bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carer and staff perspectives on supplementary suckling for treating infant malnutrition: qualitative findings from Malawi
Authors: Lelijveld Natasha , Mahebere‐Chirambo Chawanangwa , Kerac Marko 
Published: June 2013

AbstractSevere acute malnutrition (SAM) in infants aged <6 months is a major global health problem. Supplementary suckling (SS) is widely recommended as an inpatient treatment technique for infant <6 months SAM. Its aim is to re‐establish effective exclusive breastfeeding. Despite widespread support in guidelines, research suggests that field use of SS is limited in many settings. In this study, we aimed therefore to describe and understand the barriers and facilitating factors to SS as a treatment technique for infant SAM. We conducted qualitative interviews and focus group discussions in a hospital setting in Blantyre, Malawi, with ward staff and caregivers of infants <2 years. We created a conceptual framework based on five major themes identified from the data: (1) motivation; (2) breastfeeding views; (3) practicalities; (4) understanding; and (5) perceptions of hospital‐based medicine. Within each major theme, more setting‐specific subthemes can also be developed. Other health facilities considering SS roll‐out could consider their own barriers and facilitators using our framework; this will facilitate the implementation of SS, improve staff confidence and therefore give SS a better chance of success. Used to shape and guide discussions and inform action plans for implementing SS, the framework has the potential to facilitate SS roll‐out in settings other than Malawi, where this study was conducted. We hope that it will help pave the way to more widespread SS, more research into its use and effectiveness, and a stronger evidence‐base on malnutrition in infants aged <6 months.
Identification of a serine protease inhibitor which causes inclusion vacuole reduction and is lethal to Chlamydia trachomatis
Authors: Gloeckl Sarina , Ong Vanissa A. , Patel Pooja , Tyndall Joel D. A. , Timms Peter , Beagley Kenneth W. , Allan John A. , Armitage Charles W. , Turnbull Lynne , Whitchurch Cynthia B. , Merdanovic Melisa , Ehrmann Michael , Powers James C. , Oleksyszyn Jozef , Verdoes Martijn , Bogyo Matthew , Huston Wilhelmina M. 
Published: June 2013

SummaryThe mechanistic details of the pathogenesis of Chlamydia, an obligate intracellular pathogen of global importance, have eluded scientists due to the scarcity of traditional molecular genetic tools to investigate this organism. Here we report a chemical biology strategy that has uncovered the first essential protease for this organism. Identification and application of a unique CtHtrA inhibitor (JO146) to cultures of Chlamydia resulted in a complete loss of viable elementary body formation. JO146 treatment during the replicative phase of development resulted in a loss of Chlamydia cell morphology, diminishing inclusion size, and ultimate loss of inclusions from the host cells. This completely prevented the formation of viable Chlamydia elementary bodies. In addition to its effect on the human Chlamydia trachomatis strain, JO146 inhibited the viability of the mouse strain, Chlamydia muridarum, both in vitro and in vivo. Thus, we report a chemical biology approach to establish an essential role for Chlamydia CtHtrA. The function of CtHtrA for Chlamydia appears to be essential for maintenance of cell morphology during replicative the phase and these findings provide proof of concept that proteases can be targeted for antimicrobial therapy for intracellular pathogens.
Boreal feather mosses secrete chemical signals to gain nitrogen
Authors: Bay Guillaume , Nahar Nurun , Oubre Matthieu , Whitehouse Martin J. , Wardle David A. , Zackrisson Olle , Nilsson Marie‐Charlotte , Rasmussen Ulla 
Published: June 2013

Summary

The mechanistic basis of feather moss–cyanobacteria associations, a main driver of nitrogen (N) input into boreal forests, remains unknown. Here, we studied colonization by Nostoc sp. on two feather mosses that form these associations (Pleurozium schreberi and Hylocomium splendens) and two acrocarpous mosses that do not (Dicranum polysetum and Polytrichum commune). We also determined how N availability and moss reproductive stage affects colonization, and measured N transfer from cyanobacteria to mosses.

The ability of mosses to induce differentiation of cyanobacterial hormogonia, and of hormogonia to then colonize mosses and re‐establish a functional symbiosis was determined through microcosm experiments, microscopy and acetylene reduction assays. Nitrogen transfer between cyanobacteria and Pleurozium schreberi was monitored by secondary ion mass spectrometry (SIMS).

All mosses induced hormogonia differentiation but only feather mosses were subsequently colonized. Colonization on Pleurozium schreberi was enhanced during the moss reproductive phase but impaired by elevated N. Transfer of N from cyanobacteria to their host moss was observed.

Our results reveal that feather mosses likely secrete species‐specific chemo‐attractants when N‐limited, which guide cyanobacteria towards them and from which they gain N. We conclude that this signalling is regulated by N demands of mosses, and serves as a control of N input into boreal forests.
Why reregulation after the crisis is feeble: Shadow banking, offshore financial centers, and jurisdictional competition
Authors: Rixen Thomas 
Published: June 2013

AbstractA crucial element in the complex chain of factors that caused the recent financial crisis was the lack of regulation and oversight in the shadow banking sector, which is largely incorporated in offshore financial centers (OFCs), but instead of swift and radical regulatory reform in that sector after the crisis, we observe only incremental and ineffective measures. Why? This paper develops an explanation based on a two‐level game. On the international level, governments are engaged in competition for financial activity. On the domestic level, governments are prone to capture by financial interest groups, but also susceptible to demands for stricter regulation by the electorate. Governments try to square the circle between the conflicting demands by adopting incremental and symbolic, but largely ineffective, reforms. The explanation is put to empirical scrutiny by tracing the regulatory initiatives on shadow banks andOFCsat the international level and within theUnitedStates and theEuropeanUnion, where I focus onFrance,Germany, and theUnitedKingdom.
Politics of private regulation:ISEALand the shaping of transnational sustainability governance
Authors: Loconto Allison , Fouilleux Eve 
Published: June 2013

AbstractScholars describe the proliferation of sustainability standards by multi‐stakeholder initiatives as part of an organizational field for sustainability. The aim of this article is to gain a better understanding of the institutionalization process of this global organizational field by focusing on the case of theISEAL Alliance (the global association for sustainability standards). We show howISEALputs specific strategies into place to both reinforce and expand the role and influence of sustainability standards. This institutional entrepreneurship consists primarily of two dimensions: institutionalizing macro‐standards based on a market‐driven and procedural vision of sustainability; and simultaneously legitimating both the tools andISEALthrough internal and external enrolments and entanglements. The characterization ofISEAL's activities in this way brings politics back into the analysis of sustainability standard‐related technical debates and extends our understanding of how the micro‐dynamics within organizational fields are interdependent upon macro‐dynamics outside organizational fields.
A new objective histological scale for studying human photoaged skin
Authors: Kawabata K. , Kobayashi M. , Kusaka‐Kikushima A. , Akasaka E. , Mabuchi T. , Fukui T. , Sugiyama Y. , Takekoshi S. , Miyasaka M. , Ozawa A. , Sakai S. 
Published: June 2013

BackgroundA quantitative understanding of the histological alteration of the skin is important for assessing the severity of photoaging.MethodsWe performed Elastica‐van Gieson staining and immunohistochemistry for decorin on 34 facial skin sections. We evaluated the alteration of collagen fibers and decorin (a modulator for collagen fibrillogenesis), according to the 5 grades of morphological change in elastic fibers that was established by Kligman (1969). The objectivity of a stage (Stages I–VI), which was established in this study, was evaluated using weighted kappa statistical analysis based on the degree of agreement in stage determination by 11 observers using a blind procedure. Correlation between the crow's‐feet‐area wrinkles grades of another 26 women and stages was also analyzed.ResultsThe initial alteration of elastic fibers was observed in the deep dermis. Decorin was not detected in very severely altered skin. Based on the combination of changes in the elastic fibers, collagenic fibers, and decorin, skin tissues were categorized into 6 stages according to severity. The statistical analysis showed almost perfect agreement between observers. Significant positive correlation between stages and wrinkle scores was found.ConclusionsWe propose a new objective histological scale that is useful for assessing the severity of photoaging.
Enhanced pathogenicity of biofilm‐negative Staphylococcus epidermidis isolated from platelet preparations
Authors: Hodgson Scott D. , Greco‐Stewart Valerie , Jimenez Celine S. , Sifri Costi D. , Brassinga Ann Karen C. , Ramirez‐Arcos Sandra 
Published: June 2013

BackgroundThe platelet (PLT) storage environment triggers the formation of surface‐attached aggregates known as biofilms by the common PLT contaminant Staphylococcus epidermidis. The biofilm matrix is largely composed of polysaccharide intercellular adhesin (PIA) mediated by the icaADBC operon. However, PIA‐negative S. epidermidis has been reported to form biofilms in PLT concentrates (PCs). Since biofilm formation is associated with increased virulence, this study was aimed at determining if PIA‐negative S. epidermidis grown in PCs presents enhanced virulence using the nematode Caenorhabditis elegans as a host model for bacterial pathogenesis.Study Design and MethodsBiofilm‐positive S. epidermidis ATCC 35984 and 9142, which carry the icaADBC operon, and biofilm‐negative S. epidermidis ATCC 12228 and 9142 ΔicaA were grown in regular media and in PCs and biofilm formation was quantified using a crystal violet assay. The virulence of these strains after passage through PCs was tested using nematode killing assays. Nematode survival was calculated using the Kaplan‐Meier method and statistical differences were determined by log‐rank analysis.ResultsAll S. epidermidis strains were able to form biofilms in PCs. Although persistence of a biofilm‐positive phenotype in the biofilm‐negative strains grown in PCs was not observed after passage in regular medium, the virulence of all strains was significantly increased as demonstrated by shortened life spans of the nematodes in C. elegans killing assays.ConclusionOur findings highlight the potential of an increased risk of nosocomial infections caused by S. epidermidis in transfusion recipients since PC storage conditions promote biofilm formation, and possibly pathogenicity, of strains traditionally known to be attenuated for virulence.
A mass‐conserving 4D XCAT phantom for dose calculation and accumulation
Authors: Williams Christopher L. , Mishra Pankaj , Seco Joao , James Sara St. , Mak Raymond H. , Berbeco Ross I. , Lewis John H. 
Published: June 2013

Purpose:The XCAT phantom is a realistic 4D digital torso phantom that is widely used in imaging and therapy research. However, lung mass is not conserved between respiratory phases of the phantom, making detailed dosimetric simulations and dose accumulation unphysical. A framework is developed to correct this issue by enforcing local mass conservation in the XCAT lung. Dose calculations are performed to assess the implications of neglecting mass conservation, and to demonstrate an application of the phantom to calculate the accumulated delivered dose in an irregularly breathing patient.Methods:A displacement vector field (DVF) between each respiratory state and a reference image is generated from the XCAT motion model and its divergence is calculated and used to correct the lung density. A series of phantoms with regular and irregular breathing (based on patient data) are generated and modified to conserve mass. Monte Carlo methods are used to simulate conventional and SBRT treatment delivery. The calculated dose is deformed and accumulated using the DVF. Results from the mass‐conserving and original XCAT are compared. A 4DCT is simulated for the irregularly breathing patient, and a 4DCT‐based dose estimate is compared with the accumulated delivered dose.Results:The presented framework successfully conserves mass in the XCAT lung. The spatial distribution of the lung dose was qualitatively changed by the use of a mass conservation in the XCAT; however, the corresponding DVH did not change significantly. The comparison of the delivered dose with the 4DCT‐based prediction shows similar lung metric results, however dose differences of 10% can be seen in some spatial regions.Conclusions:The XCAT phantom has been successfully modified so that it conserves lung mass during respiration, enabling it to be used as a tool to perform dose accumulation studies in the lung without relying on deformable image registration. Neglecting mass conservation can result in erroneous spatial distributions of the dose in the lung. Using this tool to simulate patient treatments reveals differences between the planned dose and the calculated delivered dose for the full treatment. The software is freely available from the authors.
Reducing the Level of Undecaprenyl Pyrophosphate Synthase Has Complex Effects on Susceptibility to Cell Wall Antibiotics
Authors: Lee Yong Heon , Helmann John D. 
Published: June 2013

ABSTRACT

Undecaprenyl pyrophosphate synthase (UppS) catalyzes the formation of the C
55
lipid carrier (UPP) that is essential for bacterial peptidoglycan biosynthesis. We selected here a vancomycin (VAN)-resistant derivative of
Bacillus subtilis
W168 that contains a single-point mutation in the ribosome-binding site of the
uppS
gene designated
uppS1
. Genetic reconstruction experiments demonstrate that the
uppS1
allele is sufficient to confer low-level VAN resistance and causes reduced UppS translation. The decreased level of UppS renders
B. subtilis
slightly more susceptible to many late-acting cell wall antibiotics, including β-lactams, but significantly more resistant to fosfomycin and
d
-cycloserine, antibiotics that interfere with the very early steps of cell wall synthesis. We further show that the
uppS1
allele leads to slightly elevated expression of the σ
M
regulon, possibly helping to compensate for the stress caused by a decrease in UPP levels. Notably, the
uppS1
mutation increases resistance to VAN, fosfomycin, and
d
-cycloserine in wild-type cells, but this effect is greatly reduced or eliminated in a
sigM
mutant background. Our findings suggest that, although UppS is an attractive antibacterial target, incomplete inhibition of UppS function may lead to increased resistance to some cell wall-active antibiotics.
Daptomycin
In Vitro
Activity against Methicillin-Resistant Staphylococcus aureus Is Enhanced by
d
-Cycloserine in a Mechanism Associated with a Decrease in Cell Surface Charge
Authors: Gasch O. , Pillai S. K. , Dakos J. , Miyakis S. , Moellering R. C. , Eliopoulos G. M. 
Published: June 2013

ABSTRACT

The killing activity of daptomycin against an isogenic pair of daptomycin-susceptible and daptomycin-nonsusceptible (DNS) methicillin-resistant
Staphylococcus aureus
(MRSA) strains was enhanced by the addition of certain cell wall agents at 1× MIC. However, when high inocula of the DNS strain were used, no significant killing was observed in our experiments. Cytochrome
c
binding assays revealed
d
-cycloserine as the only agent associated with a reduction in the cell surface charge for both strains at the concentrations used.
Targeting the “Rising DAMP” during a Francisella tularensis Infection
Authors: D'Elia Riccardo V. , Laws Thomas R. , Carter Alun , Lukaszewski Roman , Clark Graeme C. 
Published: June 2013

ABSTRACT

Antibiotic efficacy is greatly enhanced the earlier it is administered following infection with a bacterial pathogen. However, in a clinical setting antibiotic treatment usually commences following the onset of symptoms, which in some cases (e.g., biothreat agents) may be too late. In a BALB/c murine intranasal model of infection for
Francisella tularensis
SCHU S4 infection, we demonstrate during a time course experiment that proinflammatory cytokines and the damage-associated molecular pattern HMGB1 were not significantly elevated above naive levels in tissue or sera until 72 h postinfection. HMGB1 was identified as a potential therapeutic target that could extend the window of opportunity for the treatment of tularemia with antibiotics. Antibodies to HMGB1 were administered in conjunction with a delayed/suboptimal levofloxacin treatment of
F. tularensis
. We found in the intranasal model of infection that treatment with anti-HMGB1 antibody, compared to an isotype IgY control antibody, conferred a significant survival benefit and decreased bacterial loads in the spleen and liver but not the lung (primary loci of infection) 4 days into infection. We also observed an increase in the production of gamma interferon in all tested organs. These data demonstrate that treatment with anti-HMGB1 antibody is beneficial in enhancing the effectiveness of current antibiotics in treating tularemia. Strategies of this type, involving antibiotics in combination with immunomodulatory drugs, are likely to be essential for the development of a postexposure therapeutic for intracellular pathogens.
Efficient crowdsourcing for multi-class labeling
Authors: Karger David R. , Oh Sewoong , Shah Devavrat 
Published: June 2013

Crowdsourcing systems like Amazon's Mechanical Turk have emerged as an effective large-scale human-powered platform for performing tasks in domains such as image classification, data entry, recommendation, and proofreading. Since workers are low-paid (a few cents per task) and tasks performed are monotonous, the answers obtained are noisy and hence unreliable. To obtain reliable estimates, it is essential to utilize appropriate inference algorithms (e.g. Majority voting) coupled with structured redundancy through task assignment. Our goal is to obtain the best possible trade-off between reliability and redundancy. In this paper, we consider a general probabilistic model for noisy observations for crowd-sourcing systems and pose the problem of minimizing the total price (i.e. redundancy) that must be paid to achieve a target overall reliability. Concretely, we show that it is possible to obtain an answer to each task correctly with probability 1-ε as long as the redundancy per task is O((K/q) log (K/ε)), where each task can have any of the $K$ distinct answers equally likely, q is the crowd-quality parameter that is defined through a probabilistic model. Further, effectively this is the best possible redundancy-accuracy trade-off any system design can achieve. Such a single-parameter crisp characterization of the (order-)optimal trade-off between redundancy and reliability has various useful operational consequences. Further, we analyze the robustness of our approach in the presence of adversarial workers and provide a bound on their influence on the redundancy-accuracy trade-off.
Unlike recent prior work [GKM11, KOS11, KOS11], our result applies to non-binary (i.e. K>2) tasks. In effect, we utilize algorithms for binary tasks (with inhomogeneous error model unlike that in [GKM11, KOS11, KOS11]) as key subroutine to obtain answers for K-ary tasks. Technically, the algorithm is based on low-rank approximation of weighted adjacency matrix for a random regular bipartite graph, weighted according to the answers provided by the workers.
The fundamentals of heavy-tails
Authors: Nair Jayakrishnan , Wierman Adam , Zwart Bert 
Published: June 2013

Heavy-tails are a continual source of excitement and confusion across disciplines as they are repeatedly "discovered" in new contexts. This is especially true within computer systems, where heavy-tails seemingly pop up everywhere -- from degree distributions in the internet and social networks to file sizes and interarrival times of workloads. However, despite nearly a decade of work on heavy-tails they are still treated as mysterious, surprising, and even controversial.
The goal of this tutorial is to show that heavy-tailed distributions need not be mysterious and should not be surprising or controversial. In particular, we will demystify heavy-tailed distributions by showing how to reason formally about their counter-intuitive properties; we will highlight that their emergence should be expected (not surprising) by showing that a wide variety of general processes lead to heavy-tailed distributions; and we will highlight that most of the controversy surrounding heavy-tails is the result of bad statistics, and can be avoided by using the proper tools.
Inhibition of AMPK and Krebs Cycle Gene Expression Drives Metabolic Remodeling of Pten-Deficient Preneoplastic Thyroid Cells
Authors: Antico Arciuch Valeria G. , Russo Marika A. , Kang Kristy S. , Di Cristofano Antonio 
Published: June 2013

Abstract
Rapidly proliferating and neoplastically transformed cells generate the energy required to support rapid cell division by increasing glycolysis and decreasing flux through the oxidative phosphorylation (OXPHOS) pathway, usually without alterations in mitochondrial function. In contrast, little is known of the metabolic alterations, if any, which occur in cells harboring mutations that prime their neoplastic transformation. To address this question, we used a Pten-deficient mouse model to examine thyroid cells where a mild hyperplasia progresses slowly to follicular thyroid carcinoma. Using this model, we report that constitutive phosphoinositide 3-kinase (PI3K) activation caused by PTEN deficiency in nontransformed thyrocytes results in a global downregulation of Krebs cycle and OXPHOS gene expression, defective mitochondria, reduced respiration, and an enhancement in compensatory glycolysis. We found that this process does not involve any of the pathways classically associated with the Warburg effect. Moreover, this process was independent of proliferation but contributed directly to thyroid hyperplasia. Our findings define a novel metabolic switch to glycolysis driven by PI3K-dependent AMPK inactivation with a consequent repression in the expression of key metabolic transcription regulators. Cancer Res; 73(17); 5459–72. ©2013 AACR.