bluuebunny/crossref_metadata_2025_split huggingface dataset:
Journey to the Center of the Mitochondria Guided by the Tail Anchor of Protein Tyrosine Phosphatase 1B
Authors: Fueller Julia , Egorov Mikhail , Walther Kirstin A. , Sabet Ola , Mallah Jana , Grabenbauer Markus , Kinkhabwala Ali 
Published: November 2013

AbstractThe canonical protein tyrosine phosphatase PTP1B has traditionally been considered to exclusively reside on the endoplasmic reticulum (ER). Using confocal microscopy, we show that endogenous PTP1B actually exhibits a higher local concentration at the mitochondria in all mammalian cell lines that we tested. Fluorescently labeled chimeras containing full-length PTP1B or only its 35 amino acid tail anchor localized identically, demonstrating the complete dependence of PTP1B’s subcellular partitioning on its tail anchor. Correlative light and electron microscopy using GFP-driven photo-oxidation of DAB revealed that PTP1B’s tail anchor localizes it to the mitochondrial interior and to mitochondrial-associated membrane (MAM) sites along the ER. Heterologous expression of the tail anchor of PTP1B in the yeastS. cerevisiaesurprisingly led to its exclusive localization to the ER/vacuole with no presence at the mitochondria. Studies with various yeast mutants of conserved membrane insertion pathways revealed a role for the GET/TRC40 pathway in ER insertion, but also emphasized the likely dominant role of spontaneous insertion. Further studies of modified tail isoforms in both yeast and mammalian cells revealed a remarkable sensitivity of subcellular partitioning to slight changes in transmembrane domain (TMD) length, C-terminal charge, and hydropathy. For example, addition of a single positive charge to the tail anchor was sufficient to completely shift the tail anchor to the mitochondria in mammalian cells and to largely shift it there in yeast cells, and a point mutation that increased TMD hydropathy was sufficient to localize the tail anchor exclusively to the ER in mammalian cells. Striking differences in the subcellular partitioning of a given tail anchor isoform in mammalian versus yeast cells most likely point to fundamental differences in the lipid composition of specific organelles (e.g. affecting membrane charge or thickness) in higher versus lower eukaryotes. Fluorescence lifetime imaging microscopy (FLIM) detection of the Förster Resonance Energy Transfer (FRET)-based interaction of the catalytic domain of PTP1B with the epidermal growth factor receptor (EGFR/ErbB1) at the mitochondria revealed a strong interaction on the cytosolic face of the outer mitochondrial membrane (OMM), suggesting the presence of a significant pool of PTP1B there and a novel role for PTP1B in the regulation of mitochondrial ErbB1 activity. In summary, in addition to its well-established general localization along the ER, our results reveal that PTP1B specifically accumulates at MAM sites along the ER and localizes as well to the OMM and mitochondrial matrix. Further elucidation of PTP1B’s roles in these different locations (including the identification of its targets) will likely be critical for understanding its complex regulation of general cellular responses, cell proliferation, and diseased states.
Genomics via Optical Mapping (I): 0-1 Laws for Mapping with Single Molecules
Authors: Anantharaman Thomas , Mishra Bud 
Published: November 2013

ABSTRACTThe genomic data that can be collected from a single DNA molecule by the best chemical and optical methods (e.g., using technologies from OpGen, BioNanoGenomics, NABSys, PacBio, etc.) are badly corrupted by many poorly understood noise processes. Thus, single molecule technology derives its utility through powerful probabilistic modeling, which can provide precise lower and upper bounds on various experimental parameters to create the correct map or validate sequence assembly. As an example, this analysis shows how as the number of “imaged” single molecules (i.e., coverage) is increased in the optical mapping data, the probability of successful computation of the map jumps from 0 to 1 for fairly small number of molecules.
Inferring tree causal models of cancer progression with probability raising
Authors: Olde Loohuis Loes , Caravagna Giulio , Graudenzi Alex , Ramazzotti Daniele , Mauri Giancarlo , Antoniotti Marco , Mishra Bud 
Published: November 2013

AbstractExisting techniques to reconstruct tree models of progression for accumulative processes, such as cancer, seek to estimate causation by combining correlation and a frequentist notion of temporal priority. In this paper, we define a novel theoretical framework called CAPRESE (CAncer PRogression Extraction with Single Edges) to reconstruct such models based on the notion of probabilistic causation defined by Suppes. We consider a general reconstruction setting complicated by the presence of noise in the data due to biological variation, as well as experimental or measurement errors. To improve tolerance to noise we define and use a shrinkage-like estimator. We prove the correctness of our algorithm by showing asymptotic convergence to the correct tree under mild constraints on the level of noise. Moreover, on synthetic data, we show that our approach outperforms the state-of-the-art, that it is efficient even with a relatively small number of samples and that its performance quickly converges to its asymptote as the number of samples increases. For real cancer datasets obtained with different technologies, we highlight biologically significant differences in the progressions inferred with respect to other competing techniques and we also show how to validate conjectured biological relations with progression models.
Developmental plasticity of growth and digestive efficiency in dependence of early‐life food availability
Authors: Kotrschal Alexander , Szidat Sönke , Taborsky Barbara 
Published: December 2013

Summary

Nutrition is a potent mediator of developmental plasticity. If food is scarce, developing organisms may invest into growth to outgrow size‐dependent mortality (short‐term benefit) and/or into an efficient digestion system (long‐term benefit).

We investigated this potential trade‐off, by determining the influence of food availability on juvenile body and organ growth, and on adult digestive efficiency in the cichlid fish Simochromis pleurospilus.

We reared two groups of fish at constant high or low food rations, and we switched four other groups between these two rations at an early and late juvenile period. We measured juvenile growth and organ sizes at different developmental stages and determined adult digestive efficiency.

Fish kept at constant, high rations grew considerably faster than low‐food fish. Nevertheless, S. pleurospilus partly buffered the negative effects of low food availability by developing heavier digestive organs, and they were therefore more efficient in digesting their food as adults.

Results of fish exposed to a ration switch during either the early or late juvenile period suggest (i) that the ability to show compensatory growth after early exposure to low food availability persists during the juvenile period, (ii) that digestive efficiency is influenced by varying juvenile food availability during the late juvenile phase and (iii) that the efficiency of the adult digestive system is correlated with the growth rate during a narrow time window of juvenile period.
3D simultaneous joint PP‐PS prestack seismic inversion at Schiehallion field, United Kingdom Continental Shelf
Authors: Barnola Anne‐Sophie , Ibram Mark 
Published: December 2013

ABSTRACTA workflow for simultaneous joint PP‐PS prestack inversion of data from the Schiehallion field on the United Kingdom Continental Shelf is presented and discussed. The main challenge, describing reasonable PS to PP data registration before any prestack or joint PP‐PS inversion, was overcome thanks to a two‐stage process addressing the signal envelope, then working directly on the seismic data to estimate appropriate time‐variant time‐shift volumes. We evaluated the benefits of including PS along with PP prestack seismic data in a joint inversion process to improve the estimated elastic property quality and also to enable estimation of density compared with other prestack and post‐stack inversion approaches. While the estimated acoustic impedance exhibited a similar quality independent of the inversion used (PP post‐stack, PP prestack or joint PP‐PS prestack inversion) the shear impedance estimation was noticeably improved by the joint PP‐PS prestack inversion when compared to the PP prestack inversion. Finally, the density estimated from joint PP and PS prestack data demonstrated an overall good quality, even where not well‐controlled. The main outcome of this study was that despite several data‐related limitations, inverting jointly correctly processed PP and PS data sets brought extra value for reservoir delineation as opposed to PP‐only or post‐stack inversion.
Evaluation of the impact of fetal fibronectin test implementation on hospital admissions for preterm labour inOntario: a multiple baseline time‐series design
Authors: Fell DB , Sprague AE , Grimshaw JM , Yasseen AS , Coyle D , Dunn SI , Perkins SL , Peterson WE , Johnson M , Bunting PS , Walker MC 
Published: December 2013

ObjectiveTo determine the impact of a health system‐wide fetal fibronectin (fFN) testing programme on the rates of hospital admission for preterm labour (PTL).DesignMultiple baseline time‐series design.SettingCanadian province ofOntario.PopulationA retrospective population‐based cohort of antepartum and delivered obstetrical admissions in allOntario hospitals between 1April 2002 and 31March 2010.MethodsInternational Classification of Diseases codes in a health system‐wide hospital administrative database were used to identify the study population and define the outcome measure. An aggregate time series of monthly rates of hospital admissions forPTLwas analysed using segmented regression models after aligning the fFNtest implementation date for each institution.Main outcome measureRate of obstetrical hospital admission forPTL.ResultsEstimated rates of hospital admission forPTLfollowing fFNimplementation were lower than predicted had pre‐implementation trends prevailed. The reduction in the rate was modest, but statistically significant, when estimated at 12 months following fFNimplementation (−0.96 hospital admissions for PTL per 100 preterm births; 95% confidence interval [CI], −1.02 to −0.90,P = 0.04). The statistically significant reduction was sustained at 24 and 36 months following implementation.ConclusionsUsing a robust quasi‐experimental study design to overcome confounding as a result of underlying secular trends or concurrent interventions, we found evidence of a small but statistically significant reduction in the health system‐level rate of hospital admissions forPTLfollowing implementation of fFNtesting in a largeCanadian province.
A comparison of intramuscular diamorphine and intramuscular pethidine for labour analgesia: a two‐centre randomised blinded controlled trial
Authors: Wee MYK , Tuckey JP , Thomas PW , Burnard S 
Published: December 2013

ObjectiveIntramuscular (i.m.) pethidine is used worldwide for labour analgesia and i.m. diamorphine usage has increased in the UK in the last 15 years. This trial aims to ascertain the relative efficacy and adverse effects of diamorphine and pethidine for labour pain.DesignProspective, parallel‐arm randomised controlled trial with blinding of participants, care‐givers and outcome assessors.SettingMaternity units in two District General Hospitals in the UK.PopulationAfter written informed consent, 484 women were randomised and recruited (244 diamorphine, 240 pethidine). Inclusion criteria included women 16 years or older, established labour, singleton pregnancy, 37–42 weeks of gestation and weight 60–120 kg.MethodsOn request of i.m. analgesia, participants received either 150 mg pethidine or 7.5 mg diamorphine based on computer‐generated block randomisation.Main outcome measuresMaternal—reduction in pain intensity from baseline (10‐cm visual analogue scale) at 60 minutes and over the 3‐hour period after drug administration. Neonatal—requirement for resuscitation and Apgar score at 1 minute.ResultsDiamorphine provided modestly improved pain relief at 60 minutes, mean difference 1 cm (95% confidence interval [CI] 0.5–1.5), and over the 3 hours, mean difference 0.7 cm (95% CI 0.3–1.1). However, average length of labour in women receiving diamorphine was 82 minutes longer (95% CI 39–124) and therefore they experienced more pain overall. There were no statistically significant differences in primary neonatal outcomes.ConclusionsThere is a modest difference between the analgesia provided by diamorphine or pethidine for labour analgesia but diamorphine is associated with significantly longer labours.
Overview of: “Translating Causal Claims: Principles and Strategies for Policy‐Relevant Criminology”
Authors: Sampson Robert J. , Winship Christopher , Knight Carly 
Published: December 2013

Research SummaryThis article reviews the causal turn in the social sciences and accompanying efforts by criminologists to make policy claims more credible. Although there has been much progress in techniques for the estimation of causal effects, we find that the link between evidence and valid policy implications remains elusive. Drawing on criminological theory and research insights from disciplines such as sociology, economics, and statistics, we assess principles and strategies for informing policy in a causally uncertain world. We identify three distinct domains of inquiry that form a part of the translational process from evidence to policy and that complicate the straightforward exportation of causal effects to policy recommendations: (a) mechanisms and causal pathways, (b) effect heterogeneity, and (c) contextualization. We elaborate these three concepts by examining research on broken windows theory, policing, video games and violence, the Moving to Opportunity voucher experiment, incarceration, and especially the rich set of experimental studies on domestic violence that originated in Minneapolis, MN in the early 1980s. We also articulate a set of conceptual tools for advancing the goal of policy translation and offer recommendations for how what we call “policy graphs”—causal graphs used to analyze the policy implications of a system of causal relations—can potentially integrate the theoretical and policy arms of criminology.Policy ImplicationsEvidence, even if causal, does not necessarily inform policy. In fact, the question of “what works,” the focus of the growing evidence‐based movement in criminology, turns out to be a different question than, “what will work?” Evidence‐based policy research must therefore be concerned with much more than providing policy makers with research on causal effects, however precisely measured. The implication is that we must separate criminology's increasing focus on causality from its policy turn and formally recognize that the latter requires a different standard of theory and evidence than does the former. In particular, criminologists interested in making policy claims must ask hard questions about the potential mechanisms through which a treatment influences an outcome, heterogeneous effects across people and time, contextual variations, and all of the real‐world phenomena to which these challenges give rise—such as unintended consequences, policies that change incentive and opportunity structures, and the scale at which policies change in meaning. Theoretically guided causal graphs enhance this goal and help inform policy in a causally uncertain world. Translational criminology is ultimately a process that entails the constant interplay of theory, research, and practice.
Evaluation of health‐related physical fitness parameters and association analysis with depression, anxiety, and quality of life in patients with fibromyalgia
Authors: Sener Umit , Ucok Kagan , Ulasli Alper M. , Genc Abdurrahman , Karabacak Hatice , Coban Necip F. , Simsek Hasan , Cevik Halime 
Published: November 2013

AbstractAimThe purpose of this study was to investigate the physical fitness parameters (maximal aerobic capacity, muscle strength and flexibility), daily physical activity, resting metabolic rate (RMR), pulmonary function tests (PFTs), body composition, depression, anxiety and health‐related quality of life (HRQoL) changes as well as the associations among these parameters in patients with fibromyalgia and to compare them with healthy controls.MethodsThirty‐nine women with fibromyalgia and 40 controls were included in this study. Physical measurements, HRQoL questionnaire, Beck Depression Inventory (BDI) score and Beck Anxiety Inventory (BAI) score were applied to all participants.ResultsMaximal aerobic capacity, trunk flexibility, daily step numbers, total energy expenditure, RMR and PFT values were not significantly different between the patients and the controls. Fibromyalgia patients had higher daily moderate activity times, active energy expenditure values, and BDI and BAI scores, while their lower handgrip strength and back‐leg strength values and Short‐form health survey (SF)‐36 scores were comparable to controls. Handgrip strength and back‐leg strength values showed moderately positive correlations with SF‐36 scores (total, physical health, mental health) and moderately negative correlations with BDI and BAI scores in patients with fibromyalgia.ConclusionOur results suggested that muscle strength, HRQoL, depression and anxiety symptomatology were impaired in fibromyalgia patients compared to healthy controls. Low muscle strength is related to reduced HRQoL and increased depression and anxiety symptomatology in patients with fibromyalgia. Also we suggest that performing daily exercises, including aerobic and strength training, as part of one's lifestyle may have beneficial effects in fibromyalgia patients.
Investigating the relationship between biodiversity and ecosystem multifunctionality: challenges and solutions
Authors: Byrnes Jarrett E. K. , Gamfeldt Lars , Isbell Forest , Lefcheck Jonathan S. , Griffin John N. , Hector Andy , Cardinale Bradley J. , Hooper David U. , Dee Laura E. , Emmett Duffy J. 
Published: December 2013

Summary

Extensive research shows that more species‐rich assemblages are generally more productive and efficient in resource use than comparable assemblages with fewer species. But the question of how diversity simultaneously affects the wide variety of ecological functions that ecosystems perform remains relatively understudied. It presents several analytical and empirical challenges that remain unresolved. In particular, researchers have developed several disparate metrics to quantify multifunctionality, each characterizing different aspects of the concept and each with pros and cons.

We compare four approaches to characterizing multifunctionality and its dependence on biodiversity, quantifying (i) magnitudes of multiple individual functions separately, (ii) the extent to which different species promote different functions, (iii) the average level of a suite of functions and (iv) the number of functions that simultaneously exceeds a critical threshold.

We illustrate each approach using data from the pan‐European BIODEPTH experiment and the R multifunc package developed for this purpose, evaluate the strengths and weaknesses of each approach and implement several methodological improvements.

We conclude that an extension of the fourth approach that systematically explores all possible threshold values provides the most comprehensive description of multifunctionality to date. We outline this method and recommend its use in future research.
Penile size in healthy Nigerian newborns: country‐based reference values and international comparisons
Authors: Jarrett OO , Ayoola OO , Jonsson B , Albertsson‐Wikland K , Ritzen EM 
Published: December 2013

AbstractAimTo establish normal reference values for penile size in Nigerian newborn boys and to compare those values with standards from other populations.MethodsA total number of 261 healthy newborn boys delivered at gestational ages of 28 weeks or more were enrolled in the study. Penile lengths and widths were measured within 72 h of birth.ResultsThe mean (±SD) penile length in the 261 Nigerian males studied was 3.4 ± 0.48 cm, while the mean mid‐shaft diameter was 1.2 ± 0.14 cm. Compared with data from other populations, Nigerian newborn boys had similar penile sizes to those reported for US Caucasian boys (mean 3.4 cm), but significantly greater penile sizes than those reported for boys from China and Hong Kong (mean 3.0 and 3.1 cm, respectively; both p < 0.001). There was a slight, but significant, difference in size between Nigerian and Malaysian boys, with Malaysian boys having greater penile sizes (mean 3.5 cm; p < 0.05).ConclusionA Nigerian newborn with a penile length of <2.39 cm can be considered to have a micropenis.
In vitro precision of fit of computer‐aided designed and computer‐aided manufactured titanium screw‐retained fixed dental prostheses before and after ceramic veneering
Authors: Katsoulis Joannis , Mericske‐Stern Regina , Enkling Norbert , Katsoulis Konstantinos , Blatz Markus B. 
Published: December 2013

AbstractObjectiveTo compare the precision of fit of full‐arch implant‐supported screw‐retained computer‐aided designed and computer‐aided manufactured (CAD/CAM) titanium‐fixed dental prostheses (FDP) before and after veneering. The null‐hypothesis was that there is no difference in vertical microgap values between pure titanium frameworks and FDPs after porcelain firing.Materials and methodsFive CAD/CAM titanium grade IV frameworks for a screw‐retained 10‐unit implant‐supported reconstruction on six implants (FDI tooth positions 15, 13, 11, 21, 23, 25) were fabricated after digitizing the implant platforms and the cuspid‐supporting framework resin pattern with a laser scanner (CARES® Scan CS2; Institut Straumann AG, Basel, Switzerland). A bonder, an opaquer, three layers of porcelain, and one layer of glaze were applied (Vita Titankeramik) and fired according to the manufacturer's preheating and fire cycle instructions at 400–800°C. The one‐screw test (implant 25 screw‐retained) was applied before and after veneering of the FDPs to assess the vertical microgap between implant and framework platform with a scanning electron microscope. The mean microgap was calculated from interproximal and buccal values. Statistical comparison was performed with non‐parametric tests.ResultsAll vertical microgaps were clinically acceptable with values <90 μm. No statistically significant pairwise difference (P = 0.98) was observed between the relative effects of vertical microgap of unveneered (median 19 μm; 95% CI 13–35 μm) and veneered FDPs (20 μm; 13–31 μm), providing support for the null‐hypothesis. Analysis within the groups showed significantly different values between the five implants of the FDPs before (P = 0.044) and after veneering (P = 0.020), while a monotonous trend of increasing values from implant 23 (closest position to screw‐retained implant 25) to 15 (most distant implant) could not be observed (P = 0.169, P = 0.270).ConclusionsFull‐arch CAD/CAM titanium screw‐retained frameworks have a high accuracy. Porcelain firing procedure had no impact on the precision of fit of the final FDPs. All implant microgap measurements of each FDP showed clinically acceptable vertical misfit values before and after veneering. Thus, the results do not only show accurate performance of the milling and firing but show also a reproducible scanning and designing process.