Immunoglobulin E (IgE) is known to activate mast cells. Prior studies have shown that mast cells contribute to diet-induced obesity and diabetes mellitus (DM). We aimed to determine whether adults with IgE sensitization were at risk of DM. We performed assays regarding serum total IgE and allergen-specific IgE levels against the house dust mite, the cockroach, and the dog on 1,528 adults randomly sampled from every age and gender group in various districts. The total and three allergen-specific IgE levels were positively correlated with fasting glucose level and insulin resistance. Subjects with increased levels of total IgE (>100 kU/L), compared to those without, had an odds ratio (OR) of 1.72  for DM after adjusting for various covariates. Further controlling for previous allergic disease did not attenuate the association between total IgE level and DM. Subjects sensitized to the house dust mite  and the cockroach  were also at increased risk of DM. We found a strong positive association between IgE sensitization and DM in a general Korean population, suggesting that IgE may be an important independent risk factor for metabolic diseases in Koreans. Inflammatory mediators released by mast cells increase capillary permeability and trigger vasoconstriction and endothelial cell remodeling in patients with atherosclerosis5. Moreover, these mediators increase cytokine-induced insulin resistance (IR) and impair insulin secretion2. Mice lacking mast cells or given the mast cell inhibitors cromolyn or ketotifen are fully protected from the development of type 2 DM1. In animal models, mast cells participate directly in the development of diet-induced obesity and diabetes, and mast cell inhibitors offer hope to patients with these common, chronic inflammatory conditions1.Prior studies have shown that mast cells contribute to diet-induced obesity and diabetes mellitus (DM)6. IgE plays a key role in the signaling response to allergens. The binding of IgE to an Fc receptor activates mast cell degranulation and the release of cytokines, chemokines, histamine, proteoglycan, and mast cell protease. Clinically, IgE levels are increased in patients with atopic dermatitis (AD), asthma, and hay fever7. Recently, IgE levels have been shown to be elevated in patients with several chronic diseases, including rheumatoid arthritis, atherosclerosis, and ischemic heart disease3. Importantly, a recent US study found a higher prevalence of type 2 DM in patients with atopic dermatitis (AD) than in the general population7. Possible explanations include shared genetic risk loci for AD and type 2 DM8; diabetogenic effects of chronic, systemic low-grade inflammation in patients with moderate-to-severe AD9; and/or a sedentary lifestyle associated with AD10. We hypothesized that IgE sensitization might play a role in the development of type 2 DM. In the present study, we analyzed nationally representative data from the Korean National Health and Nutrition Examination Survey (KNHANES) to explore whether adults with IgE sensitization were at an increased risk of DM independent of allergic disease status. We also examined the relationship between IgE sensitization and metabolic syndrome (insulin resistance syndrome).Immunoglobulin E (IgE) antibody binds to the fragment crystallizable (Fc) receptors located principally on mast cell surfaces13. The survey was performed by the Korean Ministry of Health and Welfare and had three components: a health interview survey, a health examination survey, and a nutrition survey. Notably, the 2010 KNHANES gathered information on serum total and allergen-specific IgE levels from 2,342 participants randomly chosen from every age and sex group in each district; thus, the data were representative of the general Korean population12. Of the 2,342 participants, we excluded those younger than 30 years (n = 765); those who had not fasted sufficiently prior to blood sampling (<8 h) (n = 33); and those for whom data on at least one variable were missing (n = 16). Ultimately, the study population consisted of 1,528 subjects , which is conducted by the Korea Center for Disease Control and Prevention to obtain nationally representative and reliable statistical data on the health, health behaviors, nutrition, and food intake of the Korean population. KNHANES surveys are conducted annually using a rolling sample design featuring a complex, stratified, multistage probability-cluster survey of a representative sample of the non-institutionalized civilian population of South KoreaThe health interviews and health behavior surveys included well-established questions exploring demographic and socioeconomic characteristics. Anthropometric measurements were performed by specially trained examiners. Body weight and height, which were measured with the subject barefoot and wearing light clothing, were used to calculate the body mass index (BMI). Waist circumference was measured to the nearest 0.1 cm in the horizontal plane at the level of the midpoint between the iliac crest and the costal margin at the end of a normal expiration. Blood pressure was measured three times on the right arm using a mercury sphygmomanometer  with the individual in a seated position after at least 5 min of rest. The final blood pressure was the average of the second and third measurements.13. House dust mite is the primary inhalant allergen, and cockroach is the second leading allergen. Three common indoor allergens were tested for house dust mite (Dermatophagoides farina), cockroach and dog. Those with total IgE levels >100 kU/L were categorized as having “increased IgE”15, and those with allergen-specific IgE levels ≥0.35 kU/L were considered sensitized11.Fasting blood samples were collected, processed, immediately refrigerated, and transported on ice to the Central Testing Institute in Seoul, Korea. All blood samples were analyzed within 24 h of delivery. Total IgE and allergen-specific IgE levels were measured using an immunoradiometric assay  and a 1470 Wizard gamma-counter . In Korea, house dust mite, cockroach, mugwort, oak, Japanese hop, ragweed, and dog dander are important inhalant allergens11.Allergic diseases were defined subjects having one or more of the following disorders; atopic dermatitis (AD), asthma or allergic rhinitis. The following question was used to assess physician-diagnosed AD for each participant: “Have you been diagnosed with AD by a doctor?” Physician-diagnosed asthma and allergic rhinitis were also determined by using similar questions16. The homeostasis model assessment of insulin resistance (HOMA-IR) score was calculated as follows: [fasting glucose (mmol/L) × fasting insulin (mIU/L)]/22.517. Subjects were considered to exhibit IR if their HOMA-IR scores were in the highest quartile.DM was defined by a fasting blood glucose (FBG) level ≥126 mg/dL and/or a self-report of physician diagnosis and/or the use of an antidiabetic drug. FBG concentrations were measured using an automated enzymatic assay ; hemoglobin A1C (HbA1C) levels were measured with the aid of high-performance liquid chromatography . HbA1C levels were measured in subjects with FBG levels ≥126 mg/dL and those taking insulin or oral anti-diabetic medications. Poor glycemic control was defined as an HbA1c level ≥7%18: (1) waist circumference ≥90 cm in males and ≥ 80 cm in females ; (2) systolic blood pressure (BP) and/or diastolic BP ≥130/85 mmHg or present antihypertensive drug therapy or a history of hypertension; (3) FBG level ≥100 mg/dL or current medication regimen to treat elevated glucose; (4) fasting serum triglyceride ≥150 mg/dL or current relevant medication regimen; and (5) HDL cholesterol <40 mg/dL in males and <50 mg/dL in females or current relevant medication.Metabolic syndrome (MetS) was diagnosed when a subject met at least three of the following criteriat-test to compare continuous measures and the χ2 test to compare categorical measures. To estimate odds ratios (ORs) for DM by total and allergen-specific  IgE levels, we performed both simple and multiple logistic regression analyses using a generalized linear model appropriate for evaluation of complex survey data. In multivariate analysis, adjusted ORs and 95% confidence intervals (CIs) were calculated after adjustment for age, sex, BMI, educational level, household income, and region of residence (model 1); after adjustment for model 1 plus smoking status, alcohol consumption, and regular exercise (model 2); after adjustment for models 2 plus previous allergic disease status (model 3); and after adjustment for model 3 plus white blood cell counts (model 4). Finally, we added “increased total IgE” and “sensitization of specific allergens” as separate variables in the same multivariate model (model 5). Similar analyses were performed to estimate ORs for poor glycemic control among DM patients (n = 153). All statistical analyses were performed with the aid of SAS version 9.4 software . P value < 0.05 was considered to indicate statistical significance and was not adjusted for multiple comparisons.All data are presented as means ± standard errors (SEs) unless stated otherwise. If necessary, logarithmic transformations were performed to normalize distributions. Relationships between participant characteristics and DM were sought using the Student’s The cross-sectional analyses included data on 1,528 adults  with a mean age of 49 years; 153 (10%) had DM, and this group was more likely than others to be older, male, and obese and to have a lower income, an educational level less than high school and higher white blood cell (WBC) counts , waist circumference (r = 0.191), systolic blood pressure (r = 0.136), and triglyceride level (r = 0.148) , a high FBG level, elevated blood pressure (high BP), metabolic syndrome (MetS), and IR were significantly higher in the increased IgE group than in the non-increased IgE group Fig. . In termParticipants with increased total IgE were at increased risk of DM  after adjusting for age, sex, BMI, household income, educational level, and region of residence  for DM after adjusting for age, sex, BMI, educational level, household income, region of residence, smoking status, alcohol consumption, exercise, and previous allergic disease. However, after additionally adjusting for WBC counts, the relationship was insignificant. Subjects sensitized to the cockroach also had an increased OR for DM after adjustment for various covariates  of poor glycemic control. Further controlling for previous allergic disease did not attenuate the association between IgE sensitization and poor glycemic control (data not shown).This is the first study to evaluate the association between serum IgE levels and DM in a general population. We found strong positive associations between total IgE, house dust mite and cockroach-specific IgE levels and DM, and these persisted after adjustment for many potential confounders, including lifestyle factors ; socioeconomic status ; and previous allergic disease. Moreover, cockroach-specific IgE was an independent risk factor for poor glycemic control in subjects with DM. We also found significant associations between metabolic syndrome and IgE sensitization. Our data suggest that IgE level may be an important independent risk factor for metabolic disease, especially DM, in Koreans.2. The serum IgE levels significantly increase in patients with coronary artery disease when compared to unaffected subjects19. IgE activates mast cells, which, experimentally, play a critical role in type 2 DM1. Genetic deficiency and pharmacological inactivation of mast cells prevented diet-induced type 2 DM in mice. A human epidemiological study has shown that patients with type 2 DM had increased levels of IgE and mast cell chymase2. The role of mast cells in diabetic nephropathy has been extensively reported3. Mast cells are uncommon in normal kidney tissue, but mast cell infiltration is a prominent and early response to renal injury. Mast cells trigger fibrosis and extracellular matrix accumulation in patients with diabetic nephropathy20. Therefore, it is possible that IgE participates directly in DM pathogenesis and in complications thereof.Total IgE level is a biomarker closely associated with the inflammatory response to non-specific environmental factors as well as to reactions to specific allergens22. The numbers of B-1 cells decreased in patients with type 2 DM22. Gestational DM increased the risk of AD and allergen sensitization in early childhood23. Term infants of women with gestational DM were at a 7.6-fold increased risk of AD and a 5.9-fold increased risk of allergen sensitization. Prenatal exposure to high levels of glucose increased the risks of AD and sensitization in early life23. Mothers with gestational DM had higher levels of TNF-α, leptin, and visfatin and lower levels of adiponectin. Adiponectin attenuates allergic inflammation in murine models. Thus, it is possible that the changes in adipokine levels associated with gestational DM may affect immunological development in infancy23.However, it is equally possible that DM or high FBG levels trigger IgE sensitization. In mice with DM, high FBG levels impaired B-1 cell function; the immunoglobulin profile changed24. Previous studies have explored relationships between obesity and IgE sensitization3, but the data have been inconsistent. Vieira et al.25 found that the frequency of IgE-positivity in response to a balanced mixture of common aeroallergens was three-fold greater in obese than non-obese females. However, the total IgE concentration did not differ significantly between the groups. In the present study, central obesity, measured using waist circumference as a surrogate, was significantly (positively) correlated with total and all three allergen-specific IgE levels. We also found significant associations between metabolic syndrome and increased IgE.DM, obesity, and allergen sensitization share inflammatory pathways and mediators of immune responses. Increasing epidemiological evidence suggests that obesity increases the risks of asthma, atopic eczema, and allergic rhinitis. Obesity may trigger immunological changes, reducing antigen tolerance and skewing the immune system toward a T helper 2 (Th2) profile, which is associated with a cytokine release pattern increasing the risks of allergy and other immune-mediated diseases26. PAR-2 contributes substantially to inflammatory and metabolic dysfunction, and PAR-2 antagonists inhibit diet-induced obesity, reverse IR, and glucose intolerance, and they beneficially modulate liver and pancreatic metabolic parameters27. Cockroach allergies are more common in infested areas. Low socioeconomic status has been independently associated with sensitization to cockroach allergens. We examined the effects of socioeconomic status on the association between IgE level and DM and found that neither household income nor educational level nor region of residence affected the observed associations. Sensitization of cockroach is an independent predictor of risk of DM regardless of total IgE. However, the question remains whether glucose intolerance can be improved by avoiding the sensitization of cockroaches.Higher levels of allergic cockroach sensitization increased the risk of DM in the general population, and this association was stronger than that involving house dust mite sensitization. Cockroach extracts contain pepstatins, which are A-sensitive proteases activating the PAR-2 receptors; these, in turn, induce human eosinophil activation and degranulation. PAR-2 activation has been implicated in the potent allergenicity elicited by cockroaches7 showed that AD was associated with adult-onset diabetes , reflecting higher levels of smoking and alcohol intake and a sedentary lifestyle7. In contrast, adult inpatients or outpatients with AD treated in a Danish national hospital were not at an increased risk of new-onset DM10. After adjustment for co-morbidities and medication use, the independent OR for DM decreased significantly . However, in the present study, we found that increased IgE levels were associated with a rise in the prevalence of both DM  and IR in a general population. IgE sensitization may explain the observed association between AD and the increased risk of DM.A recent US population-based study21. Immunoglobulin production is a prototypical function of B cells, and immunoglobulins also play an important role in inflammatory diseases including lupus, rheumatoid arthritis and atherosclerosis22. It was reported that decreased IgG and IgM, and increased IgA levels were independently related to the prevalence of type 2 DM22. But, no significant elevated IgE in patients with diabetes was observed in that study22. Although the reasons for this discrepancy with our results remain unclear, it may be due to the difference in the study population and the use of allergen-specific IgE. We have measured allergen-specific IgE as well as total IgE, and we found that cockroach specific IgE sensitization was significantly associated with DM. Mouse studies suggest that immature B cells in adults and neonatal B cells are more prone to IgE switching than mature B2 cells28. Immunoglobulin dysregulation might contribute to the development of DM. Further studies are needed to explore the causality and exact mechanisms of immunoglobulins in subjects with DM.B cells are emerging players in innate and adaptive immune responses associated with metabolic diseases, including obesity, type 2 DM and cardiovascular disease29. WBC as a significant inflammatory factor is both accessible and affordable. Indeed, there was a significant difference of WBC counts between DM and non-DM subjects. So, we added WBC counts into model 4 of multivariate analysis. We found that increased total IgE and sensitization to cockroach remained significantly associated with DM after adjustment for WBC counts. Third, the history of steroid use was not available in this study. Fourth, the seasons of sample collection could not be discerned. According to previous studies conducted in Korea, not only pollens but also house dust mites demonstrate seasonal variation at indoor concentrations30. However, the rate of sensitization to cockroaches was similar for all seasons, except in summer30. Seasonal changes in sensitization to house dust mites have occurred in populations with allergies. We performed additional analysis after excluding the subjects with previous allergic diseases. The results were similar compared to the total population. Lastly, we could not differentiate type 1 or gestational from type 2 diabetes from the KNHANES data set. This study was conducted for adults over 30 years of age and prevalence of type 1 or gestational diabetes is relatively low. The prevalence of type 1 diabetes during 2011–2013 was about 0.02% of the total population in Korea32. However, we could not exclude the possibility that participants with type 1 or gestational diabetes were included in this study and the association of IgE with prevalence of diabetes differed according to diabetes type33.There are limitations to our study. First, this was a cross-sectional study, and, therefore, the association found between IgE sensitization and DM may not be causal. Second, we had no data on immune elements other than IgE. A previous study indicated that markers of inflammation (such as WBC counts) were associated with the development of DM in middle-aged adultsIn conclusion, we found that, independent of any previous allergic disease, an increased IgE level and sensitization to the cockroach were risk factors for DM. Sensitization to the cockroach was significantly associated with uncontrolled DM either before or after adjustment. As we used data from a nationally representative sample of the population and adjusted for multiple confounders, our results support the hypothesis that increased serum IgE levels are associated with DM in the general population.


Reduction in angiogenesis appears to be an important oncolytic mechanism of CDV in DH82 cells, suggesting that similar mechanisms might account for human histiocytic sarcoma and maybe other tumours in conjunction with measles virus.Histiocytic sarcoma represents a rare malignant tumour with a short survival time, indicating the need of novel treatment strategies including oncolytic virotherapy. The underlying molecular mechanisms of viral oncolysis are largely unknown. As cancer in companion animals shares striking similarities with human counterparts, we chose a permanent canine histiocytic sarcoma cell line (DH82 cells) to identify global transcriptome changes following infection with canine distemper virus (CDV), a paramyxovirus closely related to human measles virus. Microarray analysis identified 3054 differentially expressed probe sets (DEPs), encoding for 892 up‐ and 869 down‐regulated unique canine genes, respectively, in DH82 cells persistently infected with the vaccine strain Onderstepoort of CDV (DH82‐Ond‐pi), compared to non‐infected DH82 cells. Up‐regulated genes were predominantly related to immune processes, as demonstrated by functional enrichment analysis. Moreover, there was substantial enrichment of genes characteristic for classically activated M1 and alternatively activated M2 macrophages in DH82‐Ond‐pi; however, significant polarization into either of both categories was lacking. ‘Angiogenesis’ was the dominant enriched functional term for the down‐regulated genes, highlighting decreased blood vessel generation as a potential mechanism of paramyxovirus‐induced oncolysis in DH82 cells. The anti‐angiogenic effect of infection was verified by immunohistochemistry, which revealed a lower blood vessel density in an  Spontaneous tumours in companion animals are increasingly acknowledged as a suitable model for human cancer One promising approach for cancer therapy is represented by the use of oncolytic viruses i) determine global transcriptome differences in non‐infected DH82 cells and DH82 cells persistently infected with CDV as a model for paramyxovirus‐induced transcriptional changes in HS with microarray technique. Moreover, in a hypothesis‐driven approach, (ii) we sought to determine the impact of CDV infection on the expression of either tumour‐suppressive M1 or tumour‐progressive M2 macrophage‐specific genes through the induction of a phenotype polarization in DH82 cells themselves, as DH82 cells unite a unique combination, that is macrophage origin and neoplastic transformation. Finally, based on the results of the global transcriptome analysis, (iii) we validated one potential mechanism of viral oncolysis in a mouse model, xenotransplanted with either persistently CDV‐infected or non‐infected DH82 cells. This study represents the first description of oncolytic effects of a persistent infection of CDV upon DH82 cells. Future studies will have to expand the presented findings with special regard to the question whether non‐persistent (i.e. acute) infection of canine HS will have similar oncolytic capacity.If CDV indeed induces oncolytic effects in canine HS, one possible future therapeutic application might consist of infection of HS with attenuated strains of CDV. As an alternative future approach, DH82 cells persistently infected with CDV might be transplanted into canine patients with HS using these cells with an established and high infection rate as a permanent virus source. Interestingly, a DH82 cell line persistently infected with the vaccine strain Onderstepoort of CDV (CDV‐Ond) has previously been developed, which consistently displays a high infection rate of more than 85% infected cells and represents a suitable model to study the effects of a stable CDV infection upon this neoplastic cell line (DH82‐Ond‐pi) 2 in a loosely adherent monolayer in minimal essential medium (MEM) with Earle's salts , supplemented with 1% penicillin/streptomycin (PAA), 10% foetal calf serum (PAA) and 1% MEM non‐essential amino acids . DH82‐Ond‐pi were available within the department since their establishment as formerly described DH82 cells, received from the European Collection of Cell Cultures, and DH82 cells persistently infected with the CDV vaccine strain Onderstepoort (DH82‐Ond‐pi) were cultivated at 37°C in the presence of 5% CO™ 3‐conjugated goat anti‐mouse IgG (H + L) antibody  as a secondary antibody. Bisbenzimide was used for nuclear counterstaining (Sigma‐Aldrich). CDV‐NP‐positive and CDV‐NP‐negative cells were counted in 10 randomly selected high power fields per well with a fluorescence microscope , and the median percentage of immunopositive cells was calculated.To confirm successful CDV infection, immunofluorescence for detection of CDV nucleoprotein (CDV‐NP) was performed at day 1 after seeding of 30,000 cells/well [non‐infected DH82 cells (passage 10) and DH82‐Ond‐pi (passage 141)] in quadruplicates on 96 microwell plates  according to a 2‐day protocol with minor variations ™ GmbH, Darmstadt, Germany), digested with RNase‐free DNase  and purified with a silica gel‐based membrane  according to the manufacturer's protocols RNA isolation was performed on four replicates of DH82‐Ond‐pi and non‐infected DH82 cells, respectively, 1 day after seeding of 750,000 cells in T25 flasks . Total RNA was extracted with TRIzol (Invitrogenhttp://www.bioconductor.org/) http://biit.cs.ut.ee/clustvis/) http://www.ebi.ac.uk/arrayexpress) under accession number E‐MTAB‐3942.Two hundred nanogram of each of the eight RNA samples was amplified and biotin‐labelled employing the 3′IVT express kit  and hybridized to GeneChip Canine Genome 2.0 arrays (Affymetrix) in a rotating hybridization oven at 45°C for 16 hrs. Afterwards, the arrays were washed and stained with a solution containing R‐phycoerythrin–streptavidin employing the Affymetrix GeneChip Fluidics Station 450 q ≤ 0.05), according to the method of Benjamini and Hochberg q ≤ 0.05) and a moderately stringent fold change (FC) filter (FC ≥ 2.0 or ≤ −2.0) 2‐transformed expression values For detection of DEPs, a one‐factorial test with the Linear Models for Microarray Data (LIMMA) algorithm, implied in Babelomics 4.3 http://www.webgestalt.org/) http://cardioserve.nantes.inserm.fr/mad/madgene/) Differentially expressed genes were assigned to functional terms in the Gene Ontology (GO) Biological Process category, applying WEB‐based GEne SeT AnaLysis Toolkit  U‐tests. Differential expression was defined by the combination of a statistical significance filter  and an FC filter (FC ≥ 2.0 or ≤ −2.0).Based on the histiocytic origin of DH82 cells and previous observations that CDV influences the polarization of canine macrophages in vivo, formalin‐fixed paraffin‐embedded (FFPE) material of a xenotransplantation in vivo mouse model, approved and authorized by the local authorities (Niedersächsisches Landesamt für Verbraucherschutz‐ und Lebensmittelsicherheit (LAVES), Oldenburg, Germany, permission number 33.9‐42502‐04‐08/1515), was used. All animal procedures were performed in accordance with the German regulations and legal requirements. A total number of 60 female severe combined immunodeficiency (SCID) mice (CB17/Icr‐Prkdcscid/lcrlcoCrl) were subcutaneously xenotransplanted with non‐infected DH82 cells  or DH82‐Ond‐pi . Tumour growth was measured every 2–3 days. For histological and immunohistochemical investigations in this study, necropsy and sample collection were performed on day 7, 14, 21, 35 and 77 after xenotransplantation (days post transplantation (dpt); n = 6 animals per time point and group). However, due to histologically determined complete regression of DH82‐Ond‐pi neoplasms in four of six animals at 35 dpt and six of six animals at 77 dpt, detailed histological and immunohistochemical analyses were only performed at 7, 14 and 21 dpt.To test whether the observed transcriptome differences between infected and non‐infected DH82 cells indeed point to a capacity of CDV of inducing oncolysis Haematoxylin–eosin‐stained histological sections of tumours were morphometrically analysed to determine total tumour area and quantify areas of necrosis. The percentage of necrotic tumour areas, characterized by hypereosinophilia, loss of cell borders, accumulation of cellular debris, karyopyknosis, karyorrhexis and karyolysis, was determined with the analySIS 3.1 software .2O2 in ethanol served as suppressor for endogenous peroxidase activity. Sections were pre‐treated with citric buffer followed by blocking (goat serum 1:5) and addition of a biotinylated goat anti‐rabbit secondary antibody (1:200). 3,3`‐diaminobenzidine‐tetrahydrochloride served as chromogen followed by slight counterstaining with Mayer's hemalaun .Immunohistochemistry with the avidin–biotin–peroxidase complex method was performed with a panel of polyclonal rabbit anti‐human antibodies. To investigate the intratumoural vascularization, a CD31/PECAM antibody  was applied as described U‐tests. P‐values below 0.05 were considered significant.Immunopositivity for cleaved caspase‐3 and Ki67 was evaluated morphometrically and was given as the percentage of immunopositive area related to total tumour area. As tumour cells of HS have previously been reported to be CD31‐immunopositive Irrespective of their infection status and consistent with the literature Principal component analysis (PCA) of the normalized data set revealed a clear distinction between the global expression data from the four replicates of infected and non‐infected DH82 cells with markedly isolated clusters Fig. . DEPs coThe used Affymetrix Canine Genome 2.0 Array also includes seven probe sets targeting different RNAs of the CDV genome DDX60 (DEAD (Asp‐Glu‐Ala‐Asp) box polypeptide 60), DLA‐79 (MHC class Ib) and CXCR7 with FCs ranging from 2198.9 to 196.6.The top hits of up‐regulated canine DEGs Table  includedSERPINB2 , member 2), TPM2 (tropomyosin 2 (β)), VEGFB , THBS2 (thrombospondin 2), SCIN (adseverin‐like), S100P  LOC608476 , GSTA3 (glutathione S‐transferase α‐3), TCEAL1 (transcription elongation factor A (SII)‐like 1) and COL4A1  with FCs ranging from −1663.8 to −208.9.The ten top hits of down‐regulated DEGs Table  comprisecollagen type I, α‐1 (COL1A1), endothelin 1 (EDN1), integrin α‐7 (ITGA7), cysteine‐rich angiogenic inducer 61 (CYR61) and chemokine (C‐X‐C motif) receptor 4 (CXCR4). Similarly, WebGestalt identified the term ‘blood vessel morphogenesis’ as being functionally enriched  being the member with the highest absolute FC of −593.2, followed by thrombospondin 2 . Besides, WebGestalt identified enriched GO terms related to cell migration, movement, localization and adhesion for the down‐regulated DEGs (Table The retrieved gene ontology (GO) terms of the biological process category are summarized in Table ed Table  with vasP < 0.001). The most significant category for the up‐regulated canine genes was ‘defence response to virus’ and ‘activation of immune response’, both with DDX60 as the gene with the highest FC (2198.9).A second confirmatory approach with a more stringent FC filter of an absolute FC value of 5.0 resulted in a list of 186 up‐ and 218 down‐regulated DEGs, which served as input data for WebGestalt (data not shown). Interestingly, and similar to the functional analyses of the DEGs with a more moderate FC filter, ‘regulation of angiogenesis’ was retrieved as enriched functional term (P ≤ 0.05). Whereas ‘positive regulation of interleukin‐8 biosynthetic process’ (P = 0.006), ‘myeloid leucocyte differentiation’ (P = 0.008), ‘chemokine‐mediated signalling pathway’ (P = 0.003) and ‘eosinophil chemotaxis’ (P = 0.001) was retrieved for the clusters of up‐regulated genes, ‘fatty acid β‐oxidation’ (P = 0.027), ‘positive regulation of inflammatory response’ (P = 0.029), ‘cardiac septum morphogenesis’ (P = 0.008) and ‘positive regulation of angiogenesis’ (P = 0.008) reached significance for the down‐regulated gene clusters.The more stringent FC filter (≥ 5.0 or ≤ −5.0) was used for unsupervised hierarchical clustering of the 404 canine DEGs. Hierarchical clustering  of the logarithmized individual FCs graphically illustrated the relatively similar proportions of up‐ and down‐regulated genes Fig.  and resuU‐test P ≤ 0.05 and FC ≤ −2.0 or ≥ 2.0) in the expression of 21 of 59 unique canine gene symbols for the M1 category , whereas 19 of 55 genes exhibited differential regulation for the M2 category , respectively  and alternative (M2) activation of macrophages is a critical determinant for the fate of malignancies. Although generally applying to TAM, the unique histogenesis of HS raises the question whether persistent infection might similarly induce a phenotypical polarization in neoplastic DH82 cells themselves, thereby potentially exerting oncolytic properties. Thus, besides the global analysis, the data set was analysed for changes in the expression of literature‐based genes specifically expressed by M1‐ or M2‐polarized macrophages P > 0.05).Fisher's exact test for significant enrichment in either of the both categories failed to reach significance , 14 (P = 0.005) and 21 (P = 0.012) in tumours composed of non‐infected DH82 cells compared to DH82‐Ond‐pi .Tumour sections of non‐infected and DH82‐Ond‐pi xenotransplants on day 7, 14 and 21 following transplantation were evaluated. Pairwise comparison revealed a significantly higher intratumoural blood vessel density on day 7 P = 0.00, 14 (P =P < 0.05).Starting at day 14 after transplantation, tumour sizes of DH82‐Ond‐pi transplants revealed a constant regression over the observed time period Fig. . OverallP < 0.05).The percentage of cleaved caspase‐3 antigen‐positive area displayed no significant differences in both infected and non‐infected tumours at 7 and 21 days after transplantation. However, at day 14, cleaved caspase‐3 antigen‐positive area was significantly larger in DH82‐Ond‐pi xenografts compared to non‐infected control tumours .Tumour cell proliferation as determined by immunohistochemistry for Ki67 was significantly higher in non‐infected transplants compared to DH82‐Ond‐pi transplants at all investigated time points  origin and malignant neoplastic behaviour of DH82 cells in vitro as determined by trypan blue staining −, CD14−, CD18−, CD45− and CD80 during long‐term passaging Functional annotation of the up‐regulated genes in DH82‐Ond‐pi predominantly yielded GO terms related to activation of immune processes. These findings demonstrate that persistent CDV infection of DH82 cells induces marked up‐regulation of immune response‐related genes, which may be attributed to the unique combination of both histiocytic (in vitroin vitro.Based on the observation of up‐regulated genes involved in immune processes, and in the light of the fact that HS cells possess properties of macrophages, we investigated whether CDV might exert oncolytic properties through the induction of a polarization in DH82 cells themselves into the tumour‐suppressive M1 or the tumour‐progressive M2 phenotype VEGFB and thrombospondin 2, which code for therapeutically relevant proteins implied in tumour angiogenesis VEGFA did not reach the FC filtering criteria. Nonetheless, this indicates that CDV infection induces a diminished expression of multiple VEGF pathway members. However, the GO terms related to blood vessel formation also comprised genes, which are known to possess anti‐angiogenic properties such as thrombospondin 2Interestingly, reduced angiogenesis has been highlighted previously as a putative oncolytic mechanism for viral oncolysis in vivo model. In this model, non‐infected transplants showed a significantly higher density of CD31‐positive blood vessels compared to persistently infected transplants at day 7, 14 and 21 after xenotransplantation, associated with a decreased tumour volume in infected transplants. This was paralleled by relatively large areas of necrosis in persistently infected tumour transplants, thus probably representing the result of ischaemic cell death. Moreover, there was a decreased proliferation index in persistently infected tumours, as demonstrated by lower mitotic rate and decreased Ki‐67 immunoreactivity. The results of the xenotransplantation model overall confirmed that persistent infection of DH82 cells with CDV is indeed accompanied by viral oncolysis and that reduced angiogenesis might represent a crucial factor for this mechanism.Based on these observations, tumour vascularization of neoplasms composed of non‐infected DH82 cells or DH82‐Ond‐pi in xenotransplanted mice was determined by immunohistochemistry in an in vivo. However, whether the observed transcriptomic changes are unique to CDV and a persistent infection state needs to be discussed carefully, as independent persistently infected cells have not been investigated in the present study. However, arguing against the assumption that the persistent nature of the infection represents a prerequisite of CDV‐induced reduced angiogenesis and favouring the hypothesis that similar mechanisms might potentially also account for acute infection models and specifically for CDV, an angiogenesis‐inhibiting effect of CDV has previously been similarly suggested in Vero cells, acutely infected with CDV Although transcriptome data identified genes, which possess both pro‐ and anti‐angiogenic properties, it appears that the dysregulation of genes involved in blood vessel generation indeed favours reduced angiogenesis in vivo, we chose a persistently infected cell line with a high number of infected cells to demonstrate virus‐induced differences between infected and non‐infected cells to the highest extend. Additional studies are needed to extend the presented findings on both acute infection models and the systemic form of this malignancy. In particular, it remains to be shown whether the persistent nature of the infection represents a prerequisite for the demonstrated oncolytic mechanisms or whether an acute CDV infection of HS is similarly capable of inducing the observed changes. If an application of attenuated vaccine strains of CDV indeed influences tumour vascularization of HS in vivo, we propose that similar mechanisms might also apply to measles virus infection of HS in human beings. The results thus validate the spontaneous canine model as an interesting translational animal model for cancer research, warranting future investigations upon the role of reduced angiogenesis in HS, infected with an oncolytic paramyxovirus.The provided results have indirect therapeutic relevance, as vaccine strains of CDV are readily available, well tolerated and raise the opportunity of a systemic application in canine patients. Although the approach prevents definitive conclusions on the effects of a more clinically relevant acute infection model of localized HS The authors confirm that there are no conflict of interest.


Currently, cannulated pedicle screws have been widely used in minimal invasive or navigation techniques. However, the stress distribution and the strength of different core diameters of cannulated screw are not clear. This study aimed to investigate the mechanical strength of cannulated screws with different inner core diameter under various lumbar spine movements using finite element analysis.The results showed that the von-Mises stress of a cannulated screw was larger than that of a solid screw in all loading conditions, especially above 2 mm in cannulated core diameter. In lateral bending, extension, and flexion, the maximum von-Mises stress was found approximate to the proximal thread for all types of screws. In rotation condition, the maximum von-Mises stress was located at the middle of the screw. Additionally, the difference in stiffness of instrumented levels was not significant among four screws under the same loading condition.Cannulated screws could provide enough stability for the vertebral body fusion comparing to solid screws. The diameter of cannulated core is suggested not to exceed 2.0 mm. Spinal fixation instrument is commonly used to improve the stability in spinal surgeries. Spinal fusion with fixation instruments has become more popular than the fusion without instruments , 2. The The cannulated pedicle screw is an alternative design of traditional solid pedicle screw, which was developed to be applied in minimal invasive or navigation techniques and inserted following the guidance wire along the planned path . AlthougChen et al.  evaluatePedicle screw breakage is one of the most common complications in spinal fusion surgeries, especial for multi-levels fusion. Different inner diameter could influence the structure strength of the cannulate pedicle screw, and at least 1.5 mm would be necessary to work with the guidance wire. Therefore, the purpose of this study was to investigate the mechanical strength of cannulated screws with different inner core diameter under various lumbar spine movements using finite element analysis. We hypothesized that the core cannulated path may lead to stress concentrations and may become a source of crack that cause failure of screw. In addition, larger inner core diameters are associated with significant increased risk of screw breakage.The intact lumbar spine model (L1–L5), which had been validated by comparison with in vitro tests and successfully used for biomechanical analyses –13, was 3.The posterolateral fusion model of L3/L4, which is the most common involved level, was used to simulate changes in post-operative conditions. In the posterolateral fusion model, the bone graft elements were placed between two adjacent transverse processes to simulate perfect fusion. The average width, thickness, and length of the bone graft was 13.1, 11.3, and 41.6 mm, respectively, with a volume of 6163 mmThe pedicle screw was reconstructed with an outer diameter of 6.5 mm and a length of 45.0 mm which is the most commonly used size in clinical. A total of four screws were designed in this study, including a solid screw (S0), a screw combined with a 1.5 mm cannulated core path (S1.5), a screw combined with a 2.0 mm cannulated core path (S2.0), and a screw combed with a 2.5 mm cannulated core path  , 11, 12.The von-Mises stress of the screws increased with the increasing inner core diameters Table . FlexionIn rotation, the maximum von-Mises stress of the S1.5, S2.0, and S2.5 increased by 87.5, 150.0, and 162.5% compared to the S0. The maximum von-Mises stress concentrated at the middle of the lower screw. In lateral bending, the maximum von-Mises stress of the S1.5, S2.0, and S2.5 increased by 23.6, 25.4, and 41.8% compared to the S0. The maximum von-Mises stress occurred at the proximal thread of the lower screw. In extension, the maximum von-Mises stress of the S1.5, S2.0, and S2.5 increased by 0, 18.4, and 28.6% compared to the S0. The maximum von-Mises stress was found at the proximal thread of the upper screw. In flexion, the maximum von-Mises stress of the S1.5, S2.0, and S2.5 increased by 4.2, 16.9, and 26.8% compared to the S0. The maximum von-Mises stress occurred at the proximal thread of the lower screw (Fig. The stiffness of different screw at the fused level under each loading condition was showed in Table The cannulated screws have become increasingly popular in orthopedic surgeries, including foot, ankle, hip, small joint, and spine fixation over past 10 years. However, the main concern of using a cannulated screw is that its mechanical strength is lower than that of a solid screw with a similar diameter . Yang etThe primary function of pedicle screw system is to stabilize the spine and share the physical loading. If the pedicle screws were broken in the early postoperative period, patients with failed constructs, which may develop progressive kyphosis subsequently, could have poor functional outcomes, progressive back pain, and may require additional surgical procedure for instrument removal . The canThe FE analysis indicated that the inner core diameter could affect the stress distribution of the whole screw. The maximum von-Mises stress increased as the inner core diameter increased. According to the results, the maximum von-Mises stress of the screw occurred at the caudal side of the screw during flexion, extension and laterals bending, but concentred at middle part during torsion Fig. . The larThe screw model in this study was designed according to commercial products. The diameter of the cannulated core is the only factor being discussed. Other factors that might affect the test result, such as the screw type, pitch, and thread’s shape, will be investigated in the future.Single-level instrumented lumbar posterolateral fusion was simulated in this model. Multi-levels posterolateral fusions were not analyzed in this study.The material properties of the vertebral body were assumed to be isotropic and homogenous.The loading conditions were not truly physiological condition because this model did not account for the mechanical effects of muscle contraction.In this study, the stress of screws was analyzed to identify the failure locations of clinical cases. Besides, the diameter of cannulated core affecting the maximum stress of pedicle screw under different loading conditions has been shown. Several limitations to this FE model analyses are noted:Although the models incorporated some assumptions and limitations, the results showed a similar pattern and trend to previous studies and clinical cases.Because the diameter of a guide pin defines its stiffness, it is important for the cannulated path of the screw to accommodate as much width as possible. A wide diameter guide pin could restrict bending when it is inserted. However, this study demonstrated that cannulation width caused a raise of stress concentration at the proximal screw shaft, and it could further increase the fatigue failure risks. From the results, the diameter of the cannulated core is suggested not to exceed 2.0 mm. Even a screw with a diameter of around 1.5 mm could decrease the effects of the loss of a screw’s strength.


The long-term trend of extreme ocean waves in the emerging ice-free waters of the summer Arctic is studied using ERA-Interim wave reanalysis, with validation by two drifting wave buoys deployed in summer 2016. The 38-year-long reanalysis dataset reveals an increase in the expected largest significant wave height from 2.3 m to 3.1 m in the ice-free water from the Laptev to the Beaufort Seas during October. The trend is highly correlated with the expected increase in highest wind speed from 12.0 m/s to 14.2 m/s over the ice-free ocean, and less so with the extent of the ice-free water. Since the storms in this area did not strengthen throughout the analysis period, the increase in the expected largest significant wave height follows from the enhanced probability of storms in ice-free waters, which is pertinent to the estimation of extreme sea conditions along the Northern Sea Route. In latitudes north of 70°N, the mean significant wave height during summer exceeds 3 m in some areas2. As the entire Arctic Ocean is expected to be ice-free by 2050, the wave height is projected to correspondingly increase3. In the last decades, the waves in the Arctic Ocean have gradually increased as substantiated by numerous studies based on satellite observations and reanalysis6. Collins et al.7 reported a significant wave height of almost 5 m in the Barents Sea based on the analysis of the ship motion. During the R/V Sikuliaq cruise in 2015, a wave buoy measured waves reaching 5 m in the Beaufort sea8. Over 200 vessels have used the Northern Sea Route (NSR) since 2011. While these vessels must comply with the ice-class rules, they also need to take into consideration the increasing height of the ocean waves in the Arctic Ocean. In the presence of high waves and low temperatures, sea-spray icing may also become a serious problem.The area of ice-covered sea in the Arctic Ocean during the boreal summer has reduced by a few million square kilometres in previous decadesHs in the ice-free waters is approximated by a Weibull distribution, k is a shape parameter, then the maximum significant wave heightN, where N is the number of data samples9. This simple relationship indicates that the largest Hs in ice-free waters is related to the distribution of Hs represented by the scale parameter N. Thomson et al.10 estimated a 0.01 m/year increase of the scale parameter 11. In contrast, the maximum Hs increases with N as well according to equation  of the significant wave height mentclass2pt{minimN, the observed maximum For a given value of M is the number of available data samples for a given time interval. While a point-by-point statistics in the ice-covered ocean requires a careful analysis12, the proposed method allows a straightforward implementation, and is also directly related to the encounter wave statistics for the NSR vessels.From observational or reanalysis data, however, it is more practical to invoke an ergodic hypothesis and estimate the mean from the time averageHs is estimated using equation  during a particular month of the analysis period, with a similar analysis conducted for the area of ice-free water, and the wind speed at a height of 10 m. A correlation analysis of the wave height, the area of ice-free water, and the wind speed is also conducted.For observing the long-term trend of the largest significant wave height in the Arctic Ocean, the expectation of the area-maximum equation . Conside13. The spatial resolution of the wave model in the Arctic Ocean is around 110 km in longitude and 110 km in latitude, with wave spectra available for 24 directions and 30 frequencies. The relatively coarse grid resolution prevents the resolution of the fine-scale structure of the ice edge in the Arctic Ocean. While the recent reanalysis assimilates significant-wave-height data from an altimeter on the Jason-2 satellite, its orbital inclination of 66.038° precludes measurement of Arctic Ocean waves, implying the Artic wave field of the ERA-Interim reanalysis system is essentially lacking any data assimilation in recent years. Since ERS-1/2 were assimilated from Aug. 1991 to Jul. 2003, and ENVISAT from Jul. 2003 to Aug. 2012, 1991 and 2011 marks the transition between assimilation free and assimilated periods, which could be critical in the trend analysis. The sea-surface temperature (SST) and the ice concentration data assimilation systems have utilized the Operational Sea Surface Temperature and Sea-Ice Analysis (OSTIA) data in recent years. As Dee et al.13 report that the surface wind speed depends strongly on the SST and extent of the ice coverage in the polar region, uncertainties in the OSTIA sea-ice cover and SST affect the magnitude of the surface wind speed. Therefore, without data assimilation, the accuracy of the ERA-interim wave field remains uncertain.The ERA-Interim reanalysis is a global atmospheric, wave and ice data assimilation system beginning in 1979 and continuing in near real-timeThe ERA-Interim wave field in the Chukchi and Beaufort Seas, interpolated on the wind and wave collocated 0.75 degrees regular grid, was validated by a 2016 wave observation campaign by The University of Tokyo. During the Mirai cruise (MR16-06) of the Japan Agency for Marine-Earth Science and Technology from 22 August to 5 October 2016, two drifting-type wave buoys (WII: Waves In Ice buoys) were deployed off Point Barrow on 10 September. The two buoys remained within an area of a few hundred square kilometres, and successfully collected wave data before contact was lost with both on 2 November 2016. The tracks of the two buoys, which are indicated by red and green trajectories in Fig. Hs at the buoy locations compares well with the observations , which is the area bounded by the orange line in Fig. Hs and U10 are calculated, along with the 38-year trends. The August, September and October climatological values of Hs are 0.85 ± 0.11 m, 1.07 ± 0.12 m and 1.26 ± 0.17 m, respectively. The highest mean wave height and greatest variability occur in October. In Table Hs and the scaling parameter of the Weibull fit are shown. On average, the linear trend of Hs is around 5 mm/year, and that of the scaling parameter of the Weibull distribution is of the same magnitude. The linear trend of the scaling parameter et al.10 which is based on 23-year reanalysis data. The difference of the data length may account for this difference implying the acceleration of the increasing trend of the average wave height in the Arctic Ocean. We can state that since 1979, the average Hs has increased by about 20%, corresponding to 0.15 m in August, 0.19 m in September, and 0.20 m in October. The estimate falls within the range of the increasing trend, 0.3–0.8%/year, detected by Wang et al.6. The wind speed over the ice-free waters, however, does not show any noticeable trend ′ ′ Table .Table 3PE[ρ]〉, and amount to 0.95 for August, 0.92 for September and 0.95 for October. Conversely, the partial correlations between ice-free water area 〈E[ρ]〉 and E[ρ]〉.High partial correlations are found between the low-pass filtered wave height and wind speed, E[ρ])′ and the wave height E[ρ])′ in September, but relatively weakly in other months. In summary, the correlation of interannual variation of the maximum wind speed While the correlation between the high-pass filtered wave height Overall, the partial correlation analysis reveals that the area-maximum significant wave height in the Arctic ice-free waters is not directly influenced by the ice coverage for both long-term and inter-annual variations, but is strongly affected by the maximum wind speed in the ice-free water area. Whether this is related to the change in storm intensity in the past several decades is discussed below.E[ρ]. That Analysis of the ERA-Interim wave field in the Arctic ice-free waters from 1979 to 2016 indicates a positive trend of the expected area-maximum wave height 19, which serve as benchmarks in the tuning of third-generation wave models. However, it is rare to find meteorological conditions with a well-defined fetch in the wind direction, including near the coast, as the fetch geometry can be rather complicated in an enclosed basin. Recent findings of wave propagation at the marginal ice-zone detected by SAR observations imply that the determination of a well defined fetch in the partially ice-covered sea can be laborious22. For the case of waves under a hurricane, an “equivalent fetch” replaces the physical distance over which the flow traverses (see the extensive review by Young23). As the ice starts to melt and ice-free water emerges in the Arctic Ocean24, the wave behaviour at this early stage may resemble that in an enclosed basin. Eventually, the area of ice-free water surpasses the scale of the storm, with conditions resembling that of waves under a hurricane. With the increase in the area of ice-free water in time, the lake-like conditions transition into hurricane-like conditions in the open waters, so that the ice-free water distance may no longer be the most relevant parameter. It is, therefore, unsurprising that 11 show that the wind waves generated by the local wind approximately follow the fetch law. However, if we limit our attention to the largest waves in the ice-free water, the ice-free water distance as represented by the area of ice-free water does not correlate well with the wave height. The fetch effect, therefore, is not the main cause of the positive trend of For flow from the land or ice to ice-free water, waves are generated and gradually grow with distance according to the so-called fetch laws derived from observationset al.25 investigated the NCEP/NCAR reanalysis dataset from 1979 to 2014 and show that there is no coherent trend in storm frequency or intensity despite the increasing loss of sea ice during summer. This is consistent with Sato and Inoue26, who show that the trend in sea-level pressure is almost negligible in contrast to the strong decrease in ice concentration. In the literature, there is also no evidence of the increase of the intensity or frequency of storms in the Arctic Ocean. This is confirmed by analyzing the ERA-Interim wind speed in the Laptev, East Siberian, Chukchi and Beaufort Seas, including the land and ice-covered areas, which shows little positive trend in the maximum wind speed  be the cumulative distribution function of the significant wave height Hs,p(Hs) is the p.d.f. of the significant wave height Hs. For N observational or grid points of a numerical wave model in ice-free waters, the largest significant wave height among these isLet N9. This simple relationship indicates that the largest Hs in ice-free waters is related to the distribution of Hs, the scale parameter N.Assuming further that the p.d.f. can be approximated by a Weibull distribution N, the observed Hs at one observational point, or at one grid point, 1 − P(Hs)N. Following Longuet-Higgins27, the probability that the maximum value of the significant wave height lies within Hs and Hs + dHs is dP(Hs)N = NP(Hs)N−1p(Hs)dHs, and thereby, the p.d.f. of the For a given number of P or the p.d.f p of Hs is known, the median, mode and mean of f. In particular, the expectation or the mean of the If the cumulative distribution function 28. The nine degrees of freedom, three-axis gyroscope, accelerometer, and compass sensor (IMU MPU9250) is placed in a drifting buoy, and the data is processed on board by an Intel Edison processor. The motion is measured at 1-, 3- and 6-h sampling intervals for a 40-min data capture length starting at 5 min past the hour. When the battery voltage level lowers, the interval can be switched to a sleeping mode.The WII buoy system developed by P.A.S. Consultants is based on a system originally designed to measure the wave-induced motion of ice floes in the Antarctic marginal ice zoneet al.28 The statistical quantities and power spectral density (p.s.d.), as well as the metadata, are transferred by Iridium satellite link to a server maintained by P. A. S. Consultants and is made accessible online. The raw data is also stored on a memory card.The accelerometer data is Fourier transformed, high-pass filtered and integrated to obtain various wave parameters. The details of the analysis method and the derived parameters are described in Kohout et al.14.The commercially available Sealite buoy was modified to include an internal electronics tube for the placement of three solar panels on its side, and to attach a 15-kg steel weight at the bottom of the keel Fig.  for a toT0,−1 = (m0/m−1)−1 agreed best with the reanalysis. Further details are given in Waseda et al.14.The low-frequency noise of an accelerometer record is commonly removed with an ideal high-pass filter. Because the WII system was originally developed for measurements in the Antarctic Ocean which is unbounded, and hence accounts for waves of much longer wave period than that found in the Arctic Ocean, the on-board processing applies a high-pass filter at a 33-s cutoff period. The mean of the p.s.d. of buoy 1 for the entire period is shown in Fig. https://ads.nipr.ac.jp/dataset/A20180306-001.The observed wave data analysed during the current study are available in the Arctic Data archive System (ADS) repository, Supplementary Materials


Interpreted in light of shifting environmental, preservation and socio-economic factors, these new data show counterintuitive trends in the intensity of reindeer hunting and other high-elevation activity. Cold temperatures may sometimes have kept humans from Norway's highest elevations, as expected based on accessibility, exposure and reindeer distributions. In times of increasing demand for mountain resources, however, activity probably continued in the face of adverse or variable climatic conditions. The use of KDE modelling makes it possible to observe this patterning without the spurious effects of noise introduced by the discrete nature of the finds and the radiocarbon calibration process.The melting of perennial ice patches globally is uncovering a fragile record of alpine activity, especially hunting and the use of mountain passes. When rescued by systematic fieldwork , this evidence opens an unprecedented window on the chronology of high-elevation activity. Recent research in Jotunheimen and surrounding mountain areas of Norway has recovered over 2000 finds—many associated with reindeer hunting (e.g. arrows). We report the radiocarbon dates of 153 objects and use a kernel density estimation (KDE) method to determine the distribution of dated events from  A new kernel density estimation (KDE) method is used to determine the distribution of radiocarbon dated events without the confounding effects of spurious peaks from the shape of the radiocarbon calibration curve [In the context of global warming , the melon curve . Thus itVariations in the intensity of activity in mountainous environments globally are often linked to climate change. Sometimes the mechanism is as straightforward as access, with fluctuating glaciers blocking or clearing alpine passes . In otheAlternatively, increasing use of high elevation resources is sometimes interpreted as a matter of economic intensification and ‘globalization’, only indirectly influenced by climate. In times of demographic and/or economic expansion, mountains, like oceans and forests, may become part of an expanding ecological frontier serving the needs of both local settlements and distant (often urban) consumers linked via long-range exchange networks –20. In NTo evaluate these alternative interpretations, which need not be mutually exclusive, it is necessary to compare archaeological evidence regarding the chronology of mountain hunting and travel with concurrent climate changes. Were variations in the abundance of ice-patch finds associated with or independent of warming and cooling, shrinking ice or growing ice? Were efflorescences of ice-patch hunting concurrent with or unrelated to periods of external demand for reindeer antler and/or fur? The new radiocarbon dated finds from Norway's ice patches reported here, combined with KDE analysis, provide a unique opportunity to address these questions. They can illuminate the interaction of climatic and socio-economic factors in an alpine context where all pre-industrial human activity is potentially susceptible to environmental limits set by accessibility, exposure and resource availability.2.Over 2000 artefacts and 375 samples of associated materials  have been recovered from Oppland's mountain ice between 2006 and 2015. Most are from stationary  ice patches rather than glaciers, because the continuous movement of the latter destroys objects at the base of the ice . Perenniet al. [Cold climate conditions in Scandinavia can be associated with either increased or decreased likelihood of precipitation . Thus thet al. , based oet al. , of shoret al. ,37 and/oet al. . Figure et al. , smootheet al. . Glacieret al. . Figure in situ vegetation, shed antlers and reindeer dung are omitted. The dated finds range from manufactured objects (e.g. arrows) to incidental traces of human journeys (e.g. horse dung). The dates have been obtained from 23 discrete ice patches, a subset of the 51 presently known artefact-yielding examples in the high mountains of northern Oppland County , elm (Ulmus glabra), willow  and especially Scots pine (Pinus sylvestris)—the latter of which can live to between 200 and 677 years in Norway based on dendrochronological research . Thus there is a high risk of old wood effect, in which radiocarbon dates are earlier than the time-period of artefact deposition. Here we divide the artefacts into groups with low and high risk of an old wood effect. The low risk materials include wool, antler, animal hide, horse dung and wood of the comparatively short-lived trees alder (Alnus spp.) and birch (Betula pubescens). Most of the arrows and many other finds are made of birch which is unlikely to exceed an age of ca 100 years [The find location, object type, raw material and radiocarbon dating information for each dated object is provided in the electronic supplementary material, table S1. Where practicable, the dates are on materials likely to have a short inherent age. However, most ice-patch finds are of wood, including long-lived taxa such as ash  [Summed probability distributions of radiocarbon dates are widely used to infer the intensity of past human activity, demographic trends and their relationship with climate change ,14,43–45n curve) . Variousn curve) .We use a new statistical method based on kernel density estimation (KDE) . This ta3.ca 4000 BCE. A subsequent gap exists between ca 3800 and ca 2200 BCE, over which time temperature and glaciation were variable. Ice-patch finds in this date range are known from elsewhere in Norway, but they are very rare [The earliest isolated ice-patch finds are from after the initial onset of Holocene neoglaciation ery rare ,49. In Oca 660 CE, when rapid cooling brought on by volcanism and sustained by a solar minimum is argued to have led to major societal collapses in Scandinavia and globally [The years of the sequential Roman Iron Age, Migration Period, Merovingian Period and early Viking Age reveal a more complex relationship between artefact chronology and climate . Here thglobally –53.Based on objects with a low risk of old wood effect, the KDE probability continues to rise in the Merovingian Period, reaching a peak in the Viking Age before declining in the Middle Ages. The chronology of hunting and all finds diverges slightly towards the end of the first millennium CE. Hunting equipment peaks in the eighth to ninth centuries CE whereas the combined distribution of dates on all finds peaks later, in the tenth century. This difference is caused by a cluster of artefacts from the mountain pass site of Lendbreen that date to late in the Viking Age. Many of the latter may relate to intra-regional travel (perhaps transhumance) rather than reindeer hunting.The KDE distributions based on objects with a high risk of old wood effect demonstrate similar overall patterns, but with a variable offset in absolute chronology as one would expect given the use of raw materials of differing inherent age . The ‘hi4.ca 4000 BCE, during the high temperatures of the early Holocene, there may have been little ice in the Oppland mountains in which artefacts could be preserved [The earliest dates on ice-patch finds are likely to reflect preservation factors. Before neoglaciation began reserved .ca 3800 and ca 2200 BCE may exist because the oldest finds have been lost to ancient melting at low elevations, and are still trapped in ice at high elevations. No finds older than 3610 ± 30 uncalibrated BP (2110–1889 BCE at 95.4% probability) were found at elevations under ca 1900 m . Thus it is reasonable to suggest that lower-elevation ice patches have melted periodically prior to this date, leading to the destruction of the artefacts they contained. Conversely, at elevations higher than ca 1900 m the only finds older than this (ca 2000 BCE) are from southerly facing exposures. At these elevations it is probable that the oldest finds, in the oldest and deepest ice, have not yet melted out from sites exposed to less summer sun.A subsequent gap between During the late Neolithic/early Bronze Age it is plausible that warm conditions were favourable for hunting at ice patches—with neither concurrent nor subsequent episodes of melting being severe enough to obliterate the evidence. In the late Bronze Age and during the Little Ice Age , conversely, cold conditions may have been less favourable for high-mountain activities, be it due to direct impacts on accessibility and reindeer distributions  or indirThis interpretation, that there was a positive association between temperature and high-elevation activity, is plausible as a generalization. However, it must be qualified based on other archaeological and historical evidence. Most intriguing are times when ice-patch finds increased during periods of cooling. These are explicable in light of regional and supra-regional archaeological evidence regarding settlement, transhumance, exchange and other mobility. The rapid increase in the number of dated artefacts around the third century CE is contemporary with archaeological evidence from rescue excavation and pollen analysis for expansion of permanent agricultural settlement in the mountain valleys of Oppland ,55,56. WThe continuing rise in ice-patch finds during the LALIA, at the transition from the Migration to Merovingian Periods, is surprising given low temperatures. Yet arguably the importance of hunting could have peaked when yields from traditional agriculture would have been low. Population is thought to have dropped across Norway and Scandinavia during and after the LALIA, based on a decrease in the number of dated graves and settlement sites ,58. ThisThere is a ‘Merovingian trough’ in the summed probability plots of the radiocarbon dates on objects with a high risk of an old wood effect . Three factors combine to create this discrepancy with the KDE model. Firstly, the peak of ‘old wood’ finds from the Roman Iron Age and Migration Period is enhanced by a time-limited fashion for the manufacture and use of composite scaring sticks (with separate staff and flag) of split pine. Scaring sticks of this date range are thus more frequent among the ‘high risk’ than the ‘low risk’ finds, contributing to a mode in the Roman Iron Age/Migration Period only for the former of these datasets. Secondly, the total number of ‘high risk’ dates  is not lBurials and farms became frequent again in Norway during the Viking Age . This inThe Viking-age peak in ice-patch finds waned before the onset of the Little Ice Age. One contributing factor was probably the replacement of bow hunting for reindeer with mass-harvesting techniques ,11,22. T5.The varying abundance of surviving and dated artefacts from Oppland's ice patches reveals the complex and sometimes counterintuitive interaction of climate change, preservation conditions, land-use history and both local and external socio-economic drivers. Hunters and farmers used their knowledge of the mountains in diverse and changing circumstances. Cold temperatures may sometimes have kept them from Norway's highest elevations, as one might expect based on factors such as accessibility, exposure and game distributions . In time


We find an abrupt 80% increase in observed Greenland ice sheet runoff in 2003 to be related to atmospheric circulation change. 2 catchment of the southwestern Greenland ice sheet. We find that an abrupt 80% increase in runoff occurring between the 1976–2002 and 2003–2014 periods is due to a shift in atmospheric circulation, with meridional exchange events occurring more frequently over Greenland, establishing the first observation-based connection between ice sheet runoff and climate change.The recent decades of accelerating mass loss of the Greenland ice sheet have arisen from an increase in both surface meltwater runoff and ice flow discharge from tidewater glaciers. Despite the role of the Greenland ice sheet as the dominant individual cryospheric contributor to sea level rise in recent decades, no observational record of its mass loss spans the 30-year period needed to assess its climatological state. We present for the first time a 40-year (1975–2014) time series of observed meltwater discharge from a >6500-km Quantifying the magnitude and variability of meltwater runoff from the Greenland ice sheet has until now only been possible to address through modeling , begins on 7 July 1975 and ends on 31 October 2014, spanning 40 years with gaps of varying duration in the data coverage. Minor gaps due to maintenance visits or periods of low battery voltage (up to 7 days) were filled using linear interpolation. In total, less than 0.57% of the time series (less than 0.19% of the discharge) used for establishing annual sums was derived from interpolated values. More extensive gaps occur during freeze-in of instrumentation (during winter periods in 1975–1979) or because of other technical failures.To determine the origin of the meltwater part of the discharge time series, we made a D-infinity delineation of the catchment based on surface slope analysis, after filling up depressions, using the Greenland Ice Mapping Project elevation model , which occur when the water volume stored in an ice-dammed lake becomes sufficient to lift the ice barrier blocking its path downstream. We identified 15 GLOFs originating from a single source lake (marked A in Q). Applying the Rodionov regime shift test on ln(Q), we confirm a significant (P = 0.003) regime shift in 2003 from a mean of 2.0 km3 a−1  during 1976–2002 to a mean of 3.6 km3 a−1  during 2003–2014 .To obtain a time series of annual runoff from the ice sheet margin from the discharge time series, we first discarded years with insufficient data coverage, then removed the part of the signal because of GLOFs, and finally subtracted runoff originating from the ice-free part of the catchment, estimated by the regional climate model HIRHAM5  . We findR2 = 0.55, P < 0.001) GBI as a predictor of ice sheet surface melt  air masses arriving at Tasersiaq, we performed an atmospheric trajectory analysis. The trajectories of air parcels were back-simulated using the Hybrid Single-Particle Lagrangian Integrated Trajectory model (HYSPLIT4) , shown as an average over the entire period 1975–2014 in We interpret this shift in the origin of the air masses arriving in southwest Greenland as supporting recent evidence , apIncreased frequency in blocking events and meridional flow has been linked to a wavier jet stream because of a reduced poleward temperature gradient, in turn an effect of the Arctic amplification of global warming . These GLOFs also occur during winter. When the inflow of water from the ice-dammed lake ceases, the following decrease in water level in Tasersiaq is in good agreement with the recession curve calculated from the stage-discharge relation. This further supports that the deviation from the stage-discharge relation in winter is limited.The uncertainty in the daily mean discharge (95% confidence level) was calculated, taking into account the uncertainty of the stage-discharge relation as well as the measurement uncertainty of the pressure transducers and the uncertainty in the determination of sensor positions (We attributed the GLOFs to a single source lake (marked A in https://sites.google.com/site/climatelogic/home (accessed on 15 June 2017). The method requires a normally distributed, independent data set. These criteria were fulfilled by the natural logarithm of the catchment ice sheet runoff, ln(Q), as was shown by Shapiro-Wilks test and autocorrelations test, respectively. The magnitude and scale of the regimes to be detected by the SRSD were controlled by two input parameters: the target significance level and the cutoff length. The target significance level is the level at which the null hypothesis that the mean values of the two regimes are equal is tested using the two-tailed Student’s t test. The lower the significance level, the larger the magnitude of the shift should be to be detected. The cutoff length determines the minimum length of the regimes that are certain to be detected. If the regimes are shorter than the cutoff length, the probability for them to be detected reduces proportionally to their length. In a sensitivity analysis, all combinations of these two parameters identified one shift in the mean. For medium cutoff lengths (7 to 15 years) and significance level of 0.05 to 0.1, a shift in 2003 was detected (P = 0.003), whereas shorter cutoff lengths (5 to 7 years) indicated a less significant shift in 2010 (P = 0.048). Huber’s weight parameter was set to 3, giving equal weight to all values when calculating the regime means.The Rodionov climate regime shift test was conducted using the Sequential Regime Shift Detector (SRSD) software package version 5.1 for test of shifts in mean (


Since 2005, a dramatic decline of the Arctic sea-ice extent is observed which results in an increase of shipping activities. Even though this provides commercial and social development opportunities, the resulting environmental impacts need to be investigated and monitored. In order to understand the impact of shipping in arctic areas, the method described in this paper determines the travel time, fuel consumption and resulting exhaust emissions of ships navigating in arctic waters. The investigated case studies are considering ship particulars as well as environmental conditions with special focus on ice scenarios. Travel time, fuel consumption and exhaust gas emission were investigated for three different vessels, using different passages of the Northern Sea Route (NSR) in different seasons of years 1960, 2000 and 2040. The presented results show the sensitivity of vessel performance and amount of exhaust emissions to optimize arctic traffic with respect to efficiency, safety and environmental impact. Since 2005, an observable decrease of the Arctic sea ice extent, peaking in a record minimum in 2011–2012 during Arctic summer period. These circumstances generated a high interest in establishing new trade routes. Ensuring exploration, access and extraction of resources in this environment is of great value concerning the prospective trend of offshore engineering and economy.2), methane (CH4), nitrogen oxides (NOx), sulphur oxides (SOx), carbon monoxide (CO) and various species of particulate matter (PM) including organic carbon (OC) and black carbon (BC). Although at present the shipping in the Arctic Ocean provides a relatively small proportion to the global shipping emissions, regional effects from substances such as BC and ozone (O3) become important to be quantified and understood.Even though increasing Arctic shipping may provide commercial and social development opportunities, the resulting environmental impacts need to be investigated in detail. Several studies have assessed the potential impacts of international shipping on climate and air pollution : (1) near shore route passing mainly south of the major Russian islands, (2) one intermediate route passing in between the larger Russian islands, (3) northern route and(4) one transpolar passage (TPP) crossing the North Pole. We consider several vessels of various ice classes for three periods in the time frame from 1960 to 2040. The environmental conditions used for the study are based on the CMIP5 climate model. The results of the different case calculations are discussed and a possible trend of emissions due to shipping along the NSR from the past to the future is given.The routing programme ICEROUTE HSVA , b is baMarine vessels are typically designed to specific operation profiles, namely a service speed that is to be achieved in environmental conditions  over a certain distance. The selection of main engine type and size is optimized to meet the demand of this operational profile. Newly built vessels usually have a better fuel efficiency compared to older vessels. Main reasons for this are hull deterioration and fast developments in the optimization of engine technology improvements.Besides their impact on ship resistance the environmental conditions will also affect the efficiency of the main engine—propeller combination. A ship that operates at moderate speed in strong head sea, wind or in ice might show a similar fuel burning rate like a ship operating at relatively high speed in calm water though sailing significantly less distance within the same time.The fuel consumption of vessels navigating in ice-covered waters depends, in addition to the sea ice conditions, on the vessel type and its ice-breaking capability, navigation instructions by authorities and ship owner or management as well as the use of auxiliary systems.To investigate the fuel consumption of a vessel, three different methods can be used: numerical calculation and prediction, actual trial measurements of fuel consumption rates or back-calculation from fuel expenses per trip.The brake-specific fuel oil consumption (BSFC) is a measure of fuel efficiency for reciprocating engines given by the engine manufacturer. BSFC is a possibility to directly compare the fuel efficiency of different reciprocating engines. In the following equation, the definition of the BSCF is given.The fuel consumption rate r is measured in grams per hour (g/h), while p is the power produced in kilowatts (kW).There are many other factors that influence the mass fuel consumption of a vessel. An average data set analysed from over 600 measured cases of a container ship at sea is used to derive an average line to correct the BSFC and relates to the actual power of the vessel.x = P/PMCR denotes the ratio of actual power and the maximum continuous rate power. The variation Practically, we use this correlation between the BSFC and the actual power when we calculate the fuel consumption of all ships. The correlation can be expressed in form of the following equation , European Union (EU), and the United States Environmental Protection Agency (EPA) came up with the Tier I exhaust gas emission norm for the existing engine in order to reduce nitrogen oxides and sulphur oxides [IMO Resolution MPEC.177 (58)]. Stricter limits for these emissions have been incorporated in Tier II (in force since 2011) and Tier III (scheduled for 2021) which were later announced for new built vessels.x and SOx in the exhaust gas emission. The diesel engine combustion process always leaves by-products of oxides of nitrogen, unburned hydrocarbons, carbon monoxides and particulate matter.Diesel fuels commonly used in marine engines are a form of residual fuel, also known as dregs or heavy fuel oil (HFO). Currently, different grades of HFO are available and sulphur restrictions are only valid in emission control areas. The Arctic is currently not an emission control area but the IMO announced a global sulphur cap of 0.5 to be implemented beginning from 2020 or 2025. Heavy fuel oil—even if it contains low sulphur—is cheaper than marine distillate fuels but contain higher amount of nitrogen, sulphur and ash content. This significantly increases the amount of NO2) and nitrogen oxide (NO). These gases are a major source of ground level ozone and are also a significant source of acid rains and soot formation. Unburned hydrocarbons come from unburned or partially burned fuel after combustion process. These hydrocarbons are toxic in nature, having adverse effects on our health and in some cases are known to cause cancer.Nitrogen oxides are a group of toxic gases formed by the reaction of nitrogen and oxygen. At extremely high temperature of combustion, these two gases react to nitrogen dioxide (NOCarbon monoxide is formed as an intermediate product of hydrocarbons fuel combustion due to the lack of adequate oxygen to form carbon dioxide or due to insufficiently high temperature.j on route k in gram (g); j in (g/kWh); j on route k and takes into account periods of manoeuvring, slow cruise and full cruise operations; j; j on route k in hour (h)A straight forward method to calculate emissions of a ship is using emission factors as shown in Formula As an input for the calculation, different scenarios are simulated according to the actual traffic along the NSR. Different routes, environmental conditions and types of vessels are investigated.Representative commercial ships using the NSR are currently tanker and bulker while liquid natural gas (LNG) carriers may play an important role in the future. A tanker and an LNG carrier are selected for the scenario calculations. Their main parameters are given in Table Many available configurations can be considered for each ship type. With regard to the propeller type, for example, a ship can be equipped with controllable pitch propellers (CPP), fixed pitch propellers (FPP) or podded drives. In the calculations, the effects of using FPP, CPP or a podded configuration will have a strong impact on the ability of a design to maintain speed in harsh ice conditions. Vessels equipped with a FPP are commonly optimized for a single specific speed, which usually is the design condition in calm water with a small margin for heavier sea states. Thus, the FPP is over-loaded or under-loaded for certain other operation conditions. A CPP is a propeller arrangement that can adjust the blades’ pitch along their longitudinal axis. A configuration with a CPP is able to react to specific load cases and therefore avoids a reduction of the total available main engine power while a podded configuration with electric drives is able to operate at higher loads as well. Likewise more complex and thus more expensive propulsion configuration make it possible to operate efficient under very different environmental scenarios but can be less economic concerning the single propeller operating point.Considering the engine type, the most common type would be a diesel engine fuelled with heavy fuel oil, but nowadays to fulfil the strict regulations on exhaust gases in sensitive regions (emission control areas), vessels are sometimes equipped with new kinds of engines as dual fuel configurations. Additionally, many vessels which are able to operate under heavy ice conditions are equipped with diesel-electric machinery.Figure Thus, a ship travelling at a low ice concentration would potentially reach a maximum speed above the safe speed, which would result in a higher fuel consumption compared to safe speed. The regulations and permissions are described specifically for each ship in the ice certificate (Ice Passport) acknowledged by the Northern Sea Route Administration. For these scenario calculations, the safe speed curves are not available for each vessel and ice conditions. Thereby a simplified approach is used using only a single speed limitation (representing an average ice thickness) of 7–8 knots relative/to the occurrence of ice.Additionally, an economic speed for travelling in open water is defined and used for consumption analysis in ice-free waters. Due to the safe speed and economic speed in open water, the simulations show part load conditions in most simulations.Comparing these assumptions to a realistic crew operating the vessel, the vessel would operate with the target to minimize the travelling time but still satisfying the rules. This is not always the case as a combination of economic sailing and schedule requirements define the speed profile of the vessel. Therefore, the assumptions lead to conservative fuel consumption.The Northern Sea Route (NSR) is a shipping lane officially defined by the Russian government from the Atlantic Ocean (Kara Gate) to the Pacific Ocean running along the Russian Arctic coast from Murmansk on the Barents Sea, along Siberia, to the Bering Strait and Far East. The entire route leads through Arctic waters. Several parts are ice free for 2 months per year. At the western end of the NSR, routes from Murmansk across the Barents Sea and Kara Sea, and up the Yenissei River to Dudinka, have been used regularly since the 1980s, but were not used by commercial transits until 2009.Regardless of explicit routing, the NSR extends to about 3000 nautical miles. The actual length of the route in each particular case depends on ice conditions and on the choice of variants of passage resulting in individual leg-lengths.near shore route 1 —Murmansk to Bering Strait via Kara gate, south of Severnaya Zemlya and south of New Siberian Islands;intermediate route 2 —Murmansk to Bering Strait via north of Novaya Zemlya, south of Severnaya Zemlya and north of New Siberian Islands;northern route 3 —Murmansk to Bering Strait via north of Novaya Zemlya, north of Severnaya Zemlya and north of New Siberian Islands;transpolar passage route 4 —Murmansk to Bering Strait via north of Novaya Zemlya, north of Severnaya Zemlya close to the geographical north pole and north of New Siberian Islands.The investigated route profiles can be described by the following approximate way points while several additional way points are used for the calculations Fig. :Fig. 4DiThe main factor influencing navigation in Arctic waters is the presence of sea ice. The navigation season for transit passages on the NSR starts approximately at the beginning of July and lasts through to the second half of November. There are no specific dates for commencement and completion of navigation as it depends on the particular ice conditions. In 2011, the navigation season on the NSR routes for large vessels constituted 141 days in total.For the investigated scenarios and periods, ice data of the coupled global climate model MPI-ESM-LR  and an ice-breaking LNG carrier (ice class PC3).In Table For the September voyages, the data show almost no difference between 1960 and 2000; the same is valid for 2013 and 2040. A significant difference between these two groups can be seen in the fuel consumption while only minor variations occur for the travelling time. This finding can be explained by the speed limit which is coming into effect in the case of presence of ice. Additionally, the comparison is based on single data points of these specific years, which may not reflect the average of the surrounding years. In contrast to remote sensing data as well as actual observations on-board of vessels during the past five years—which indicated an almost ice-free NSR in September—the sea ice model shows the presence of ice on several locations along the NSR. A comparison of the two vessels shows a minor benefit for both, travel time and fuel consumption, for the PC5 class ice-going Tanker.Figure The LNG Carrier completed two transits during July and September 1960, eight transits for present ice conditions, and will be able to manage almost all ice conditions at any time in the future. This is reasonable as the vessel has a high ice-breaking capability due to optimized hull shape and 36 MW installed power.Travel time and fuel consumption for both vessels increase with higher latitude, from coast to pole route (indicated by black arrows in Fig. The results clearly show that higher ice class than PC5 is needed for vessels navigating the NSR during other periods than August to October in the past and even at present conditions. In the future, ice class PC5 seems to be suitable to use the NSR from June to November. Vessels with ice class PC3 or higher will allow year-round transit even using the pole route according to the scenarios.x, because of the dual fuel propulsion concepts, whereas ships equipped with two-stroke engines exhaust SOx. The ice conditions on the route chosen for this comparison are the maximum conditions for Tanker 01, which results in relatively long travel time and high fuel consumption. The LNG Carrier with significant higher ice-breaking capability has a shorter travelling time for the same route. Despite the 40% higher installed power, this vessel still consumes less fuel resulting in a lower emission. Beside carbon oxide, all other emitted components are lower for the LNG Carrier than for Tanker 01.The resulting emissions will have a particular impact on the environment. We choose Route 1 in November 2000 as an example of the conditions Fig. . It is iThe simulations of travelling time, fuel consumption and exhaust gas emission are very sensitive to environmental parameters like ice thickness and concentration, ridge mightiness and frequency, wind speed and direction, current speed and direction and the resulting ice drift speed and direction as well as the lateral ice pressure. Furthermore, pollution calculation based on BSFC and emission factors—as well as determination of the ice resistance using semi-empirical formulas.The global approach of the climate model gives a good overview of the general conditions in the Arctic Ocean. Predictions of the local climate, for example, in the vicinity of islands and near to the mainland shore, can be imprecise.A tendency of decreased travel time and fuel consumption from past over present to future is observed for November passages. The outcomes emphasize that navigation on the NSR was impossible for an ice-going vessel with ice class PC5 in the past during the beginning of the Arctic winter but will become possible in the future. The PC3 class vessel had no problems to use NSR in the past and at present; in the future this route will be profitable when transporting goods.The shortest of the investigated routes is the transpolar passage, TPP. Our findings show that there is no reason for a PC5 class vessel to use the TPP instead of the other route options in the future as the travel time is lower and additionally the fuel consumption higher. There is an advantage for the PC3 LNG Carrier using the TPP as travel time as well as fuel consumption are lower, navigating along the NSR.When comparing the required travel time and fuel consumption of the Suez-Route to different scenarios on the Northern Sea Route, it becomes obvious that the main influence parameter is the occurrence of ice. All routes in September (marked green in Table The investigation was performed using the programme ICEROUTE. The transit simulations show a clear trend of decreasing travelling time for all ship types using the NSR due to the decline of the Arctic sea ice extend and thickness. This finding together with fuel savings due to lower power requirement consequently results in lower exhaust gas emissions of the vessels. A comparison of the travel time and fuel consumption using the NSR compared with the Suez-Route shows clear savings regarding time and fuel already today and even more so in the future. The results are influenced by the fact that the vessel velocity is limited to a safe speed even in regions with only small ice coverage resulting in low fuel consumption and consequently small exhaust gas emissions.By the restriction to safe speed, slow steaming scenarios lead to lower fuel consumption and exhaust gas emissions compared to conventional routes like the Suez-Route. Travelling along other routes in certain periods other than September, the fuel consumption increases rapidly for vessels with low ice class. Using the programme ICEROUTE, certain scenarios can be easily simulated and compared and the influence of the Arctic shipping on the environmental pollution can be assessed. The future forecasts denote a widening of operation windows for transits on all routes and especially in the freeze-up periods of October to November. To predict future scenarios, the sea ice forecast is the main uncertainty of the calculations. Actually, harsh and unpredictable ice conditions protect the area from pollution as a commercial service is not economically viable. In order to predict future exhausts emissions for the Arctic region, the number of ships that travel along the NSR under reasonable safe and economic conditions has to be determined. In addition to ice conditions, the number of ships will depend on the development of the region and its infrastructure as well as on freight rates and type of goods to be transported along the Northern Sea Route in both West–East and East–West directions.