 years for periods of 2, 4, 6 and 8 min. The top and cross-sectional view of the Al/DNA/Al surface-type Schottky diode fabricated is shown in A glass substrate was cleaned for 15 min using deionized water  in an ultrasonic cleaner and later dried in a dust-free environment. Thin films of Al (thickness ~325 nm) were deposited on the glass substrate using an Edward Auto 306 vacuum coater with a diffusion pumping system  and Al metal wire  of 99.999% purity). While depositing the Al thin film, the pressure inside the chamber was kept at 10in-situ capacitance and resistance values versus RH measurements of the Al/DNA/Al sensor at ambient temperature (25 ± 1 °C), were carried-out by placing the device in the hermetically sealed humidity chamber capable of providing a humidity range of 20–99.9% RH. The humidity meter and the Al/DNA/Al placed in a closed chamber were exposed to irradiation of alpha particles in a controlled humidity environment. The chamber has built-in input and output valves for gas flow. Nitrogen gas was then passed through water and then channeled into the chamber to control and maintain a certain humidity level within the chamber. LCR Meter (Instruments Instek LCR-829 LCR Meter) was used to measure the capacitance of the sensor. The How to cite this article: Al-Ta’ii, H. M. J. et al. Humidity influenced capacitance and resistance of an Al/DNA/Al Schottky diode irradiated by alpha particles. Sci. Rep.6, 25519; doi: 10.1038/srep25519 (2016).