bluuebunny/crossref_metadata_2025 huggingface dataset:
Hollow Li20B60 Cage: Stability and Hydrogen Storage
Authors: Wang Jing , Wei Zhi-Jing , Zhao Hui-Yan , Liu Ying
Published: April 2016

A stable hollow Li20B60 cage with D2 symmetry has been identified using first-principles density functional theory studies. The results of vibrational frequency analysis and molecular dynamics simulations demonstrate that this Li20B60 cage is exceptionally stable. The feasibility of functionalizing Li20B60 cage for hydrogen storage was explored theoretically. Our calculated results show that the Li20B60 molecule can adsorb a maximum of 28 hydrogen molecules. With a hydrogen uptake of 8.190 wt% and an average binding energy of 0.336 eV/H2, Li20B60 is a remarkable high-capacity storage medium.
Recovery of infrastructure networks after localised attacks
Authors: Hu Fuyu , Yeung Chi Ho , Yang Saini , Wang Weiping , Zeng An
Published: April 2016

The stability of infrastructure network is always a critical issue studied by researchers in different fields. A lot of works have been devoted to reveal the robustness of the infrastructure networks against random and malicious attacks. However, real attack scenarios such as earthquakes and typhoons are instead localised attacks which are investigated only recently. Unlike previous studies, we examine in this paper the resilience of infrastructure networks by focusing on the recovery process from localised attacks. We introduce various preferential repair strategies and found that they facilitate and improve network recovery compared to that of random repairs, especially when population size is uneven at different locations. Moreover, our strategic repair methods show similar effectiveness as the greedy repair. The validations are conducted on simulated networks, and on real networks with real disasters. Our method is meaningful in practice as it can largely enhance network resilience and contribute to network risk reduction.
Structural and functional properties of prefibrillar α-synuclein oligomers
Authors: Pieri Laura , Madiona Karine , Melki Ronald
Published: April 2016

The deposition of fibrillar alpha-synuclein (α-syn) within inclusions (Lewy bodies and Lewy neurites) in neurons and glial cells is a hallmark of synucleinopathies. α-syn populates a variety of assemblies ranging from prefibrillar oligomeric species to fibrils whose specific contribution to neurodegeneration is still unclear. Here, we compare the specific structural and biological properties of distinct soluble prefibrillar α-syn oligomers formed either spontaneously or in the presence of dopamine and glutaraldehyde. We show that both on-fibrillar assembly pathway and distinct dopamine-mediated and glutaraldehyde-cross-linked α-syn oligomers are only slightly effective in perturbing cell membrane integrity and inducing cytotoxicity, while mature fibrils exhibit the highest toxicity. In contrast to low-molecular weight and unstable oligomers, large stable α-syn oligomers seed the aggregation of soluble α-syn within reporter cells although to a lesser extent than mature α-syn fibrils. These oligomers appear elongated in shape. Our findings suggest that α-syn oligomers represent a continuum of species ranging from unstable low molecular weight particles to mature fibrils via stable elongated oligomers composed of more than 15 α-syn monomers that possess seeding capacity.
Thrombospondin-4 reduces binding affinity of [3H]-gabapentin to calcium-channel α2δ-1-subunit but does not interact with α2δ-1 on the cell-surface when co-expressed
Authors: Lana Beatrice , Page Karen M. , Kadurin Ivan , Ho Shuxian , Nieto-Rostro Manuela , Dolphin Annette C.
Published: April 2016

The α2δ proteins are auxiliary subunits of voltage-gated calcium channels and influence their trafficking and biophysical properties. The α2δ ligand gabapentin interacts with α2δ-1 and inhibits calcium channel trafficking. However, α2-1 has also been proposed to play a synaptogenic role, independent of calcium channel function. In this regard, α2δ-1 was identified as a ligand of thrombospondins, with the interaction involving the thrombospondin synaptogenic domain and the α2δ-1 von-Willebrand-factor domain. Co-immunoprecipitation between α2δ-1 and the synaptogenic domain of thrombospondin-2 was prevented by gabapentin. We therefore examined whether interaction of thrombospondin with α2δ-1 might reciprocally influence 3H-gabapentin binding. We concentrated on thrombospondin-4, because, like α2δ-1, it is upregulated in neuropathic pain models. We found that in membranes from cells co-transfected with α2δ-1 and thrombospondin-4, there was a Mg2+ -dependent reduction in affinity of 3H-gabapentin binding to α2δ-1. This effect was lost for α2δ-1 with mutations in the von-Willebrand-factor-A domain. However, the effect on 3H-gabapentin binding was not reproduced by the synaptogenic EGF-domain of thrombospondin-4. Partial co-immunoprecipitation could be demonstrated between thrombospondin-4 and α2δ-1 when co-transfected, but there was no co-immunoprecipitation with thrombospondin-4-EGF domain. Furthermore, we could not detect any association between these two proteins on the cell-surface, indicating the demonstrated interaction occurs intracellularly.
The HER2 inhibitor TAK165 Sensitizes Human Acute Myeloid Leukemia Cells to Retinoic Acid-Induced Myeloid Differentiation by activating MEK/ERK mediated RARα/STAT1 axis
Authors: Shao Xuejing , Liu Yujia , Li Yangling , Xian Miao , Zhou Qian , Yang Bo , Ying Meidan , He Qiaojun
Published: April 2016

The success of all-trans retinoic acid (ATRA) in differentiation therapy for patients with acute promyelocytic leukemia (APL) highly encourages researches to apply this therapy to other types of acute myeloid leukemia (AML). However, AML, with the exception of APL, fails to respond to differentiation therapy. Therefore, research strategies to further sensitize cells to retinoids and to extend the range of AMLs that respond to retinoids beyond APLs are urgently needed. In this study, we showed that TAK165, a HER2 inhibitor, exhibited a strong synergy with ATRA to promote AML cell differentiation. We observed that TAK165 sensitized the AML cells to ATRA-induced cell growth inhibition, G0/G1 phase arrest, CD11b expression, mature morphologic changes, NBT reduction and myeloid regulator expression. Unexpectedly, HER2 pathway might not be essential for TAK165-enhanced differentiation when combined with ATRA, while the enhanced differentiation was dependent on the activation of the RARα/STAT1 axis. Furthermore, the MEK/ERK cascade regulated the activation of STAT1. Taken together, our study is the first to evaluate the synergy of TAK165 and ATRA in AML cell differentiation and to assess new opportunities for the combination of TAK165 and ATRA as a promising approach for future differentiation therapy.
Photoinduced reversible formation of a superhydrophilic surface by crystal growth of diarylethene
Authors: Takase Kazuki , Hyodo Kengo , Morimoto Masakazu , Kojima Yuko , Mayama Hiroyuki , Yokojima Satoshi , Nakamura Shinichiro , Uchida Kingo
Published: April 2016

The surface covered with lumpy crystals shows superhydrophilicity that can be reversibly controlled by alternating irradiation with UV and visible light.
Selone-stabilized aryltellurenyl cations
Authors: Yadav Sangeeta , Raju Saravanan , Singh Harkesh B. , Butcher Ray J.
Published: April 2016

Selone (L) causes cleavage of the Te–Te bond of RTe(Br)2TeR (R = 2,6-Me2Ph) to give the first selone adduct of the 2,6-dimethylphenyltellurenyl cation with the 2,6-dimethylphenyltellurium dibromide anion, [(2,6-Me2C6H3)Te(L)]+[(2,6-Me2C6H3)TeBr2]−.
Improved δ-valerolactam templates for the assembly of Aβ-miniamyloids by boronic ester formation
Authors: Wuttke André , Fischer Sebastian Nils , Nebel Annika , Marsch Michael , Geyer Armin
Published: April 2016

Numerically defined oligomers of amyloidogenic peptides were obtained by boronic ester formation with synthetic polyol templates.
Antimicrobial and fluorescence finishing of woolen yarn with Terminalia arjuna natural dye as an ecofriendly substitute to synthetic antibacterial agents
Authors: Rather Luqman Jameel , Shahid-ul-Islam Shahid-ul-Islam , Azam Mudsser , Shabbir Mohd , Bukhari Mohd Nadeem , Shahid Mohammad , Khan Mohd Ali , Rizwanul Haque Qazi Mohd. , Mohammad Faqeer
Published: April 2016

Current study reflects the use of T. arjuna natural dye as an ecofriendly finishing agent for producing highly functional antimicrobial and fluorescent woolen yarn with the evaluation of kinetic and thermodynamic adsorption characteristics.
Fullerenol nanoparticles as a new delivery system for doxorubicin
Authors: Jović Danica S. , Seke Mariana N. , Djordjevic Aleksandar N. , Mrđanović Jasminka Ž. , Aleksić Lidija D. , Bogdanović Gordana M. , Pavić Aleksandar B. , Plavec Janez
Published: April 2016

Fullerenol as a promising intracellular targeting carrier for the efficient delivery of antitumor drugs into tumor cells.
Penicillanthone and penicillidic acids A–C from the soil-derived fungus Penicillium aculeatum PSU-RSPG105
Authors: Daengrot Charuwan , Rukachaisirikul Vatcharin , Tadpetch Kwanruthai , Phongpaichit Souwalak , Bowornwiriyapan Kawitsara , Sakayaroj Jariya , Shen Xu
Published: April 2016

A new xanthone (penicillanthone, 1) and three new diphenyl ether derivatives (penicillidic acids A–C, 2–4) together with 14 known compounds (5–18) were isolated from the soil-derived fungus Penicillium aculeatum PSU-RSPG105.
Theoretical insights on morphology and charge transport properties of two-dimensional N,N′-ditridecylperylene-3,4,9,10-tetra carboxylic diimide aggregates
Authors: Lorenzoni Andrea , Gallino Federico , Muccini Michele , Mercuri Francesco
Published: April 2016

An integrated computational approach, based on molecular dynamics and density functional theory, reveals an interplay between morphology, processing and charge transport properties in layered aggregates of PTCDI-C13.
Ag:BiVO4 dendritic hybrid-architecture for high energy density symmetric supercapacitors
Authors: Patil Santosh S. , Dubal Deepak P. , Tamboli Mohaseen S. , Ambekar Jalindar D. , Kolekar Sanjay S. , Gomez-Romero Pedro , Kale Bharat B. , Patil Deepak R.
Published: April 2016

Hydrothermally synthesized Ag:BiVO4 with a dendritic structure as an excellent electrode material for symmetric supercapacitors.
Multiple phase and dielectric transitions on a novel multi-sensitive [TPrA][M(dca)3] (M: Fe2+, Co2+ and Ni2+) hybrid inorganic–organic perovskite family
Authors: Bermúdez-García J. M. , Sánchez-Andújar M. , Yáñez-Vilar S. , Castro-García S. , Artiaga R. , López-Beceiro J. , Botana L. , Alegría A. , Señarís-Rodríguez M. A.
Published: April 2016

The hybrids [TPrA][M(dca)3] (M: Fe2+, Co2+ and Ni2+) are unique multi-sensitive materials that display multiple phase and dielectric transitions.
Mechanism of protein oxidative damage that is coupled to long-range electron transfer to high-valent haems
Authors: Ma Zhongxin , Williamson Heather R. , Davidson Victor L.
Published: April 2016

In the absence of its substrate, the auto-reduction of the high-valent bis-Fe(IV) state of the dihaem enzyme MauG is coupled to oxidative damage of a methionine residue. Transient kinetic and solvent isotope effect studies reveal that this process occurs via two sequential long-range electron transfer (ET) reactions from methionine to the haems. The first ET is coupled to proton transfer (PT) to the haems from solvent via an ordered water network. The second ET is coupled to PT at the methionine site and occurs during the oxidation of the methionine to a sulfoxide. This process proceeds via Compound I- and Compound II-like haem intermediates. It is proposed that the methionine radical is stabilized by a two-centre three-electron (2c3e) bond. This provides insight into how oxidative damage to proteins may occur without direct contact with a reactive oxygen species, and how that damage can be propagated through the protein.
Safety Issues of Plasma-Derived Products for Treatment of Inherited Bleeding Disorders
Authors: Farrugia Albert
Published: April 2016

The infection by blood-borne pathogens of a large proportion of the treated hemophilia population over the 1970s to 1990s represents a major tragedy that is embedded in the history of this condition. To avoid this historical repetition, the community of patients, treaters, and policy makers that contribute to hemophilia care need to learn from the events that gave rise to it. This requires an appreciation of the measures, which, through scientific developments, have enhanced greatly the safety of plasma-derived coagulation factor concentrates (pd CFCs). The objective conditions underlying and influencing the safety of all biological materials also require recognition. Although the stringent measures which ensure the safety of pd CFCs are very effective, pathogen transmission by other blood-derived therapeutics has continued due to a lack of effective technology and the continued emergence of new agents which transmit disease. This emphasizes the reality that the basic environmental factors influencing blood pathogen safety have not changed, albeit our capacity to counter them has improved greatly. These factors lead to threats to blood safety that are unpredictable and imposable on a global scale. The likelihood of a continued role for pd CFCs in hemophilia care, particularly in emerging countries challenged to maintain blood safety measures, ensures that these issues are more current than historical.
Idiopathic Spinal Cord Herniation—Case Report
Authors: Sacco Rogerio , Gepp Ricardo , Quiroga Marco , Souza Henrique , Aguiar Vitor , Santos Romel
Published: April 2016

Idiopathic spinal cord herniation is a rare cause of progressive myelopathy, especially in the absence of a history of spinal or surgical trauma. The radiological diagnosis is made through a myelography or an MRI exam. The spinal cord is pushed anteriorly, buffering the dural defect and leading in most cases to Brown-Séquard syndrome. The present study describes the case of a male patient with a clinical picture of progressive thoracic myelopathy. In the clinical and radiological investigation, an idiopathic spinal cord herniation on the chest level was identified. During the surgery, the spinal cord was reduced to the natural site, taking its usual elliptical shape, and the dural defect was repaired with a dural substitute. The numbness of the patient improved, and the shocks in the lower limbs disappeared. A postoperative MRI confirmed the surgical reduction of the herniation and the restoration of the anterior cerebrospinal fluid (CSF) column to the spinal cord. The authors describe the clinical, radiological, intraoperative, and postoperative evolution.
Theoretical Investigation of Oxidative Cleavage of Cholesterol by Dual O2 Activation and Sulfide Reduction
Authors: Lee Richmond , Coote Michelle L.
Published: April 2016

Theoretical calculations are used to explore a plausible mechanism for oxidative cleavage of cholesterol mediated by two ground-state O2 molecules. It is shown that cholesterol can form a stable pre-complex with the two triplet dioxygen molecules, which could be further stabilized in an enzyme environment by methionine (modelled here as Me2S). Triplet O2 can then react to form a metastable biradical species that is then further stabilized by reaction with a second triplet O2, resulting in an intermediate that undergoes an intersystem crossing to form a diperoxy intermediate. This in turn is reduced to the final cholesterol secosterol aldehyde product by the same methionine, which may provide an explanation for the presence of methionine sulfoxide fractions in Aβ amyloid peptide. The mechanistic theozyme model predicts an energetically viable pathway that is unusual in that triplet oxygen is normally considered to be unreactive in this context unless first excited to the singlet state. Although we show that the same reaction can also proceed via photosensitization of the complex if an appropriate cofactor is available, the energetics for the triplet oxygen reaction are competitive. Reactivity studies revealed that the reaction can also occur with other unsaturated substrates, with the lowest barriers occurring with more nucleophilic alkenes, or by rendering the 3O2 more electrophilic via non-covalent interactions with Me2S.
Global warming as affected by incorporation of variably aged biomass of hairy vetch for rice cultivation
Authors: Haque Md Mozammel , Biswas Jatish Chandra , Waghmode Tatoba R. , Kim Pil Joo
Published: April 2016

Hairy vetch (Vicia villosa Roth) is cultivated during the cold fallow season in paddy soils of temperate countries such as South Korea and Japan, mostly as animal feed and green manure. Information on the effect of ageing of hairy vetch incorporation in relation to greenhouse gas (GHG) emissions and global warming potential (GWP) is not available. Therefore, hairy vetch biomass of ages 183, 190, 197, and 204 days was incorporated in paddy soil to estimate GWP during rice cultivation. The emission rates of methane (CH4), carbon dioxide (CO2), and nitrous oxide (N2O) gases were monitored once a week by using the closed-chamber method. The net ecosystem carbon budget was used to estimate pure CO2 emission fluxes. Biomass production of hairy vetch was 6.5 Mg ha–1 at 204 days, which was similar to other treatments. The GWP was lower with the 204-day-old vetch biomass incorporation than with other treatments. High content of cellulose and lignin in 204-day-old hairy vetch might have affected decomposition rate and subsequently reduced GHGs emissions during rice cultivation. Our results suggest that hairy vetch can be allowed to grow for 204 days before incorporation at 3 Mg ha–1 without sacrificing rice yield, while maximising biomass production and minimising GWP during rice cultivation.
Cross-generational prosodic convergence in South Texas Spanish
Authors: Carter Phillip M. , Wolford Tonya
Published: April 2016

This study investigates variation in the prosodic system of Spanish in the speech of three generations of Mexican Americans living in a Mexican American-majority community in South Texas, United States, characterized by high levels of bilingualism and long-term, sustained contact between languages. Low and Grabe’s (1995) Pairwise Variability Index was used to quantify prosodic rhythm in the Spanish and the English of community members across generations in order to: (1) assess differences between contact and non-contact varieties of Spanish, (2) investigate the cross-generational stability of prosodic rhythm in the community, and (3) ascertain the type of influence from English, if any, on Spanish prosody. Findings show that while the oldest generations maintain separate systems of rhythm in Spanish and English, the youngest generation demonstrates prosodic convergence.
A beginner’s guide to getting involved in science advocacy
Authors: Ruppersburg Chelsey Chandler , York Amanda L.
Published: April 2016

Every scientist in the United States likely has a story of how the federal funding crisis for biomedical research has affected him or her personally. The sharing of these powerful anecdotes will enable policy makers to fully grasp the extent to which the decline in federal funding has negatively affected the scientific community. However, many scientists do not know where to begin or are uncertain that their advocacy efforts will have an impact. In an effort to encourage more scientists to become involved in science advocacy, we describe how to form and maintain a student science advocacy group.
Ezetimibe-sensitive cholesterol uptake by NPC1L1 protein does not require endocytosis
Authors: Johnson Tory A. , Pfeffer Suzanne R.
Published: April 2016

Human NPC1L1 protein mediates cholesterol absorption in the intestine and liver and is the target of the drug ezetimibe, which is used to treat hypercholesterolemia. Previous studies concluded that NPC1L1-GFP protein trafficking is regulated by cholesterol binding and that ezetimibe blocks NPC1L1-GFP function by inhibiting its endocytosis. We used cell surface biotinylation to monitor NPC1L1-GFP endocytosis and show that ezetimibe does not alter the rate of NPC1L1-GFP endocytosis in cultured rat hepatocytes grown under normal growth conditions. As expected, NPC1L1-GFP endocytosis depends in part on C-terminal, cytoplasmically oriented sequences, but endocytosis does not require cholesterol binding to NPC1L1’s N-terminal domain. In addition, two small- molecule inhibitors of general (and NPC1L1-GFP) endocytosis failed to inhibit the ezetimibe-sensitive uptake of [3H]cholesterol from taurocholate micelles. These experiments demonstrate that cholesterol uptake by NPC1L1 does not require endocytosis; moreover, ezetimibe interferes with NPC1L1’s cholesterol adsorption activity without blocking NPC1L1 internalization in RH7777 cells.
Developing new pathways into the biomedical informatics field: the AMIA High School Scholars Program
Authors: Unertl Kim M , Finnell John T , Sarkar Indra Neil
Published: April 2016

Increasing access to biomedical informatics experiences is a significant need as the field continues to face workforce challenges. Looking beyond traditional medical school and graduate school pathways into the field is crucial for expanding the number of individuals and increasing diversity in the field. This case report provides an overview of the development and initial implementation of the American Medical Informatics Association (AMIA) High School Scholars Program. Initiated in 2014, the program’s primary goal was to provide dissemination opportunities for high school students engaged in biomedical informatics research. We discuss success factors including strong cross-institutional, cross-organizational collaboration and the high quality of high school student submissions to the program. The challenges encountered, especially around working with minors and communicating program expectations clearly, are also discussed. Finally, we present the path forward for the continued evolution of the AMIA High School Scholars Program.
First detection of 3He+ in the planetary nebula IC 418
Authors: Guzman-Ramirez L. , Rizzo J. R. , Zijlstra A. A. , García-Miró C. , Morisset C. , Gray M. D.
Published: April 2016

The 3He isotope is important to many fields of astrophysics, including stellar evolution, chemical evolution, and cosmology. The isotope is produced in low-mass stars which evolve through the planetary nebula (PN) phase. 3He abundances in PNe can help test models of the chemical evolution of the Galaxy. We present the detection of the 3He+ emission line using the single dish Deep Space Station 63, towards the PN IC 418. We derived a 3He/H abundance in the range 1.74 ± 0.8 × 10−3 to 5.8 ± 1.7 × 10−3, depending on whether part of the line arises in an outer ionized halo. The lower value for 3He/H ratio approaches values predicted by stellar models which include thermohaline mixing, but requires that large amounts of 3He are produced inside low-mass stars which enrich the interstellar medium (ISM). However, this overpredicts the 3He abundance in H ii regions, the ISM, and protosolar grains, which is known to be of the order of 10−5. This discrepancy questions our understanding of the evolution of the 3He, from circumstellar environments to the ISM.
Differential Effects of Azithromycin, Doxycycline, and Cotrimoxazole in Ingested Blood on the Vectorial Capacity of Malaria Mosquitoes
Authors: Gendrin Mathilde , Yerbanga Rakiswendé Serge , Ouedraogo Jean Bosco , Lefèvre Thierry , Cohuet Anna , Christophides George K.
Published: April 2016

Background.  The gut microbiota of malaria vector mosquitoes grows after a blood meal and limits Plasmodium infection. We previously showed that penicillin and streptomycin in the ingested blood affect bacterial growth and positively impact mosquito survival and permissiveness to Plasmodium. In this study, we examine the effects of doxycycline, azithromycin, and co-trimoxazole. All 3 antibiotics are used in mass drug administration programs and have antimicrobial activities against bacteria and various stages of malaria parasites.

Methods.  The effects of blood meal supplementation with antibiotics on the mosquito microbiota, lifespan, and permissiveness to Plasmodium falciparum were assessed.

Results.  Ingestion of any of the 3 antibiotics significantly affected the mosquito microbiota. Azithromycin decreased P falciparum infection load and mosquito lifespan, whereas at high concentrations, doxycycline increased P falciparum infection load. Co-trimoxazole negatively impacted infection intensity but had no reproducible effect on mosquito lifespan.

Conclusions.  Our data suggest that the overall effect of antibiotic treatment on parameters critical for mosquito vectorial capacity is drug specific. The negative effect of azithromycin on malaria transmission is consistent with current efforts for disease elimination, whereas additional, larger scale investigations are required before conclusions can be drawn about doxycycline.
A switching cost for motor planning
Authors: Orban de Xivry Jean-Jacques , Lefèvre Philippe
Published: April 2016

Movement planning consists of choosing the endpoint of the movement and selecting the motor program that will bring the effector on the endpoint. It is widely accepted that movement endpoint is updated on a trial-by-trial basis with respect to the observed errors and that the motor program for a given movement follows the rules of optimal feedback control. Here, we show clear limitations of these predictions because of the existence of a switching cost for motor planning. First, this cost prevented participants from tuning their motor program appropriately for each individual trial. This was true even when the participants selected the width of the target that they reached toward or when they had learned the appropriate motor program previously. These data are compatible with the existence of a switching cost such as those found in cognitive studies. Interestingly, this cost of switching shares many features of costs reported in cognitive task switching experiments and, when tested in the same participants, was correlated with it. Second, we found that randomly changing the width of a target over the course of a reaching experiment prevents the motor system from updating the endpoint of movements on the basis of the performance on the previous trial if the width of the target has changed. These results provide new insights into the process of motor planning and how it relates to optimal control theory and to a selection by consequences process rather than to an error-based process for action selection.
Subtle stratification confounds estimates of heritability from rare variants
Authors: Bhatia Gaurav , Gusev Alexander , Loh Po-Ru , Finucane Hilary , Vilhjálmsson Bjarni J. , Ripke Stephan ,   Schizophrenia Working Group of the Psychiatric Genomics Consortium, Purcell Shaun , Stahl Eli , Daly Mark , de Candia Teresa R , Lee Sang Hong , Neale Benjamin M , Keller Matthew C. , Zaitlen Noah A. , Pasaniuc Bogdan , Patterson Nick , Yang Jian , Price Alkes L.
Published: April 2016

Genome-wide significant associations generally explain only a small proportion of the narrow-sense heritability of complex disease (h2). While considerably more heritability is explained by all genotyped SNPs (hg2), for most traits, much heritability remains missing (hg2<h2). Rare variants, poorly tagged by genotyped SNPs, are a major potential source of the gap betweenhg2andh2. Recent efforts to assess the contribution of both sequenced and imputed rare variants to phenotypes suggest that substantial heritability may lie in these variants. Here we analyze sequenced SNPs, imputed SNPs and haploSNPs— haplotype variants constructed from within a sample, without using a reference panel— and show that studies of heritability from these variants may be strongly confounded by subtle population stratification. For example, when meta-analyzing heritability estimates from 22 randomly ascertained case-control traits from the GERA cohort, we observe a statistically significant increase in heritability explained by imputed SNPs even after correcting for principal components (PCs) from genotyped (or imputed) SNPs. However, this increase is eliminated when correcting for stratification using PCs from a larger number of haploSNPs. We note that subtle stratification may also impact estimates of heritability from array SNPs, although we find that this is generally a less severe problem. Overall, our results suggest that estimating the heritability explained by rare variants for case-control traits requires exquisite control for population stratification, but current methods may not provide this level of control.
Assembly of Long Error-Prone Reads Using de Bruijn Graphs
Authors: Lin Yu , Yuan Jeffrey , Kolmogorov Mikhail , Shen Max W. , Pevzner Pavel A.
Published: April 2016

The recent breakthroughs in assembling long error-prone reads (such as reads generated by Single Molecule Real Time technology) were based on the overlap-layout-consensus approach and did not utilize the strengths of the alternative de Bruijn graph approach to genome assembly. Moreover, these studies often assume that applications of the de Bruijn graph approach are limited to short and accurate reads and that the overlap-layout-consensus approach is the only practical paradigm for assembling long error-prone reads. Below we show how to generalize de Bruijn graphs to assemble long error-prone reads and describe the ABruijn assembler, which results in more accurate genome reconstructions than the existing state-of-the-art algorithms.
Effects of variable mutation rates and epistasis on the distribution of allele frequencies in humans
Authors: Harpak Arbel , Bhaskar Anand , Pritchard Jonathan K.
Published: April 2016

The site frequency spectrum (SFS) has long been used to study demographic history and natural selection. Here, we extend this summary by examining the SFS conditional on the alleles found at the same site in other species. We refer to this extension as the “phylogenetically-conditioned SFS” or cSFS. Using recent large-sample data from the Exome Aggregation Consortium (ExAC), combined with primate genome sequences, we find that human variants that occurred independently in closely related primate lineages are at higher frequencies in humans than variants with parallel substitutions in more distant primates. We show that this effect is largely due to sites with elevated mutation rates causing significant departures from the widely-used infinite sites mutation model. Our analysis also suggests substantial variation in mutation rates even among mutations involving the same nucleotide changes. We additionally find evidence for epistatic effects on the cSFS: namely, that parallel primate substitutions at nonsynonymous sites are more informative about constraint in humans when the parallel substitution occurs in a closely related species. In summary, we show that variable mutation rates and local sequence context are important determinants of the SFS in humans.
A Transferable Model For Chromosome Architecture
Authors: Pierro Michele Di , Zhang Bin , Aiden Erez Lieberman , Wolynes Peter G. , Onuchic José N.
Published: April 2016

In vivo, the human genome folds into a characteristic ensemble of three-dimensional structures. The mechanism driving the folding process remains unknown. We report a theoretical model for chromatin (MinimalChromatinModel) that explains the folding of interphase chromosomes and generates chromosome conformations consistent with experimental data. The energy landscape of the model was derived by using the maximum entropy principle and relies on two experimentally derived inputs: a classification of loci into chromatin types and a catalog of the positions of chromatin loops. First, we trained our energy function using the Hi-C contact map of chromosome 10 from human GM12878 lymphoblastoid cells. Then we used the model to perform molecular dynamics simulations producing an ensemble of 3D structures for all GM12878 autosomes. Finally, we used these 3D structures to generate contact maps. We found that simulated contact maps closely agree with experimental results for all GM12878 autosomes.

The ensemble of structures resulting from these simulations exhibited unknotted chromosomes, phase separation of chromatin types, and a tendency for open chromatin to lie at the periphery of chromosome territories.

One Sentence Summary:

We report a model for chromatin that explains and accurately reproduces the three-dimensional structure of chromosomes in interphase.
Zika virus, a new threat for Europe?
Authors: Jupille Henri , Seixas Goncalo , Mousson Laurence , Sousa Carla A. , Failloux Anna-Bella
Published: April 2016

Background:

Since its emergence in 2007 in Micronesia and Polynesia, the arthropod-borne flavivirus Zika virus (ZIKV) has spread in the Americas and the Caribbean, following first detection in Brazil in May 2015. The risk of ZIKV emergence in Europe increases as imported cases are repeatedly reported. Together with chikungunya virus (CHIKV) and dengue virus (DENV), ZIKV is transmitted byAedesmosquitoes. Any countries where these mosquitoes are present could be potential sites for future ZIKV outbreak.

Methodology/Principal Findings:

Mosquito females were challenged with an Asian genotype of ZIKV. Fully engorged mosquitoes were then maintained in insectary conditions (28°±1°C, 16h:8h light:dark cycle and 80% humidity). 16-24 mosquitoes from each population were examined at 3, 6, 9 and 14 days postinfection to estimate the infection, disseminated infection and transmission rates. Based on these experimental infections, we demonstrated thatAe. albopictusfrom France were not very susceptible to ZIKV.

Conclusions/Significance:

In combination with the restricted distribution and lower population densities of EuropeanAe. albopictus, our results corroborate the low risk for ZIKV to expand into most parts of Europe with the possible exception of the warmest regions bordering the Mediterranean coastline.

Author summary

In May 2015, local transmission of Zika virus (ZIKV) was reported in Brazil and since then, more than 1.5 million human cases have been reported in Latin America and the Caribbean. This arbovirus, primarily found in Africa and Asia, is mainly transmitted byAedesmosquitoes,Aedes aegyptiandAedes albopictus. Viremic travelers returning from America to European countries whereAe. albopictusis established can become the source for local transmission of ZIKV. In order to estimate the risk of seeding ZIKV into local mosquito populations, the ability of EuropeanAe. aegyptiandAe. albopictusto transmit ZIKV was measured using experimental infections. We demonstrated thatAe. albopictusandAe. aegyptifrom Europe were not very susceptible to ZIKV. The threat for a Zika outbreak in Europe should be limited.
Posterior inferotemporal cortex cells use multiple visual pathways to complement fine and coarse discriminations
Authors: Ponce C. R. , Lomber S. G. , Livingstone M. S.
Published: April 2016

In the macaque monkey brain, posterior inferior temporal cortex (PIT) cells are responsible for visual object recognition. They receive concurrent inputs from visual areas V4, V3 and V2. We asked how these different anatomical pathways contribute to PIT response properties by deactivating them while monitoring PIT activity. Using cortical cooling of areas V2/V3 or V4 and a hierarchical model of visual recognition, we conclude that these distinct pathways do not transmit different classes of visual features, but serve instead to maintain a balance of local-and global-feature selectivity in IT.
Long Range Force Transmission in Fibrous Matrices Enabled by Tension-Driven Alignment of Fibers
Authors: Wang Hailong , Abhilash A.S. , Chen Christopher S. , Wells Rebecca G. , Shenoy Vivek B.
Published: April 2016

Cells can sense and respond to mechanical signals over relatively long distances across fibrous extracellular matrices. Recently proposed models suggest that long-range force transmission can be attributed to the nonlinear elasticity or fibrous nature of collagen matrices, yet the mechanism whereby fibers align remains unknown. Moreover, cell shape and anisotropy of cellular contraction are not considered in existing models, although recent experiments have shown that they play crucial roles. Here, we explore all of the key factors that influence long-range force transmission in cell-populated collagen matrices: alignment of collagen fibers, responses to applied force, strain stiffening properties of the aligned fibers, aspect ratios of the cells, and the polarization of cellular contraction. A constitutive law accounting for mechanically-driven collagen fiber reorientation is proposed. We systematically investigate the range of collagen fiber alignment using both finite element simulations and analytical calculations. Our results show that tension-driven collagen fiber alignment plays a crucial role in force transmission. Small critical stretch for fiber alignment, large fiber stiffness and fiber strain-hardening behavior enable long-range interaction. Furthermore, the range of collagen fiber alignment for elliptical cells with polarized contraction is much larger than that for spherical cells with diagonal contraction. A phase diagram showing the range of force transmission as a function of cell shape and polarization and matrix properties is presented. Our results are in good agreement with recent experiments, and highlight the factors that influence long-range force transmission, in particular tension-driven alignment of fibers. Our work has important relevance to biological processes including development, cancer metastasis and wound healing, suggesting conditions whereby cells communicate over long distances.
The gendered discourse of ‘equal opportunities for men and women’ in Iranian EFL textbooks
Authors: Salami Ali , Ghajarieh Amir
Published: April 2016

Purpose

The purpose of this paper is to examine the representations of male and female social actors within the subversive gendered discourse of “equal opportunities for men and women” in Iranian English as a foreign language (EFL) textbooks.

Design/methodology/approach

From the methodological perspective, this study fused van Leeuwen’s (2003) “Social Actor Network Model” and Sunderland’s (2004) “Gendered Discourses Model”.

Findings

Data obtained from this study showed the subversive gendered discourse of “equal opportunities” was supported through such representations within a narrow perspective in line with dominant gender ideologies in Iran. The findings suggest the resistance against such subversive gendered discourse in Iranian EFL textbooks underpins gender norms and religious ideologies existing in Iran.

Originality/value

Such representations of male and female social actors in school textbooks show inclusive education and the discourse of “equal opportunities” have yet to be realised in education system of many countries, including Iran.
A social cognitive investigation of Australian independent school Boards as teams
Authors: Krishnan Aparna , Barnett Kerry , McCormick John , Newcombe Geoffrey
Published: April 2016

Purpose

The purpose of this exploratory study was to investigate independent school Boards as teams using a social cognitive perspective. Specifically, the study investigated Board processes and the nature of relationships between Board member self-efficacy, Board collective efficacy and performance of independent school Boards in New South Wales, Australia.

Design/methodology/approach

A multiple case study design that used qualitative research methods was employed. An expert steering group provided advice on the categorization of governance structures. A stratified purposeful sample of eight independent school Boards within the Sydney metropolitan area, New South Wales Australia participated. Data were collected from individual, semi-structured, face-to-face interviews with the Head of school, Board Chair and two Board members from each school. The interviews were digitally recorded and transcribed verbatim. Data were analyzed using qualitative data analysis procedures suggested in the literature.

Findings

The findings provide evidence that for independent school Board members in this study, self-efficacy and collective efficacy beliefs were related to perceptions of Board performance. Board member self-efficacy and Board collective efficacy appeared to be linked. Self-efficacy beliefs were primarily based on mastery experiences. Collective efficacy (at the individual level) primarily was based on members’ perceptions of Board past performance.

Originality/value

This paper provides insight into individual Board member beliefs likely to shape processes associated with independent school Board performance in New South Wales, Australia. The study is one of only a few that have adopted an empirical and descriptive approach, rather than only providing normative direction and imperatives.
The effects of integrated transformational leadership on achievement
Authors: Boberg John Eric , Bourgeois Steven J.
Published: April 2016

Purpose

Greater understanding about how variables mediate the relationship between leadership and achievement is essential to the success of reform efforts that hold leaders accountable for student learning. This multi-source, quantitative study tests a model of integrated transformational leadership including three important school mediators.

Design/methodology/approach

5,392 students provided data on student engagement, and 569 teachers provided survey data on principal leadership and the collective teacher efficacy and extra effort of their colleagues. Data were analyzed at the school-level (N = 51) using mediation analysis with the PROCESS macro to calculate the direct and indirect effects of all of the variables in the serial multiple mediator model.

Findings

The model explained a significant amount of variance in both reading (38%) and mathematics (35%). Collective teacher efficacy and student engagement mediated all of the leadership effects, demonstrating the importance of teacher and student relations in school improvement. The combined effect sizes are significantly greater than the effects of earlier TL models.

Originality/value

This study contributes to “leadership for learning” research by demonstrating that refining TLBs to include instructional management can enhance a leader's impact on achievement. As one of the few studies to examine student engagement as a mediator along with teacher mediators, the current study highlights the importance of teacher-student relations in school improvement. While collective efficacy mediated all of the effects of leadership on achievement, student emotional engagement also contributed to mathematics achievement. The study’s findings advance research into mutual influence processes, indicating that reciprocity may extend throughout the leader-teacher-student loop.
Fabrication and characterization of Cu-Sn-Ni-Cu interconnection microstructure for electromigration studies in 3D integration
Authors: Xiao Ming , Munief Walid Madhat , Wu Fengshun , Lilischkis Rainer , Oberbillig Tobias , Saumer Monika , Xia Weisheng
Published: April 2016

Purpose

The purpose of this paper is to fabricate a new Cu-Sn-Ni-Cu interconnection microstructure for electromigration studies in 3D integration.

Design/methodology/approach

The Cu-Sn-Ni-Cu interconnection microstructure is fabricated by a three-mask photolithography process with different electroplating processes. This microstructure consists of pads and conductive lines as the bottom layer, Cu-Sn-Ni-Cu pillars with the diameter of 10-40 μm as the middle layer and Cu conductive lines as the top layer. A lift-off process is adopted for the bottom layer. The Cu-Sn-Ni-Cu pillars are fabricated by photolithography with sequential electroplating processes. To fabricate the top layer, a sputtered Cu layer is introduced to prevent the middle-layer photoresist from being developed. With the final Cu electroplating processes, the Cu-Sn-Ni-Cu interconnection microstructure is successfully achieved.

Findings

The surface morphology of Cu-Sn pillars consists of densely packed clusters which are formed by an ordered arrangement of tetragonal Sn grains. The diffusion of Cu atoms into the Sn phases is observed at the Cu/Sn interface. Furthermore, the obtained Cu-Sn-Ni-Cu pillars have a flat surface with an average roughness of 13.9 nm. In addition, the introduction of Ni layer between the Sn and the top Cu layers in the Cu-Sn-Ni-Cu pillars can mitigate the diffusion of Cu atoms into Sn phases. The process is verified by checking the electrical performance using four-point probe measurements.

Originality/value

The method described in this paper which combined a three-mask photolithography process with sequential Cu, Sn, Ni and Cu electroplating processes provides a new way to fabricate the interconnection microstructure for future electromigration studies.
A conceptual model of critical success factors for Indian social enterprises
Authors: Satar Mir Shahid , John Shibu
Published: April 2016

Purpose

There have been global upsurge in the social enterprise research & practice considering social enterprise as a rapidly growing thought worldwide. The renewed significance of social enterprises (SE’s) has arisen primarily on account of their assumed potential in solving a range of social problems. The evidences supporting the budding role of SE’s in fostering sustained socio-economic development of regions & communities across globe are evolving continuously.
Even though, social entrepreneurship & SE’s have remained central thought provoking domain in the realm of scholarly investigation for a past couple of decades, the emerging literature on SE’s & their role in economic development is riddled with theoretical inconsistencies & definitional controversies. Thus, very little is known about functioning & management of SE’s. For the sake of advancing the field, the purpose of this paper is to identify and analyze the critical success factors (CSF’s) of SE’s operating in different social settings in India. Further, a conceptual model is developed incorporating different factors of social enterprise operation in an integrated framework.

Design/methodology/approach

Based on the review of the extant literature, three categories of success factors comprising a total of 38 success factors for SE’s were initially identified. Under each category, the success factors were then classified and reduced to appropriate numbers based upon their importance to SE’s and their repeated manifestations in the literature, making a total of 13 CSF’s under all 3 categories. Based on these 3 categories of CSF’s, a conceptual model was developed.

Findings

The study determines thirteen critical factors as contributing to the success of social enterprises: (1) Business planning skills (2) entrepreneurship orientation; (3) leadership; (4) networking; (5) Innovative financing (6) triple bottom line planning; (7) social enterprise marketing; (8) community engagement; (9) human capital; (10) organizational culture; (11) Social Impact Evaluation (12) Frugal innovation & (13) Government support.

Originality/value

The paper presents a theoretical research model incorporating factors and determinants of social enterprise success to direct a future research agenda. The paper can further be used by researchers to empirically test critical success factors of social enterprises. Moreover, practitioners can also gain benefits from the conceptual framework & promote social entrepreneurship.