bluuebunny/crossref_metadata_2025 huggingface dataset:
AKR1B10 activates diacylglycerol (DAG) second messenger in breast cancer cells
Authors: Huang Chenfei , Cao Zhe , Ma Jun , Shen Yi , Bu Yiwen , Khoshaba Ramina , Shi Guiyuan , Huang Dan , Liao Duan‐Fang , Ji Haitao , Jin Junfei , Cao Deliang
Published: May 2018

Aldo‐keto reductase 1B10 (AKR1B10) is upregulated in breast cancer and promotes tumor growth and metastasis. However, little is known of the molecular mechanisms of action. Herein we report that AKR1B10 activates lipid second messengers to stimulate cell proliferation. Our data showed that ectopic expression of AKR1B10 in breast cancer cells MCF‐7 promoted lipogenesis and enhanced levels of lipid second messengers, including phosphatidylinositol bisphosphate (PIP2), diacylglycerol (DAG), and inositol triphosphate (IP3). In contrast, silencing of AKR1B10 in breast cancer cells BT‐20 and colon cancer cells HCT‐8 led to decrease of these lipid messengers. Qualitative analyses by liquid chromatography‐mass spectrum (LC‐MS) revealed that AKR1B10 regulated the cellular levels of total DAG and majority of subspecies. This in turn modulated the phosphorylation of protein kinase C (PKC) isoforms PKCδ (Thr505), PKCµ (Ser744/748), and PKCα/βII (Thr638/641) and activity of the PKC‐mediated c‐Raf/MEK/ERK signaling cascade. A pan inhibitor of PKC (Go6983) blocked ERK1/2 activation by AKR1B10. In these cells, phospho‐p90RSK, phospho‐MSK, and Cyclin D1 expression was increased by AKR1B10, and pharmacological inhibition of the ERK signaling cascade with MEK1/2 inhibitors U0126 and PD98059 eradicated induction of phospho‐p90RSK, phospho‐MSK, and Cyclin D1. In breast cancer cells, AKR1B10 promoted the clonogenic growth and proliferation of breast cancer cells in two‐dimension (2D) and three‐dimension (3D) cultures and tumor growth in immunodeficient female nude mice through activation of the PKC/ERK pathway. These data suggest that AKR1B10 stimulates breast cancer cell growth and proliferation through activation of DAG‐mediated PKC/ERK signaling pathway.
Diet of Striped Bass and Muskellunge Downstream of a Large Hydroelectric Dam: A Preliminary Investigation into Suspected Atlantic Salmon Smolt Predation
Authors: Andrews S. N. , Zelman K. , Ellis T. , Linnansaari T. , Curry R. A.
Published: May 2018

Top predators, such as the Striped Bass Morone saxatilis and Muskellunge Esox masquinongy, can impact food webs and alter ecosystem structure through the regulation of prey populations. Within the Saint John River, New Brunswick, Canada, both predators have long been hypothesized to impart significant mortality on smolts of the endangered Atlantic Salmon Salmo salar. As a consequence, current management practices entail euthanizing Muskellunge (an introduced species) that enter fish passage facilities along the Saint John River. Furthermore, the recovery and protection of a native Striped Bass population have largely been ignored. To assess seasonal diet, gastric lavage was performed on Striped Bass (n = 244) and Muskellunge (n = 96) captured in the downstream proximity of the Mactaquac Dam from April to November 2016. Clupeids dominated the stomach contents by number (92% for Striped Bass; 49% for Muskellunge) and mass (71% for Striped Bass; 96% for Muskellunge). Other prey species included White Perch Morone americana, Yellow Perch Perca flavescens, American Shad Alosa sapidissima, and American Eels Anguilla rostrata. No Atlantic Salmon smolts or other regionally recognized recreational fish species were identified in any of the stomach samples (n = 340) examined. Concurrently, this study observed little temporal overlap between the smolt migratory period and the arrival of Striped Bass to the Mactaquac Dam. Some Striped Bass (n = 33) were observed to be in spawning condition, releasing eggs and milt when handled, although reproduction by this species in the Saint John River was thought to have ceased long ago.
Efficacy and Safety of Probiotics and Synbiotics in Liver Transplantation
Authors: Jorgenson Margaret R. , Descourouez Jillian L. , Siodlak Magdalena , Tjugum Shelby , Rice John P. , Fernandez Luis A.
Published: May 2018

This article summarizes available literature regarding the utilization of probiotic and synbiotics in liver transplant (LTX) recipients, reviewing efficacy in both decreasing infectious complications and immunomodulation, as well as exploring safety concerns. Data suggest that the use of probiotics containing Lactobacillus spp, either alone or in combination with prebiotics (referred to as synbiotics), may be effective in reducing infectious complications after LTX, a major contributor to graft loss, hospital length of stay, and mortality. Literature evaluating the use of probiotics to induce tolerance, reduce rejection, and prevent damage associated with ischemia–reperfusion injury is limited to animal models but compelling, as it suggests the use of probiotics may augment deleterious immune‐mediated processes in this population. While the benefits of probiotics should be weighed against potential risks, these concerns are largely theoretical in the LTX recipient, with the majority of evidence extrapolated from case reports in other immunosuppressed populations. Based on available literature, it may be prudent to avoid products containing Saccharomyces sp, as these were not used in the efficacy studies, and the majority of the adverse event reporting stems from the use of products containing this organism. Further evaluation of the safety and efficacy of probiotic therapy is warranted. Studies specifically designed to elucidate the optimal product and initiation scenario and delineate safety in this population are needed to allow expanded use of this inexpensive, relatively nontoxic, and potentially beneficial therapeutic option after LTX.
Tacrolimus Elimination in Four Patients With a CYP3A5*3/*3 CYP3A4*22/*22 Genotype Combination
Authors: Scheibner Aileen , Remmel Rory , Schladt David , Oetting William S. , Guan Weihua , Wu Baolin , Dorr Casey , Israni Ajay , Jacobson Pamala A.
Published: May 2018

Cytochrome P450 3A5 (CYP3A5) and cytochrome P450 3A4 (CYP3A4) are the predominate enzymes responsible for tacrolimus metabolism. The presence of CYP3A4 and CYP3A5 genetic variants significantly affects tacrolimus clearance and dose requirements. CYP3A5*3 is a loss‐of‐function variant resulting in no CYP3A5 enzyme production. CYP3A4*22 is a variant that reduces production of functional CYP3A4 protein. Caucasians commonly carry these variant alleles but are very rarely homozygous for both CYP3A5*3 and CYP3A4*22. This report describes four kidney transplant recipients who carry a rare genotype combination (CYP3A5*3/*3 and CYP3A4*22/*22). These patients were identified from a larger cohort of Caucasian kidney transplant recipients (n=1366). To understand the significance of this genotype combination on tacrolimus troughs and doses, we compared these patients to recipients without this combination. Patients homozygous for both variants are at risk for profound reductions in metabolism of CYP3A substrates. A 342% and a 90.6% increase in the median dose‐normalized trough was observed, when the CYP3A5*3/*3 and CYP3A4*22/*22 genotype combination was compared to the CYP3A5*1/*1 and CYP3A4*1/*1 genotype combination and the CYP3A5*3/*3 and CYP3A4*1/*1 genotype combination, respectively. These four individuals only required on average 2.5 mg/day of tacrolimus. Knowledge of these genotypes would be useful in selecting appropriate tacrolimus doses to avoid overexposure.
Targeted Chemo‐Photothermal Therapy: A Nanomedicine Approximation to Selective Melanoma Treatment
Authors: Villaverde Gonzalo , Gómez‐Graña Sergio , Guisasola Eduardo , García Isabel , Hanske Christoph , Liz‐Marzán Luis M. , Baeza Alejandro , Vallet‐Regí Maria
Published: May 2018

Melanoma is one of the most severe public health issues worldwide, not only because of the high number of cases but also for its poor prognosis in late stages. Therefore, early diagnosis and efficient treatment are key toward a future solution. However, melanoma is highly resistant to cytotoxicity in its metastatic form. In this context, a therapeutic strategy based on a targeted chemo‐photothermal nanotransporter for cytotoxic compounds is proposed. This approach comprises the use of core–multishell gold nanorods, coated with mesoporous silica and further covered with a thermosensitive polymer, which is vectorized for selective internalization in melanoma cells. The proposed nanoformulation is capable of releasing the transported cytotoxic compounds on demand, in response to near‐IR irradiation, with high selectivity and efficacy against malignant cells, even at low concentrations, thereby providing a new tool against melanoma disease.
Review of Gasless Pyrotechnic Time Delays
Authors: Focke Walter W. , Tichapondwa Shepherd M. , Montgomery Yolandi C. , Grobler Johannes M. , Kalombo Michel L.
Published: May 2018

Gasless pyrotechnic delay compositions for time‐sequencing energetic events are reviewed. They are mixtures of powdered fuels and oxidants capable of a highly exothermic oxidation‐reduction reaction. Trends favor ‘green’ compositions targeted to replace compositions containing perchlorates, chromates, lead and barium. Thermite‐based reactions dominate but intermetallics (especially multi‐layered versions) and hybrids appear promising considering progress in self‐propagating high temperature synthesis technology. Improving computer modelling will require better description of condensed phase reactions. Progress was made with the development of “hot spot” models and expressing reactivity in terms of the number of contact points (or contact surface area) between particles. Promising processing advances include mechanochemical synthesis of reactive particle composites by arrested milling or comminution of cold‐rolled multilayer intermetallics. Dry mixing of reactive powders has made way for slurry mixing followed by spray drying.
Curved Fragmented Graphenic Hierarchical Architectures for Extraordinary Charging Capacities
Authors: Lian Hong‐Yuan , Dutta Saikat , Tominaka Satoshi , Lee Yu‐An , Huang Shu‐Yun , Sakamoto Yasuhiro , Hou Chia‐Hung , Liu Wei‐Ren , Henzie Joel , Yamauchi Yusuke , Wu Kevin C.‐W.
Published: May 2018

An approach to assemble hierarchically ordered 3D arrangements of curved graphenic nanofragments for energy storage devices is described. Assembling them into well‐defined interconnected macroporous networks, followed by removal of the template, results in spherical macroporous, mesoporous, and microporous carbon microball (3MCM) architectures with controllable features spanning nanometer to micrometer length scales. These structures are ideal porous electrodes and can serve as lithium‐ion battery (LIB) anodes as well as capacitive deionization (CDI) devices. The LIBs exhibit high reversible capacity (up to 1335 mAh g−1), with great rate capability (248 mAh g−1 at 20 C) and a long cycle life (60 cycles). For CDI, the curved graphenic networks have superior electrosorption capacity (i.e., 5.17 mg g−1 in 0.5 × 10−3m NaCl) over conventional carbon materials. The performance of these materials is attributed to the hierarchical structure of the graphenic electrode, which enables faster ion diffusion and low transport resistance.
Grounding and ontological dependence
Authors: Rydéhn Henrik
Published: May 2018

Recent metaphysics has seen a surge of interest in grounding—a relation of non-causal determination underlying a distinctive kind of explanation common in philosophy. In this article, I investigate the connection between grounding and another phenomenon of great interest to metaphysics: ontological dependence. There are interesting parallels between the two phenomena: for example, both are commonly invoked through the use of “dependence” terminology, and there is a great deal of overlap in the motivations typically appealed to when introducing them. I approach the question of the relationship between grounding and ontological dependence through an investigation of their modal connections (or lack thereof). I argue, firstly, that on the common assumption that grounding is factive, it can be shown that no known variety of rigid ontological dependence is either necessary or sufficient for grounding. I also offer some suggestions in support of the claim that this generalizes to every possible form of rigid ontological dependence. I then broaden the discussion by considering a non-factive conception of grounding, as well as by looking at forms of generic (rather than rigid) ontological dependence. I argue that there is at least one form of rigid ontological dependence that is sufficient for non-factive grounding, and that a form of generic dependence may be necessary (but not sufficient) both for factive and non-factive grounding. However, justifying even these fairly weak modal connections between grounding and ontological dependence turns out to require some quite specific and substantive assumptions about the two phenomena that have only rarely been discussed.
Case study on aircraft tyre wear in Y12 aircraft tyres
Authors: Dulani Daminda Kuruppu K. A. , Hettiarachchi C. J.
Published: May 2018

The primary objective of this research was to analyse the discrepancies in polymeric properties in Y12 aircraft tyres after 50 landings. Tensile strength and elongation test, abrasion test and hardness tests were carried out for the nose and main gear tyres after the completion of 50 landings. Surface morphologies of the tyre samples were observed using SEM. ISO specifications were followed for each experimental method during testing. There was a reduction in both median tensile strength and elongation at break in aircraft tyres after 50 landings but the reduction rate of both parameters were lower in Tyre 2 (nose wheel tyre) compared with Tyre 1 (left main wheel tyre) and Tyre 3 (right main wheel tyre). The highest percentage of mean volume loss was reported for Tyre 3 (3.88%). In addition, the least percentage of mean volume loss was obtained in Tyre 2 (2.98%). The percentage of hardness reduction was highest in Tyre 2 (6.9%). The surface roughness was induced to the tyre surface after completion of 50 landings.
Ice cream rounds: The adaptation, implementation, and evaluation of a peer-support wellness rounds in an emergency medicine resident training program
Authors: Calder-Sprackman Samantha , Kumar Thara , Gerin-Lajoie Caroline , Kilvert Megan , Sampsel Kari
Published: May 2018

Introduction/Innovation Concept

Emergency medicine (EM) requires physicians to deal with acutely ill patients in a fast-paced and dynamic environment, which creates a barrier to debriefing after critical events. These unique challenges can negatively impact wellness. We sought to adapt and implement a peer-support wellness program called ‘Ice Cream Rounds’ in an EM residency setting.

Methods

A needs assessment survey was conducted among EM residents at The University of Ottawa to gauge interest and obtain resident input regarding program design. The structure of the sessions was adapted from similar initiatives in Canadian Pediatric Residency programs.

Curriculum, Tool or Material

Confidential peer-support sessions were created and piloted. Residents preferred peer facilitators, rather than staff, so two residents obtained training the Faculty of Medicine’s Wellness Program to lead sessions. Attendance at rounds was voluntary; however, overall attendance was recorded along with feedback from pilot sessions. Discussion topics included difficult patient encounters, poor patient outcomes, challenges in residency, and ethical issues. Post implementation feedback demonstrated that Ice Cream Rounds was a helpful forum for residents to discuss important issues with colleagues.

Conclusions

This is the first Canadian EM training program to adapt, implement, and evaluate peer-support wellness rounds for debriefing, and this initiative can be easily adopted by any EM training program.
Linguliform brachiopods across a Cambrian–Ordovician (Furongian, Early Ordovician) biomere boundary: the Sunwaptan–Skullrockian North American Stage boundary in the Wilberns and Tanyard formations of central Texas
Authors: Freeman Rebecca L. , Miller James F. , Dattilo Benjamin F.
Published: May 2018

The Cambrian-Ordovician Diversity Plateau, between the Cambrian Explosion and the Ordovician Radiation, is punctuated by a series of well-documented Laurentian trilobite extinction events. These events define the bounding surfaces of trilobite ‘biomeres’ that correspond to North American stages, including those of the Sunwaptan and Skullrockian. Trilobites show a consistent pattern of recovery across these boundaries, and commonly each extinction and replacement of taxa is interpreted as a single event as changing environmental conditions spurred shoreward migration of shelf or oceanic faunas that displaced established cratonic faunas. Linguliform brachiopods are also abundant in strata of this interval, and we investigate their stratigraphic distribution across the Sunwaptan–Skullrockian Stage boundary in Texas through high-resolution stratigraphic sampling of subtidal sediments. We document complete genus- and species-level turnover of the linguliform brachiopod fauna coincident with trilobite extinction events, suggesting that these brachiopods were affected by the same factors that affected trilobites. The Skullrockian replacement fauna was cosmopolitan, with ties to Gondwana and Kazakhstan and to the Laurentian shelf environment. The timing of appearances of taxa suggests that the faunal migration onto the Laurentian shelf came from elsewhere during a transgression. The disappearance of the Sunwaptan fauna and the arrival of the Skullrockian fauna are distinct events. We suggest that ‘biomere’ events may be complex, and the cause of the extinction is not necessarily the same event that facilitates the appearance of a replacement fauna. We describe one new species,Schizambon langei.

UUID:http://zoobank.org/f6a5c11f-cd3d-4c16-b184-d808d3a5285f
Misunderstandings Concerning the Significance of AMS Background 14C Measurements
Authors: Taylor R E , Southon John R , Santos Guaciara M
Published: May 2018

We consider one misconception of those who currently reject the general validity of radiocarbon (14C) age determinations older than, at most, 10,000 BP. There is an allegation that the presence of 14C reported by accelerator mass spectrometry (AMS) laboratories in their measurements of 14C infinite age (>100,000 years) organics used to define background levels, support their point of view. This article has been written for a general audience, primarily for those who have questions about the validity of these arguments. However, they may not be familiar with the literature relevant to providing a clear response to the claims of these individuals. We conclude that, in our view, of all of the possible explanations for the reports of the presence of 14C in these background samples, the least probable explanation has been advanced by those rejecting the validity of the 14C time scale in excess of, at most, 10,000 BP.
Consumption of transglycosylated starch down-regulates expression of mucosal innate immune response genes in the large intestine using a pig model
Authors: Metzler-Zebeli Barbara U. , Newman Monica A. , Grüll Dietmar , Zebeli Qendrim
Published: May 2018

Benefits of resistant starch (RS) consumption on host physiology encompass microbial activity-derived attenuation of intestinal inflammation. However, little is known about anti-inflammatory properties of RS of type 4. This study compared the effects of transglycosylated starch (TGS) consumption on the jejunal barrier function and expression of genes related to inflammation, barrier function and the mucosal defence in jejunum, ileum, caecum and colon of pigs. Moreover, interactions of TGS-induced alterations in bacterial metabolites and composition with host mucosal responses were assessed using sparse partial least squares regression and relevance network analysis. Intestinal samples were collected after pigs (n8/diet; 4 months of age) were fed the experimental diets for 10 d. Consumption of TGS did not modify jejunal barrier function and gene expression. By contrast, TGS down-regulated the caecal expression of zonula occludens-1 and mucin 2 and of genes within the toll-like receptor 4 and NF-κB pro-inflammatory signalling cascade. Relevance networks revealed a microbiome signature on ileal, caecal and colonic mucosal signalling as TGS-derived changes in bacterial genera and fermentation acids, such as propionic acid, correlated with the differently expressed genes in ileum, caecum and colon of pigs. In conclusion, the present findings suggest certain anti-inflammatory capabilities of TGS by down-regulating the expression of pro-inflammatory pathways in the caecal mucosa, which seems to be mediated, at least in part, by TGS-induced changes in microbial action in the large intestine.
The gender distribution of real property ownership in late medieval Brussels (1356–1460)
Authors: BARDYN ANDREA
Published: May 2018

Although ownership of real property was crucial to the economic opportunities of medieval urban women, few studies systematically investigate the gender distribution of medieval real property over time. Usingcensiers(rarely used sources), this article approaches this question through a socio-geographical analysis of Brussels. The study finds that, despite the region's egalitarian inheritance laws, female ownership of real property was relatively limited, and it declined during the late Middle Ages. This decrease accelerated during economic crises, and especially affected the property of non-elite women. Further research on the changing economic opportunities of medieval women would benefit from a more explicit discussion of non-labour income sources and social status.
Trends and internal dynamics of illegitimacy in north-west Spain: rural Galicia, 1570–1899
Authors: DUBERT ISIDRO
Published: May 2018

Galicia is a region located in the north-west of the Iberian Peninsula, where, historically, illegitimacy was often high compared with levels elsewhere in Europe. At the same time, Galicia's coastal and inland areas have always differed greatly in terms of farming structure, population growth, migration patterns, family types and inheritance systems. The aim of this article is to establish to what extent the trends in and levels of illegitimacy between 1570 and 1899 were influenced by these different historical contexts. It also offers an in-depth examination of unmarried mothers, showing that the trend towards bearing more than one illegitimate child rose over time. Ultimately, the article argues that illegitimacy is best studied at a local or regional level, rather than at the macro level that historians have often employed elsewhere in Europe.
Why did medieval villagers buy earthenware? Pottery and consumer behaviour in the Valencian countryside (1280–1450)
Authors: ALMENAR FERNÁNDEZ LUIS
Published: May 2018

Recent scholarship has suggested that villagers participated in the general proliferation of goods that seems to have occurred in late medieval Europe. How and why they did so is far from clear. This article addresses this issue through a case study of pottery consumption (with particular attention to earthenware) in late medieval rural Valencia. A quantitative analysis of 251 probate inventories (1280s–1450s) supports the argument that not only did medieval villagers acquire more of these goods, but also that the reasons behind such a process challenge many of the traditional interpretations of changes in consumption patterns.
‘Not that of mere accident, but of humane treatment’: natural increase and ‘amelioration’ on Grand Sable Estate, St Vincent
Authors: SMITH S. D.
Published: May 2018

This article investigates the demographic history of the Grand Sable sugar estate on nineteenth-century St Vincent. Exceptionally for a Caribbean plantation, Grand Sable's enslaved population achieved natural increase (a surplus of births over deaths). Pro-slavery campaigners seized on this achievement to support the cause of gradualist amelioration and to oppose metropolitan regulation of slavery, especially emancipation. Explanations of demographic success advanced by opponents of abolition are found wanting and alternatives proposed that are more consistent with the surviving evidence. The role played by anomalies in shaping discourse on both sides of the slavery debate is highlighted.
Introduction to generic rectangular floor plans
Authors: Shekhawat Krishnendra , Duarte José P.
Published: May 2018

An important task in the initial stages of most architectural design processes is the design of planar floor plans, that are composed of non-overlapping rooms divided from each other by walls while satisfying given topological and dimensional constraints. The work described in this paper is part of a larger research aimed at developing the mathematical theory for examining the feasibility of given topological constraints and providing a generic floor plan solution for all possible design briefs.

In this paper, we mathematically describe universal (or generic) rectangular floor plans with n rooms, that is, the floor plans that topologically contain all possible rectangular floor plans with n rooms. Then, we present a graph-theoretical approach for enumerating generic rectangular floor plans upto nine rooms. At the end, we demonstrate the transformation of generic floor plans into a floor plan corresponding to a given graph.
Trends in proportion of older HIV-infected people in care in Latin America and the Caribbean: a growing challenge
Authors: Caro-Vega Y. , Belaunzarán-Zamudio P. F. , Crabtree-Ramírez B. , Shepherd B. E. , Mejia F. , Giganti M. J. , Patterson P. , Grinsztejn B. , Wolff M. , Pape J. W. , Padgett D. , Castilho J. L. , McGowan C. , Sierra-Madero J. G.
Published: May 2018

We aimed to quantify the proportion of people receiving care for HIV-infection that are 50 years or older (older HIV patients) in Latin America and the Caribbean between 2000 and 2015 and to estimate the contribution to the growth of this population of people enrolled before (<50yo) and after 50 years old (yo) (⩾50yo). We used a series of repeated, cross-sectional measurements over time in the Caribbean, Central and South American network (CCASAnet) cohort. We estimated the percentage of patients retained in care each year that were older HIV patients. For every calendar year, we divided patients into two groups: those who enrolled before age 50 and after age 50. We used logistic regression models to estimate the change in the proportion of older HIV patients between 2000 and 2015. The percentage of CCASAnet HIV patients over 50 years had a threefold increase (8% to 24%) between 2000 and 2015. Most of the growth of this population can be explained by the increasing proportion of people that enrolled before 50 years and aged in care. These changes will impact needs of care for people living with HIV, due to multiple comorbidities and high risk of disability associated with aging.
Serological survey on Leptospira infection in slaughtered swine in North-Central Italy
Authors: Bertelloni F. , Turchi B. , Vattiata E. , Viola P. , Pardini S. , Cerri D. , Fratini F.
Published: May 2018

Swine can act as asymptomatic carriers of some Leptospira serovars. In this study, 1194 sera from 61 farms located in five different Regions of North-West Italy were collected from slaughtered healthy pigs. Presence of antibody against four Leptospira serovars was evaluated. Overall, 52.5% of analysed farms presented at least one positive animal and 34.4% presented at least one positive swine with titre ⩾1:400. A percentage of 16.6% sera was positive and 5.9% samples presented a positive titre ⩾1:400. Tuscany and Lombardy showed the highest percentage of positive farms (64.3% and 54.6%, respectively) and sera (28.5% and 13.3%, respectively), probably due to environmental conditions and potential risk factors, which promote maintenance and spreading of Leptospira in these areas. The main represented serogroups were Australis (21.3% positive farms, 8.2% positive sera) and Pomona (18.0% positive farms, 8.1% positive sera). In swine, these serogroups are the most detected worldwide; however, our results seem to highlight a reemerging of serogroup Pomona in pigs in investigated areas. A low percentage of sera (0.6%) scored positive to Canicola, leaving an open question on the role of pigs in the epidemiology of this serovar. Higher antibody titres were detected for serogroups Australis and Pomona. Swine leptospirosis is probably underestimated in Italy and could represent a potential risk for animal and human health.
Applying the zero-inflated Poisson model with random effects to detect abnormal rises in school absenteeism indicating infectious diseases outbreak
Authors: Song X. X. , Zhao Q. , Tao T. , Zhou C. M. , Diwan V. K. , Xu B.
Published: May 2018

Records of absenteeism from primary schools are valuable data for infectious diseases surveillance. However, the analysis of the absenteeism is complicated by the data features of clustering at zero, non-independence and overdispersion. This study aimed to generate an appropriate model to handle the absenteeism data collected in a European Commission granted project for infectious disease surveillance in rural China and to evaluate the validity and timeliness of the resulting model for early warnings of infectious disease outbreak. Four steps were taken: (1) building a ‘well-fitting’ model by the zero-inflated Poisson model with random effects (ZIP-RE) using the absenteeism data from the first implementation year; (2) applying the resulting model to predict the ‘expected’ number of absenteeism events in the second implementation year; (3) computing the differences between the observations and the expected values (O–E values) to generate an alternative series of data; (4) evaluating the early warning validity and timeliness of the observational data and model-based O–E values via the EARS-3C algorithms with regard to the detection of real cluster events. The results indicate that ZIP-RE and its corresponding O–E values could improve the detection of aberrations, reduce the false-positive signals and are applicable to the zero-inflated data.
Childhood infectious diseases and risk of multiple myeloma: an analysis of the Italian multicentre case-control study
Authors: Stagnaro E. , Parodi S. , Costantini A. Seniori , Crosignani P. , Miligi L. , Nanni O. , Piro S. , Ramazzotti V. , Rodella S. , Tumino R. , Vindigni C. , Vineis P.
Published: May 2018

Common childhood infectious diseases have been associated with a reduced risk of following haematopoietic malignancies, but investigations on multiple myeloma (MM) are scarce. Information about 213 MM cases and 1128 healthy controls were obtained from a multicentre population-based Italian case-control study. The association between chickenpox, measles, mumps, pertussis and rubella and the MM risk was estimated by unconditional logistic regression, adjusting for age, gender and residence area. No association was found between MM risk and any considered infectious disease. The number of infections was slightly inversely associated with the risk of MM, but statistical significance was not reached (OR 0.87, 95% CI 0.55–1.4 for 1-2 diseasesvs.none and OR 0.68, 95% CI 0.41–1.1 for 3-5 diseases, respectively,P= 0.131). We did not find a clear evidence that common infections during childhood are associated with the subsequent risk of developing MM.
Moral Enhancement in Russia: Lessons from the Past
Authors: TISCHENKO PAVEL
Published: May 2018

Against the contemporary debates on techniques of “moral enhancement,” this article reviews the interpretation and methods of moral enhancement during the Stalin years in Russia: (1) the GULAG and (2) the abuse of psychiatry. The article serves as a cautionary tale for today’s policy debates, from the personal experiences of the author.
Safety of psychotropic medicines: contribution from observational evidence
Authors: Verdoux H.
Published: May 2018

The risks associated with psychotropic drugs use should be accurately documented at the population level in view of the growing number of persons exposed to these drugs. The strengths of observational studies regarding the identification of drug-related harms mirror the limitations of randomised controlled trials and vice-versa. Observational studies can be carried out in large samples of unselected participants treated in real-life conditions and who may be followed up over long periods. Serious adverse effects undetected during pre-marketing clinical trials may be observed only in post-marketing use, such as metabolic effects of second-generation antipsychotics. Observational studies play a key role in the identification of teratogenic risks, such as those induced by prenatal exposure to anticonvulsants. These studies are the main source of information to investigate the long-term effects of drugs, such as the possible increased risk of dementia in benzodiazepine users. They may also contribute to the accurate assessment at population level of risks overestimated by studies carried out in non-representative samples, such as the risk of congenital heart diseases in babies prenatally exposed to lithium. Owing to the lack of random allocation of drugs, confounding by indication or by disease severity are the major sources of biases in observational studies exploring drug safety. An adverse outcome may be wrongly imputed to drug exposure while it is a symptom/outcome of the disease motivating the decision to prescribe. Such a bias may occur in studies investigating the link between exposure to antidepressants and suicidality. As several methods have been developed to lessen the impact of such biases, pharmaco-epidemiological studies based upon stringent methodological designs should be regarded as a valid approach for assessing psychotropic drug safety.
Warming‐Induced Earlier Greenup Leads to Reduced Stream Discharge in a Temperate Mixed Forest Catchment
Authors: Kim Ji Hyun , Hwang Taehee , Yang Yun , Schaaf Crystal L. , Boose Emery , Munger J. William
Published: May 2018

The phenological response of vegetation to ongoing climate change may have great implications for hydrological regimes in the eastern United States. However, there have been few studies that analyze its resultant effect on catchment discharge dynamics, separating from dominant climatic controls. In this study, we examined the net effect of phenological variations on the long‐term and interannual gross primary production (GPP) and evapotranspiration (ET) fluxes in a temperate deciduous forest, as well as on the catchment discharge behavior in a mixed deciduous‐conifer forest catchment. First, we calibrated the spring and autumn leaf phenology models for the Harvard Forest in the northeastern United States, where the onsets of greenup and senescence have been significantly advanced and delayed, 10.3 and 6.0 days respectively, over the past two decades (1992–2011). We then integrated the phenology models into a mechanistic watershed ecohydrological model (RHESSys), which improved the interannual and long‐term simulations of both the plot‐scale daily GPP and ET fluxes and the catchment discharge dynamics. We found that the phenological changes amplified the long‐term increases in GPP and ET driven by the climatic controls. In particular, the earlier greenup onsets resulted in increases in annual ET significantly, while the delayed senescence onsets had less influence. Consequently, the earlier greenup onsets reduced stream discharge not only during the growing season but also during the following dormant season due to soil water depletion. This study highlights the importance of understanding vegetation response to ongoing climate change in order to predict the future hydrological nonstationarity in this region.
Quantitative analysis of focal adhesion dynamics using photonic resonator outcoupler microscopy (PROM)
Authors: Zhuo Yue , Choi Ji Sun , Marin Thibault , Yu Hojeong , Harley Brendan A. , Cunningham Brian T.
Published: May 2018

Focal adhesions are critical cell membrane components that regulate adhesion and migration and have cluster dimensions that correlate closely with adhesion engagement and migration speed. We utilized a label-free approach for dynamic, long-term, quantitative imaging of cell–surface interactions called photonic resonator outcoupler microscopy (PROM) in which membrane-associated protein aggregates outcoupled photons from the resonant evanescent field of a photonic crystal biosensor, resulting in a highly localized reduction of the reflected light intensity. By mapping the changes in the resonant reflected peak intensity from the biosensor surface, we demonstrate the ability of PROM to detect focal adhesion dimensions. Similar spatial distributions can be observed between PROM images and fluorescence-labeled images of focal adhesion areas in dental epithelial stem cells. In particular, we demonstrate that cell–surface contacts and focal adhesion formation can be imaged by two orthogonal label-free modalities in PROM simultaneously, providing a general-purpose tool for kinetic, high axial-resolution monitoring of cell interactions with basement membranes.
Vapor transport deposition of antimony selenide thin film solar cells with 7.6% efficiency
Authors: Wen Xixing , Chen Chao , Lu Shuaicheng , Li Kanghua , Kondrotas Rokas , Zhao Yang , Chen Wenhao , Gao Liang , Wang Chong , Zhang Jun , Niu Guangda , Tang Jiang
Published: May 2018

Antimony selenide is an emerging promising thin film photovoltaic material thanks to its binary composition, suitable bandgap, high absorption coefficient, inert grain boundaries and earth-abundant constituents. However, current devices produced from rapid thermal evaporation strategy suffer from low-quality film and unsatisfactory performance. Herein, we develop a vapor transport deposition technique to fabricate antimony selenide films, a technique that enables continuous and low-cost manufacturing of cadmium telluride solar cells. We improve the crystallinity of antimony selenide films and then successfully produce superstrate cadmium sulfide/antimony selenide solar cells with a certified power conversion efficiency of 7.6%, a net 2% improvement over previous 5.6% record of the same device configuration. We analyze the deep defects in antimony selenide solar cells, and find that the density of the dominant deep defects is reduced by one order of magnitude using vapor transport deposition process.
Quantifying birefringence in the bovine model of early osteoarthritis using polarisation-sensitive optical coherence tomography and mechanical indentation
Authors: Goodwin Matthew , Bräuer Bastian , Lewis Stephen , Thambyah Ashvin , Vanholsbeeck Frédérique
Published: May 2018

Recent studies have shown potential for using polarisation sensitive optical coherence tomography (PS-OCT) to study cartilage morphology, and to be potentially used as an in vivo, non-invasive tool for detecting osteoarthritic changes. However, there has been relatively limited ability of this method to quantify the subtle changes that occur in the early stages of cartilage degeneration. An established mechanical indenting technique that has previously been used to examine the microstructural response of articular cartilage was employed to fix the bovine samples in an indented state. The samples were subject to creep loading with a constant compressive stress of 4.5 MPa and, when imaged using PS-OCT, enabled birefringent banding patterns to be observed. The magnitude of the birefringence was quantified using the birefringence coefficient (BRC) and statistical analysis revealed that PS-OCT is able to detect and quantify significant changes between healthy and early osteoarthritic cartilage (p < 0.001). This presents a novel utilization of PS-OCT for future development as an in vivo assessment tool.
Use of Hemagglutinin Stem Probes Demonstrate Prevalence of Broadly Reactive Group 1 Influenza Antibodies in Human Sera
Authors: Yassine Hadi M. , McTamney Patrick M. , Boyington Jeffery C. , Ruckwardt Tracy J. , Crank Michelle C. , Smatti Maria K. , Ledgerwood Julie E. , Graham Barney S.
Published: May 2018

A better understanding of the seroprevalence and specificity of influenza HA stem-directed broadly neutralizing antibodies (bNAbs) in the human population could significantly inform influenza vaccine design efforts. Here, we utilized probes comprising headless, HA stabilized stem (SS) to determine the prevalence, binding and neutralization breadth of antibodies directed to HA stem-epitope in a cross-sectional analysis of the general population. Five group-1 HA SS probes, representing five subtypes, were chosen for this analyses. Eighty-four percent of samples analyzed had specific reactivity to at least one probe, with approximately 60% of the samples reactive to H1 probes, and up to 45% reactive to each of the non-circulating subtypes. Thirty percent of analyzed sera had cross-reactivity to at least four of five probes and this reactivity could be blocked by competing with F10 bNAb. Binding cross-reactivity in sera samples significantly correlated with frequency of H1+H5+ cross-reactive B cells. Interestingly, only 33% of the cross-reactive sera neutralized both H1N1 and H5N1 pseudoviruses. Cross-reactive and neutralizing antibodies were more prevalent in individuals >50 years of age. Our data demonstrate the need to use multiple HA-stem probes to assess for broadly reactive antibodies. Further, a universal vaccine could be designed to boost pre-existing B-cells expressing stem-directed bNAbs.
A novel regulation mechanism of the T7 RNA polymerase based expression system improves overproduction and folding of membrane proteins
Authors: Angius Federica , Ilioaia Oana , Amrani Amira , Suisse Annabelle , Rosset Lindsay , Legrand Amélie , Abou-Hamdan Abbas , Uzan Marc , Zito Francesca , Miroux Bruno
Published: May 2018

Membrane protein (MP) overproduction is one of the major bottlenecks in structural genomics and biotechnology. Despite the emergence of eukaryotic expression systems, bacteria remain a cost effective and powerful tool for protein production. The T7 RNA polymerase (T7RNAP)-based expression system is a successful and efficient expression system, which achieves high-level production of proteins. However some foreign MPs require a fine-tuning of their expression to minimize the toxicity associated with their production. Here we report a novel regulation mechanism for the T7 expression system. We have isolated two bacterial hosts, namely C44(DE3) and C45(DE3), harboring a stop codon in the T7RNAP gene, whose translation is under the control of the basal nonsense suppressive activity of the BL21(DE3) host. Evaluation of hosts with superfolder green fluorescent protein (sfGFP) revealed an unprecedented tighter control of transgene expression with a marked accumulation of the recombinant protein during stationary phase. Analysis of a collection of twenty MP fused to GFP showed an improved production yield and quality of several bacterial MPsand of one human monotopic MP. These mutant hosts are complementary to the other existing T7 hosts and will increase the versatility of the T7 expression system.
Substoichiometric Silicon Nitride – An Anode Material for Li-ion Batteries Promising High Stability and High Capacity
Authors: Ulvestad Asbjørn , Andersen Hanne F. , Jensen Ingvild J. T. , Mongstad Trygve T. , Mæhlen Jan Petter , Prytz Øystein , Kirkengen Martin
Published: May 2018

Silicon is often regarded as a likely candidate to replace graphite as the main active anode material in next-generation lithium ion batteries; however, a number of problems impacting its cycle stability have limited its commercial relevance. One approach to solving these issues involves the use of convertible silicon sub-oxides. In this work we have investigated amorphous silicon sub-nitride as an alternative convertible silicon compound by comparing the electrochemical performance of a-SiNx thin films with compositions ranging from pure Si to SiN0.89. We have found that increasing the nitrogen content gradually reduces the reversible capacity of the material, but also drastically increases its cycling stability, e.g. 40 nm a-SiN0.79 thin films exhibited a stable capacity of more than 1,500 mAh/g for 2,000 cycles. Consequently, by controlling the nitrogen content, this material has the exceptional ability to be tuned to satisfy a large range of different requirements for capacity and stability.
Processing and Properties of High-Entropy Ultra-High Temperature Carbides
Authors: Castle Elinor , Csanádi Tamás , Grasso Salvatore , Dusza Ján , Reece Michael
Published: May 2018

Bulk equiatomic (Hf-Ta-Zr-Ti)C and (Hf-Ta-Zr-Nb)C high entropy Ultra-High Temperature Ceramic (UHTC) carbide compositions were fabricated by ball milling and Spark Plasma Sintering (SPS). It was found that the lattice parameter mismatch of the component monocarbides is a key factor for predicting single phase solid solution formation. The processing route was further optimised for the (Hf-Ta-Zr-Nb)C composition to produce a high purity, single phase, homogeneous, bulk high entropy material (99% density); revealing a vast new compositional space for the exploration of new UHTCs. One sample was observed to chemically decompose; indicating the presence of a miscibility gap. While this suggests the system is not thermodynamically stable to room temperature, it does reveal further potential for the development of new in situ formed UHTC nanocomposites. The optimised material was subjected to nanoindentation testing and directly compared to the constituent mono/binary carbides, revealing a significantly enhanced hardness (36.1 ± 1.6 GPa,) compared to the hardest monocarbide (HfC, 31.5 ± 1.3 GPa) and the binary (Hf-Ta)C (32.9 ± 1.8 GPa).
Native electrospray mass spectrometry approaches to probe the interaction between zinc and an anti-angiogenic peptide from histidine-rich glycoprotein
Authors: Martin Esther M. , Kondrat Frances D. L. , Stewart Alan J. , Scrivens James H. , Sadler Peter J. , Blindauer Claudia A.
Published: May 2018

Zinc modulates the biological function of histidine-rich glycoprotein (HRG) through binding to its His-rich region (HRR). The Zn2+-binding properties of a 35 amino-acid biologically-active peptide mimic of the HRR, HRGP330, were investigated using dissociative mass spectrometry approaches in addition to travelling-wave ion mobility mass spectrometry (TWIM-MS). Native mass spectrometry confirmed zinc binding to HRGP330; however, broadening of the 1H NMR resonances upon addition of Zn2+ ions precluded the attainment of structural information. A complementary approach employing TWIM-MS indicated that HRGP330 has a more compact structure in the presence of Zn2+ ions. Top-down MS/MS data supported a metal-binding-induced conformational change, as fewer fragments were observed for Zn2+-bound HRGP330. Zn2+-bound fragments of both N-terminal and C-terminal ends of the peptide were identified from collision-induced dissociation (CID) and electron transfer dissociation/proton transfer reaction (ETD/PTR) experiments, suggesting that multiple binding sites exist within this region of HRG. The combination of mass spectrometry and NMR approaches provides new insight into the highly dynamic interaction between zinc and this His-rich peptide.