bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ditch the niche – is the niche a useful concept in ecology or species distribution modelling?
Authors: McInerny Greg J. , Etienne Rampal S. 
Published: November 2012

AbstractIn this first of three papers we examine the use of niche concepts in ecology and especially in species distribution modelling (SDM). This paper deliberately focuses on the lack of clarity found in the term ‘niche’. Because its meanings are so diverse, the term niche tends to create confusion and requires constant qualification. The literature houses many idiosyncratic ideas of what the niche is, but few examples where niche is more explanatory than the terminologies of population and community ecology or the statistical methods used to implement SDM analyses. In many cases the original (and inspirational) concepts are not directly applicable to our modern applications (e.g. set theory). There are some conceptual limitations found in individual definitions of niche (e.g. the fundamental niche concept), so it is perhaps understandable why more neutral terminology is becoming popular in SDM. An examination of the literature reveals a wide range of uncritical use of niche terminology. Our findings in this paper do not necessarily support the position of niche as a universally useful concept.
Transport of the areca nut alkaloid arecaidine by the human proton-coupled amino acid transporter 1 (hPAT1)
Authors: Voigt Valerie , Laug Linda , Zebisch Katja , Thondorf Iris , Markwardt Fritz , Brandsch Matthias 
Published: November 2012

Abstract

Objectives
The pyridine alkaloid arecaidine is an ingredient of areca nut preparations. It is responsible for many physiological effects observed during areca nut chewing. However, the mechanism underlying its oral bioavailability has not yet been studied. We investigated whether the H+-coupled amino acid transporter 1 (PAT1, SLC36A1), which is expressed in the intestinal epithelium, accepts arecaidine, arecoline, isoguvacine and other derivatives as substrates.

Methods
Inhibition of l-[3H]proline uptake by arecaidine and derivatives was determined in Caco-2 cells expressing hPAT1 constitutively and in HeLa cells transiently transfected with hPAT1-cDNA. Transmembrane transport of arecaidine and derivatives was measured electrophysiologically in Xenopus laevis oocytes.

Key findings
Arecaidine, guvacine and isoguvacine but not arecoline strongly inhibited the uptake of l-[3H]proline into Caco-2 cells. Kinetic analyses revealed the competitive manner of l-proline uptake inhibition by arecaidine. In HeLa cells transfected with hPAT1-cDNA an affinity constant of 3.8 mm was obtained for arecaidine. Electrophysiological measurements at hPAT1-expressing X. laevis oocytes demonstrated that arecaidine, guvacine and isoguvacine are transported by hPAT1 in an electrogenic manner.

Conclusion
We conclude that hPAT1 transports arecaidine, guvacine and isoguvacine across the apical membrane of enterocytes and that hPAT1 might be responsible for the intestinal absorption of these drug candidates.
Quantitative analysis of the intra‐ and inter‐subject variability of the whole salivary proteome
Authors: Jehmlich N. , Dinh K. H. D. , Gesell‐Salazar M. , Hammer E. , Steil L. , Dhople V. M. , Schurmann C. , Holtfreter B. , Kocher T. , Völker U. 
Published: November 2012

Background and ObjectiveInterest in human saliva is increasing for disease‐specific biomarker discovery studies. However, protein composition of whole saliva can grossly vary with physiological and environmental factors over time and it comprises human as well as bacterial proteins.Material and MethodsWe compared intra‐ and inter‐subject variabilities using complementary gel‐based (two‐dimensional difference gel electrophoresis, 2‐D DIGE) and gel‐free (liquid chromatography tandem mass spectrometry, LC‐MS/MS) proteomics profiling of saliva. Unstimulated whole saliva of four subjects was examined at three different time‐points (08.00 h, 12.00 h and 17.00 h) and variability of the saliva proteome was analyzed on two successive days by LC‐MS/MS.ResultsIn the 2‐D DIGE experiment, the median coefficient of variation (CV) for intra‐subject variability was significantly lower (CV of 0.39) than that for inter‐subject variability (CV of 0.57; CV of technical replicates 0.17). LC‐MS/MS data confirmed the significantly lower variation within subjects over time (CV of 0.37) than the inter‐subject variability (CV of 0.53; CV of technical replicates 0.11), and that the inter‐subject variability was not time‐dependent.ConclusionBoth techniques revealed similar trends of variations on technical, intra‐ and inter‐subject level but provided peptide and protein focused information and should thus be used as complementary approaches. The data presented indicate that 2‐D DIGE as well as LC‐MS/MS approaches are suitable for biomarker screening in saliva.
Effects of nutritional supplementation combined with conventional pulmonary rehabilitation in muscle‐wasted chronic obstructive pulmonary disease: A prospective, randomized and controlled study
Authors: Gurgun Alev , Deniz Sami , Argın Mehmet , Karapolat Hale 
Published: November 2012

AbstractBackground and objectiveNutritional depletion in chronic obstructive pulmonary disease (COPD) adversely affects health status and mortality. We aimed to evaluate the effects of nutritional supplementation (NS) with pulmonary rehabilitation (PR) on body composition, mid‐thigh cross‐sectional area (CSA), dyspnoea, exercise capacity, health‐related quality of life, anxiety and depression in advanced COPD patients.MethodsForty‐six patients were randomized to PR and nutritional support (PRNS), PR or the control group. Dyspnoea was measured with Medical Research Council and BORG scales. Exercise capacity was measured through 6‐min walk test and shuttle tests; health‐related quality of life was assessed with St. George's Respiratory Questionnaire. Psychological status was measured with Hospital Anxiety and Depression Scale. Body weight and body mass indexes (BMI) were also evaluated. Fat‐free mass was measured through bioelectrical impedance analyser. The CSA of quadriceps was calculated in mid‐level of the thigh with magnetic resonance imaging.ResultsDyspnoea and total scores of St. George's Respiratory Questionnaire improved in both groups (P < 0.05). Six‐minute walk test and incremental shuttle walk test distances in PRNS and PR patients increased significantly as (62.6 ± 42.4 m, 43.3 ± 59.2 m, both P = 0.001; and 63.3 ± 70.1 m and 69.3 ± 69.7 m, both P = 0.001). Although anxiety improved in both groups (P < 0.05), there was no change in depression. Body weight, BMI and fat‐free mass index (FFMI) (1.1 ± 0.9 kg, 0.2 ± 1.4 kg/m2 and 0.6 ± 0.5 kg/m2, P < 0.05) in PRNS, whereas body weight and FFMI (0.6 ± 0.7 kg, 0.1 ± 0.6 kg/m2 P < 0.05) increased in PR after the intervention. There was a significant increase in mid‐thigh CSA (2.5 ± 4.1 cm2) only in PRNS (P = 0.04).ConclusionThe combination of NS with PR resulted in improvements particularly in lean body mass and mid‐thigh CSA. This study suggests combining NS with PR in reversing weight loss and muscle wasting in COPD.
Biogenesis of photosynthetic complexes in the chloroplast of Chlamydomonas reinhardtii requires ARSA1, a homolog of prokaryotic arsenite transporter and eukaryotic TRC40 for guided entry of tail‐anchored proteins
Authors: Formighieri Cinzia , Cazzaniga Stefano , Kuras Richard , Bassi Roberto 
Published: November 2012

Summaryas1, for antenna size mutant 1, was obtained by insertion mutagenesis of the unicellular green alga Chlamydomonas reinhardtii. This strain has a low chlorophyll content, 8% with respect to the wild type, and displays a general reduction in thylakoid polypeptides. The mutant was found to carry an insertion into a homologous gene, prokaryotic arsenite transporter (ARSA), whose yeast and mammal counterparts were found to be involved in the targeting of tail‐anchored (TA) proteins to cytosol‐exposed membranes, essential for several cellular functions. Here we present the characterization in a photosynthetic organism of an insertion mutant in an ARSA‐homolog gene. The ARSA1 protein was found to be localized in the cytosol, and yet its absence in as1 leads to a small chloroplast and a strongly decreased chlorophyll content per cell. ARSA1 appears to be required for optimal biogenesis of photosynthetic complexes because of its involvement in the accumulation of TOC34, an essential component of the outer chloroplast membrane translocon (TOC) complex, which, in turn, catalyzes the import of nucleus‐encoded precursor polypeptides into the chloroplast. Remarkably, the effect of the mutation appears to be restricted to biogenesis of chlorophyll‐binding polypeptides and is not compensated by the other ARSA homolog encoded by the C. reinhardtii genome, implying a non‐redundant function.
On–off asymmetries in oxygen consumption kinetics of single Xenopus laevis skeletal muscle fibres suggest higher‐order control
Authors: Wüst Rob C.I. , van der Laarse Willem J. , Rossiter Harry B. 
Published: November 2012

Key points
Skeletal muscles increase oxygen consumption to produce energy during exercise; however, the processes controlling the rate of adaptation (its kinetics) at exercise onset and offset are not well understood.
Here we measure kinetics in single frog skeletal muscle fibres using a unique experimental system that allows features of intracellular control mechanisms to be elucidated.
We show for the first time that at contractions onset skeletal muscle kinetics are best described by a biphasic ‘activation’ and ‘exponential’ profile, whereas at cessation recovers with a single smooth exponential.
Additionally these features were dependent on oxidative capacity and the intensity of stimulated contractions.
These data show that the intracellular processes that activate oxidative energy provision at the onset of contractions are far more complex than previously suggested.
Abstract  The mechanisms controlling skeletal muscle oxygen consumption () during exercise are not well understood. We determined whether first‐order control could explain kinetics at contractions onset () and cessation () in single skeletal muscle fibres differing in oxidative capacity, and across stimulation intensities up to . Xenopus laevis fibres (n= 21) were suspended in a sealed chamber with a fast response electrode to measure every second before, during and after stimulated isometric contractions. A first‐order model did not well characterise on‐transient kinetics. Including a time delay (TD) in the model provided a significantly improved characterisation than a first‐order fit without TD (F‐ratio; P < 0.05), and revealed separate ‘activation’ and ‘exponential’ phases in 15/21 fibres contracting at (mean ± SD TD: 14 ± 3 s). On‐transient kinetics () was weakly and linearly related to (R2= 0.271, P= 0.015). Off‐transient kinetics, however, were first‐order, and was greater in low‐oxidative ( < 0.05 nmol mm−3 s−1) than high‐oxidative fibres ( > 0.10 nmol mm−3 s−1; 170 ± 70 vs. 29 ± 6 s, P < 0.001). was proportional to (R2= 0.727, P < 0.001), unlike in the on‐transient. The calculated oxygen deficit was larger (P < 0.05) than the post‐contraction volume of consumed oxygen at all intensities except . These data show a clear dissociation between the kinetic control of at the onset and cessation of contractions and across stimulation intensities. More complex models are therefore required to understand the activation of mitochondrial respiration in skeletal muscle at the start of exercise.
Intensification of Antiretroviral Therapy through Addition of Enfuvirtide in Naive HIV-1-Infected Patients with Severe Immunosuppression Does Not Improve Immunological Response: Results of a Randomized Multicenter Trial (ANRS 130 Apollo)
Authors: Joly Véronique , Fagard Catherine , Grondin Carine , Descamps Diane , Yazdanpanah Yazdan , Charpentier Charlotte , Colin de Verdiere Nathalie , Tabuteau Sophie , Raffi François , Cabie André , Chene Geneviève , Yeni Patrick ,   the ANRS 130 Apollo Trial Group
Published: November 2012

ABSTRACTWe studied whether addition of enfuvirtide (ENF) to a background combination antiretroviral therapy (cART) would improve the CD4 cell count response at week 24 in naive patients with advanced HIV disease. ANRS 130 Apollo is a randomized study, conducted in naive HIV-1-infected patients, either asymptomatic with CD4 counts of <100/mm3or stage B/C disease with CD4 counts of <200/mm3. Patients received tenofovir-emtricitabine with lopinavir-ritonavir (LPV/r) or efavirenz and were randomized to receive ENF for 24 weeks (ENF arm) or not (control arm). The primary endpoint was the proportion of patients with CD4 counts of ≥200/mm3at week 24. A total of 195 patients were randomized: 73% had stage C disease, 78% were male, the mean age was 44 years, the median CD4 count was 30/mm3, and the median HIV-1 RNA load was 5.4 log10copies/ml. Eighty-one percent of patients received LPV/r. One patient was lost to follow-up, and eight discontinued the study (four in each arm). The proportions of patients with CD4 counts of ≥200/mm3at week 24 were 34% and 38% in the ENF and control arms, respectively (P= 0.53). The proportions of patients with HIV-1 RNA loads of <50 copies/ml were 74% and 58% at week 24 in the ENF and control arms, respectively (P< 0.02), and the proportion reached 79% in both arms at week 48. Twenty (20%) and 12 patients (13%) in the ENF and control arms, respectively, experienced at least one AIDS event during follow-up (P= 0.17). Although inducing a more rapid virological response, addition of ENF to a standard cART does not improve the immunological outcome in naive HIV-infected patients with severe immunosuppression.
In Vitro
Activity of Calcineurin and Heat Shock Protein 90 Inhibitors against Aspergillus fumigatus Azole- and Echinocandin-Resistant Strains
Authors: Lamoth Frédéric , Juvvadi Praveen R. , Gehrke Christopher , Steinbach William J. 
Published: November 2012

ABSTRACT

Due to the limited number of antifungals and the emergence of resistance, new therapies against invasive aspergillosis are needed. We show that calcineurin inhibitors are active
in vitro
against both azole- and echinocandin-resistant
Aspergillus fumigatus
strains. The heat shock protein 90 (Hsp90) inhibitor geldanamycin had modest activity when used alone, but its combination with caspofungin or tacrolimus (FK506) resulted in fungicidal activity against azole-resistant strains. Targeting the Hsp90-calcineurin axis is a promising alternative strategy against azole-resistant
A. fumigatus
strains.
Vaccination coverage and out-of-sequence vaccinations in rural Guinea-Bissau: an observational cohort study
Authors: Hornshøj Linda , Benn Christine Stabell , Fernandes Manuel , Rodrigues Amabelia , Aaby Peter , Fisker Ane Bærent 
Published: November 2012

ObjectiveThe WHO aims for 90% coverage of the Expanded Program on Immunization (EPI), which in Guinea-Bissau included BCG vaccine at birth, three doses of diphtheria−tetanus−pertussis vaccine (DTP) and oral polio vaccine (OPV) at 6, 10 and 14 weeks and measles vaccine (MV) at 9 months when this study was conducted. The WHO assesses coverage by 12 months of age. The sequence of vaccines may have an effect on child mortality, but is not considered in official statistics or assessments of programme performance. We assessed vaccination coverage and frequency of out-of-sequence vaccinations by 12 and 24 months of age.DesignObservational cohort study.Setting and participantsThe Bandim Health Project's (BHP) rural Health and Demographic Surveillance site covers 258 randomly selected villages in all regions of Guinea-Bissau. Villages are visited biannually and vaccination cards inspected to ascertain vaccination status. Between 2003 and 2009 vaccination status by 12 months of age was assessed for 5806 children aged 12–23 months; vaccination status by 24 months of age was assessed for 3792 children aged 24–35 months.Outcome measuresCoverage of EPI vaccinations and frequency of out-of-sequence vaccinations.ResultsHalf of 12-month-old children and 65% of 24-month-old children had completed all EPI vaccinations. Many children received vaccines out of sequence: by 12 months of age 54% of BCG-vaccinated children had received DTP with or before BCG and 28% of measles-vaccinated children had received DTP with or after MV. By 24 months of age the proportion of out-of-sequence vaccinations was 58% and 35%, respectively, for BCG and MV.ConclusionsIn rural Guinea-Bissau vaccination coverage by 12 months of age was low, but continued to increase beyond 12 months of age. More than half of all children received vaccinations out of sequence. This highlights the need to improve vaccination services.
Childhood motocross truncal injuries: high-velocity, focal force to the chest and abdomen
Authors: Kennedy Raelene D , Potter D Dean , Osborn John B , Zietlow Scott , Zarroug Abdalla E , Moir Christopher R , Ishitani Michael B , McIntosh Amy 
Published: November 2012

ObjectivesTo review the need for operative intervention and critical care services for motocross truncal injuries in children.Design cohortRetrospective review of patients identified via the hospital trauma registry.SettingOur Level 1 Pediatric Trauma Center serves five motocross tracks. These patients require frequent medical care for injuries.ParticipantsAll patients ≤17 years of age with truncal injuries sustained during motocross activities, between 2000 and 2011, were identified through the trauma registry.Primary and secondary outcome measuresOperative intervention, intensive care unit (ICU) admission, length of stay, morbidity and demographics were reviewed.ResultsMotocross injured 162 children. Thirty (18.5%) were thoracic or abdominal injuries. Operative intervention was required in eight (27%) patients. Mean injury severity score (ISS) was 11.8. ICU admission was required in 50% and average hospital length of stay was 4.1 days. The most common injuries include pulmonary contusion, pneumothorax, spleen and liver lacerations. 13% of subjects suffered truncal injury from motocross on more than one occasion.ConclusionsPaediatric motocross-related truncal injuries are significant. Surgical intervention is required in 27% of patients. The lower ISS incurred from motocross combined with high surgical and ICU admission rates suggests focal high-impact injuries to the chest and abdomen. Despite significant injury, 13% of motocross patients suffer recurrent injuries. Parents and children need injury prevention education.
Spline-based modelling of trends in the force of HIV infection, with application to the UNAIDS Estimation and Projection Package
Authors: Hogan Daniel R , Salomon Joshua A 
Published: November 2012

ObjectiveWe previously developed a flexible specification of the UNAIDS Estimation and Projection Package (EPP) that relied on splines to generate time-varying values for the force of infection parameter. Here, we test the feasibility of this approach for concentrated HIV/AIDS epidemics with very sparse data and compare two methods for making short-term future projections with the spline-based model.MethodsPenalised B-splines are used to model the average infection risk over time within the EPP 2011 modelling framework, which includes antiretroviral treatment effects and CD4 cell count progression, and is fit to sentinel surveillance prevalence data with a Bayesian algorithm. We compare two approaches for future projections: (1) an informative prior related to equilibrium prevalence and (2) a random walk formulation.ResultsThe spline-based model produced plausible fits across a range of epidemics, which included 87 subpopulations from 14 countries with concentrated epidemics and 75 subpopulations from 33 countries with generalised epidemics. The equilibrium prior and random walk approaches to future projections yielded similar prevalence estimates, and both performed well in tests of out-of-sample predictive validity for prevalence. In contrast, in some cases the two approaches varied substantially in estimates of incidence, with the random walk formulation avoiding extreme changes in incidence.ConclusionsA spline-based approach to allowing the force of infection parameter to vary over time within EPP 2011 is robust across a diverse array of epidemics, including concentrated ones with limited surveillance data. Future work on the EPP model should consider the impact that different modelling approaches have on estimates of HIV incidence.
Formal verification of monad transformers
Authors: Huffman Brian 
Published: November 2012

We present techniques for reasoning about constructor classes that (like the monad class) fix polymorphic operations and assert polymorphic axioms. We do not require a logic with first-class type constructors, first-class polymorphism, or type quantification; instead, we rely on a domain-theoretic model of the type system in a universal domain to provide these features. These ideas are implemented in the Tycon library for the Isabelle theorem prover, which builds on the HOLCF library of domain theory. The Tycon library provides various axiomatic type constructor classes, including functors and monads. It also provides automation for instantiating those classes, and for defining further subclasses.
We use the Tycon library to formalize three Haskell monad transformers: the error transformer, the writer transformer, and the resumption transformer. The error and writer transformers do not universally preserve the monad laws; however, we establish datatype invariants for each, showing that they are valid monads when viewed as abstract datatypes.
Operational semantics using the partiality monad
Authors: Danielsson Nils Anders 
Published: November 2012

The operational semantics of a partial, functional language is often given as a relation rather than as a function. The latter approach is arguably more natural: if the language is functional, why not take advantage of this when defining the semantics? One can immediately see that a functional semantics is deterministic and, in a constructive setting, computable.
This paper shows how one can use the coinductive partiality monad to define big-step or small-step operational semantics for lambda-calculi and virtual machines as total, computable functions (total definitional interpreters). To demonstrate that the resulting semantics are useful type soundness and compiler correctness results are also proved. The results have been implemented and checked using Agda, a dependently typed programming language and proof assistant.