bluuebunny/crossref_metadata_2025 huggingface dataset:
Choice of estimand and analysis methods in diabetes trials with rescue medication
Authors: Holzhauer Björn , Akacha Mouna , Bermann Georgina
Published: September 2015

The analysis of clinical trials aiming to show symptomatic benefits is often complicated by the ethical requirement for rescue medication when the disease state of patients worsens. In type 2 diabetes trials, patients receive glucose‐lowering rescue medications continuously for the remaining trial duration, if one of several markers of glycemic control exceeds pre‐specified thresholds. This may mask differences in glycemic values between treatment groups, because it will occur more frequently in less effective treatment groups. Traditionally, the last pre‐rescue medication value was carried forward and analyzed as the end‐of‐trial value. The deficits of such simplistic single imputation approaches are increasingly recognized by regulatory authorities and trialists. We discuss alternative approaches and evaluate them through a simulation study. When the estimand of interest is the effect attributable to the treatments initially assigned at randomization, then our recommendation for estimation and hypothesis testing is to treat data after meeting rescue criteria as deterministically ‘missing’ at random, because initiation of rescue medication is determined by observed in‐trial values. An appropriate imputation of values after meeting rescue criteria is then possible either directly through multiple imputation or implicitly with a repeated measures model. Crucially, one needs to jointly impute or model all markers of glycemic control that can lead to the initiation of rescue medication. An alternative for hypothesis testing only are rank tests with outcomes from patients ‘requiring rescue medication’ ranked worst, and non‐rescued patients ranked according to final visit values. However, an appropriate ranking of not observed values may be controversial. Copyright © 2015 John Wiley & Sons, Ltd.
Diets high in fruits and low in gum exudates promote the occurrence and development of dental disease in pygmy slow loris (Nycticebus pygmaeus)
Authors: Cabana Francis , Nekaris K.A.I.
Published: September 2015

Asian slow lorises are found in zoos and rescue centres worldwide with Nycticebus pygmaeus, the pygmy slow loris, boasting the largest population in captivity. Diet are reportedly high in fruit and concentrates and low in insects and exudates. Wild feeding studies place insects, nectar, and gums as the most important diet components. Captive populations also show high incidences of health afflictions, many of which may be caused by nutrition. Our study, aims at identifying a causative agent within the diets of N. pygmaeus in regards to diseases prominent within captive populations. We sent out 55 diet and health questionnaires to institutions worldwide. Returned diets were nutritionally analyzed. Nutrient values and proportions of each ingredient were used in a principle components analysis. Resulting factors were used as variables in a binary logistic regression (BLR), with dental disease as the dependent variable. 39 questionnaires were returned with a total of 47 diets. 20 (51.7%) institutions reported the presence of diseases with dental issues being prominent. Factors that were significant in the principle components analysis included gum, nectar, protein, acid detergent fibre, calcium, ash, phosphorus, potassium, Ca:P, magnesium, vitamin D, and energy. Gum was the only significant predictor in the BLR. Lastly, a chi square test for association was performed with the presence of dental disease as the dependent variable and the amount of fruit in the diet. The combination of high fruits and little to no gum promotes the occurrence of dental diseases. Current captive diets do not reflect the evolutionary adaptations of Nycticebus primates. Zoo Biol. 34:547–553, 2015. © 2015 Wiley Periodicals, Inc.
BTK Signaling in B Cell Differentiation and Autoimmunity
Authors: Corneth Odilia B. J. , Klein Wolterink Roel G. J. , Hendriks Rudi W.
Published: September 2015

Since the original identification of Bruton’s tyrosine kinase (BTK) as the gene defective in the primary immunodeficiency X-linked agammaglobulinemia (XLA) in 1993, our knowledge on the physiological function of BTK has expanded impressively. In this review, we focus on the role of BTK during B cell differentiation in vivo, both in the regulation of expansion and in the developmental progression of pre-B cells in the bone marrow and as a crucial signal transducer of signals downstream of the IgM or IgG B cell antigen receptor (BCR) in mature B cells governing proliferation, survival, and differentiation. In particular, we highlight BTK function in B cells in the context of host defense and autoimmunity. Small-molecule inhibitors of BTK have very recently shown impressive anti-tumor activity in clinical studies in patients with various B cell malignancies. Since promising effects of BTK inhibition were also seen in experimental animal models for lupus and rheumatoid arthritis, BTK may be a good target for controlling autoreactive B cells in patients with systemic autoimmune disease.
Macro-scale heat transfer in periodically developed flow through isothermal solids
Authors: Buckinx G. , Baelmans M.
Published: September 2015

This paper presents spatially averaged temperature equations for modelling macro-scale heat transfer in periodic solid structures such as fin and tube arrays. The governing equations for the periodically developed heat transfer regime in isothermal solids are derived. It is shown that the appropriate macro-scale temperature in the periodically developed heat transfer regime is obtained by averaging the temperature with a specific weighting function which is adapted to the temperature decay rate. This matched weighting function allows the representation of the macro-scale interfacial heat transfer and thermal dispersion source by means of a spatially constant interfacial heat transfer coefficient and thermal dispersion vector, which both can be calculated from the periodic rescaled temperature on a unit cell of the solid structures. Moreover, it is proved that for small temperature decay rates, the matched weighting function yields the same macro-scale description as repeated volume averaging. The theoretical framework of this paper is applied to a case study, describing the heat transfer between a fluid and an array of solid cylinders at constant temperature.
Laminar–turbulent transition and wave–turbulence interaction in stratified horizontal two-phase pipe flow
Authors: Birvalski M. , Tummers M. J. , Delfos R. , Henkes R. A. W. M.
Published: September 2015

Stratified cocurrent flow of air and water was studied experimentally in a 5 cm diameter horizontal pipe. The velocity in the liquid phase was measured using planar particle image velocimetry, and the instantaneous interfacial profile was recorded using a separate camera. The resulting velocity fields extended from the pipe wall to the wavy interface. The principal aims of the study were to investigate the laminar–turbulent transition of the liquid phase in stratified gas–liquid flow, and to explore the interaction between the transition process and the interfacial waves. The boundaries of transition were determined in both the smooth and the wavy region. The occurrence of waves had the effect of increasing the Reynolds numbers at the end of transition. On the other hand, the transition to turbulence caused a change from the ‘2D small-amplitude’ to the ‘3D small-amplitude’ wave pattern, which were seen to correspond to the capillary–gravity and gravity–capillary solutions of the dispersion relationship respectively. In light of this, the flowmap of the wavy region was recast into Weber number–Froude number coordinates, which provided a physical interpretation of the interaction between the developing turbulence and the changing wave patterns.
Prediction and validation of total and regional skeletal muscle volume using B-mode ultrasonography in Japanese prepubertal children
Authors: Midorikawa Taishi , Ohta Megumi , Hikihara Yuki , Torii Suguru , Sakamoto Shizuo
Published: September 2015

Very few effective field methods are available for accurate, non-invasive estimation of skeletal muscle volume (SMV) and mass in children. We aimed to develop regression-based prediction equations for SMV, using ultrasonography, in Japanese prepubertal children, and to assess the validity of these equations. In total, 145 healthy Japanese prepubertal children aged 6–12 years were randomly divided into two groups: the model development group (sixty boys, thirty-seven girls) and the validation group (twenty-nine boys, nineteen girls). Reference data in the form of contiguous MRI with 1-cm slice thickness were obtained from the first cervical vertebra to the ankle joints. The SMV was calculated by the summation of digitised cross-sectional areas. Muscle thickness was measured using B-mode ultrasonography at nine sites in different regions. In the model development group, strong, statistically significant correlations were observed between the site-matched SMV (total, arms, trunk, thigh and lower legs) measured by MRI and the muscle thickness×height measures obtained by ultrasonography, for both boys and girls. When these SMV prediction equations were applied to the validation groups, the measured total and regional SMV were also very similar to the values predicted for boys and girls, respectively. With the exception of the trunk region in girls, the Bland–Altman analysis for the validation group did not indicate any bias for either boys or girls. These results suggest that ultrasonography-derived prediction equations for boys and girls are useful for the estimation of total and regional SMV.
Memory by Consensus: Remembering the American Revolutionary War in Chicago
Authors: YOUNG CHRISTOPHER J.
Published: September 2015

This article explores how a city remembered a national event that took place before its own existence. To this end, two public works of art in the city of Chicago that have American Revolutionary War participants as their subjects are examined. Particular attention is paid to the historical context surrounding Revolutionary War-themed public art in Chicago as well as to the two men who were responsible for erecting the sculptures – Robert R. McCormick and Barnet Hodes. McCormick, the publisher of the Chicago Daily Tribune, chose to immortalize the doomed Revolutionary spy, Nathan Hale, while Hodes, an attorney for the city of Chicago, centered his attention on a monument that included representations of General George Washington and immigrant financiers Robert Morris and Haym Salomon. By doing so, this article considers what motivated Chicagoans during the 1930s and 1940s to remember the American Revolutionary War. The general consensus that surrounded these acts of remembrance suggests the limitations of otherwise useful and important approaches that focus on conflict and healing in public memory formation.
Larval migration of the ascarid nematode Toxocara canis following infection and re-infection in the gerbil Meriones unguiculatus
Authors: Flecher M.C. , Musso C. , Martins I.V.F. , Pereira F.E.L.
Published: September 2015

A morphological and immunohistochemical study of larval migration patterns was performed in gerbils that were infected once (primary infected group) or twice (secondary infected group) with 1500 eggs of Toxocara canis. Animals from the primary infected and the re-infected group were killed at different times after infection, and larvae were counted in the intestines, liver, lungs and brain. Fragments of all organs were formalin fixed and paraffin embedded for histology and immunohistochemistry analyses (using polyclonal anti-Toxocara serum raised in rabbits infected with T. canis). In the primary infected group, larvae were more abundant in the intestine at 24 h, in the liver and lungs between 24 and 72 h and in the brain after 96 h; larvae predominated in the brain for up to 60 days after infection. In the re-infected group, an increase in the number of larvae in the liver and a reduction in the number of larvae in the brain was observed up to 60 days after re-infection. Inflammatory reactions were absent or limited. Eosinophils and loose granulomata were observed around the larvae and their antigens in the primary infected group and were more severe. Many eosinophils and typical epithelioid granulomata were observed around larvae in the re-infected group. These results demonstrate that the migration pattern of T. canis larvae in gerbils is similar to that in mice and rats, exhibiting a late neurotropic stage. In the re-infected group, there was histological evidence of an adaptive T-helper 2 (Th-2) response, and larvae were apparently retained within granulomata in the liver, without obvious signs of destruction.
The importance of not only individual, but also community and society factors in resilience in later life
Authors: Bennett Kate Mary , Windle Gillian
Published: September 2015

Little work has focused on resilience amongst older adults, and few factors have been identified that promote their resilience. Kalisch et al. suggest that socioenvironmental factors are distant influences. We argue, however, that community and societal influences are as important as individual ones. Further, an ecological framework explains why some older adults are resilient whilst others are not.
Appreciating methodological complexity and integrating neurobiological perspectives to advance the science of resilience
Authors: Kleim Birgit , Galatzer-Levy Isaac R.
Published: September 2015

Kalisch and colleagues identify several routes to a better understanding of mechanisms underlying resilience and highlight the need to integrate findings from neuroscience and animal learning. We argue that appreciating methodological complexity and integrating neurobiological perspectives will advance the science of resilience and ultimately help improve the lives of those exposed to stress and adversity.
Resilience: The role of accurate appraisal, thresholds, and socioenvironmental factors
Authors: Southwick Steven M. , Pietrzak Robert H. , Charney Dennis S. , Krystal John H.
Published: September 2015

Adding to the resilience model of Kalisch and colleagues, we suggest that resilience is associated with accurate rather than excessively positive or negative appraisal or reappraisal styles; that complex systems do not always change in linear fashion; that linkages of individuals, families, and communities markedly affect individual resilience; and that resilience research focus on specific factors or mechanisms as well as more global ones.
PRICES AND WAGES IN THE 1890 CRISIS IN BUENOS AIRES
Authors: Vence Conti Agustina , Cuesta Eduardo Martín
Published: September 2015

The growth of Argentina’s economy in the late nineteenth and early twentieth century was so great that it was called “The Great Expansion”. This explains the interest of economic historians to observe, analyze and explain the conditions under which such growth occurred. One of the topics is the 1890 crisis, or “Baring Crisis”. This was seen by contemporaries as the worst economic debacle of the nineteenth century. Studies in economic history have seen this crisis both their macroeconomic aspects, and from the impact that would have occurred in the population. Also, in recent years there has been a renewed interest in the production and analysis of series of prices and wages, as key to analyzing economic indicators economy conditions and living conditions and inequality. Given this historiographical renewal, in this article a new series of prices and wages of Buenos Aires in the late nineteenth century are presented. With this new information, and open discussion with previous works, a new perspective on the evolution of prices and wages is provided, with a different perspective on the impact of the 1890 crisis.
Corticocortical connection patterns reveal two distinct visual cortical areas bordering dorsal V2 in marmoset monkey
Authors: JEFFS JANELLE , FEDERER FREDERICK , ANGELUCCI ALESSANDRA
Published: September 2015

The organization of the cortex located immediately anterior to the second visual area (V2), i.e., the third tier visual cortex, remains controversial, especially in New World primates. In particular, there is lack of consensus regarding the exact location and extent of the lower visual quadrant representation of the third visual area V3 (or ventrolateral posterior –VLP – of a different nomenclature). Microelectrode and connectional mapping studies have revealed the existence of an upper visual quadrant representation abutting dorsal V2 anteriorly, and bordered medially and laterally by representations of the lower visual quadrant. It remains unclear whether these lower field regions are both part of a single area V3, which is split into two patches by an interposed region of upper field representation, or whether they are the lower field representations of two different areas, the dorsomedial area (DM) and area V3/VLP, respectively. To address this question, we quantitatively analyzed the patterns of corticocortical afferent connections labeled by tracer injections targeted to these two lower field regions in the dorsal aspect of the third tier cortex. We found different inter-areal connectivity patterns arising from these two regions, strongly suggesting that they belong to two different visual areas. In particular, our results indicate that the dorsal aspect of the third tier cortex consists of two distinct areas: a full area DM, representing the lower quadrant medially, and the upper quadrant laterally, and the lower quadrant representation of V3/VLP, located laterally to upper field DM. DM is predominantly connected with areas of the dorsal visual stream, and V3/VLP with areas of the ventral stream. These results prompt further functional investigations of the third tier cortex, as previous studies of this cortical territory may have pooled response properties of two very different areas into a single area V3.
A cortical locus for anisotropic overlay suppression of stimuli presented at fixation
Authors: HANSEN BRUCE C. , RICHARD BRUNO , ANDRES KRISTIN , JOHNSON AARON P. , THOMPSON BENJAMIN , ESSOCK EDWARD A.
Published: September 2015

Human contrast sensitivity for narrowband Gabor targets is suppressed when superimposed on narrowband masks of the same spatial frequency and orientation (referred to as overlay suppression), with suppression being broadly tuned to orientation and spatial frequency. Numerous behavioral and neurophysiological experiments have suggested that overlay suppression originates from the initial lateral geniculate nucleus (LGN) inputs to V1, which is consistent with the broad tuning typically reported for overlay suppression. However, recent reports have shown narrowly tuned anisotropic overlay suppression when narrowband targets are masked by broadband noise. Consequently, researchers have argued for an additional form of overlay suppression that involves cortical contrast gain control processes. The current study sought to further explore this notion behaviorally using narrowband and broadband masks, along with a computational neural simulation of the hypothesized underlying gain control processes in cortex. Additionally, we employed transcranial direct current stimulation (tDCS) in order to test whether cortical processes are involved in driving narrowly tuned anisotropic suppression. The behavioral results yielded anisotropic overlay suppression for both broadband and narrowband masks and could be replicated with our computational neural simulation of anisotropic gain control. Further, the anisotropic form of overlay suppression could be directly modulated by tDCS, which would not be expected if the suppression was primarily subcortical in origin. Altogether, the results of the current study provide further evidence in support of an additional overlay suppression process that originates in cortex and show that this form of suppression is also observable with narrowband masks.
A planar multiband Koch snowflake fractal antenna for cognitive radio
Authors: Sivasundarapandian S. , Suriyakala C.D.
Published: September 2015

This paper of lettering reveals about a modified Koch snowflake fractal multiband antenna for cognitive radio applications. Multiband antennas can be employed for spectrum sensing in cognitive radio. This new microstrip-modified Koch fractal antenna exhibits multiple actions in four dissimilar resonant frequencies at 3.2, 5.2, 6, and 9.5 GHz correspondingly that covers the frequency bands such as S, C, and X bands. Its multiband behavior was analyzed by designing and simulating in ADS EMDS software. Three iterations were carried out to study the performance of modified Koch snowflake fractal antenna. The outer ring and a small rectangular slot in the center of the antenna are used for 50 Ω impedance matching and to increase the number of resonant frequencies. The fractal antenna parameters such as gain, directivity, and its radiation pattern are also analyzed in this paper. The measured results show good agreement with the simulated results.
Independent Replication and Meta-Analysis for Endometriosis Risk Loci
Authors: Sapkota Yadav , Fassbender Amelie , Bowdler Lisa , Fung Jenny N. , Peterse Daniëlle , O Dorien , Montgomery Grant W. , Nyholt Dale R. , D'Hooghe Thomas M.
Published: September 2015

Endometriosis is a complex disease that affects 6–10% of women in their reproductive years and 20–50% of women with infertility. Genome-wide and candidate-gene association studies for endometriosis have identified 10 independent risk loci, and of these, nine (rs7521902, rs13394619, rs4141819, rs6542095, rs1519761, rs7739264, rs12700667, rs1537377, and rs10859871) are polymorphic in European populations. Here we investigate the replication of nine SNP loci in 998 laparoscopically and histologically confirmed endometriosis cases and 783 disease-free controls from Belgium. SNPs rs7521902, rs13394619, and rs6542095 show nominally significant (p < .05) associations with endometriosis, while the directions of effect for seven SNPs are consistent with the original reports. Association of rs6542095 at the IL1A locus with ‘All’ (p = .066) and ‘Grade_B’ (p = .01) endometriosis is noteworthy because this is the first successful replication in an independent population. Meta-analysis with the published results yields genome-wide significant evidence for rs7521902, rs13394619, rs6542095, rs12700667, rs7739264, and rs1537377. Notably, three coding variants in GREB1 (near rs13394619) and CDKN2B-AS1 (near rs1537377) also showed nominally significant associations with endometriosis. Overall, this study provides important replication in a uniquely characterized independent population, and indicates that the majority of the original genome-wide association findings are not due to chance alone.
Largest Grains Dominate River Bedrock Erosion Rates
Authors: Cook Terri
Published: September 2015

The effect of particle size on bedrock erosion rates adds complexity to modeling bedrock channel evolution.
Edge mixing dynamics in graphene p–n junctions in the quantum Hall regime
Authors: Matsuo Sadashige , Takeshita Shunpei , Tanaka Takahiro , Nakaharai Shu , Tsukagoshi Kazuhito , Moriyama Takahiro , Ono Teruo , Kobayashi Kensuke
Published: September 2015

Massless Dirac electron systems such as graphene exhibit a distinct half-integer quantum Hall effect, and in the bipolar transport regime co-propagating edge states along the p–n junction are realized. Additionally, these edge states are uniformly mixed at the junction, which makes it a unique structure to partition electrons in these edge states. Although many experimental works have addressed this issue, the microscopic dynamics of electron partition in this peculiar structure remains unclear. Here we performed shot-noise measurements on the junction in the quantum Hall regime as well as at zero magnetic field. We found that, in sharp contrast with the zero-field case, the shot noise in the quantum Hall regime is finite in the bipolar regime, but is strongly suppressed in the unipolar regime. Our observation is consistent with the theoretical prediction and gives microscopic evidence that the edge states are uniquely mixed along the p–n junction.
Non-covalent synthesis of supermicelles with complex architectures using spatially confined hydrogen-bonding interactions
Authors: Li Xiaoyu , Gao Yang , Boott Charlotte E. , Winnik Mitchell A. , Manners Ian
Published: September 2015

Nature uses orthogonal interactions over different length scales to construct structures with hierarchical levels of order and provides an important source of inspiration for the creation of synthetic functional materials. Here, we report the programmed assembly of monodisperse cylindrical block comicelle building blocks with crystalline cores to create supermicelles using spatially confined hydrogen-bonding interactions. We also demonstrate that it is possible to further program the self-assembly of these synthetic building blocks into structures of increased complexity by combining hydrogen-bonding interactions with segment solvophobicity. The overall approach offers an efficient, non-covalent synthesis method for the solution-phase fabrication of a range of complex and potentially functional supermicelle architectures in which the crystallization, hydrogen-bonding and solvophobic interactions are combined in an orthogonal manner.
Origin and dynamics of vortex rings in drop splashing
Authors: Lee Ji San , Park Su Ji , Lee Jun Ho , Weon Byung Mook , Fezzaa Kamel , Je Jung Ho
Published: September 2015

A vortex is a flow phenomenon that is very commonly observed in nature. More than a century, a vortex ring that forms during drop splashing has caught the attention of many scientists due to its importance in understanding fluid mixing and mass transport processes. However, the origin of the vortices and their dynamics remain unclear, mostly due to the lack of appropriate visualization methods. Here, with ultrafast X-ray phase-contrast imaging, we show that the formation of vortex rings originates from the energy transfer by capillary waves generated at the moment of the drop impact. Interestingly, we find a row of vortex rings along the drop wall, as demonstrated by a phase diagram established here, with different power-law dependencies of the angular velocities on the Reynolds number. These results provide important insight that allows understanding and modelling any type of vortex rings in nature, beyond just vortex rings during drop splashing.
Nitrogen-embedded buckybowl and its assembly with C60
Authors: Yokoi Hiroki , Hiraoka Yuya , Hiroto Satoru , Sakamaki Daisuke , Seki Shu , Shinokubo Hiroshi
Published: September 2015

Curved π-conjugated molecules have attracted considerable interest because of the unique properties originating from their curved π surface. However, the synthesis of such distorted molecules requires harsh conditions, which hamper easy access to heteroatom-containing curved π systems. Here we report the synthesis of a π-extended azacorannulene with nitrogen in its centre. The oxidation of 9-aminophenanthrene provides tetrabenzocarbazole, which is converted to the azabuckybowl through palladium-catalysed intramolecular coupling. The electron-donating nature and curved π surface of the azabuckybowl enable its tight association with C60 in solution and solid states. High charge mobility is observed for the azabuckybowl/C60 assembly. This compound may be of interest in the fields of curved π systems as fullerene hosts, anisotropic π donors and precursors to nitrogen-containing nanocarbon materials.
Strong, spectrally-tunable chirality in diffractive metasurfaces
Authors: De Leon Israel , Horton Matthew J. , Schulz Sebastian A. , Upham Jeremy , Banzer Peter , Boyd Robert W.
Published: September 2015

Metamaterials and metasurfaces provide a paradigm-changing approach for manipulating light. Their potential has been evinced by recent demonstrations of chiral responses much greater than those of natural materials. Here, we demonstrate theoretically and experimentally that the extrinsic chiral response of a metasurface can be dramatically enhanced by near-field diffraction effects. At the core of this phenomenon are lattice plasmon modes that respond selectively to the illumination’s polarization handedness. The metasurface exhibits sharp features in its circular dichroism spectra, which are tunable over a broad bandwidth by changing the illumination angle over a few degrees. Using this property, we demonstrate an ultra-thin circular-polarization sensitive spectral filter with a linewidth of ~10 nm, which can be dynamically tuned over a spectral range of 200 nm. Chiral diffractive metasurfaces, such as the one proposed here, open exciting possibilities for ultra-thin photonic devices with tunable, spin-controlled functionality.
The motility-proliferation-metabolism interplay during metastatic invasion
Authors: Hecht Inbal , Natan Sari , Zaritsky Assaf , Levine Herbert , Tsarfaty Ilan , Ben-Jacob Eshel
Published: September 2015

Metastasis is the major cause for cancer patients’ death and despite all the recent advances in cancer research it is still mostly incurable. Understanding the mechanisms that are involved in the migration of the cells in a complex environment is a key step towards successful anti-metastatic treatment. Using experimental data-based modeling, we focus on the fundamentals of metastatic invasion: motility, invasion, proliferation and metabolism and study how they may be combined to maximize the cancer’s ability to metastasize. The modeled cells’ performance is measured by the number of cells that succeed in migration in a maze, which mimics the extracellular environment. We show that co-existence of different cell clones in the tumor, as often found in experiments, optimizes the invasive ability in a frequently-changing environment. We study the role of metabolism and stimulation by growth factors and show that metabolism plays a crucial role in the metastatic process and should therefore be targeted for successful treatment.
NF-κB signaling is essential for resistance to heat stress-induced early stage apoptosis in human umbilical vein endothelial cells
Authors: Liu Yanan , Zhou Gengbiao , Wang Zhenglian , Guo Xiaohua , Xu Qiulin , Huang Qiaobing , Su Lei
Published: September 2015

Cell apoptosis induced by heat stress is regulated by a complex signaling network. We previously reported that a p53-dependent pathway is involved. Here, we present evidence that NF-κB signaling plays a crucial role in preventing heat stress-induced early apoptosis. Human umbilical vein endothelial cells (HUVECs) were examined and increased phosphorylation of p65 and IκBα were detected, without IκBα degradation. When NF-κB signaling was inhibited by BAY11-7082, or a small interference RNA (siRNA) targeting p65, a significant increase in cell apoptosis and caspase-3 activity was observed, as well as reduced expression and translocation of HSP27 into the nucleus, an accumulation of reactive oxygen species and prolonged phosphorylation of mitogen-activated protein kinases (MAPKs). In addition, an association between HSP27 and p65 was identified which may enhance NF-κB activation. When HSP27 was overexpressed, pretreatment of HUVECs with the antioxidant, apocynin, or N-acetyl cysteine, suppressed apoptosis. Similarly, inhibition of JNK and p38 with SP600125 and SB203580, respectively, also suppressed apoptosis, whereas siRNA-mediated HSP27 knockdown and treatment with the ERK 1/2 inhibitor PD98059 did otherwise. In conclusion, these findings suggest a novel role for an NF-κB signaling pathway involving HSP27, ROS and MAPKs that confers a protective effect against heat stress-induced cell apoptosis.
Chick tendon fibroblast transcriptome and shape depend on whether the cell has made its own collagen matrix
Authors: Yeung Ching-Yan Chloé , Zeef Leo A. H. , Lallyett Chloe , Lu Yinhui , Canty-Laird Elizabeth G. , Kadler Karl E.
Published: September 2015

Collagen- and fibrin-based gels are extensively used to study cell behaviour. However, 2D–3D and collagen-fibrin comparisons of gene expression, cell shape and mechanotransduction, with an in vivo reference, have not been reported. Here we compared chick tendon fibroblasts (CTFs) at three stages of embryonic development with CTFs cultured in collagen- or fibrin-based tissue engineered constructs (TECs). CTFs synthesised their own collagen matrix in fibrin-based TECs and better recapitulated the gene expression, collagen fibril alignment and cell shape seen in vivo. In contrast, cells in 3D collagen gels exhibited a 2D-like morphology and expressed fewer of the genes expressed in vivo. Analysis of YAP/TAZ target genes showed that collagen gels desensitise mechanotransduction pathways. In conclusion, gene expression and cell shape are similar on plastic and 3D collagen whereas cells in 3D fibrin have a shape and transcriptome better resembling the in vivo situation. Implications for wound healing are discussed.
Light pollution disrupts sleep in free-living animals
Authors: Raap Thomas , Pinxten Rianne , Eens Marcel
Published: September 2015

Artificial lighting can alter individual behaviour, with often drastic and potentially negative effects on biological rhythms, daily activity and reproduction. Whether this is caused by a disruption of sleep, an important widespread behaviour enabling animals to recover from daily stress, is unclear. We tested the hypothesis that light pollution disrupts sleep by recording individual sleep behaviour of great tits, Parus major, that were roosting in dark nest-boxes and were exposed to light-emitting diode light the following night. Their behaviour was compared to that of control birds sleeping in dark nest-boxes on both nights. Artificial lighting caused experimental birds to wake up earlier, sleep less (–5%) and spent less time in the nest-box as they left their nest-box earlier in the morning. Experimental birds did not enter the nest-box or fall asleep later than controls. Although individuals in lit nest-boxes did not wake up more often nor decreased the length of their sleep bouts, females spent a greater proportion of the night awake. Our study provides the first direct proof that light pollution has a significant impact on sleep in free-living animals, in particular in the morning and highlights a mechanism for potential effects of light pollution on fitness.
Clinicopathological Significance of CDKN2A Promoter Hypermethylation Frequency with Pancreatic Cancer
Authors: Tang Bo , Li Yang , Qi Guangying , Yuan Shengguang , Wang Zhenran , Yu Shuiping , Li Bo , He Songqing
Published: September 2015

The prognosis of pancreatic cancer patients is very poor, with a 5-year survival of less than 6%. Previous studies demonstrated that the loss of function of CDKN2A is mainly caused by the hypermethylation of CDKN2A gene promoter; however, whether or not it is associated with the incidence of pancreatic cancer still remains unclear. In this study, we systematically reviewed the association between CDKN2A promoter methylation and pancreatic cancer using meta-analysis methods. The pooled data were analyzed by Review Manager 5.2. Fourteen studies eligible studies, including 418 pancreatic cancer, 155 pancreatic intraepithelial neoplasia (PanINs) and 45 chronic pancreatitis (CP) patients were analyzed. We observed that the frequency of CDKN2A methylation was significantly higher in pancreatic cancer patients than in normal healthy controls, the pooled OR = 17.19, 95% CI = 8.72–33.86, P < 0.00001. The frequency of CDKN2A methylation was also significantly higher in PanINs patients than that in normal individual controls, OR = 12.35, 95% CI = 1.70–89.89, P = 0.01. In addition, CDKN2A methylation was associated with worse survival in pancreatic cancer, HR = 4.46, 95% CI = 1.37–14.53, P = 0.01. The results strongly suggest that CDKN2A methylation is correlated with an increased risk of pancreatic cancer. CDKN2A methylation plays a critical role in pancreatic carcinogenesis and may serve as a prognostic marker.
The comparative cost-effectiveness of colorectal cancer screening using faecal immunochemical test vs. colonoscopy
Authors: Wong Martin CS , Ching Jessica YL , Chan Victor CW , Sung Joseph JY
Published: September 2015

Faecal immunochemical tests (FITs) and colonoscopy are two common screening tools for colorectal cancer(CRC). Most cost-effectiveness studies focused on survival as the outcome and were based on modeling techniques instead of real world observational data. This study evaluated the cost-effectiveness of these two tests to detect colorectal neoplastic lesions based on data from a 5-year community screening service. The incremental cost-effectiveness ratio (ICER) was assessed based on the detection rates of neoplastic lesions and costs including screening compliance, polypectomy, colonoscopy complications and staging of CRC detected. A total of 5,863 patients received yearly FIT and 4,869 received colonoscopy. Compared with FIT, colonoscopy detected notably more adenomas (23.6% vs. 1.6%) and advanced lesions or cancer (4.2% vs. 1.2%). Using FIT as control, the ICER of screening colonoscopy in detecting adenoma, advanced adenoma, CRC and a composite endpoint of either advanced adenoma or stage I CRC was US$3,489, US$27,962, US$922,762 and US$23,981 respectively. The respective ICER was US$3,597, US$439,513, -US$2,765,876 and US$32,297 among lower-risk subjects; whilst the corresponding figure was US$3,153, US$14,852, US$184,162 and US$13,919 among higher-risk subjects. When compared to FIT, colonoscopy is considered cost-effective for screening adenoma, advanced neoplasia and a composite endpoint of advanced neoplasia or stage I CRC.
Highly Efficient Photocatalytic Hydrogen Production of Flower-like Cadmium Sulfide Decorated by Histidine
Authors: Wang Qizhao , Lian Juhong , Li Jiajia , Wang Rongfang , Huang Haohao , Su Bitao , Lei Ziqiang
Published: September 2015

Morphology-controlled synthesis of CdS can significantly enhance the efficiency of its photocatalytic hydrogen production. In this study, a novel three-dimensional (3D) flower-like CdS is synthesized via a facile template-free hydrothermal process using Cd(NO3)2•4H2O and thiourea as precursors and L-Histidine as a chelating agent. The morphology, crystal phase and photoelectrochemical performance of the flower-like CdS and pure CdS nanocrystals are carefully investigated via various characterizations. Superior photocatalytic activity relative to that of pure CdS is observed on the flower-like CdS photocatalyst under visible light irradiation, which is nearly 13 times of pure CdS. On the basis of the results from SEM studies and our analysis, a growth mechanism of flower-like CdS is proposed by capturing the shape evolution. The imidazole ring of L-Histidine captures the Cd ions from the solution and prevents the growth of the CdS nanoparticles. Furthermore, the photocatalytic contrast experiments illustrate that the as-synthesized flower-like CdS with L-Histidine is more stable than CdS without L-Histidine in the hydrogen generation.
A novel recombinant slow-release TNF α-derived peptide effectively inhibits tumor growth and angiogensis
Authors: Ma Yi , Zhao Shaojun , Shen Shutao , Fang Shixiong , Ye Zulu , Shi Zhi , Hong An
Published: September 2015

RMP16, a recombinant TNF α-derived polypeptide comprising a specific human serum albumin (HSA)-binding 7-mer peptide identified by phage display screening (WQRPSSW), a cleavage peptide for Factor Xa (IEGR) and a 20-amino acid bioactive peptide P16 (TNF α segment including amino acid residues 75–94), was prepared by gene-engineering technology. RMP16 showed prolonged half-life, 13.11 hours in mice (half-lives of P16 and TNF α are 5.77 and 29.0 minutes, respectively) and obviously higher receptor selectivity for TNFRI than TNF α. RMP16 had significant inhibition effects for multiple tumor cells, especially prostate cancer Du145 cells and human vascular endothelial cells but not for human mammary non-tumorigenic epithelial cells. RMP16 can more effectively induce apoptosis and inhibit proliferation for DU145 cells than P16 and TNF α via the caspase-dependent apoptosis pathway and G0/G1 cell cycle arrest. In nude mice with transplanted tumor of DU145 cells, RMP16 significantly induced apoptosis and necrosis of tumor tissues but causing less side effects and tumor inhibitory rate reached nearly 80%, furthermore, RMP16 can potently inhibit tumor angiogenesis and neovascularization. These findings suggest that RMP16 may represent a promising long-lasting antitumor therapeutic peptide with less TNF α-induced toxicity.
The nitric oxide synthase 3 G894T polymorphism associated with Alzheimer’s disease risk: a meta-analysis
Authors: Liu Shengyuan , Zeng Fangfang , Wang Changyi , Chen Zhongwei , Zhao Bin , Li Keshen
Published: September 2015

The association between the G894T polymorphism (Glu298Asp) of nitric oxide synthase 3 (NOS3) and risk of Alzheimer’s disease (AD) was explored by performing a meta-analysis of case-control studies. Bibliographical searches were conducted in the MEDLINE, EMBASE and China National Knowledge Infrastructure (CNKI) databases without any language limitations. Two investigators independently assessed abstracts for relevant studies and reviewed all eligible studies. We adopted regrouping in accordance with the most probably appropriate genetic model. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of this association. We performed a meta-analysis including 21 published articles with 23 case-control studies (5,670 cases and 5,046 controls). In the analyses, we found significant association between G894T polymorphism and AD risk under a complete overdominant model (GG + TT vs. GT) (OR = 1.18; 95%CI, 1.04–1.35; P = 0.010). When stratified by time of AD onset, we found the association between this polymorphism and AD susceptibility to be more substantial among late onset patients than among early onset patients (OR for late vs. early onset: 1.33 vs. 1.02, P interaction = 0.049). The meta-analysis showed that the polymorphism G894T of NOS3 was associated with risk of AD.
Hypoxia-induced carbonic anhydrase IX facilitates lactate flux in human breast cancer cells by non-catalytic function
Authors: Jamali Somayeh , Klier Michael , Ames Samantha , Felipe Barros L. , McKenna Robert , Deitmer Joachim W. , Becker Holger M.
Published: September 2015

The most aggressive tumour cells, which often reside in hypoxic environments, rely on glycolysis for energy production. Thereby they release vast amounts of lactate and protons via monocarboxylate transporters (MCTs), which exacerbates extracellular acidification and supports the formation of a hostile environment. We have studied the mechanisms of regulated lactate transport in MCF-7 human breast cancer cells. Under hypoxia, expression of MCT1 and MCT4 remained unchanged, while expression of carbonic anhydrase IX (CAIX) was greatly enhanced. Our results show that CAIX augments MCT1 transport activity by a non-catalytic interaction. Mutation studies in Xenopus oocytes indicate that CAIX, via its intramolecular H+-shuttle His200, functions as a “proton-collecting/distributing antenna” to facilitate rapid lactate flux via MCT1. Knockdown of CAIX significantly reduced proliferation of cancer cells, suggesting that rapid efflux of lactate and H+, as enhanced by CAIX, contributes to cancer cell survival under hypoxic conditions.
Associations between antioxidant vitamins and the risk of invasive cervical cancer in Chinese women: A case-control study
Authors: Guo Liyuan , Zhu Hong , Lin Chengjun , Che Jianhua , Tian Xiujuan , Han Shiyu , Zhao Honghui , Zhu Yumei , Mao Dongwei
Published: September 2015

Previous studies on the associations between dietary antioxidant vitamins and the risk of cervical cancer remain inconsistent and little evidence is available for serum antioxidant vitamins, which provide more accurate measurements of these nutrients. We conducted a case-control study of 458 incident cases with invasive cervical cancer and 742 controls to assess the effects of diet or serum antioxidant vitamins. Higher serum antioxidant vitamins were associated with a lower risk of cervical cancer after adjusting for potential confounders. The odds ratios (ORs) for the highest (vs. lowest) quartile were 0.66 (95% confidence interval [CI] = 0.46–0.93; P = 0.024) for α-carotene, 0.63 (95% CI = 0.45–0.90; P = 0.006) for β-carotene, 0.53 (95% CI = 0.37–0.74; P < 0.001) for vitamin E and 0.48 (95% CI = 0.33–0.69; P < 0.001) for vitamin C. Dietary intakes of vitamins E and C were inversely associated with the risk of cervical cancer. Risk of cervical cancer from serum antioxidant vitamins was more evident in passive smokers than non-passive smokers. These findings indicated that antioxidant vitamins (mainly α-carotene, β-carotene and vitamins E and C) might be beneficial in reducing the risk of invasive cervical cancer in Chinese women, especially in passive smokers.
Dimeric interactions and complex formation using direct coevolutionary couplings
Authors: dos Santos Ricardo N. , Morcos Faruck , Jana Biman , Andricopulo Adriano D. , Onuchic José N.
Published: September 2015

We develop a procedure to characterize the association of protein structures into homodimers using coevolutionary couplings extracted from Direct Coupling Analysis (DCA) in combination with Structure Based Models (SBM). Identification of dimerization contacts using DCA is more challenging than intradomain contacts since direct couplings are mixed with monomeric contacts. Therefore a systematic way to extract dimerization signals has been elusive. We provide evidence that the prediction of homodimeric complexes is possible with high accuracy for all the cases we studied which have rich sequence information. For the most accurate conformations of the structurally diverse dimeric complexes studied the mean and interfacial RMSDs are 1.95Å and 1.44Å, respectively. This methodology is also able to identify distinct dimerization conformations as for the case of the family of response regulators, which dimerize upon activation. The identification of dimeric complexes can provide interesting molecular insights in the construction of large oligomeric complexes and be useful in the study of aggregation related diseases like Alzheimer’s or Parkinson’s.
Acoustic build-up in on-chip stimulated Brillouin scattering
Authors: Wolff C. , Steel M. J. , Eggleton B. J. , Poulton C. G.
Published: September 2015

We investigate the role of the spatial evolution of the acoustic field in stimulated Brillouin scattering processes in short high-gain structures. When the gain is strong enough that the gain length becomes comparable to the acoustic wave decay length of order 100 microns, standard approximations treating the acoustic field as a local response no longer apply. Treating the acoustic evolution more accurately, we find that the backward SBS gain of sub-millimetre long waveguides is significantly reduced from the value obtained by the conventional treatment because the acoustic mode requires several decay lengths to build up to its nominal value. In addition, the corresponding resonance line is broadened with the development of side bands. In contrast, we argue that intra-mode forward SBS is not expected to show these effects. Our results have implications for several recent proposals and experiments on high-gain stimulated Brillouin scattering in short semiconductor waveguides.