bluuebunny/crossref_metadata_2025 huggingface dataset:
Autoantibody profiling on a plasmonic nano-gold chip for the early detection of hypertensive heart disease
Authors: Li Xiaoyang , Kuznetsova Tatiana , Cauwenberghs Nicholas , Wheeler Matthew , Maecker Holden , Wu Joseph C. , Haddad Francois , Dai Hongjie
Published: July 2017

Significance

Hypertension affects one in four adults in the United States and is a major risk factor for heart failure. A plasmonic nano-gold platform with excellent reproducibility and sensitivity is developed to address the currently unmet need of profiling circulating cardiovascular autoantibodies in hypertensive patients. We observed that patients with early-stage hypertensive heart diseases displayed a higher level of cardiovascular autoantibodies than hypertensive patients with normal cardiac function. Autoantibodies to troponin I, adrenergic beta-1 receptor, and annexin-A5 could best discriminate hypertensive heart disease. Ultimately, this nanoscience-based platform could be deployed to facilitate screening autoantibodies and identify at-risk patients for early stages of heart failure. Furthermore, this platform could have broad applications in myocarditis, heart transplantation, and other autoimmune diseases.
Evolutionary radiation of lanthipeptides in marine cyanobacteria
Authors: Cubillos-Ruiz Andres , Berta-Thompson Jessie W. , Becker Jamie W. , van der Donk Wilfred A. , Chisholm Sallie W.
Published: July 2017

Significance

Lanthipeptides are a large family of microbial natural products of ribosomal origin. Prochlorosins are a group of unusually diverse lanthipeptides found in strains of the marine cyanobacteria
Prochlorococcus
and
Synechococcus
—the most abundant photosynthetic microorganisms on Earth. By analyzing the prochlorosin biosynthesis genes from cultured strains and wild cyanobacteria, we show that the global collective of these microorganisms has evolved thousands of structurally distinct lanthipeptides via a process of evolutionary radiation favoring the sustained emergence of new structures over refinement of an existing one. The evolutionary history of prochlorosins suggests a fundamentally different structure-to-function relationship compared with other lanthipeptides and opens the question of how structural diversification contributes to their function and mode of action in the marine environment.
The deep, hot biosphere: Twenty-five years of retrospection
Authors: Colman Daniel R. , Poudel Saroj , Stamps Blake W. , Boyd Eric S. , Spear John R.
Published: July 2017

Twenty-five years ago this month, Thomas Gold published a seminal manuscript suggesting the presence of a “deep, hot biosphere” in the Earth’s crust. Since this publication, a considerable amount of attention has been given to the study of deep biospheres, their role in geochemical cycles, and their potential to inform on the origin of life and its potential outside of Earth. Overwhelming evidence now supports the presence of a deep biosphere ubiquitously distributed on Earth in both terrestrial and marine settings. Furthermore, it has become apparent that much of this life is dependent on lithogenically sourced high-energy compounds to sustain productivity. A vast diversity of uncultivated microorganisms has been detected in subsurface environments, and we show that H
2
, CH
4
, and CO feature prominently in many of their predicted metabolisms. Despite 25 years of intense study, key questions remain on life in the deep subsurface, including whether it is endemic and the extent of its involvement in the anaerobic formation and degradation of hydrocarbons. Emergent data from cultivation and next-generation sequencing approaches continue to provide promising new hints to answer these questions. As Gold suggested, and as has become increasingly evident, to better understand the subsurface is critical to further understanding the Earth, life, the evolution of life, and the potential for life elsewhere. To this end, we suggest the need to develop a robust network of interdisciplinary scientists and accessible field sites for long-term monitoring of the Earth’s subsurface in the form of a deep subsurface microbiome initiative.
Enhancing T
1
magnetic resonance imaging contrast with internalized gadolinium(III) in a multilayer nanoparticle
Authors: Marangoni Valeria S. , Neumann Oara , Henderson Luke , Kaffes Caterina C. , Zhang Hui , Zhang Runmin , Bishnoi Sandra , Ayala-Orozco Ciceron , Zucolotto Valtencir , Bankson James A. , Nordlander Peter , Halas Naomi J.
Published: July 2017

Significance

We demonstrate a magnetic resonance image-enhancing nanoparticle with the potential for use in multiple biomedical imaging and therapeutic applications. The nanoparticle contains internal gadolinium ions for T
1
imaging contrast, located between an inner core and outer Au layer, in a multilayered geometry. The proton relaxivity is enhanced through longer-range interactions with the protons outside the nanoparticle, a radical departure from the molecular chelates currently in use for MRI. This geometry provides a very large relaxivity enhancement (r
1
∼ 24 mM
−1
⋅s
−1
) compared with conventional chelating agents (Gd-DOTA: r
1
∼ 3 mM
−1
⋅s
−1
) at high magnetic fields (4.7 T). This MRI-enhancing nanoparticle geometry opens opportunities for the development of multifunctional MRI-active nanoparticles for biomedical applications.
Convergent immunological solutions to Argentine hemorrhagic fever virus neutralization
Authors: Zeltina Antra , Krumm Stefanie A. , Sahin Mehmet , Struwe Weston B. , Harlos Karl , Nunberg Jack H. , Crispin Max , Pinschewer Daniel D. , Doores Katie J. , Bowden Thomas A.
Published: July 2017

Significance

An estimated 5 million people are at risk of infection by Junín virus (JUNV), the causative agent of Argentine hemorrhagic fever. JUNV displays a glycoprotein spike complex on the surface of the viral envelope that is responsible for negotiating host-cell recognition and entry. Herein, we show that monoclonal antibodies that have gone through different germline selection pathways have converged to target the host-cell receptor-binding site on the JUNV glycoprotein spike. Immunofocusing of the antibody response to mimic natural host–receptor interactions reveals a key point of vulnerability on the JUNV surface.
Targeting reactive nitrogen species suppresses hereditary pancreatic cancer
Authors: Li Mo , Chen Qian , Ma Teng , Yu Xiaochun
Published: July 2017

Significance

Germline mutations of BRCA2 associate with tissue-specific cancers, such as familial pancreatic cancer. However, it is unclear why BRCA2 mutation causes tissue-specific cancer. Here, we show that pancreas-specific reactive nitrogen species (RNS) causes oxidative damage and DNA double-strand breaks. Lacking BRCA2, cells could not repair DNA lesions, which led to genomic instability and pancreatic tumorigenesis. On the basis of the mechanistic analysis, we treated Brca2-deficient mice with antioxidant. Interestingly, the antioxidant treatment suppressed RNS-induced lesions and delayed the onset of pancreatic tumorigenesis. Thus, our study reveals a potential approach for the eradication of BRCA2 mutation-associated pancreatic cancer.
Global Sustainable Development priorities 500 y after Luther:
Sola schola et sanitate
Authors: Lutz Wolfgang
Published: July 2017

Significance

In 2015, all countries of the world agreed to an ambitious set of 17 Sustainable Development Goals, including 169 specific targets. Whether these goals will be achieved and lead to the desired sustainability transition will depend on the degree to which they can energize and mobilize policy makers, donors, nongovernmental organizations, private industry, and the public. There is a fear that this rather technocratic set of 169 overlapping and partly contradictory targets lacks the sense of clear priority that is needed. This paper proposes a clear priority focus on human capital (education and health) as a root cause of development that, together with maintaining natural capital, is prerequisite for all other Sustainable Development Goals, offering a vision for an achievable and sustainable future.
Multiple layers of heterogeneity and subset diversity in human MAIT cell responses to distinct microorganisms and to innate cytokines
Authors: Dias Joana , Leeansyah Edwin , Sandberg Johan K.
Published: July 2017

Significance

Mucosa-associated invariant T (MAIT) cells are a large subset of unconventional T cells in humans, recognizing microbial riboflavin metabolites presented by the monomorphic MR1 molecule. The extraordinary level of conservation of MR1 and the limited diversity of riboflavin-derived antigens have suggested that MAIT cells are homogeneous, and their functional specialization has not been thoroughly investigated. Here, we show that MAIT cell responses against two distinct riboflavin biosynthesis-competent microorganisms display microbe-specific response patterns with multiple layers of heterogeneity. Furthermore, a set of natural killer cell-associated receptors define a subset with enhanced capacity to respond to innate cytokine stimulus. Thus, MAIT cells harbor multiple layers of functional heterogeneity and can adapt their antimicrobial responses to the type of microbial stimuli.
Structural complexity and molecular heterogeneity of a butterfly ejaculate reflect a complex history of selection
Authors: Meslin Camille , Cherwin Tamara S. , Plakke Melissa S. , Hill Jason , Small Brandon S. , Goetz Breanna J. , Wheat Christopher W. , Morehouse Nathan I. , Clark Nathan L.
Published: July 2017

Significance

Male ejaculates exhibit remarkable diversity, including variation in their spatial and temporal molecular composition. This complexity suggests that ejaculates provide functions far beyond the delivery of sperm. Here, we investigated the molecular and functional specificity of the butterfly spermatophore, a structurally complex ejaculate. We discovered that its two distinct parts originate from separate regions of the male reproductive tract, are transferred sequentially during mating, and seem to be the result of a complex evolutionary history. We also highlight a large and previously unrecognized female contribution to the spermatophore, which calls into question traditional characterizations of females as passive recipients of these male ejaculates.
Possessive inflection in Proto-Zamucoan
Authors: Ciucci Luca , Bertinetto Pier Marco
Published: July 2017

This paper presents a comparative analysis of possessive inflection in the three known Zamucoan languages: Ayoreo and Chamacoco – still spoken in the Chaco area between Bolivia and Paraguay – plus †Old Zamuco, described by the Jesuit father Ignace Chomé in the first half of the 18th century. The comparison allows us to build a plausible reconstruction of Proto-Zamucoan possessive inflection. Old Zamuco appears to be the most conservative language among the three, while Chamacoco appears to be the most innovative, although it exhibits relics of special importance for reconstructive purposes. Our analysis identifies in Zamucoan a series of features of general interest for the typology of person marking.
AlloSigMA: allosteric signaling and mutation analysis server
Authors: Guarnera Enrico , Tan Zhen Wah , Zheng Zejun , Berezovsky Igor N
Published: July 2017

Motivation

Allostery is an omnipresent mechanism of the function modulation in proteins via either effector binding or mutations in the exosites. Despite the growing number of online servers and databases devoted to prediction/classification of allosteric sites and their characteristics, there is a lack of resources for an efficient and quick estimation of the causality and energetics of allosteric communication.

Results

The AlloSigMA server implements a unique approach on the basis of the recently introduced structure-based statistical mechanical models of allosteric signaling. It provides an interactive framework for estimating the allosteric free energy as a result of the ligand(s) binding, mutation(s) and their combinations. Latent regulatory exosites and allosteric effect of mutations can be detected and explored, facilitating the research efforts in protein engineering and allosteric drug design.

Availability and implementation

The AlloSigMA server is freely available at http://allosigma.bii.a-star.edu.sg/home/.
On the Pitman–Yor process with spike and slab base measure
Authors: Canale A. , Lijoi A. , Nipoti B. , Prünster I.
Published: July 2017

For the most popular discrete nonparametric models, beyond the Dirichlet process, the prior guess at the shape of the data-generating distribution, also known as the base measure, is assumed to be diffuse. Such a specification greatly simplifies the derivation of analytical results, allowing for a straightforward implementation of Bayesian nonparametric inferential procedures. However, in several applied problems the available prior information leads naturally to the incorporation of an atom into the base measure, and then the Dirichlet process is essentially the only tractable choice for the prior. In this paper we fill this gap by considering the Pitman–Yor process with an atom in its base measure. We derive computable expressions for the distribution of the induced random partitions and for the predictive distributions. These findings allow us to devise an effective generalized Pólya urn Gibbs sampler. Applications to density estimation, clustering and curve estimation, with both simulated and real data, serve as an illustration of our results and allow comparisons with existing methodology. In particular, we tackle a functional data analysis problem concerning basal body temperature curves.
Quantitative 3D Ultrastructure of Thalamocortical Synapses from the “Lemniscal” Ventral Posteromedial Nucleus in Mouse Barrel Cortex
Authors: Rodriguez-Moreno Javier , Rollenhagen Astrid , Arlandis Jaime , Santuy Andrea , Merchan-Pérez Angel , DeFelipe Javier , Lübke Joachim H R , Clasca Francisco
Published: July 2017

Thalamocortical synapses from “lemniscal” neurons of the dorsomedial portion of the rodent ventral posteromedial nucleus (VPMdm) are able to induce with remarkable efficacy, despite their relative low numbers, the firing of primary somatosensory cortex (S1) layer 4 (L4) neurons. To which extent this high efficacy depends on structural synaptic features remains unclear. Using both serial transmission (TEM) and focused ion beam milling scanning electron microscopy (FIB/SEM), we 3D-reconstructed and quantitatively analyzed anterogradely labeled VPMdm axons in L4 of adult mouse S1. All VPMdm synapses are asymmetric. Virtually all are established by axonal boutons, 53% of which contact multiple (2–4) elements (overall synapse/bouton ratio = 1.6). Most boutons are large (mean 0.47 μm3), and contain 1–3 mitochondria. Vesicle pools and postsynaptic density (PSD) surface areas are large compared to others in rodent cortex. Most PSDs are complex. Most synapses (83%) are established on dendritic spine heads. Furthermore, 15% of the postsynaptic spines receive a second, symmetric synapse. In addition, 13% of the spine heads have a large protrusion inserted into a membrane pouch of the VPMdm bouton. The unusual combination of structural features in VPMdm synapses is likely to contribute significantly to the high efficacy, strength, and plasticity of these thalamocortical synapses.
Pregnancy changes and early pregnancy complications
Authors: Doumouchtsis Stergios K. , Arulkumaran S. , Arulkumaran S. , Chandraharan Edwin , Coroyannakis Christina , Hayes Kevin , Kirk Emma
Published: July 2017

This chapter discusses pregnancy changes and early pregnancy complications. It includes physiological changes in pregnancy (cardiovascular, haematological, respiratory, renal and urinary tract, and metabolic changes), gestational trophoblastic disease (GTD), and nausea and vomiting.
Concerns for the fetus and surveillance
Authors: Doumouchtsis Stergios K. , Arulkumaran S. , Bhide Amar , Deshpande Deepika , Vankayalapati Padma
Published: July 2017

This chapter discusses concerns to the fetus, and fetal surveillance. It includes abnormal antenatal fetal surveillance tests (biochemical, ultrasound, fetal arterial and venous Doppler flow studies, and cardiotocography), and late intrauterine deaths and stillbirths.
Intrapartum procedures and complications
Authors: Doumouchtsis Stergios K. , Arulkumaran S. , Chrysanthopoulou Eleftheria L. , Doumouchtsis Stergios K. , Mukhopadhyay Sambit , Nikolopoulos Kostis I. , Nygaard Christiana , Schroeder Frank , Turnbull Hilary , Vinayagam Dimuth , Wendler Renate
Published: July 2017

This chapter discusses the diagnosis of labour, and describes what to do in the case of cord prolapse, abnormal fetal heart rate patterns in labour, continuous abdominal pain in labour, instrumental delivery for fetal distress in the second stage of labour, shoulder dystocia, acute tocolysis, symphysiotomy and destructive operations, along with twin delivery, breech delivery, abnormal lie or presentation in labour, and anaesthetic complications on the labour ward.
Post-delivery procedures and complications
Authors: Doumouchtsis Stergios K. , Arulkumaran S. , Basu Maya , Doumouchtsis Stergios K. , Iancu George , Nygaard Christiana , Richards Justin , Vinayagam Dimuth
Published: July 2017

This chapter explores post-delivery procedures and complications, including retained placenta, postpartum haemorrhage (PPH), vaginal and perineal lacerations, uterine inversion, vulval or perineal haematoma, and resuscitation of the newborn.
Sepsis in pregnancy
Authors: Doumouchtsis Stergios K. , Arulkumaran S. , Doumouchtsis Stergios K. , Ugwumadu Austin
Published: July 2017

This chapter discusses sepsis in pregnancy, and outlines the causes, risk factors, symptoms, investigations, and management of maternal sepsis and postpartum infections such as endometritis, septic pelvic thrombophlebitis, urinary tract infections, mastitis and breast abscess, and wound and episiotomy infection.
Chronic and acute abdominal pain
Authors: Doumouchtsis Stergios K. , Arulkumaran S. , Doumouchtsis Stergios K.
Published: July 2017

This chapter discusses chronic and acute abdominal pain. Chronic abdominal pain is one of the common presenting complaints, accounting for about 10% of referrals to the gynaecology outpatient clinic. This chapter discusses the potential causes, symptoms and signs, investigations, and treatments of chronic abdominal pain. Acute abdominal pain, defined as pain that is sudden in onset (less than 24 hours) usually associated with signs of peritonism (guarding, rebound, rigidity), is also discussed, including causes, history, examination, investigations, diagnosis, and treatment.
Intraoperative emergencies
Authors: Doumouchtsis Stergios K. , Arulkumaran S. , Talaulikar Vikram S. , Arulkumaran S.
Published: July 2017

This chapter describes intraoperative emergencies, including haemorrhage, perforated uterus, and damage to the urinary tract, blood vessels, or bowel, and details the recommended treatment options for each of these emergencies.
Ovarian hyperstimulation syndrome
Authors: Doumouchtsis Stergios K. , Arulkumaran S. , Ojha Kamal
Published: July 2017

This chapter outlines ovarian hyperstimulation syndrome (OHSS), the most serious complication of ovulation induction. OHSS is characterized by massive cystic enlargement of the ovaries, an increase in vascular permeability, and a shift of fluid to the extravascular compartments (mainly the peritoneal cavity), with the formation of ascites. The management and prevention of OHSS is described in this chapter.
Contraception and termination of pregnancy
Authors: Doumouchtsis Stergios K. , Arulkumaran S. , Radhakrishnan Sheila , Ojha Kamal
Published: July 2017

This chapter explores contraception and termination of pregnancy, one of the commonest gynaecological procedures performed all over the world. It discusses unprotected intercourse and emergency contraception, and complications associated with termination of pregnancy (procedure-related, anaesthesia-related, and psychological complications).
Miscellaneous topics in gynaecology
Authors: Doumouchtsis Stergios K. , Arulkumaran S. , Basu Maya , Domoney Claudine , Doumouchtsis Stergios K. , Mukhopadhyay Sambit , Turnbull Hilary
Published: July 2017

This chapter outlines miscellaneous topics in gynaecology, such as urinary retention, sexual assault (including incidence, risks, examination, and management), and pharmacotherapeutics in gynaecology (drugs used in the treatment of pelvic inflammatory disease (PID), prophylactic antibiotics for emergency surgery, genital herpes, menorrhagia and dysmenorrhoea, and medical management of ectopic pregnancy and miscarriage).
The 2015 superoutburst of QZ Virginis: Detection of growing superhumps between the precursor and main superoutburst
Authors: Imada Akira , Kato Taichi , Isogai Keisuke , Hambsch Franz-Josef , Dubovsky Pavol A. , Kudzej Igor , Pickard Roger D. , Akazawa Hidehiko , Kasai Kiyoshi , Itoh Hiroshi , Cook Lewis M. , Kiyota Seiichiro
Published: July 2017

We report on time-resolved photometry of the 2015 February–March superoutburst of QZ Virginis. The superoutburst consisted of a separated precursor, main superoutburst, and rebrightening. We detected superhumps with a period of 0.061181(42) d between the precursor and main superoutburst. Based on analyses of period changes and amplitudes of superhumps, the observed superhumps were identified as growing superhumps (stage A superhumps). The duration of the stage A superhumps was about 5 d, unusually long for SU UMa-type dwarf novae. Using the obtained stage A superhump period, we estimated the mass ratio of QZ Vir to be 0.108(3). This value suggests that QZ Vir is an SU UMa-type dwarf nova evolving toward the period minimum. Based on the present and previous observations regarding long-lasting stage A superhumps, the time scale for stage A superhumps is likely to be determined by the mass ratio of the system and the temperature of the accretion disk.
Lingering single-strand breaks trigger Rad51-independent homology-directed repair of collapsed replication forks in polynucleotide kinase/phosphatase mutant of fission yeast
Authors: Sanchez Arancha , Gadaleta Mariana C. , Limbo Oliver , Russell Paul
Published: July 2017

The DNA repair enzyme polynucleotide kinase/phosphatase (PNKP) protects genome integrity by restoring ligatable 5’-phosphate and 3’-hydroxyl termini at single-strand breaks (SSBs). In humans, PNKP mutations underlie the neurological disease known as MCSZ, but these individuals are not predisposed for cancer, implying effective alternative repair pathways in dividing cells. Homology-directed repair (HDR) of collapsed replication forks was proposed to repair SSBs in PNKP-deficient cells, but the critical HDR protein Rad51 is not required in PNKP-null (pnk1Δ) cells ofSchizosaccharomyces pombe.Here, we report thatpnk1Δcells have enhanced requirements for Rad3 (ATR/Mec1) and Chk1 checkpoint kinases, and the multi-BRCT domain protein Brc1 that binds phospho-histone H2A (γH2A) at damaged replication forks. The viability ofpnk1Δcells depends on Mre11 and Ctp1 (CtIP/Sae2) double-strand break (DSB) resection proteins, Rad52 DNA strand annealing protein, Mus81-Eme1 Holliday junction resolvase, and Rqh1 (BLM/WRN/Sgs1) DNA helicase. Eliminating Pnk1 strongly sensitizesmre11Δ pku80Δcells to DNA damaging agents that collapse replication forks, indicating a requirement for Mre11-Rad50-Nbs1 (MRN) protein complex that cannot be efficiently replaced by Exo1 5’-3’ exonuclease. Coupled with increased sister chromatid recombination and Rad52 repair foci inpnk1Δcells, these findings indicate that lingering SSBs inpnk1Δcells trigger Rad51-independent homology-directed repair of collapsed replication forks.

AUTHOR SUMMARY

DNA is constantly damaged by normal cellular metabolism, for example production of reactive oxygen species, or from exposure to external DNA damaging sources, such as radiation from the sun or chemicals in the environment. These genotoxic agents create thousands of single-strand breaks/cell/day in the human body. An essential DNA repair protein known as polynucleotide kinase/phosphatase (PNKP) makes sure the single-strand breaks have 5’ phosphate and 3’ hydroxyl ends suitable for healing by DNA ligase. Mutations that reduce PNKP activity cause a devastating neurological disease but surprisingly not cancer, suggesting that other DNA repair mechanisms step into the breach in dividing PNKP-deficient cells. One popular candidate was homology-directed repair (HDR) of replication forks that collapse at single-strand breaks, but the crucial HDR protein Rad51 was found to be non-essential in PNKP-deficient cells of fission yeast. In this study, Sanchez and Russell revive the HDR model by showing that SSBs in PNKP-deficient cells are repaired by a variant HDR mechanism that bypasses the requirement for Rad51. Notably, Mus81 endonuclease that resolves sister chromatid recombination structures formed during HDR of collapsed replication forks was found to be essential in PNKP-deficient cells.
NanoJ-SQUIRREL: quantitative mapping and minimisation of super-resolution optical imaging artefacts
Authors: Culley Siân , Albrecht David , Jacobs Caron , Pereira Pedro Matos , Leterrier Christophe , Mercer Jason , Henriques Ricardo
Published: July 2017

Most super-resolution microscopy methods depend on steps that contribute to the formation of image artefacts. Here we present NanoJ-SQUIRREL, an ImageJ-based analytical approach providing a quantitative assessment of super-resolution image quality. By comparing diffraction-limited images and super-resolution equivalents of the same focal volume, this approach generates a quantitative map of super-resolution defects, as well as methods for their correction. To illustrate its broad applicability to super-resolution approaches we apply our method to Localization Microscopy, STED and SIM images of a variety of in-cell structures including microtubules, poxviruses, neuronal actin rings and clathrin coated pits. We particularly focus on single-molecule localisation microscopy, where super-resolution reconstructions often feature imperfections not present in the original data. By showing the quantitative evolution of data quality over these varied sample preparation, acquisition and super-resolution methods we display the potential of NanoJ-SQUIRREL to guide optimization of superresolution imaging parameters.
Defining kinetic properties of HIV-specific CD8+T-cell responses in acute infection
Authors: Yang Yiding , Ganusov Vitaly V.
Published: July 2017

Multiple lines of evidence indicate that CD8+T cells are important in the control of HIV-1 (HIV) replication. However, CD8+T cells induced by natural infection cannot eliminate the virus or reduce viral loads to acceptably low levels in most infected individuals. Understanding the basic quantitative features of CD8+T-cell responses induced during the course of HIV infection may therefore inform us about the limits that HIV vaccines, which aim to induce protective CD8+T-cell responses, must exceed. Using previously published experimental data from a cohort of HIV-infected individuals with sampling times from acute to chronic infection we defined the quantitative properties of CD8+T-cell responses to the whole HIV proteome. In contrast with a commonly held view, we found that the relative number of HIV-specific CD8+T-cell responses (response breadth) changed little over the course of infection (first 400 days post-infection), with moderate but statistically significant changes occurring only during the first 35 symptomatic days. This challenges the idea that a change in the T-cell response breadth over time is responsible for the slow speed of viral escape from CD8+T cells in the chronic infection. The breadth of HIV-specific CD8+T-cell responses was not correlated with the average viral load for our small cohort of patients. Metrics of relative immunodominance of HIV-specific CD8+T-cell responses such as Shannon entropy or the Evenness index were also not significantly correlated with the average viral load. Our mathematical-model-driven analysis suggested extremely slow expansion kinetics for the majority of HIV-specific CD8+T-cell responses and the presence of intra- and interclonal competition between multiple CD8+T-cell responses; such competition may limit the magnitude of CD8+T-cell responses, specific to different epitopes, and the overall number of T-cell responses induced by vaccination. Further understanding of mechanisms underlying interactions between the virus and virus-specific CD8+T-cell response will be instrumental in determining which T-cell-based vaccines will induce T-cell responses providing durable protection against HIV infection.

Abbreviations

CTL

cytotoxic T lymphocyte

HIV

human immunodeficiency virus

SE

Shannon entropy

EI

Evenness index

PBMC

peripheral blood mononuclear cells

SFC

spot-forming cells

IFN

interferon
Spring frost controls spring tree phenology along elevational gradients on the southeastern Tibetan Plateau
Authors: Wang Yafeng , Case Bradley , Rossi Sergio , Zhu Liping , Liang Eryuan , Ellison Aaron M.
Published: July 2017

Temperature is considered to be a main driver of spring phenology, whereas the role of climate extremes (such as spring frosts) has long been neglected. A large elevational gradient of mature forests on the Tibetan Plateau provides a powerful space-for-time ‘natural experiment’ to explore driving forces of spring phenology. Combining 5-yr of in situ phenological observations of Smith fir (Abies georgeivar.smithii) with concurrent air temperature data along two altitudinal gradients on the southeastern Tibetan Plateau, we tested the hypothesis that spring frost was a major factor regulating the timing of spring phenology. Onset of bud swelling and leaf unfolding in the study years occurred ≈ 18 or 17 days earlier, respectively, at the lowest (3800 m a.s.l.) elevation relative to upper treelines (4360 or 4380 m a.s.l.). The frequency of freezing events and last freezing date were critical factors in determining the timing of bud swelling along two altitudinal gradients, whereas onset of leaf unfolding was primarily controlled by the onset of bud swelling. This finding provides evidence for detrimental impacts of spring frost on spring phenology, which have been underappreciated in research on phenological sensitivity to climate but should be included in phenology models. It contributes to explain the declining global warming effects on spring phenophases, because climatic extreme events (e.g. spring frosts) tend to increase with warming.
Robust diagnosis of Ewing sarcoma by immunohistochemical detection of super-enhancer-driven EWSR1-ETS targets
Authors: Baldauf Michaela C. , Orth Martin F. , Dallmayer Marlene , Marchetto Aruna , Gerke Julia S. , Alba Rubio Rebeca , Kiran Merve M. , Musa Julian , Knott Maximilian M. L. , Ohmura Shunya , Li Jing , Akpolat Nusret , Akatli Ayse N. , Özen Özlem , Dirksen Uta , Hartmann Wolfgang , de Alava Enrique , Baumhoer Daniel , Sannino Giuseppina , Kirchner Thomas , Grünewald Thomas G. P.
Published: July 2017

Ewing sarcoma is an undifferentiated bone-associated cancer. Although molecular detection of pathognomonicEWSR1-ETSfusions such asEWSR1-FLI1enables definitive diagnosis, substantial confusion can arise if molecular diagnostics are unavailable. Diagnosis based solely on the conventional immunohistochemical marker CD99 is unreliable due to its abundant expression in morphological mimics. This study aimed to identify novel diagnostic immunohistochemical markers for Ewing sarcoma.

We analyzed 768 expression microarrays representing 21 tumor entities including Ewing-like sarcomas to nominate candidate biomarkers. These candidates were validated by immunohistochemistry (IHC) in a tissue microarray (TMA) comprising 174 samples. Microarray, chromatin immunoprecipitation and sequencing (ChIP-Seq) data, and reporter assays were employed to analyze their EWSR1-FLI1-dependency.

Our comparative expression analyses revealed thatATP1A1, BCL11B, andGLG1constitute specific markers for Ewing sarcoma. Analysis of ChIP-Seq and microarray datasets showed that their expression is EWSR1-FLI1-dependent. This outcome corresponded to EWSR1-FLI1-binding to proximal super-enhancers, which showed high activity in reporter assays. Consistently, high ATP1A1, BCL11B, and GLG1 expressions were detected by IHC. Automated cut-off-finding and combination-testing in the TMA demonstrated that detection of high BCL11B and/or GLG1 expression is sufficient to reach 96% specificity for Ewing sarcoma. While 88% of tested Ewing-like sarcomas displayed strong CD99-immunoreactivity, none displayed combined high expression of BCL11B and GLG1.

Collectively, we provide evidence thatATP1A1, BCL11B, andGLG1are EWSR1-FLI1 targets, of which BCL11B and GLG1 offer a fast, simple and cost-efficient way to diagnose Ewing sarcoma by IHC. We anticipate that these markers will significantly reduce the number of misdiagnosed patients, and thus improve patient care.
Predicting users’ demographic characteristics in a Chinese social media network
Authors: Wang Qiangbing , Ma Shutian , Zhang Chengzhi
Published: July 2017

Purpose

Based on user-generated content from a Chinese social media platform, this paper aims to investigate multiple methods of constructing user profiles and their effectiveness in predicting their gender, age and geographic location.

Design/methodology/approach

This investigation collected 331,634 posts from 4,440 users of Sina Weibo. The data were divided into two parts, for training and testing . First, a vector space model and topic models were applied to construct user profiles. A classification model was then learned by a support vector machine according to the training data set. Finally, we used the classification model to predict users’ gender, age and geographic location in the testing data set.

Findings

The results revealed that in constructing user profiles, latent semantic analysis performed better on the task of predicting gender and age. By contrast, the method based on a traditional vector space model worked better in making predictions regarding the geographic location. In the process of applying a topic model to construct user profiles, the authors found that different prediction tasks should use different numbers of topics.

Originality/value

This study explores different user profile construction methods to predict Chinese social media network users’ gender, age and geographic location. The results of this paper will help to improve the quality of personal information gathered from social media platforms, and thereby improve personalized recommendation systems and personalized marketing.
Effectuation in the undergraduate classroom: three barriers to entrepreneurial learning
Authors: Günzel-Jensen Franziska , Robinson Sarah
Published: July 2017

Purpose

Since Sarasvathy’s (2001) research on decision-making logics of expert entrepreneurs, effectuation has become a cornerstone in entrepreneurship education. Effectuation is not only subjectified in entrepreneurship education, but has also become conceptualized as a method in the learning process. The purpose of this paper is to explore how students, who are novice entrepreneurs, react to working effectually and which barriers they face when applying effectual decision-making logics in a university course.

Design/methodology/approach

A student-centered process course in entrepreneurship with 142 students provides a unique opportunity to explore the phenomena. Participant/teacher observations, written and oral work from the students and finally formal and informal written evaluations of the course by the students provide comprehensive data.

Findings

The authors find that students experience three barriers to using effectuation. These are: noviceness, regarding the project as a “school project,” perceived lack of legitimacy of both the instructors and the process.

Originality/value

The contribution of this study is threefold: first, to contribute to the understanding of the applicability of effectuation for novice entrepreneurs in the classroom; second, to articulate the factors that hinder entrepreneurial learning when effectuation is used in a process course; and third, to shed light on the importance of contextual factors for individual learning.
Understanding students’ emotional reactions to entrepreneurship education
Authors: Jones Sally , Underwood Sarah
Published: July 2017

Purpose

The purpose of this paper is to focus on approaches that acknowledge and make explicit the role of emotion in the entrepreneurship education classroom. As entrepreneurship educators, the authors are aware of the affective impacts that entrepreneurship education has on the students and the authors continuously reflect on and support the students through, what is acknowledged in practice, an emotionally charged experience. With this in mind, the authors outline how a variety of disciplines engage with the role of emotions and how an interdisciplinary approach to the topic can support pedagogy.

Design/methodology/approach

The authors synthesise relevant arguments from four discrete disciplines: neuroscience; psychology, education and entrepreneurship, which have not previously been combined. The authors argue that the role of emotion in learning generally, has been investigated across these disparate disciplines, but has not been brought together in a way that provides practical implications for the development of pedagogy.

Findings

By synthesising the findings from four bodies of knowledge that engage with emotion, entrepreneurship and education, the authors start to develop a theoretical model based around the concept of the emotional ecology of the classroom.

Practical implications

The role of emotion in entrepreneurship education is an emerging topic and the authors’ synthesis of research supports further investigation. The authors’ insights will support educators to develop classroom environments that acknowledge relationships between students and between students and educators. Such engagement could help educators and students to appreciate, acknowledge and address the emotional aspects of entrepreneurship education.

Originality/value

The paper starts to develop new theory around emotions in entrepreneurship education, developing the idea of the emotional “ecology” of teaching environments and highlighting how this might support future research agendas.
Agricultural entrepreneurship orientation: is academic training a missing link?
Authors: Mohammadinezhad Soodeh , Sharifzadeh Maryam
Published: July 2017

Purpose

The purpose of this paper is to investigate the importance of academic courses on agricultural entrepreneurship.

Design/methodology/approach

Modified global entrepreneurship and development index (GEDI) was used to determine entrepreneurial dimensions among 19 graduated students of agricultural colleges resided in Iran. Fuzzy analytical hierarchy process was applied to understand agricultural graduates’ preferences on effectiveness of university courses (core, free elective and restricted elective).

Findings

Results suggested the importance of professional restricted elective courses to provide students with necessary skills. These courses were successful in providing a context for entrepreneurial profile.

Research limitations/implications

Innate talent or acquired skills were always the place of debate on entrepreneurial development. The paper builds on the premise that entrepreneurs are made through education and continuing reconstruction of experience, further research is required as the field develops in experience and complexity.

Practical implications

The paper provides strategies to effectively modify practical route in higher education to enhance entrepreneurial orientation among students.

Originality/value

The paper is innovative at a conceptual level in modifying GEDI elements in individual-level variables based on GEDI configuration theory. This approach is particularly useful in addressing the bottleneck problems of entrepreneurship profile and focusses on the information interpreted at weights of the individual-level data.
Influence of seam types on seam quality of outdoor clothing
Authors: Shi Hui , Zhang Lingxi , Wang Jianping
Published: July 2017

Purpose

The purpose of this paper is to propose a rational and complete design scheme of seam type of outdoor clothing, so as to improve the seam efficiency and appearance of outdoor clothing, as well as to provide an optimal seam base for the subsequent pressure adhesive process.

Design/methodology/approach

Four types of common outdoor fabrics and four seam types were selected. Seam strength and thickness were measured. Seam efficiency and seam thickness strain were calculated to evaluate seam quality. Multiple linear regression analysis was adopted to analyze the influence of seam type essential factors on seam strength.

Findings

Among the component factors of seam type, based on two stitches, seam strength was significantly affected by stitch distance, followed by fabric layer on the seam side. The increase of stitch and the interaction among fabrics can effectively improve the seam efficiency. The methods are as follows: the increase of stitches, stitch distance shortening, the increase of fabric layers, etc. The change of seam type had no significant influence on seam thickness strain. A seam-type design scheme of outdoor clothing with good mechanical and appearance properties was designed by choosing the seam types FX1, FX2 and FX4.

Originality/value

This paper designed a practical scheme of seam-type design of outdoor clothing, which has been applied in the industrial production process. It is important for guiding the improvement of seam quality and the production efficiency of outdoor clothing.
Numerical simulation of foam cup molding process for mold head design
Authors: Wu Long , Yick Kit-Lun , Yip Joanne , Ng Sun-Pui
Published: July 2017

Purpose

One of the crucial steps in the molded bra production is the process of developing the mold head. The purpose of this paper is to determine the final cups style and size. Compared with traditional development process of the mold head, less time-consuming and a more quantitative method is needed for the design and modification of the mold head.

Design/methodology/approach

A three-dimensional (3D) numerical model for the simulation of large compressive deformation was built in this paper to research the foam bra cup molding process. Since the head cones have more representative than the mold heads, the male and female head cones were used in the simulation. All of the solid shapes are modeled by using 3D Solid 164 elements as well as an automatic surface-to-surface contact between head cones.

Findings

Simulation of the foam cup molding process is conducted by inputting different properties of the foam material and stress-strain curves under different molding temperatures.

Research limitations/implications

In order to simulate the laminated foam moulding process, heat transfer through a layered textile assembly can be studied by using the thermo-mechanical coupled FE model.

Practical implications

According to the different foam performance parameters under different temperatures along with different head cone shapes, distribution and variation in the stress field can be obtained as well as the ultimate capacity of foam materials.

Social implications

A computer-aided parametric design system for the mold heads provides an effective solution to improving the development process of mold heads.

Originality/value

The distribution and variation in the stress fields can be analyzed through simulation, providing a reference for the mold head design.
Computer reconstruction of 19th century trousers
Authors: Kuzmichev Victor , Moskvin Aleksei , Surzhenko Evgenii , Moskvina Mariia
Published: July 2017

Purpose

Designing of clothes using the historical prototypes is very popular in contemporary practice. The purpose of this paper is to apply 2D and 3D computer-aided design (CAD) systems to reconstruct the historical pattern block and get the virtual image in accordance with the prototypes. New algorithm has been proved for men trousers taken from the nineteenth century.

Design/methodology/approach

Our approach is to develop a method of CAD to reconstruct historical trousers through analyzing and rebuilding of historical algorithms used to pattern blocks making, old anthropometrical database, and the pattern blocks shaping. Trousers construction, methods of trousers shaping by hands, body sizes schedule, manuals of 36 pattern cutting systems, and its sketches from nineteenth century have been analyzed. Then, by means of parameterization of historical pattern blocks, we have developed the universal trousers pattern cutting algorithm. The final step of the research has been devoted to virtual fitting technology that helps to determine the differences between historical trousers chosen as prototype and virtual image reconstructed by 3D CAD.

Findings

The authors have developed the parametrical module of 2D CAD and expanded the application of 3D CAD to re-designing of completely new object such as nineteenth century trousers pattern blocks in accordance with the historical method of shaping by hands. The conformity between the style of historical trousers and the virtual images reconstructed from two resources – pattern block and sketch silhouette – has been achieved.

Originality/value

This study demonstrated the contemporary approach to historical garments reconstruction by means of CAD. This study should help researchers of historical costume and practical specialists in apparel industry to apply historical heritage in a contemporary way.
On increasing of integration rate of elements in a multi-level inverter
Authors: Pankratov Evgeny L. , Bulaeva Elena Alexeevna
Published: July 2017

Purpose

The purpose of this paper is to analyze the redistribution of dopant and radiation defects to determine conditions which correspond to decreasing of elements in the considered inverter and at the same time to increase their density.

Design/methodology/approach

In this paper, the authors introduce an approach to increase integration rate of elements in a three-level inverter. The approach is based on decrease in the dimension of elements of the inverter (diodes and bipolar transistors) due to manufacturing of these elements by diffusion or ion implantation in a heterostructure with specific configuration and optimization of annealing of dopant and radiation defects.

Findings

The authors formulate recommendations to increase density of elements of the inverter with a decrease in their dimensions.

Practical implications

Optimization of manufacturing of integrated circuits and their elements.

Originality/value

The results of this paper are based on original analysis of transport of dopant with account transport and interaction of radiation defects.
Improving conventional method on precast concrete building maintenance
Authors: Ismail Zul-Atfi
Published: July 2017

Purpose

The purpose of this paper is to discuss the principles for managing precast concrete (PC) building in the context of Malaysian maintenance practice. A large number of clients/contractors in a PC building maintenance project faced many issues due to poor service delivery, less-competent contractor and defect repetition. Meanwhile, conventional method practices tend to be ineffective in Malaysian PC building.

Design/methodology/approach

Case studies were used to investigate the practice of maintenance management with eight professional engineers working in the Malaysian PC building maintenance departments.

Findings

Interviews were held with these departments and content analysis was used to identify themes that demonstrate effective PC building maintenance management practice. The frontline approaches (new system development with the integration of BIM) and underlying approach such as decision making in defect diagnosis are presented to address the maintenance management problems on PC building such as defect repetition and less-competent contractor.

Originality/value

The underlying approaches include sustaining existing maintenance quality and providing decision making in diagnosis support while the frontline approaches include the use of emerging technologies, efficient control of building performance-based design and monitor the defect component operation in maintenance.