bluuebunny/crossref_metadata_2025 huggingface dataset:
Euthanasia: An Inclusive Definition
Authors: Mazzarella Patricia
Published: June 2017

We continue to share with our remotest ancestors the most tangled and evasive attitudes about death, despite the great distance we have come in understanding some of the profound aspects of biology. We have as much distaste for talking about personal death as for thinking about it; it is an indelicacy, like talking in mixed company about venereal disease or abortion in the old days. Death on a grand scale does not bother us in the same special way: we can sit around a dinner table and discuss war, involving 60 million volatized human deaths, as though we were talking about the weather; we can watch abrupt bloody death every day, in color, on films and television, without blinking back a tear. It is when the numbers of dead are very small and very close that we begin to think in scurrying circles. 1

Lewis Thomas, The Lives of a Cell
The Art and Science of Medicine: Do We have Too much Science and Too Little Art?
Authors: Alpar John J.
Published: June 2017

“Dicebat Bernardus Carnotensis nos esse quasi nanos, gigantium humeris insidentes, ut possimus plura eis et remotiora videre non utique proprii visus acumine, aut eminentia corporis, sed quia in altum subvehimur et extollimur magnitudine gigantica.” 1
“You Can't be any Poorer than Dead”: Difficulties in Recognizing Artificial Nutrition and Hydration as Medical Treatments
Authors: Heaney Stephen J.
Published: June 2017

The President's Commission Report Deciding to Forego Life-Sustaining Treatment comes down squarely in favor of two propositions: 1) artificial provision of nutrition and hydration are medical treatments, and 2) as such, these medical treatments may be foregone by certain categories of patients or their proxies. This latter conclusion is based on roughly consequentialist grounds; the former is more assumed than argued

There is a school of thought opposed to both of these conclusions. After first demonstrating that nourishment is not medicine, a non-consequentialist or natural law argument is employed to show that nourishment may not be foregone insofar as it violates the principle, “First, do no harm.”

I was once a member of this school, and this paper was to argue its position. In the end, however, this paper adopts the position that artificial provision of nourishment and hydration can be medical treatments, and as such may be foregone by certain categories of patients, without violating a natural law understanding of “First, do no harm “Still, exposing my retained sympathies for my former position, the paper attempts to argue for a very careful standard for non-treatment.

As a result, the argument of the paper takes four steps. First, I present the argument that artificial provision of nutrition is never medical treatment, giving as much strength to that argument as possible. Second, I show how the focus of that argument leads it astray, and that artificial provision of nourishment is medical treatment. Third, I try to show by what standard patients (or proxies) can legitimately forego this medical treatment Fourth, I point out where my former position has valid criticisms of certain arguments used by those who hold that such treatment may be withdrawn, and urge great caution in deciding to forego treatment.
If the Kingdom has Come, How Come Nothing has Changed?
Authors: Riga Peter J.
Published: June 2017

If you had faith like a mustard seed, you would say this to the mulberry free, ‘Be uprooted and be planted in the sea ‘; and it would obey you. (Luke 17:5)
KDM5A demethylase: Erasing histone modifications to promote repair of DNA breaks
Authors: Price Brendan D.
Published: June 2017

Repairing DNA breaks within the complexity of the cell chromatin is challenging. In this issue, Gong et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201611135) identify the histone demethylase KDM5A as a critical editor of the cells’ “histone code” that is required to recruit DNA repair complexes to DNA breaks.
Genetic subclone architecture of tumor clone-initiating cells in colorectal cancer
Authors: Giessler Klara M. , Kleinheinz Kortine , Huebschmann Daniel , Balasubramanian Gnana Prakash , Dubash Taronish D. , Dieter Sebastian M. , Siegl Christine , Herbst Friederike , Weber Sarah , Hoffmann Christopher M. , Fronza Raffaele , Buchhalter Ivo , Paramasivam Nagarajan , Eils Roland , Schmidt Manfred , von Kalle Christof , Schneider Martin , Ulrich Alexis , Scholl Claudia , Fröhling Stefan , Weichert Wilko , Brors Benedikt , Schlesner Matthias , Ball Claudia R. , Glimm Hanno
Published: June 2017

A hierarchically organized cell compartment drives colorectal cancer (CRC) progression. Genetic barcoding allows monitoring of the clonal output of tumorigenic cells without prospective isolation. In this study, we asked whether tumor clone-initiating cells (TcICs) were genetically heterogeneous and whether differences in self-renewal and activation reflected differential kinetics among individual subclones or functional hierarchies within subclones. Monitoring genomic subclone kinetics in three patient tumors and corresponding serial xenografts and spheroids by high-coverage whole-genome sequencing, clustering of genetic aberrations, subclone combinatorics, and mutational signature analysis revealed at least two to four genetic subclones per sample. Long-term growth in serial xenografts and spheroids was driven by multiple genomic subclones with profoundly differing growth dynamics and hence different quantitative contributions over time. Strikingly, genetic barcoding demonstrated stable functional heterogeneity of CRC TcICs during serial xenografting despite near-complete changes in genomic subclone contribution. This demonstrates that functional heterogeneity is, at least frequently, present within genomic subclones and independent of mutational subclone differences.
Size-based indicators show depth-dependent change over time in the deep sea
Authors: Mindel Beth L , Neat Francis C , Webb Thomas J , Blanchard Julia L
Published: June 2017

Size-based indicators are well established as a management tool in shelf seas as they respond to changes in fishing pressure and describe important aspects of community function. In the deep sea, however, vital rates are much slower and body size relationships vary with depth, making it less clear how size-based indicators can be applied and whether they are appropriate for detecting changes through time. The deep-sea fish stocks of the North Atlantic underwent a period of exploitation followed by management and conservation action that relieved this pressure. We used data from a deep-water bottom trawl survey in the Rockall Trough, at depths of 300–2000 m, to test whether size-based indicators changed over a 16-year period, during which fishing pressure decreased. We applied four indicators to these data: mean body length, mean maximum length, large fish indicator (LFI), and the slope of the biomass spectrum. Patterns were analysed within four different depth bands. The LFI and slope of the biomass spectrum showed positive change over time, suggesting recovery from fishing pressure. This response was generally most apparent in the shallowest depth band, where most fishing activity has been distributed. Values of the LFI were much higher overall than in shelf seas, so the same reference points cannot be applied to all marine ecosystems. These findings imply that size-based indicators can be usefully applied to the deep sea and that they potentially track changes in fishing pressure in the medium term.
Evidence for orbital motion of CW Leonis from ground-based astrometry
Authors: Sozzetti A. , Smart R. L. , Drimmel R. , Giacobbe P. , Lattanzi M.G.
Published: June 2017

Recent Atacama Large Millimeter/submillimeter Array (ALMA) observations indicate that CW Leo, the closest carbon-rich asymptotic giant branch star to Sun, might have a low-mass stellar companion. We present archival ground-based astrometric measurements of CW Leo obtained within the context of the Torino Parallax Program and with >6 yr (1995–2001) of time baseline. The residuals to a single-star solution show significant curvature, and they are strongly correlated with the well-known I-band photometric variations due to stellar pulsations. We describe successfully the astrometry of CW Leo with a variability-induced motion (VIM) + acceleration model. We obtain proper motion and parallax of the centre-of-mass of the binary, the former in fair agreement with recent estimates, the latter at the near end of the range of inferred distances based on indirect methods. The VIM + acceleration model results allow us to derive a companion mass in agreement with that inferred by ALMA, they point towards a somewhat longer period than implied by ALMA, but are not compatible with much longer period estimates. These data will constitute a fundamental contribution towards the full understanding of the orbital architecture of the system when combined with Gaia astrometry, providing an ∼25 yr time baseline.
Novel insights of microRNAs in the development of systemic lupus erythematosus
Authors: Le Xiong , Yu Xiang , Shen Nan
Published: June 2017

Purpose of review

To provide a brief overview of recent progress in microRNA biogenesis and homeostasis, its function in immune system and systemic lupus erythematosus (SLE), as well as successful microRNA-based therapy in vivo.

Recent findings

Stepwise microRNA biogenesis is elaborately regulated at multiple levels, ranging from transcription to ultimate function. Mature microRNAs have inhibitory effects on various biological molecules, which are crucial for stabilizing and normalizing differentiation and function of immune cells. Abnormality in microRNA expression contributes to dysfunction of lupus immune cells and resident cells in local tissues. Manipulation of dysregulated microRNAs in vivo through microRNA delivery or targeting microRNA might be promising for SLE treatment.

Recent advances highlight that microRNAs are important in immunity, lupus autoimmunity and as potential therapy target for SLE.
Perceived Maternal Behavioral Control, Infant Behavior, and Milk Supply: A Qualitative Study
Authors: Peacock-Chambers Elizabeth , Dicks Kaitlin , Sarathy Leela , Brown Allison A. , Boynton-Jarrett Renée
Published: June 2017

Objective:

Disparities persist in breastfeeding exclusivity and duration despite increases in breastfeeding initiation. The objective of this study was to examine factors that influence maternal decision making surrounding infant feeding practices over time in a diverse inner-city population.

Methods:

We conducted a prospective qualitative study with 20 mothers recruited from 2 urban primary care clinics. Participants completed open-ended interviews and demographic questionnaires in English or Spanish administered at approximately 2 weeks and 6 months postpartum. Transcripts were analyzed using a combined technique of inductive (data-driven) and deductive (theory-driven, based on the Theory of Planned Behavior) thematic analysis using 3 independent coders and iterative discussion to reach consensus.

Results:

All women initiated breastfeeding, and 65% reported perceived insufficient milk (PIM). An association between PIM and behavioral control emerged as the overarching theme impacting early breastfeeding cessation and evolved over time. Early postpartum, PIM evoked maternal distress—strong emotional responses to infant crying and need to control infant behaviors. Later, mothers accepted a perceived lack of control over milk supply with minimal distress or as a natural process. Decisions to stop breastfeeding occurred through an iterative process, informed by trials of various strategies and observations of subsequent changes in infant behavior, strongly influenced by competing psychosocial demands.

Conclusion:

Infant feeding decisions evolve over time and are influenced by perceptions of control over infant behavior and milk supply. Tailored anticipatory guidance is needed to provide time-sensitive strategies to cope with challenging infant behaviors and promote maternal agency over breastfeeding in low-income populations.
Safety Culture in the Operating Room: Variability Among Perioperative Healthcare Workers
Authors: Pimentel Marc Philip T. , Choi Stephanie , Fiumara Karen , Kachalia Allen , Urman Richard D.
Published: June 2017

Introduction

Safety culture is defined as the product of individual and group values, attitudes, perceptions, competencies, and patterns of behavior that determine an organization’s health and safety management. There is a lack of studies assessing patient safety culture in the perioperative setting.

Objectives

We examined safety culture at a single tertiary care hospital, across all types of surgery, using previously collected data from a validated survey tool. We aim to understand how safety culture varies among perioperative staff.

Methods

The Hospital Survey on Patient Safety Culture was administered at a single tertiary care hospital in 2014. We identified 431 respondents as perioperative healthcare workers: surgery attending physician, surgery trainee physician, anesthesia attending physician, anesthesia trainee physician, nurse, and technician. We calculated percent positive scores for each dimension of safety culture, as well as a composite score. Pairwise comparisons were calculated via analysis of variance.

Results

The average response rate was 67%. The dimensions with the highest average percent positive scores were teamwork within hospital units (69%) and organizational learning and continuous improvement (57%). The dimensions with the lowest scores were feedback and communication about error (34%) and hospital handoffs and transitions (30%). Surgery attending physicians perceived the strongest safety climate overall, whereas nurses and surgical technicians perceived significantly worse safety climate.

Conclusions

We observed significant variability in perioperative safety culture, across dimensions of safety climate, professional roles, and levels of training. These variations in safety culture should be addressed when implementing culture change programs in the perioperative setting.
Improving leukemic CD34+/CD38−blasts characterization with single-cell transcriptome sequencing
Authors: Sartori Ambra , Cheng Phil , Falconnet Emilie , Ribaux Pascale , Aubry-Lachainaye Jean-Pierre , Levesque Mitchell P. , Antonarakis Stylianos E. , Matthes Thomas , Borel Christelle
Published: June 2017

SUMMARY / ABSTRACT

Acute myeloid leukemia (AML) is a particularly aggressive blood cancer that is difficult to treat because of the incomplete eradication of rare blast cells that possess self-renewal and leukemia-initiating properties. To characterize resistant blasts, we analyzed for the first time the transcriptomes of individual CD34+/CD38−blasts by single-cell mRNA sequencing of 359 CD33+/CD34+/CD38−/+sorted cells from two patients with AML and four unaffected individuals. We demonstrated that the captured blasts possess the transcriptomic hallmarks of self-renewal and leukemia-initiating ability. The effects of somatic mutations on the cancer cells are visible at the transcriptional level, and the cellular signaling pathway activity of the blasts is altered, revealing disease-associated gene networks. We also identified a core set of transcription factors that were co-activated in blasts, which suggests a joint transcription program among blasts. Finally, we revealed that leukemogenesis and putative prognostic gene-expression signatures are present at diagnosis in leukemic CD33+/CD34+/CD38−cells and can be detected using a single-cell RNA sequencing approach.
The reproducibility of research and the misinterpretation ofPvalues
Authors: Colquhoun David
Published: June 2017

We wish to answer this question If you observe a “significant”Pvalue after doing a single unbiased experiment, what is the probability that your result is a false positive?. The weak evidence provided byPvalues between 0.01 and 0.05 is explored by exact calculations of false positive risks.

When you observeP= 0.05, the odds in favour of there being a real effect (given by the likelihood ratio) are about 3:1. This is far weaker evidence than the odds of 19 to 1 that might, wrongly, be inferred from thePvalue. And if you want to limit the false positive risk to 5 %, you would have to assume that you were 87% sure that there was a real effect before the experiment was done.

If you observeP=0.001 in a well-powered experiment, it gives a likelihood ratio of almost 100:1 odds on there being a real effect. That would usually be regarded as conclusive, But the false positive risk would still be 8% if the prior probability of a real effect were only 0.1. And, in this case, if you wanted to achieve a false positive risk of 5% you would need to observeP= 0.00045.

It is recommended that the terms “significant” and “non-significant” should never be used. Rather,Pvalues should be supplemented by specifying the prior probability that would be needed to produce a specified (e.g. 5%) false positive risk. It may also be helpful to specify the minimum false positive risk associated with the observedPvalue.

Despite decades of warnings, many areas of science still insist on labelling a result ofP< 0.05 as “statistically significant”. This practice must contribute to the lack of reproducibility in some areas of science. This is before you get to the many other well-known problems, like multiple comparisons, lack of randomisation andP-hacking. Precise inductive inference is impossible and replication is the only way to be sure,

Science is endangered by statistical misunderstanding, and by senior people who impose perverse incentives on scientists.
The cell polarity proteins Boi1p and Boi2p stimulate vesicle fusion at the plasma membrane of yeast cells
Authors: Kustermann Jochen , Wu Yehui , Rieger Lucia , Dedden Dirk , Phan Tamara , Walther Paul , Dünkler Alexander , Johnsson Nils
Published: June 2017

Eukaryotic cells can direct secretion to defined regions of their plasma membrane. These regions are distinguished by an elaborate architecture of proteins and lipids that are specialized to capture and fuse post-Golgi vesicles. Here we show that the proteins Boi1p and Boi2p are important elements of this area of active exocytosis at the tip of growing yeast cells. Cells lacking Boi1p and Boi2p accumulate secretory vesicles in their bud. The essential PH domains of Boi1p and Boi2p interact with Sec1p, a protein required for SNARE complex formation and vesicle fusion. Sec1p loses its tip localization in cells depleted of Boi1p and Boi2p but can partially compensate for their loss upon overexpression. The capacity to simultaneously bind phospholipids, Sec1p, multiple subunits of the exocyst, Cdc42p, and the module for generating active Cdc42p identify Boi1p and Boi2p as essential mediators between exocytosis and polar growth.

Summary statement

A novel protein complex connects vesicle fusion with Cdc42p activation. Genetic and protein interaction data suggest that its central members Boi1p and Boi2p chaperone the formation of the docking complex.
Protein profiling in cancer cell lines and tumor tissue using reverse phase protein arrays
Authors: Jing Xiaohong , Wang Weiqing , Gauthier Nicholas P. , Kaushik Poorvi , Root Alex , Stein Richard R. , Korkut Anil , Sander Chris
Published: June 2017

Reverse phase protein array (RPPA) technology is an antibody-based high-throughput assay for protein profiling of biological specimens that allows for many measurements with very small amounts of cell lysate. Here, we report the sensitivity, reproducibility, and accuracy of a particular RPPA platform called Zeptosens. We customized the RPPA protocol for our in-house setup, and measured more than 80 total protein and phospho-protein levels in various cancer samples, including cell lines, organoids, tumor chunks, core needle biopsies, and laser-capture microdissected tissue samples. We discuss pros and cons of the RPPA platform, and describe results from profiling 15 cancer cell line cells using RPPA.
Immunometric Antibody Sandwich Enzyme-Linked Immunosorbent Assay
Authors: Kohl Thomas O. , Ascoli Carl A.
Published: June 2017

The antibody sandwich enzyme-linked immunosorbent assay (ELISA) is the most commonly used assay for rapid and accurate detection of antigens. It displays greater sensitivity compared with the indirect ELISA and can be used to determine absolute antigen concentrations in unknown samples provided purified antigen standards are available, although it requires the use of two different antibodies. Briefly, wells are coated with antigen-specific capture antibody then incubated with samples containing unknown antigen. Washing removes unbound antigen and exogenous sample protein before incubation with a second antigen-specific detection antibody, washing, and reincubation with a reporter-labeled tertiary antibody. After tertiary antibody is washed off, substrate is added and hydrolysis is measured spectrophotometrically. The signal intensity is directly proportional to the concentration of the antigen in the test sample.
Immunometric Double-Antibody Sandwich Enzyme-Linked Immunosorbent Assay
Authors: Kohl Thomas O. , Ascoli Carl A.
Published: June 2017

The double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) is preferentially used to determine the concentration of unknown antibody in a sample. Pure antigen is not required in this assay; however, the use of a reporter-labeled detection antibody is essential. The double-antibody sandwich ELISA is suitable for epitope mapping of different monoclonal antibodies that have been generated against a single antigen. First, plates are coated with a capture antibody specific for immunoglobulins generated by immunization of a host species. Next, the test antibody solution (e.g., serum) is incubated with the capture antibody to facilitate binding. The plates are washed to remove unbound antibody, and then antigen is added. The plates are washed again followed by the addition of an antigen-specific reporter-labeled antibody. Following incubation, unbound reporter antibody is washed off, and reporter-specific substrate is added. Reporter-mediated substrate hydrolysis is visualized and measured. The signal is proportional to the number of test antibodies present in the serum.
Die Symmetrie von Spiralketten
Authors: Müller Ulrich
Published: June 2017

In crystals, polymeric chain molecules often adopt helical structures. Neglecting small distortions possibly caused by an anisotropic environment within the crystal, the symmetry of the single helix can be described by a rod group, which has translational symmetry in one dimension. The rod groups have Hermann–Mauguin symbols similar to space groups, beginning with a script style \scr p followed by a screw-axis symbol; the order of the screw axis can adopt any value. In a crystal, the rod-site symmetry, the so-called penetration rod group, must be a common crystallographic rod subgroup of the molecular rod group and the space group. Instructions are given for the derivation of the rod subgroups in question for a molecular helical rod group of any order. In polymer chemistry, a helix is designated by a (chemical) symbol like 7/2, which means 7 repeating units in 2 coil turns of covalent bonds per translational period. The corresponding Hermann–Mauguin screw-axis symbol is easily derived with a simple formula from this chemical symbol; for a 7/2 helix it is 73or 74, depending on chirality. However, it is not possible to deduce the chemical symbol from the Hermann–Mauguin symbol, because it depends on where the covalent bonds are assumed to exist. Covalent bonds are irrelevant for symmetry considerations; a symmetry symbol does not depend on them. A chemically right-handed helix can have a left-handed screw axis. The derivation of the Hermann–Mauguin symbol of a multiple helix is not that easy, as it depends on the mutual position of the interlocked helices; conversion formulae for simpler cases are presented. Instead of covalent bonds, other kinds of linking can serve to define the chemical helix, for example, edge- or face-sharing coordination polyhedra.
The hydrogen bond between N—H or O—H and organic fluorine: favourable yes, competitive no
Authors: Taylor Robin
Published: June 2017

A study was made ofX—H...F—C interactions (X= N or O) in small-molecule crystal structures. It was primarily based on 6728 structures containingX—H and C—F and no atom heavier than chlorine. Of the 28 451 C—F moieties in these structures, 1051 interact withX—H groups. However, over three-quarters of these interactions are either the weaker components of bifurcated hydrogen bonds (so likely to be incidental contacts) or occur in structures where there is a clear insufficiency of good hydrogen-bond acceptors such as oxygen, nitrogen or halide. In structures where good acceptors are entirely absent, there is about a 2 in 3 chance that a givenX—H group will donate to fluorine. Viable alternatives areX—H...π hydrogen bonds (especially to electron-rich aromatics) and dihydrogen bonds. The average H...F distances ofX—H...F—C interactions are significantly shorter for CR3F (R= C or H) and Csp2—F acceptors than for CRF3. TheX—H...F angle distribution is consistent with a weak energetic preference for linearity, but that of H...F—C suggests a flat energy profile in the range 100–180°.X—H...F—C interactions are more likely when the acceptor is Csp2—F or CR3F, and when the donor is C—NH2. They also occur significantly more often in structures containing tertiary alcohols or solvent molecules, or withZ′ > 1,i.e.when there may be unusual packing problems. It is extremely rare to findX—H...F—C interactions in structures where there are several unused good acceptors. When it does happen, there is often a clear reason,e.g.awkwardly shaped molecules whose packing isolates a donor group from the good acceptors.
Effect of adding nanoparticle on squeezing flow and heat transfer improvement using KKL model
Authors: Sheikholeslami M. , Ganji D.D.
Published: June 2017

Purpose

Nanofluid flow which is squeezed between parallel plates is studied using differential transformation method (DTM). The fluid in the enclosure is water containing different types of nanoparticles: Al2O3 and CuO. The effective thermal conductivity and viscosity of nanofluid are calculated by Koo–Kleinstreuer–Li (KKL) correlation. The comparison between the results from DTM and numerical method are in well agreement which proofs the capability of this method for solving such problems. Effects of the squeeze number and nanofluid volume fraction on flow and heat transfer are examined. Results indicate that Nusselt number augment with increase of the nanoparticle volume fraction. Also, it can be found that heat transfer enhancement of CuO is higher than Al2O3.

Design/methodology/approach

The problem of nanofluid flow which is squeezed between parallel plates is investigated analytically using DTM. The fluid in the enclosure is water containing different types of nanoparticles: Al2O3 and CuO. The effective thermal conductivity and viscosity of nanofluid are calculated by KKL correlation. In this model, effect of Brownian motion on the effective thermal conductivity is considered. The comparison between the results from DTM and numerical method are in well agreement which proves the capability of this method for solving such problems. The effect of the squeeze number and the nanofluid volume fraction on flow and heat transfer is investigated. The results show that Nusselt number increase with increase of the nanoparticle volume fraction. Also, it can be found that heat transfer enhancement of CuO is higher than Al2O3.

Findings

The effect of the squeeze number and the nanofluid volume fraction on flow and heat transfer is investigated. The results show that Nusselt number increase with increase of the nanoparticle volume fraction. Also, it can be found that heat transfer enhancement of CuO is higher than Al2O3.

Originality/value

This paper is original.
Reduced order modelling for efficient numerical optimisation of a hot-wall chemical vapour deposition reactor
Authors: Borzacchiello Domenico , Aguado Jose Vicente , Chinesta Francisco
Published: June 2017

Purpose

The purpose of this paper is to present a reduced order computational strategy for a multi-physics simulation involving a fluid flow, electromagnetism and heat transfer in a hot-wall chemical vapour deposition reactor. The main goal is to produce a multi-parametric solution for fast exploration of the design space to perform numerical prototyping and process optimisation.

Design/methodology/approach

Different reduced order techniques are applied. In particular, proper generalized decomposition is used to solve the parameterised heat transfer equation in a five-dimensional space.

Findings

The solution of the state problem is provided in a compact separated-variable format allowing a fast evaluation of the process-specific quantities of interest that are involved in the optimisation algorithm. This is completely decoupled from the solution of the underlying state problem. Therefore, once the whole parameterised solution is known, the evaluation of the objective function is done on-the-fly.

Originality/value

Reduced order modelling is applied to solve a multi-parametric multi-physics problem and generate a fast estimator needed for preliminary process optimisation. Different order reduction techniques are combined to treat the flow, heat transfer and electromagnetism problems in the framework of separated-variable representations.
Conceptualizing virtual communities as enablers of community-based entrepreneurship and resilience
Authors: Sankaran K. , Demangeot Catherine
Published: June 2017

Purpose

This paper aims to demonstrate the potential of virtual communities in enabling community-based entrepreneurship and resilience. Resilience is an important attribute for a community to overcome adverse circumstances it may face.

Design/methodology/approach

Weaving together diverse strands of scholarship, the authors show how virtual communities centered around specific interests (Obst et al., 2002) can endow geographic communities with resilience.

Findings

The paper establishes the desirability of resilience in contemporary communities, which can be enhanced through internet-mediated entrepreneurship. Five specific phenomena are identified as facilitating the emergence of community-based entrepreneurship through membership in virtual communities. Community-based entrepreneurship can augment or even replace institutional support that has until recently been considered by policy makers as the only means of addressing resilience issues, especially in disadvantaged communities.

Research limitations/implications

This paper is conceptual in nature; the conceptualization provides a rich opportunity to empirically validate the argumentation advanced here.

Social implications

This research points to major policy implications, as internet-enabled, community-based entrepreneurship may be an important key to overcome many of the adverse circumstances faced by communities the world over, such as climate change, terrorism and paucity of funds for social action.

Originality/value

The paper contributes to the literature on community-based entrepreneurship by developing the notion of internet-enabled community resilience, showing how internet-enabled communities can prompt entrepreneurial behavior and result in the enhanced resilience of geographic communities.
Management under uncertainty – the unavoidable risk-taking
Authors: Vahlne Jan-Erik , Hamberg Mattias , Schweizer Roger
Published: June 2017

Purpose

Accentuating the concept of management under uncertainty in the Uppsala internationalization process model, the purpose of this paper is to develop a model for describing how managers act while keeping uncertainty at an acceptable level.

Design/methodology/approach

The authors perform two empirical studies to underpin the model they construct. First, a survey of 309 chief executive officers and chief financial officers in large, publicly listed international firms in the Nordic region on managerial risk perceptions and, second, a case study of Volvo Car Corporation and its endeavors when developing new car models for the Chinese market on a new platform – a process characterized by unprecedented uncertainty.

Findings

The proposed model describing managers’ behavior under uncertainty contains elements such as adjusting/proceeding in small steps, reducing uncertainty via learning, building relationships with important parties in the environment to avoid unforeseen changes and re-dos (i.e. starting all over again) and, perhaps most important, acting despite uncertainty.

Originality/value

The paper highlights a central, though forgotten, concept of the Uppsala internationalization process model, i.e. management under uncertainty, and, thereby, opens a new path for research on how manager behave under the sway of uncertainty.
Angiotensin‐converting enzyme inhibitory and starter culture activities in probiotic yoghurt: Effect of sodium–calcium caseinate and whey protein concentrate
Authors: Akalin Ayse Sibel , Unal Gülfem , Dinkci Nayil
Published: June 2017

This study investigated the effect of fortification with sodium–calcium caseinate (SCaCN), whey protein concentrate (WPC) or a blend of those ingredients on some properties of probiotic yoghurt. At the beginning of the storage, the highest angiotensin‐converting enzyme inhibitory activity (ACEI %) was obtained from yoghurts with SCaCN. However, the levels of proteolytic and ACEI activities were highest in WPC‐supplemented yoghurt after 14 and 28 days. The highest Bifidobacterium animalis subsp. lactis Bb12 viability was obtained in yoghurts with WPC or the SCaCN–WPC blend. A gradual increase in lactic acid was also obtained in the yoghurts supplemented with WPC or with the SCaCN–WPC blend; there was no increase in acetic acid.
Factors associated with early extubation after superior cavopulmonary connection: analysis from single ventricle reconstruction trial
Authors: Zakaria D. , Rettiganti M. , Gossett J. M. , Gupta P.
Published: June 2017

Background

To evaluate the landscape of early extubation, and identify factors associated with early extubation (≤ 24 h) after superior cavopulmonary connection (stage 2 operation) among children with single ventricle anatomy.

Methods

Patients undergoing stage 2 operation after Norwood operation from the Pediatric Heart Network Single Ventricle Reconstruction (SVR) trial public‐use dataset were included. Elastic net regularized logistic regression models were fitted to evaluate the factors associated with early extubation after stage 2 operation.

Results

In total, 390 patients from 15 North American centers qualified for inclusion. Of these, 42 patients (10.8%) were extubated in operating room, 151 patients (38.7%) were extubated outside the operating room within the first 24 h after stage 2 operation, and the remaining 197 patients (50.5%) required mechanical ventilation for > 24 h. In adjusted models, factors associated with early extubation after stage 2 operation were elective timing of stage 2 operation, lower incidence of post‐Norwood complications, shorter CPB duration for stage 2 operation, and no cardiac catheterization after Stage 2 operation. We also performed multiple other alternative analyses to identify factors associated with early extubation that demonstrated same associations as the primary model. The mean hospital length of stay after Stage 2 operation was 20% shorter among patients with early extubation.

Conclusions

Data from this large multicenter study demonstrate that approximately one‐half of the patients undergoing operation for superior cavopulmonary connection are extubated within 24 h after heart operation. Furthermore, early extubation is associated with shorter hospital length of stay.
Mitochondrial DNA analysis of ancient sheep from Altai
Authors: Dymova M. A. , Zadorozhny A. V. , Mishukova O. V. , Khrapov E. A. , Druzhkova A. S. , Trifonov V. A. , Kichigin I. G. , Tishkin A. A. , Grushin S. P. , Filipenko M. L.
Published: June 2017

A comparative analysis of the genetic diversity of ancient and modern sheep can shed light on the origin of these animals and their distribution as well as help to evaluate the role of humans at each formation stage of different sheep breeds. Here we isolated ancient DNA and performed sequencing of the mitochondrial DNA D‐loop from 17 sheep bone remains (~4000–1000 years old) found in the archaeological complexes in the south of Altai (Western Siberia). The length of the sequences obtained ranged between 318 and 586 bp. The haplotype diversity and nucleotide diversity were 0.801 ± 0.081 and 0.0096 ± 0.0014 respectively. The average number of nucleotide differences was ~3.1. Nucleotide sequence analysis revealed that 15 specimens were nested within previously described A,B,C,D and E lineages and that two specimens had a basal position relative to the rest of the analyzed samples. A relatively high diversity of sheep haplotypes, including the presence of two basal haplotypes, indicates that the Altai region may have been a transport route of human migration. Further ancient DNA analysis of other specimens and deeper genome sequencing of samples with novel haplotypes is needed to better understand the demographic history of sheep in Southern Siberia.
Optimization of Interphase Intervals to Enhance the Evoked Muscular Responses of Transcutaneous Neuromuscular Electrical Stimulation
Authors: Vargas Luna Jose Luis , Krenn Matthias , Mayr Winfried , Cortés Ramírez Jorge Armando
Published: June 2017

Neuromuscular electrical stimulation (NMES) is a widely used technique for clinical diagnostic, treatment, and research. Normally, it applies charge‐balanced biphasic pulses, which several publications have reported to be less efficient than monophasic pulses. A good alternative is the use of interphase intervals (IPI) on biphasic pulses that allows to achieve similar responses than those evoked by monophasic stimulation. This study analyzes the enhancing mechanism of the IPI and provides guidelines on how to optimize the IPI in order to reduce secondary effects such as the electrode corrosion. The tibial nerve was excited by NMES biphasic pulses with different IPI durations and polarities. Then, the elicited responses were recorded on the soleus muscle via electromyography. When cathodic‐first pulses were applied, the responses increased proportionally to the IPI until the duration of 250 µs, where the increase saturated at 30% of the original amplitude. The responses evoked during anodic‐first were 6% to 30% smaller than those evoked during cathodic‐first pulses and continuously increased until the IPI duration of 2500 µs, where the responses reached an increase of around 30%. The results suggest that when a cathodic‐first pulse is used, the IPI could be optimized (based on the setup geometry) to allow the action potentials to travel out of the hyperpolarization zone induced by the anodic phase. When anodic‐first stimuli are applied, the IPI duration allows the fiber to recover from an apparent insensitive state induced by the anodic phase. The use of IPI is a viable option to improve the efficiency of actual stimulation systems, since only small modifications are required to significantly reduce the electrical charge required and boost the stimulation efficiency.
Factors Associated With Functional Capacity in Hemodialysis Patients
Authors: Garcia Rodrigo Schinniger Assun , Lucinda Leda Marília Fonseca , Ramos Fábio Amaral , Bueno Gabriela de Souza , de Oliveira Gustavo Moreira Ribeiro , Bonisson Lígia Sant'Ana , Silva Marco Antonio , Zolli Thomaz Izola , Pinheiro Bruno Valle , Paula Rogério Baumgratz de , Pazeli José Muniz , Reboredo Maycon Moura
Published: June 2017

Hemodialysis patients have a marked decrease in functional capacity when compared to healthy individuals. We evaluated the factors associated with functional capacity in hemodialysis patients. A total of 102 hemodialysis patients were evaluated. The patients were submitted to a 6‐min walk test, peripheral muscle strength tests, and an evaluation of quality of life, anxiety, and depression. The laboratory data were measured. The 6‐min walk test distance correlated significantly with age, educational level, hemoglobin, creatinine, number of comorbidities, peripheral muscle strength, and some domains of SF‐36 quality of life questionnaire and depression (P < 0.05). Multiple linear regression showed that educational level, hemoglobin, peripheral muscle strength, and depression significantly affected the 6‐min walk test distance (P < 0.05). The multiple correlation coefficient was 0.74, and the squared multiple correlation coefficient adjusted was 0.52. In conclusion, functional capacity was significantly associated with educational level, hemoglobin, peripheral muscle strength, and depression in hemodialysis patients.
Reproductive performance and expression of imprinted genes in somatic cell cloned boars
Authors: Kawarasaki Tatsuo , Enya Satoko , Otake Masayoshi , Shibata Masatoshi , Mikawa Satoshi
Published: June 2017

To assess the performance of boars derived by somatic cell cloning, we analyzed various aspects of their reproductive characteristics and the expression of two imprinted genes. Cloned boars (cloned Duroc × Jinhua) were analyzed for birth weight, growth rate, age at first ejaculation, semen characteristics and fertility, in comparison with naturally bred control boars of the same strain. The expression of imprinted genes was analyzed using the microsatellite marker SWC9 for the paternally expressed gene insulin‐like growth factor ‐2 (IGF2) and with single nucleotide polymorphisms (SNPs) for the gene maternally expressed 3 (MEG3). The cloned boars had high production of semen and were nearly equal in level of fertility to conventional pigs; they showed similar characteristics as naturally bred boars of the same strains. The expression of IGF2 was partially disturbed, but this disturbed expression was not linked to a change in developmental fate or reproductive performance. These results indicate that use of cloned boars could be highly effective for proliferation of pigs with desirable characteristics, preservation of genetic resources and risk reduction against epidemic diseases, such as foot‐and‐mouth disease, through storage of somatic cells as a precautionary measure for use in regenerating pig populations after a future pandemic.
Winding back Wnt signalling: potential therapeutic targets for treating gastric cancers
Authors: Flanagan Dustin J , Vincan Elizabeth , Phesse Toby J
Published: June 2017

Gastric cancer persists as a frequent and deadly disease that claims over 700 000 lives annually. Gastric cancer is a multifactorial disease that is genetically, cytologically and architecturally more heterogeneous than other gastrointestinal cancers, making it therapeutically challenging. As such, and largely attributed to late‐stage diagnosis, gastric cancer patients show only partial response to standard chemo and targeted molecular therapies, highlighting an urgent need to develop new targeted therapies for this disease. Wnt signalling has a well‐documented history in the genesis of many cancers and is, therefore, an attractive therapeutic target. As such, drug discovery has focused on developing inhibitors that target multiple nodes of the Wnt signalling cascade, some of which have progressed to clinical trials. The collective efforts of patient genomic profiling has uncovered genetic lesions to multiple components of the Wnt pathway in gastric cancer patients, which strongly suggest that Wnt‐targeted therapies could offer therapeutic benefits for gastric cancer patients. These data have been supported by studies in mouse models of gastric cancer, which identify Wnt signalling as a driver of gastric tumourigenesis. Here, we review the current literature regarding Wnt signalling in gastric cancer and highlight the suitability of each class of Wnt inhibitor as a potential treatment for gastric cancer patients, in relation to the type of Wnt deregulation observed.

Linked Articles

This article is part of a themed section on WNT Signalling: Mechanisms and Therapeutic Opportunities. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.24/issuetoc
Transthyretin stability is critical in assisting beta amyloid clearance– Relevance of transthyretin stabilization in Alzheimer's disease
Authors: Alemi Mobina , Silva Sara C. , Santana Isabel , Cardoso Isabel
Published: June 2017

Background

The absence of transthyretin (TTR) in AD mice decreases brain Aβ clearance and reduces the low‐density lipoprotein receptor‐related protein 1 (LRP1). It is possible that neuroprotection by TTR is dependent on its tetramer structural stability, as studies using TTR mutants showed that unstable L55P TTR has low affinity for Aβ, and TTR tetrameric stabilizers such as iododiflunisal ameliorate AD features in vivo.

Methods

We firstly investigated TTR folding status in human plasma measuring the resistance to urea denaturation. The importance of TTR stability on Aβ internalization was studied in human cerebral microvascular endothelial (hCMEC/D3) and hepatoma cells (HepG2), by flow cytometry. To investigate the fate of Aβ at the blood–brain barrier, Aβ efflux from hCMEC/D3 cells seeded on transwells was measured using ELISA. Further, to assess Aβ colocalization with lysosomes, Lysotracker was used. Moreover, levels of LRP1 were assessed in the liver and plasma of mice with different TTR backgrounds or treated with iododiflunisal.

Results

We showed that TTR stability is decreased in AD and that WT TTR and drug‐stabilized L55P TTR are able to increase uptake of Aβ. Furthermore, measurement of Aβ efflux showed that stable or stabilized TTR increased Aβ efflux from the basolateral to the apical side. Moreover, HepG2 cells incubated with Aβ in the presence of WT TTR, but not L55P TTR, showed an increased number of lysosomes. Further, in the presence of WT TTR, Aβ peptide colocalized with lysosomes, indicating that only stable TTR assists Aβ internalization, leading to its degradation. Finally, we demonstrated that only stable TTR can increase LRP1 levels.

Conclusion

TTR stabilization exerts a positive effect on Aβ clearance and LRP1 levels, suggesting that TTR protective role in AD is dependent on its stability. These results provide relevant information for the design of TTR‐based therapeutic strategies for AD.
PD‐1 and PD‐L1 in neoplastic cells and the tumor microenvironment of Merkel cell carcinoma
Authors: Mitteldorf Christina , Berisha Arbeneshe , Tronnier Michael , Pfaltz Monique C. , Kempf Werner
Published: June 2017

Background

Merkel cell carcinoma (MCC) is an aggressive neoplasm, which is often associated with Merkel cell polyomavirus (MCPyV). Programmed death‐1 (PD‐1) and its ligand PD‐L1 are key players of the tumor microenvironment (TME).

Methods

Fourteen paraffin‐embedded tissue samples of MCC were stratified by their MCPyV detection. Apart from PD‐L1 and PD‐1, the TME was further characterized for the expression of CD33, FOXP3 and MxA.

Results

We observed PD‐1 in 2 of 12 tumors. PD‐L1 expression by tumor cells was found in 7 of 8 MCPyV(+) samples and was detected particularly in the periphery. The tumor cells were surrounded by a shield of PD‐L1/CD33 immune cells. Expression of PD‐L1 by the tumor cells was higher in areas with a denser immune infiltrate. CD33(+) cells without direct tumor contact were PD‐L1 negative. Only a low number of FOXP3(+) regulatory T‐cells was admixed. Tumor cells of MCPyV(−) samples were mostly PD‐L1 negative.

Conclusions

Our data demonstrate that PD‐L1 expression occurs in tumor and immune cells, in areas in which they are close in contact. Interferon seems to play a role in this interaction. We postulate that PD‐L1(+)/CD33(+) cells shield the tumor against attacking PD‐1(+) immune cells. Therefore, next to anti‐PD‐1/PD‐L1 antibodies, blockade of CD33 seems to be a promising therapeutic approach.