bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pedagogy, Provocation and Paradox:Denmark'sKunstnernesStudieskole
Authors: Greaves Kerry 
Published: December 2013

AbstractThe last two decades of the nineteenth century witnessed an apparent revolution in art education inDenmark with the establishment of the ‘Free Schools’, a group of alternative schools that provided students with a choice other than theRoyalAcademy. The most important of these schools, theKunstnernesStudieskole(Artists'StudySchool, established in 1882), was subsidised by the government and headed by Laurits Tuxen,P.S. Krøyer, and Kristian Zahrtmann,Academy‐trained artists who modeled the school's education on the French atelier system. The debate that formed theStudySchool was at its core one of democratization, which was perceived to be synonymous with international modernism. Yet its artists functioned within a network of fluid roles designed to openly augment the existing pedagogical structure from within – a specificallyDanish phenomenon. This article proposes an alternative framework for late‐nineteenth‐centuryDanish art education systems that situates theStudySchool within the context ofDanish culture and as an extension of the social democratic tendencies proliferating at this time, which were significantly influenced by the preacherN.F.S. Grundtvig.Danish artists' actual situation had more to do with assimilating a myriad of local and international impulses into a specificallyDanish version of modernism.
Cognitive Distance and Obstacles to Subsidiary Business Success‐The Experience of Chinese Companies in Germany
Authors: Si Yuefang , Liefner Ingo 
Published: December 2013

AbstractThe success of foreign direct investment (FDI) from developing countries to developed countries is critically dependent on managing the differences in the knowledge bodies of the regions and players involved. The theories that at least partly explain successful FDI of this kind use the terms cognitive distance and embeddedness. Most of the empirical research takes the perspective of regions and has addressed the problem of becoming embedded in the host regions. This paper takes the firm perspective and examines cognitive distance regarding not only the host region, but also the knowledge of the firms involved. It uses qualitative information from an extensive study of Chinese affiliates in Germany. In contrast to many other studies, this paper shows that a fast and successful process of becoming embedded in the host region can hamper the subsidiary's success, as it may cause conflict with the parent firm.
Mapping the Green Building Industry: How Local are Architects and General Contractors?
Authors: Cidell Julie 
Published: December 2013

AbstractThis paper is an empirical analysis of the geography of the green building economy within the United States, based on the location of the architects and contractors involved in producing green buildings in a selection of metropolitan areas. An overwhelming percentage of both architects and contractors are locally‐based, suggesting that rather than green building expertise clustering in a few cities, it has diffused nationwide. This has positive implications for the spread of knowledge about how to build more sustainably and also suggests that economic geographers need to broaden their study of the architecture industry beyond iconic buildings in world cities.
Dengue epidemics and adverse obstetrical outcomes in French Guiana: a semi‐ecological study
Authors: Hanf Matthieu , Friedman Eleanor , Basurko Celia , Roger Amaury , Bruncher Pascal , Dussart Philippe , Flamand Claude , Carles Gabriel , Buekens Pierre , Breart Gerard , Carme Bernard , Nacher Mathieu 
Published: December 2013

AbstractObjectiveTo determine whether dengue epidemics are associated with an increase in adverse obstetrical outcomes.MethodsSemi‐ecological study combining individual data on obstetrical events from the perinatal registry and aggregated exposure data from the epidemiologic surveillance of dengue in Cayenne, French Guiana between 2004 and 2007.ResultsAfter adjustment for individual risk factors, analysis showed that an epidemic level of dengue transmission during the first trimester was associated with an increased risk of post‐partum haemorrhage and preterm birth. The associated risks seemed to depend on the epidemic level.ConclusionsDespite its limitations, this study suggests that dengue in the first trimester may be related to preterm birth and to post‐partum bleeding, thus leading to specific hypotheses that should be tested in prospective studies.
The non‐linear elasticity of the muscle sarcomere and the compliance of myosin motors
Authors: Fusi Luca , Brunello Elisabetta , Reconditi Massimo , Piazzesi Gabriella , Lombardi Vincenzo 
Published: December 2013

Key points
The force in the half‐sarcomere (hs), the functional unit of muscle, is due to the contributions of individual myosin motors arranged in parallel in the half‐myosin filament and pulling on the opposing actin filament.
According to a linear hs model, during an isometric contraction the force rises to its maximal steady value (T0) in proportion to the number of actin‐attached motors, while the hs strain rises with a slope that depends on the compliance of the myofilaments.
We measured the hs stiffness, superimposing small 4 kHz length oscillations on the development of isometric contraction, and found an elastic element in parallel to the myosin motors with a constant stiffness ∼1/20th that of the motor array at T0.
The results support a structural model in which myosin motors are distributed in multiple substates, of which only the first ones are occupied during isometric force generation, causing a motor strain of ∼1.7 nm.
AbstractForce in striated muscle is due to attachment of the heads of the myosin, the molecular motors extending from the myosin filament, to the actin filament in each half‐sarcomere, the functional unit where myosin motors act in parallel. Mechanical and X‐ray structural evidence indicates that at the plateau of isometric contraction (force T0), less than half of the elastic strain of the half‐sarcomere is due to the strain in the array of myosin motors (s), with the remainder being accounted for by the compliance of filaments acting as linear elastic elements in series with the motor array. Early during the development of isometric force, however, the half‐sarcomere compliance has been found to be less than that expected from the linear elastic model assumed above, and this non‐linearity may affect the estimate of s. This question is investigated here by applying nanometre–microsecond‐resolution mechanics to single intact fibres from frog skeletal muscle at 4°C, to record the mechanical properties of the half‐sarcomere throughout the development of force in isometric contraction. The results are interpreted with mechanical models to estimate the compliance of the myosin motors. Our conclusions are as follows: (i) early during the development of an isometric tetanus, an elastic element is present in parallel with the myosin motors, with a compliance of ∼200 nm MPa−1 (∼20 times larger than the compliance of the motor array at T0); and (ii) during isometric contraction, s is 1.66 ± 0.05 nm, which is not significantly different from the value estimated with the linear elastic model.
Activity‐dependent regulation of NMDA receptors in substantia nigra dopaminergic neurones
Authors: Wild Angela R. , Jones Susan , Gibb Alasdair J. 
Published: December 2013

Key points
Calcium ion influx through N‐methyl‐d‐aspartate receptors (NMDARs) may contribute to substantia nigra pars compacta (SNc) dopaminergic neurone dysfunction in Parkinson's disease.
Responses of NMDARs in dopaminergic neurones showed use‐dependent run‐down that was not readily reversible and was partly dependent on Ca2+ influx and partly dependent on clathrin‐mediated endocytosis.
Thus, we report regulation of NMDARs in SNc dopaminergic neurones by intracellular Ca2+ at both synaptic and extrasynaptic sites and provide evidence for activity‐dependent changes in receptor trafficking.
AbstractN‐Methyl‐d‐aspartate receptors (NMDARs) are Ca2+‐permeable glutamate receptors that play a critical role in synaptic plasticity and promoting cell survival. However, overactive NMDARs can trigger cell death signalling pathways and have been implicated in substantia nigra pars compacta (SNc) pathology in Parkinson's disease. Calcium ion influx through NMDARs recruits Ca2+‐dependent proteins that can regulate NMDAR activity. The surface density of NMDARs can also be regulated dynamically in response to receptor activity via Ca2+‐independent mechanisms. We have investigated the activity‐dependent regulation of NMDARs in SNc dopaminergic neurones. Repeated whole‐cell agonist applications resulted in a decline in the amplitude of NMDAR currents (current run‐down) that was use dependent and not readily reversible. Run‐down was reduced by increasing intracellular Ca2+ buffering or by reducing Ca2+ influx but did not appear to be mediated by the same regulatory proteins that cause Ca2+‐dependent run‐down in hippocampal neurones. The NMDAR current run‐down may be mediated in part by a Ca2+‐independent mechanism, because intracellular dialysis with a dynamin‐inhibitory peptide reduced run‐down, suggesting a role for clathrin‐mediated endocytosis in the regulation of the surface density of receptors. Synaptic NMDARs were also subject to current run‐down during repeated low‐frequency synaptic stimulation in a Ca2+‐dependent but dynamin‐independent manner. Thus, we report, for the first time, regulation of NMDARs in SNc dopaminergic neurones by changes in intracellular Ca2+ at both synaptic and extrasynaptic sites and provide evidence for activity‐dependent changes in receptor trafficking. These mechanisms may contribute to intracellular Ca2+ homeostasis in dopaminergic neurones by limiting Ca2+ influx through the NMDAR.
Sarcomere‐length dependence of myosin filament structure in skeletal muscle fibres of the frog
Authors: Reconditi Massimo , Brunello Elisabetta , Fusi Luca , Linari Marco , Martinez Manuel Fernandez , Lombardi Vincenzo , Irving Malcolm , Piazzesi Gabriella 
Published: December 2013

Key points
Contraction of skeletal muscle is thought to be regulated by a structural change in the actin‐containing thin filaments of the sarcomere, but recent results have suggested that a structural change in the myosin‐containing thick filaments may also be involved.
We show that thick filament structure in resting muscle depends on the overlap with the thin filaments of the region of the thick filament containing myosin binding protein C (MyBP‐C).
During isometric contraction, the regions of the thick filaments that do not overlap with thin filaments are highly disordered, in contrast to their helical order in resting muscle.
The results provide strong support for the role of a structural transition in the thick filaments, mediated by an interaction between MyBP‐C and the thin filaments, in the physiological regulation of contraction in skeletal muscle.
AbstractX‐ray diffraction patterns were recorded at beamline ID02 of the European Synchrotron Radiation Facility from small bundles of skeletal muscle fibres from Rana esculenta at sarcomere lengths between 2.1 and 3.5 μm at 4°C. The intensities of the X‐ray reflections from resting fibres associated with the quasi‐helical order of the myosin heads and myosin binding protein C (MyBP‐C) decreased in the sarcomere length range 2.6–3.0 μm but were constant outside it, suggesting that an OFF conformation of the thick filament is maintained by an interaction between MyBP‐C and the thin filaments. During active isometric contraction the intensity of the M3 reflection from the regular repeat of the myosin heads along the filaments decreased in proportion to the overlap between thick and thin filaments, with no change in its interference fine structure. Thus, myosin heads in the regions of the thick filaments that do not overlap with thin filaments are highly disordered during isometric contraction, in contrast to their quasi‐helical order at rest. Heads in the overlap region that belong to two‐headed myosin molecules that are fully detached from actin are also highly disordered, in contrast to the detached partners of actin‐attached heads. These results provide strong support for the concept of a regulatory structural transition in the thick filament involving changes in both the organisation of the myosin heads on its surface and the axial periodicity of the myosin tails in its backbone, mediated by an interaction between MyBP‐C and the thin filaments.
New Dosing Strategies for an Old Antibiotic: Pharmacodynamics of Front-Loaded Regimens of Colistin at Simulated Pharmacokinetics in Patients with Kidney or Liver Disease
Authors: Rao Gauri G. , Ly Neang S. , Haas Curtis E. , Garonzik Samira , Forrest Alan , Bulitta Jurgen B. , Kelchlin Pamela A. , Holden Patricia N. , Nation Roger L. , Li Jian , Tsuji Brian T. 
Published: December 2013

ABSTRACT

Increasing evidence suggests that colistin monotherapy is suboptimal at currently recommended doses. We hypothesized that front-loading provides an improved dosing strategy for polymyxin antibiotics to maximize killing and minimize total exposure. Here, we utilized an
in vitro
pharmacodynamic model to examine the impact of front-loaded colistin regimens against a high bacterial density (10
8
CFU/ml) of
Pseudomonas aeruginosa
. The pharmacokinetics were simulated for patients with hepatic (half-life [
t
1/2
] of 3.2 h) or renal (
t
1/2
of 14.8 h) disease. Front-loaded regimens (
n
= 5) demonstrated improvement in bacterial killing, with reduced overall free drug areas under the concentration-time curve (
f
AUC) compared to those with traditional dosing regimens (
n
= 14) with various dosing frequencies (every 12 h [q12h] and q24h). In the renal failure simulations, front-loaded regimens at lower exposures (
f
AUC of 143 mg · h/liter) obtained killing activity similar to that of traditional regimens (
f
AUC of 268 mg · h/liter), with an ∼97% reduction in the area under the viable count curve over 48 h. In hepatic failure simulations, front-loaded regimens yielded rapid initial killing by up to 7 log
10
within 2 h, but considerable regrowth occurred for both front-loaded and traditional regimens. No regimen eradicated the high bacterial inoculum of
P. aeruginosa
. The current study, which utilizes an
in vitro
pharmacodynamic infection model, demonstrates the potential benefits of front-loading strategies for polymyxins simulating differential pharmacokinetics in patients with hepatic and renal failure at a range of doses. Our findings may have important clinical implications, as front-loading polymyxins as a part of a combination regimen may be a viable strategy for aggressive treatment of high-bacterial-burden infections.
Genomic Analyses of DNA Transformation and Penicillin Resistance in Streptococcus pneumoniae Clinical Isolates
Authors: Fani Fereshteh , Leprohon Philippe , Zhanel George G. , Bergeron Michel G. , Ouellette Marc 
Published: December 2013

ABSTRACT

Alterations in penicillin-binding proteins, the target enzymes for β-lactam antibiotics, are recognized as primary penicillin resistance mechanisms in
Streptococcus pneumoniae
. Few studies have analyzed penicillin resistance at the genome scale, however, and we report the sequencing of
S. pneumoniae
R6 transformants generated while reconstructing the penicillin resistance phenotypes from three penicillin-resistant clinical isolates by serial genome transformation. The genome sequences of the three last-level transformants T2-18209, T5-1983, and T3-55938 revealed that 16.2 kb, 82.7kb, and 137.2 kb of their genomes had been replaced with 5, 20, and 37 recombinant sequence segments derived from their respective parental clinical isolates, documenting the extent of DNA transformation between strains. A role in penicillin resistance was confirmed for some of the mutations identified in the transformants. Several multiple recombination events were also found to have happened at single loci coding for penicillin-binding proteins (PBPs) that increase resistance. Sequencing of the transformants with MICs for penicillin similar to those of the parent clinical strains confirmed the importance of mosaic PBP2x, -2b, and -1a as a driving force in penicillin resistance. A role in resistance for mosaic PBP2a was also observed for two of the resistant clinical isolates.
Validation of a Novel Murine Wound Model of Acinetobacter baumannii Infection
Authors: Thompson Mitchell G. , Black Chad C. , Pavlicek Rebecca L. , Honnold Cary L. , Wise Matthew C. , Alamneh Yonas A. , Moon Jay K. , Kessler Jennifer L. , Si Yuanzheng , Williams Robert , Yildirim Suleyman , Kirkup Benjamin C. , Green Romanza K. , Hall Eric R. , Palys Thomas J. , Zurawski Daniel V. 
Published: December 2013

ABSTRACTPatients recovering from traumatic injuries or surgery often require weeks to months of hospitalization, increasing the risk for wound and surgical site infections caused by ESKAPE pathogens, which includeA. baumannii(the ESKAPE pathogens areEnterococcus faecium,Staphylococcus aureus,Klebsiella pneumoniae,Acinetobacter baumannii,Pseudomonas aeruginosa, andEnterobacterspecies). As new therapies are being developed to counterA. baumanniiinfections, animal models are also needed to evaluate potential treatments. Here, we present an excisional, murine wound model in which a diminutive inoculum of a clinically relevant, multidrug-resistantA. baumanniiisolate can proliferate, form biofilms, and be effectively treated with antibiotics. The model requires a temporary, cyclophosphamide-induced neutropenia to establish an infection that can persist. A 6-mm-diameter, full-thickness wound was created in the skin overlying the thoracic spine, and after the wound bed was inoculated, it was covered with a dressing for 7 days. Uninoculated control wounds healed within 13 days, whereas infected, placebo-treated wounds remained unclosed beyond 21 days. Treated and untreated wounds were assessed with multiple quantitative and qualitative techniques that included gross pathology, weight loss and recovery, wound closure, bacterial burden, 16S rRNA community profiling, histopathology, peptide nucleic acid-fluorescencein situhybridization, and scanning electron microscopy assessment of biofilms. The range of differences that we are able to identify with these measures in antibiotic- versus placebo-treated animals provides a clear window within which novel antimicrobial therapies can be assessed. The model can be used to evaluate antimicrobials for their ability to reduce specific pathogen loads in wounded tissues and clear biofilms. Ultimately, the mouse model approach allows for highly powered studies and serves as an initial multifacetedin vivoassessment prior to testing in larger animals.
Retrospective Analysis of the Efficacies of Two Different Regimens of Aqueous Penicillin G Administered to Children with Pneumonia
Authors: Brandão Alyson , Simbalista Raquel , Borges Igor C. , Andrade Dafne C. , Araújo Marcelo , Nascimento-Carvalho Cristiana M. 
Published: December 2013

ABSTRACT

Community-acquired pneumonia (CAP) is an important childhood health problem. Penicillin remains appropriate for treating children with CAP. Clinical data are lacking on disease evolution in children treated with different posologic schemes of aqueous penicillin G. To assess if there were differences in disease evolution between children with CAP treated with 6 or 4 daily doses of aqueous penicillin G, we reviewed the medical charts of hospitalized patients 2 months to 11.5 years of age. Pneumonia was radiologically confirmed based on the detection of pulmonary infiltrate or pleural effusion on the chest radiograph taken on admission and read by a pediatric radiologist blinded to the clinical data. The total daily dose of aqueous penicillin G was 200,000 IU/kg of body weight. Data were recorded on admission, during disease evolution up to the 7th day of treatment, and at the final outcome. The results of hospitalization and the daily frequency of physical signs suggestive of pneumonia were assessed. The subgroups comprised 120 and 144 children who received aqueous penicillin G in 6 or 4 daily doses, respectively. Children ≥5 years of age were more frequent in the 4-daily-doses subgroup (16.0% versus 4.2%; respectively,
P
= 0.02). There were no differences between the compared subgroups in terms of final outcomes, lengths of hospitalization, durations of aqueous penicillin G use, frequencies of aqueous penicillin G substitution, or daily frequencies of tachypnea, fever, chest retraction, lower chest recession, nasal flaring, and cyanosis up to the 7th day of treatment. The studied posologic regimens were similarly effective in treating children hospitalized with a radiologically confirmed CAP diagnosis. Aqueous penicillin G (200,000 IU/kg/day) may be given in 4 daily doses to children with CAP.
Antibiotic Utilization for Acute Respiratory Tract Infections in U.S. Emergency Departments
Authors: Donnelly John P. , Baddley John W. , Wang Henry E. 
Published: December 2013

ABSTRACT
Inappropriate use of antibiotics for acute respiratory tract infections (ARTIs) has decreased in many outpatient settings. For patients presenting to U.S. emergency departments (EDs) with ARTIs, antibiotic utilization patterns are unclear. We conducted a retrospective cohort study of ED patients from 2001 to 2010 using data from the National Hospital Ambulatory Medical Care Survey (NHAMCS). We identified patients presenting to U.S. EDs with ARTIs and calculated rates of antibiotic utilization. Diagnoses were classified as antibiotic appropriate (otitis media, sinusitis, pharyngitis, tonsillitis, and nonviral pneumonia) or antibiotic inappropriate (nasopharyngitis, unspecified upper respiratory tract infection, bronchitis or bronchiolitis, viral pneumonia, and influenza).There were 126 million ED visits with a diagnosis of ARTI, and antibiotics were prescribed in 61%. Between 2001 and 2010, antibiotic utilization decreased for patients aged <5 presenting with antibiotic-inappropriate ARTI (rate ratio [RR], 0.94; confidence interval [CI], 0.88 to 1.00). Utilization also decreased significantly for antibiotic-inappropriate ARTI patients aged 5 to 19 years (RR, 0.89; CI, 0.85 to 0.94). Utilization remained stable for antibiotic-inappropriate ARTI among adult patients aged 20 to 64 years (RR, 0.99; CI, 0.97 to 1.01). Among adults, rates of quinolone use for ARTI increased significantly from 83 per 1,000 visits in 2001 to 2002 to 105 per 1,000 in 2009 to 2010 (RR, 1.08; CI, 1.03 to 1.14). Although significant progress has been made toward reduction of antibiotic utilization for pediatric patients with ARTI, the proportion of adult ARTI patients receiving antibiotics in U.S. EDs is inappropriately high. Institution of measures to reduce inappropriate antibiotic use in the ED setting is warranted.