bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative impact of thymic selection on Foxp3
+
and Foxp3
−
subsets of self-peptide/MHC class II-specific CD4
+
T cells
Authors: Moon James J. , Dash Pradyot , Oguin Thomas H. , McClaren Jennifer L. , Chu H. Hamlet , Thomas Paul G. , Jenkins Marc K.
Published: August 2011

It is currently thought that T cells with specificity for self-peptide/MHC (pMHC) ligands are deleted during thymic development, thereby preventing autoimmunity. In the case of CD4
+
T cells, what is unclear is the extent to which self-peptide/MHC class II (pMHCII)-specific T cells are deleted or become Foxp3
+
regulatory T cells. We addressed this issue by characterizing a natural polyclonal pMHCII-specific CD4
+
T-cell population in mice that either lacked or expressed the relevant antigen in a ubiquitous pattern. Mice expressing the antigen contained one-third the number of pMHCII-specific T cells as mice lacking the antigen, and the remaining cells exhibited low TCR avidity. In mice lacking the antigen, the pMHCII-specific T-cell population was dominated by phenotypically naive Foxp3
−
cells, but also contained a subset of Foxp3
+
regulatory cells. Both Foxp3
−
and Foxp3
+
pMHCII-specific T-cell numbers were reduced in mice expressing the antigen, but the Foxp3
+
subset was more resistant to changes in number and TCR repertoire. Therefore, thymic selection of self-pMHCII–specific CD4
+
T cells results in incomplete deletion within the normal polyclonal repertoire, especially among regulatory T cells.
Interleukin 37 expression protects mice from colitis
Authors: McNamee Eóin N. , Masterson Joanne C. , Jedlicka Paul , McManus Martine , Grenz Almut , Collins Colm B. , Nold Marcel F. , Nold-Petry Claudia , Bufler Philip , Dinarello Charles A. , Rivera-Nieves Jesús
Published: August 2011

IL-37, a newly described member of the IL-1 family, functions as a fundamental inhibitor of innate inflammation and immunity. In the present study, we examined a role for IL-37 during experimental colitis. A transgenic mouse strain was generated to express human IL-37 (hIL-37tg), and these mice were subjected to dextran sulfate sodium (DSS)-induced colitis. Despite the presence of a CMV promoter to drive expression of IL-37, mRNA transcripts were not present in colons at the resting state. Expression was observed only upon disruption of the epithelial barrier, with a six- to sevenfold increase (P= 0.02) on days 3 and 5 after continuous exposure to DSS. During the development of colitis, clinical disease scores were reduced by 50% (P< 0.001), and histological indices of colitis were one-third less in hIL-37tg mice compared with WT counterparts (P< 0.001). Reduced inflammation was associated with decreased leukocyte recruitment into the colonic lamina propria. In addition, release of IL-1β and TNFα from ex vivo colonic explant tissue was decreased 5- and 13-fold, respectively, compared with WT (P≤ 0.005), whereas IL-10 was increased sixfold (P< 0.001). However, IL-10 was not required for the anti-inflammatory effects of IL-37 because IL-10-receptor antibody blockade did not reverse IL-37-mediated protection. Mechanistically, IL-37 originating from hematopoietic cells was sufficient to exert anti-inflammatory effects because WT mice reconstituted with hIL-37tg bone marrow were protected from colitis. Thus, IL-37 emerges as key modulator of intestinal inflammation.
Shelf life and time horizons in the historiography of linguistics
Authors: Cram David
Published: August 2011

The aim of this paper is to outline an approach to linguistic historiography which is informed by 20th-century phenomenology and hermeneutics, but which is formulated in linguistic terms. The key concept is that of the ‘time horizons’ which delimit the context which is relevant to the interpretation of an event or text. The idea of the time horizon is here illustrated by the everyday notion of the shelf-life of consumable items. The main thrust of the argument is that the interpretation of historical events and texts necessarily involves not one but two cognitive contexts, that of the historical protagonist and that of the modern observer. The approach sets up a three-level contrast between chronography (getting the facts right), reconstruction (recounting the historical story), and interpretation (making sense of the past story in terms of present-day understandings).
Letters, sounds and things
Authors: Isermann Michael M.
Published: August 2011

For a long time, and well beyond the publication of John Wilkins’sEssay Towards a Real Character(1668), a latent tension characterised the orthographic tradition. It was caused by two incompatible principles whose problematic relationship had never been addressed. One is the idea of the logical, chronological and semiotic primacy of speech over writing, or of sound over character, a principle which lives on in modern linguistics. The other is the doctrine of an abstract unity of sound/potestasand character/figurain the letter/littera, an axiom that appears to have been abandoned only with the emancipation of modern phonetics from its former orthographic frame of reference. With the advent of the real-character movement in the 17th century, a way was suddenly opened up for the problematic issue to be discussed and resolved. Since a real, i.e., non-sound-related, character implied at least a non-priority of speech over writing — if not a priority of writing —, the first principle could be reformulated so as to be made consonant with the idea of an abstractlittera. This paper tries to bring out Wilkins’s sophisticated discussion of thelittera, his attempt to localise the abstract unity of sound and character in the configuration of the articulatory organs, as well as the utilisation of hislitteraconcept for his design of a real character of sounds. In a parallel line of argument, it is claimed that Wilkins’s orthography, or doctrine of letters, forms the conceptual equivalent to his metaphysics, or science of things. More than that, the two disciplines are so interlocked that things and letters can be seen to converge in letter-things, or thing-letters.
Pronouncing the “P”
Authors: Brewer Charlotte
Published: August 2011

During the course of the 19th century, many English dictionaries carrying information on pronunciation directed that Greek-derived words beginning ps- should be pronounced with a silent initialp. In the relevant section of theOED, however (published 1909), the editor J. A. H. Murray (1837–1915) advised that, contrary to general practice, pronouncing the p was preferable, since it made clear the etymology of such words thus enhancing their intelligibility. Dictionaries after theOEDhave reportedpas an optional pronunciation for many years subsequently — even as late as the 1970s — though their conflicting evidence supports the hypothesis that pronouncing the p was a dictionary chimaera never adopted by more than a handful of pedantic philologists. The article concludes that claims to descriptivism rather than prescriptivism, even by the most reputable dictionaries, should be taken with a pinch of salt.
The work of Richard John Lloyd (1846–1906) and “the crude system of doctrine which passes at present under the name of Phonetics”
Authors: MacMahon Michael K. C.
Published: August 2011

Richard John Lloyd (1846–1906) was a well-known Liverpool businessman who also pursued the study of phonetics, English language, literature, sociology and philosophy. His wide intellectual background embraced mathematics and physics too. His work in phonetics is characterised by a particular emphasis on the acoustics of vowel sounds, as well as by close attention to the fine detail of articulation (what he called “minute phonetics”). Alongside a small group of scientists in Europe, he was actively involved in research into the formant structure of vowels. His relatively early death meant that his work never achieved the prominence it deserved, and hence his influence has remained negligible. His work, however, bears comparison with that of colleagues in articulatory and experimental phonetics later in the 20th century.
Algonquian and Indo-European gender in a Historiographic Perspective
Authors: Kilarski Marcin
Published: August 2011

This article examines shared motifs in the history of the study of grammatical gender in North American Indian and Indo-European languages. Specifically, I investigate the degree of semantic and cultural motivation attributed to gender in Algonquian languages, and present analogies with accounts of gender in Indo-European. The presence of exceptions within animate gender in Algonquian has led to conflicting interpretations: while some focused on the arbitrary nature of the categorization, others regarded them as culturally based. Algonquian languages provide an example of how claims that have traditionally been made about Indo-European gender, particularly its supposed semantic arbitrariness, have been extended to languages apparently less suited for the purpose.
The impact of internal and external factors on linguistic performance in the home language and in L2 among Russian-Hebrew and Russian-German preschool children
Authors: Armon-Lotem Sharon , Walters Joel , Gagarina Natalia
Published: August 2011

This paper evaluates the contribution of external background factors which pertain to the child’s environment (e.g., parents’ education, parents’ occupation, family size, etc.), and internal ones which reflect the child’s time related experience with language (e.g., chronological age, age of L2 onset, etc.) to the development of linguistic skills in the two languages of bilingual children. 65 Russian-German (Mean age: 66mo, Range: 47-86mo) and 78 Russian-Israeli migrant children (Mean age: 70mo, Range: 58-81) with comparable mean length of L2 exposure (M=37mo) and family size (1.88 children) but different Socio-Economic Status (SES), were tested with a battery of language tasks and their parents were interviewed. Overall, internal, temporal, factors showed a stronger relationship to language measures than external, environmental, factors: age of L2 onset and length of L2 exposure correlated with L2, while parents’ education/occupation showed positive correlations with both L1 and L2 measures. In the Russian-German cohort, which had a sub-group with relatively lower SES, SES positively correlated with L1 success as well.
Differential effects of internal and external factors on the development of vocabulary, tense morphology and morpho-syntax in successive bilingual children
Authors: Chondrogianni Vasiliki , Marinis Theodoros
Published: August 2011

The present study investigates the effects of child internal (age/time) and child external/environmental factors on the development of a wide range of language domains in successive bilingual (L2) Turkish-English children of homogeneously low SES. Forty-three L2 children were tested on standardized assessments examining the acquisition of vocabulary and morpho-syntax. The L2 children exhibited a differential acquisition of the various domains: they were better on the general comprehension of grammar and tense morphology and less accurate on the acquisition of vocabulary and (complex) morpho-syntax. Profile effects were confirmed by the differential effects of internal and external factors on the language domains. The development of vocabulary and complex syntax was affected by internal and external factors, whereas external factors had no contribution to the development of tense morphology. These results are discussed in light of previous studies on the impact of internal and external factors in child L2 acquisition.
Developmental timing of CCM2 loss influences cerebral cavernous malformations in mice
Authors: Boulday Gwénola , Rudini Noemi , Maddaluno Luigi , Blécon Anne , Arnould Minh , Gaudric Alain , Chapon Françoise , Adams Ralf H. , Dejana Elisabetta , Tournier-Lasserve Elisabeth
Published: August 2011

Cerebral cavernous malformations (CCM) are vascular malformations of the central nervous system (CNS) that lead to cerebral hemorrhages. Familial CCM occurs as an autosomal dominant condition caused by loss-of-function mutations in one of the three CCM genes. Constitutive or tissue-specific ablation of any of the Ccm genes in mice previously established the crucial role of Ccm gene expression in endothelial cells for proper angiogenesis. However, embryonic lethality precluded the development of relevant CCM mouse models. Here, we show that endothelial-specific Ccm2 deletion at postnatal day 1 (P1) in mice results in vascular lesions mimicking human CCM lesions. Consistent with CCM1/3 involvement in the same human disease, deletion of Ccm1/3 at P1 in mice results in similar CCM lesions. The lesions are located in the cerebellum and the retina, two organs undergoing intense postnatal angiogenesis. Despite a pan-endothelial Ccm2 deletion, CCM lesions are restricted to the venous bed. Notably, the consequences of Ccm2 loss depend on the developmental timing of Ccm2 ablation. This work provides a highly penetrant and relevant CCM mouse model.
The Post-Heroic Generation: American Independent Inventors, 1900–1950
Authors: Hintz Eric S.
Published: August 2011

By World War I, the public (and later, many historians) had come to believe that teams of anonymous scientists in corporate research and development (R&D) laboratories had displaced “heroic” individual inventors like Thomas Edison and Alexander Graham Bell as the wellspring of innovation. However, the first half of the twentieth century was actually a long transitional period when lesser known independents like Chester Carlson (Xerox copier), Earl Tupper (Tupperware), Samuel Ruben (Duracell batteries), and Edwin Land (Polaroid camera) continued to make notable contributions to the overall context of innovation. Accordingly, my dissertation considers the changing fortunes of American independent inventors from approximately 1900 to 1950, a period of expanding corporate R&D, the Great Depression, and two world wars. Contrary to most interpretations of this period, I argue that individual, “post-heroic” inventors remained an important, though less visible, source of inventions in the early twentieth century.
Structural Resolution of the Complex between a Fungal Polygalacturonase and a Plant Polygalacturonase-Inhibiting Protein by Small-Angle X-Ray Scattering
Authors: Benedetti Manuel , Leggio Claudia , Federici Luca , De Lorenzo Giulia , Pavel Nicolae Viorel , Cervone Felice
Published: August 2011

We report here the low-resolution structure of the complex formed by the endo-polygalacturonase from Fusarium phyllophilum and one of the polygalacturonase-inhibiting protein from Phaseolus vulgaris after chemical cross-linking as determined by small-angle x-ray scattering analysis. The inhibitor engages its concave surface of the leucine-rich repeat domain with the enzyme. Both sides of the enzyme active site cleft interact with the inhibitor, accounting for the competitive mechanism of inhibition observed. The structure is in agreement with previous site-directed mutagenesis data and has been further validated with structure-guided mutations and subsequent assay of the inhibitory activity. The structure of the complex may help the design of inhibitors with improved or new recognition capabilities to be used for crop protection.
Voriconazole versus itraconazole for antifungal prophylaxis following allogeneic haematopoietic stem‐cell transplantation
Authors: Marks David I. , Pagliuca Antonio , Kibbler Christopher C. , Glasmacher Axel , Heussel Claus‐Peter , Kantecki Michal , Miller Paul J.S. , Ribaud Patricia , Schlamm Haran T. , Solano Carlos , Cook Gordon ,   for the IMPROVIT Study Group
Published: August 2011

Antifungal prophylaxis for allogeneic haematopoietic stem‐cell transplant (alloHCT) recipients should prevent invasive mould and yeast infections (IFIs) and be well tolerated. This prospective, randomized, open‐label, multicentre study compared the efficacy and safety of voriconazole (234 patients) versus itraconazole (255 patients) in alloHCT recipients. The primary composite endpoint, success of prophylaxis, incorporated ability to tolerate study drug for ≥100 d (with ≤14 d interruption) with survival to day 180 without proven/probable IFI. Success of prophylaxis was significantly higher with voriconazole than itraconazole (48·7% vs. 33·2%, P < 0·01); more voriconazole patients tolerated prophylaxis for 100 d (53·6% vs. 39·0%, P < 0·01; median total duration 96 vs. 68 d). The most common (>10%) treatment‐related adverse events were vomiting (16·6%), nausea (15·8%) and diarrhoea (10·4%) for itraconazole, and hepatotoxicity/liver function abnormality (12·9%) for voriconazole. More itraconazole patients received other systemic antifungals (41·9% vs. 29·9%, P < 0·01). There was no difference in incidence of proven/probable IFI (1·3% vs. 2·1%) or survival to day 180 (81·9% vs. 80·9%) for voriconazole and itraconazole respectively. Voriconazole was superior to itraconazole as antifungal prophylaxis after alloHCT, based on differences in the primary composite endpoint. Voriconazole could be given for significantly longer durations, with less need for other systemic antifungals.
Strict regulation of morphological differentiation and secondary metabolism by a positive feedback loop between two global regulators AdpA and BldA in Streptomyces griseus
Authors: Higo Akiyoshi , Horinouchi Sueharu , Ohnishi Yasuo
Published: August 2011

AdpA is a global transcriptional regulator that is induced by the microbial hormone A‐factor and activates many genes required for morphological differentiation and secondary metabolism in Streptomyces griseus. We confirmed that the regulatory tRNA gene bldA was required for translation of TTA‐containing adpA. We also demonstrated that AdpA bound two sites upstream of the bldA promoter and activated transcription of bldA. Thus, we revealed a unique positive feedback loop between AdpA and BldA in S. griseus. Forced expression of bldA in an A‐factor‐deficient mutant resulted in the partial restoration of aerial mycelium formation and streptomycin production, suggesting that the positive feedback loop could prevent premature transcriptional activation of the AdpA‐target genes in the wild‐type strain. We revealed that the morphological defect of the bldA mutant could be attributed mainly to the TTA codons of only two genes: adpA and amfR. amfR encodes a transcriptional activator essential for aerial mycelium formation and is a member of the AdpA regulon. Thus, amfR is regulated by a feedforward mechanism involving AdpA and BldA. We concluded that the central regulatory unit composed of AdpA and BldA plays important roles in the initiation of morphological differentiation and secondary metabolism triggered by A‐factor.
The prevalence of actinic cheilitis in farmers in a semi‐arid northeastern region of Brazil
Authors: Martins‐Filho Paulo Ricardo Saquete , Da Silva Luiz Carlos Ferreira , Piva Marta Rabello
Published: August 2011

Background  Actinic cheilitis (AC) is a potentially malignant disorder of the lip caused by chronic exposure to solar radiation. Despite being a relatively common lesion in tropical countries, the data related to AC prevalence in Brazil are sparse, particularly in regions with high levels of ultraviolet radiation.

Objective  To estimate AC prevalence among farmers in a semiarid northeastern Brazil.

Methods  Cross‐sectional study was carried out involving a representative sample (n = 240) of the farm workers. Sociodemographic, clinical, and histopathological variables were analyzed.

Results  AC prevalence was 16.7% [95% confidence interval (CI): 12.0% to 21.4%]. The disease was more prevalent in males [prevalence ratio (PR) = 2.72; 95% CI: 1.52–4.90], fair‐skinned farmers (PR = 2.07; 95% CI: 1.00–4.30), age over 50 years (PR = 2.91; 95% CI: 1.40–6.04), daily exposure time more than eight hours (PR = 1.84; 95% CI: 1.03–3.27), and among smokers/ex‐smokers (PR = 2.17; 95% CI: 1.22–3.87). Mantel–Haenszel test showed a positive relationship between cumulative exposure time and development of AC (P < 0.001). Two cases were diagnosed as microinvasive squamous cell carcinoma.

Conclusions  Our results suggest that farmers in this semiarid area have a high risk of lip cancer and indicate the need for health public programs in the early detection of AC and education to teach the population about precautions to be taken during sun exposure.
Pneumocystis pneumonia in patients with immunobullous dermatoses
Authors: Li Feng , Jin Hong‐Zhong , Su Fei , Jia Li , Sun Qiu‐Ning
Published: August 2011

Background  Immunobullous dermatoses are usually treated with immunosuppressive agents, which make patients susceptible to pneumocystis pneumonia (PCP). The aim of this study was to evaluate the incidence and clinical characteristics of PCP in patients with immunobullous diseases.

Methods  We analyzed computerized medical records to obtain a retrospective evaluation of the incidence and clinical characteristics of PCP in patients with immunobullous diseases, hospitalized at the Peking Union Medical College Hospital from January 2004 to December 2009.

Results  Of 202 patients with immunobullous disorders, four (1.9%) had PCP; two of them had pemphigus vulgaris (PV), one had pemphigus foliaceus (PF), and one suffered from bullous pemphigoid (BP). All four patients had been treated with corticosteroids and a cytotoxic agent before diagnosis of PCP. Three of the four patients developed PCP within 14 weeks of the diagnosis of an immunobullous disease. Average and maximal prednisone doses were 0.98 mg/kg per day and 1.8 mg/kg per day, respectively. The median durations of prednisone doses >1.0 mg/kg per day and >1.5 mg/kg per day were 6.5 weeks and 4 weeks, respectively. Lymphocyte counts ranged from 330/μl to 1200/μl at the time of diagnosis of PCP. Additional complicating infections were found in three of the four patients. In all four patients, PCP was treated with trimethoprim‐sulfamethoxazole and corticosteroids. Skin lesions were under control at the onset of PCP and did not flare during the treatment of PCP; however, two of the four patients died.

Conclusions  Fewer than 2% of subjects in our large series of patients with immunobullous diseases contracted PCP. Nevertheless, it is important to remain alert for PCP in patients with immunobullous diseases who are undergoing treatment with prednisone and cytotoxic agent(s).
Post‐kala‐azar dermal leishmaniasis: recent developments
Authors: Singh Sarman , Sharma Umakant , Mishra Jyotsna
Published: August 2011

A substantial number of patients who recover from kala‐azar will develop dermatosis [commonly known as post‐kala‐azar dermal leishmaniasis (PKDL)]. It usually occurs in the Indian subcontinent and East Africa. As many as 10–20% of Indian cases and 50–60% of Sudanese cases develop PKDL after successful treatment of visceral leishmaniasis. Most cases occur after infection with Leishmania donovani and less commonly after Leishmania infantum. However, the PKDL is extremely rare in patients infected with Leishmania chagasi. Though exact pathology is not yet fully known, here we review various evidence, which suggest that the pathogenesis is largely immunologically mediated. Our group has been of the opinion that PKDL disease manifestation is a result of in‐vivo generation of quasi‐species either as in‐vivo hybridization of various circulating and latent populations of the causative species within the host cells or due to external reinfection. We, and other scientists, have recently demonstrated that strains of Leishmania that cause visceral diseases differ genetically from those that cause PKDL. We feel that this review will incite interest in several parasitologists and molecular biologists in the pathogenesis of this important manifestation of the infection, often blamed as the source of outbreaks of leishmaniasis.
Cats during gestation and lactation fed with canned food ad libitum: energy and protein intake, development of body weight and body composition
Authors: Wichert B. , Signer M. , Uebelhart D.
Published: August 2011

The NRC recommendations for cats for energy and protein supply during gestation and lactation are based on limited data. This study aimed to answer the question: Can the energy requirement be met with canned food or is the volume restrictive? Therefore, balance trials were conducted in 10 queens before mating, during the 4th and 7th week of gestation and during the 2nd and 6th week of lactation. The cats were fed with canned food ad libitum. Additionally, the body composition of the queens was measured by dual‐energy X‐ray absorptiometry (Dexa) before mating, after parturition and after weaning. Eight of 10 cats presented increased body fat content and lean body mass during gestation. The weight loss during lactation led to a loss of lean body mass, but only six cats lost body fat of widely differing amounts. It was evident that the queens’ dry matter intake was consistent with that of queens fed ad libitum with dry food. The cats lost lean body mass during lactation and had negative protein balances in the 2nd week of lactation. This seems to be physiological in early lactation. Nevertheless, the protein recommendations for lactation seem to be too low.
Weak large‐scale population genetic structure in a philopatric seabird, the European Shag Phalacrocorax aristotelis
Authors: BARLOW EMILY J. , DAUNT FRANCIS , WANLESS SARAH , ÁLVAREZ DAVID , REID JANE M. , CAVERS STEPHEN
Published: August 2011

Quantifying population genetic structure is fundamental to testing hypotheses regarding gene flow, population divergence and dynamics across large spatial scales. In species with highly mobile life‐history stages, where it is unclear whether such movements translate into effective dispersal among discrete philopatric breeding populations, this approach can be particularly effective. We used seven nuclear microsatellite loci and mitochondrial DNA (ND2) markers to quantify population genetic structure and variation across 20 populations (447 individuals) of one such species, the European Shag, spanning a large geographical range. Despite high breeding philopatry, rare cross‐sea movements and recognized subspecies, population genetic structure was weak across both microsatellites and mitochondrial markers. Furthermore, although isolation‐by‐distance was detected, microsatellite variation provided no evidence that open sea formed a complete barrier to effective dispersal. These data suggest that occasional long‐distance, cross‐sea movements translate into gene flow across a large spatial scale. Historical factors may also have shaped contemporary genetic structure: cluster analyses of microsatellite data identified three groups, comprising colonies at southern, mid‐ and northern latitudes, and similar structure was observed at mitochondrial loci. Only one private mitochondrial haplotype was found among subspecies, suggesting that this current taxonomic subdivision may not be mirrored by genetic isolation.
Mutation of tryptophanase gene tnaA in Edwardsiella tarda reduces lipopolysaccharide production, antibiotic resistance and virulence
Authors: Han Yin , Yang Chun‐Li , Yang Qian , Qi Zizhong , Liu Wenzheng , Xu Zhi‐Hong , Zhu Wei‐Ming , Bossier Peter , Zhang Xiao‐Hua
Published: August 2011

A fish pathogen Edwardsiella tarda LTB‐4 produced various indole alkaloids, including indole, 2‐(1H‐indol‐3‐yl)ethanol, 4‐di(1H‐indol‐3‐yl)methylphenol, tri(1H‐indol‐3‐yl)methane and 2‐[2,2‐bis(1H‐indol‐3‐yl)]ethylphenylamine. Indole was the most abundant among these indole alkaloids. E. tarda LTB‐4 produced indoles during its whole growth phase and maintained a high level (around 35.5 µM) during the stationary phase. The relevant tryptophanase (TnaA) gene tnaA was cloned from LTB‐4 and conditionally expressed in Escherichia coli; the recombinant TnaA catalysed L‐tryptophan to indole. A tnaA in‐frame deletion mutant ΔtnaA was constructed through double cross‐over allelic exchange by means of the suicide vector pRE118; deletion of tnaA caused some phenotypic changes including decreased swarming and twitching motility, lipopolysaccharide production and multiple antibiotic resistances. Also, subtherapeutic doses of chloromycetin, carbenicillin and tetracyline could cause the decrease of bacterial growth, but greatly induce the production of indole by E. tarda. Most importantly, attenuated virulence of the ΔtnaA mutant to zebra fish by increasing the LD50 for about 55‐fold indicated that TnaA involved in the virulence of E. tarda.
Excessive erythrocytosis compromises the blood–endothelium interface in erythropoietin‐overexpressing mice
Authors: Richter Vincent , Savery Michele D. , Gassmann Max , Baum Oliver , Damiano Edward R. , Pries Axel R.
Published: August 2011

Non‐Technical Summary  Elevated systemic haematocrit (Hct) increases cardiovascular risk, such as stroke and myocardial infarction. One possible pathophysiological mechanism could be a disturbance of the blood–endothelium interface. It has been shown that blood interacts with the endothelial surface via a gel‐like layer (the ‘glycocalyx’, or ‘endothelial surface layer’– ESL) that modulates various biological processes, including inflammation, permeability and atherosclerosis. However, the consequences of an elevated Hct on the functional properties of this interface are incompletely understood. In a transgenic mouse (tg6) model exhibiting systemic Hct levels of about 0.85 the glycocalyx/ESL was nearly abolished. The corresponding increase in vessel diameter had only minor effects on peripheral flow resistance. This suggests that the pathological effects of elevated Hct may relate more strongly to the biological corollaries of a reduced ESL thickness and alterations of the blood–endothelium interface than to an increased flow resistance.
Pulsatile Poiseuille Flow of a Viscoplastic Fluid in the Gap Between Coaxial Cylinders
Authors: Daprà Irene , Scarpi Giambattista
Published: August 2011

Several materials that are of interest in engineering present a yield stress and behave as viscoplastic fluids. This paper investigates numerically the motion of a Bingham fluid between two coaxial cylinders due to a periodic pressure gradient and/or to the periodic displacement of the internal cylinder. The constitutive equation presents a discontinuity at the zero shear rate. To overcome the difficulty, the rheologic law has been regularized using a smooth function based on the error function. The velocity fields have been calculated using an implicit finite difference method. The procedure has been validated, comparing the numerical results with the analytical solution of the same problem for a Newtonian fluid. The nonlinear behavior of the fluid is emphasized, comparing the effects due to the simultaneous action of the pressure gradient and the displacement of the internal wall with the sum of the effects due to the single actions. In all cases, the mean discharge in a period increases. The comparison between the effects of the forcing agents shows that if the dimensionless frequency is less than 10 the increases of the discharge obtained by applying the pulsatile pressure gradient or moving the internal wall are similar. At low frequencies the action of the gradient exceeds that of the moving wall, whereas for higher frequencies the effect of the moving wall increases rapidly because a fixed displacement of the internal cylinder leads to very great values for the velocity of the internal wall.
The elusive d’Alembert-Lagrange dynamics of nonholonomic systems
Authors: Flannery M. R.
Published: August 2011

While the d’Alembert-Lagrange principle has been widely used to derive equations of state for dynamical systems under holonomic (geometric) and non-integrable linear-velocity (kinematic) constraints, its application to general kinematic constraints with a general velocity and acceleration-dependence has remained elusive, mainly because there is no clear method, whereby the set of linear conditions that restrict the virtual displacements can be easily extracted from the equations of constraint. We show how this limitation can be resolved by requiring that the states displaced by the variation are compatible with the kinematic constraints. A set of linear auxiliary conditions on the displacements is established and adjoined to the d’Alembert-Lagrange equation via Lagrange’s multipliers to yield the equations of state. As a consequence, new transpositional relations satisfied by the velocity and acceleration displacements are also established. The theory is tested for a quadratic velocity constraint and for a nonholonomic penny rolling and turning upright on an inclined plane.
Thermodynamic Venn diagrams: Sorting out forces, fluxes, and Legendre transforms
Authors: Kerr W. C. , Macosko J. C.
Published: August 2011

We show how to use a Venn diagram to illuminate the relations among the different thermodynamic potentials, forces, and fluxes of a simple system. A single diagram shows all of the thermodynamic potentials obtainable by Legendre transformations starting from the internal energy as the fundamental potential. From the diagram, we can also read off the Maxwell relations deduced from each of these potentials. We construct a second Venn diagram that shows the analogous information for the Massieu functions, obtained by Legendre transformations starting from the entropy as the fundamental thermodynamic function.
Motion on a vertical loop with friction
Authors: Kłobus Waldemar
Published: August 2011

A well known problem in elementary mechanics is the minimum height needed for an object sliding down a frictionless inclined plane to reach the top of a frictionless circular loop. A generalization of this problem to include the effects of sliding friction is studied. A comparison of different elliptical shapes of the track is discussed.
TBK1 Mediates Crosstalk Between the Innate Immune Response and Autophagy
Authors: Weidberg Hilla , Elazar Zvulun
Published: August 2011

Phosphorylation of an autophagy adaptor by a kinase involved in innate immune responses limits pathogenic bacterial growth.
ArmA Methyltransferase in a Monophasic Salmonella enterica Isolate from Food
Authors: Granier Sophie A. , Hidalgo Laura , San Millan Alvaro , Escudero Jose Antonio , Gutierrez Belen , Brisabois Anne , Gonzalez-Zorn Bruno
Published: August 2011

The 16S rRNA methyltransferase ArmA is a worldwide emerging determinant that confers high-level resistance to most clinically relevant aminoglycosides. We report here the identification and characterization of a multidrug-resistant
Salmonella enterica
subspecies I.4,12:i:− isolate recovered from chicken meat sampled in a supermarket on February 2009 in La Reunion, a French island in the Indian Ocean. Susceptibility testing showed an unusually high-level resistance to gentamicin, as well as to ampicillin, expanded-spectrum cephalosporins and amoxicillin-clavulanate. Molecular analysis of the 16S rRNA methyltransferases revealed presence of the
armA
gene, together with
bla
TEM-1
,
bla
CMY-2
, and
bla
CTX-M-3
. All of these genes could be transferred
en bloc
through conjugation into
Escherichia coli
at a frequency of 10
−5
CFU/donor. Replicon typing and S1 pulsed-field gel electrophoresis revealed that the
armA
gene was borne on an ∼150-kb broad-host-range IncP plasmid, pB1010. To elucidate how
armA
had integrated in pB1010, a PCR mapping strategy was developed for Tn
1548
, the genetic platform for
armA.
The gene was embedded in a Tn
1548
-like structure, albeit with a deletion of the macrolide resistance genes, and an IS
26
was inserted within the
mel
gene. To our knowledge, this is the first report of ArmA methyltransferase in food, showing a novel route of transmission for this resistance determinant. Further surveillance in food-borne bacteria will be crucial to determine the role of food in the spread of 16S rRNA methyltransferase genes worldwide.
Meningeal Inflammation Increases Artemether Concentrations in Cerebrospinal Fluid in Papua New Guinean Children Treated with Intramuscular Artemether
Authors: Manning Laurens , Laman Moses , Page-Sharp Madhu , Salman Sam , Hwaiwhanje Ilomo , Morep Namar , Siba Peter , Mueller Ivo , Karunajeewa Harin A. , Davis Timothy M. E.
Published: August 2011

Although the artemisinin-associated neurotoxicity identified
in vitro
and in animal studies has not been confirmed clinically, only one adult study has measured cerebrospinal fluid (CSF) concentrations after administration of conventional doses. Potential artemisinin neurotoxicity could be serious in children, especially those with meningitis and, consequently, a compromised blood-brain barrier. We measured CSF/plasma artemether and dihydroartemisinin (DHA) concentrations in 32 Papua New Guinean children with a mean age of 39 months with suspected or proven severe falciparum malaria who underwent a single lumbar puncture after intramuscular artemether administration. CSF artemether concentrations were 0 to 43.5 μg/liter and CSF concentration/plasma concentration ratios were 0 to 38.1%. DHA was measurable in CSF in only two children. The seven children with meningeal inflammation (CSF white cell count > 20/mm
3
) had higher CSF artemether concentration/plasma artemether concentration ratios than those without (median, 6.7% [interquartile ratio, 2.5 to 27.8%]% versus 0.0% [interquartile ratio, 0.0 to 2.5%];
P
= 0.002). Meningeal inflammation was associated with a 4.6-fold increase in the CSF artemether concentration/plasma artemether concentration ratio in a population pharmacokinetic model. These data suggest that pharmacovigilance should be heightened when intramuscular artemether is given to severely ill children with evidence of meningeal inflammation.
Daptomycin, Fosfomycin, or Both for Treatment of Methicillin-Resistant Staphylococcus aureus Osteomyelitis in an Experimental Rat Model
Authors: Poeppl W. , Tobudic S. , Lingscheid T. , Plasenzotti R. , Kozakowski N. , Lagler H. , Georgopoulos A. , Burgmann H.
Published: August 2011

The
in vivo
activities of daptomycin, fosfomycin, and a combination of both antibiotics against a clinical isolate of methicillin-resistant
Staphylococcus aureus
(daptomycin MIC, 0.25 μg/ml; fosfomycin MIC, 0.5 μg/ml) were evaluated in a rat model of osteomyelitis. A total of 37 rats with experimental osteomyelitis were treated for 4 weeks with either 60 mg/kg of body weight of daptomycin subcutaneously once daily, 75 mg/kg fosfomycin intraperitoneally once daily, a combination of both drugs, or a saline placebo. After the completion of treatment, animals were euthanized, and the infected tibiae were processed for quantitative bacterial culture. Bone cultures were found to be positive for methicillin-resistant
S. aureus
in 9 of 9 (100%) animals of the placebo group, in 9 of 9 (100%) animals treated with daptomycin, in 1 of 10 (10%) fosfomycin-treated rats, and in 1 of 9 (22.2%) rats comprising the combination group. Results of bacterial counts in the bone samples were expressed as log
10
CFU/g of bone and analyzed by using the Mann-Whitney U test followed by Bonferroni's multiple-comparison test. Based on bacterial counts, treatment with daptomycin was significantly superior to placebo, although it remained inferior to treatment with fosfomycin. No synergistic or antagonistic effect was observed for the combination therapy. No development of resistance against daptomycin or fosfomycin was observed after the 4-week treatment period.
A Burkholderia pseudomallei Macrophage Infectivity Potentiator-Like Protein Has Rapamycin-Inhibitable Peptidylprolyl Isomerase Activity and Pleiotropic Effects on Virulence
Authors: Norville Isobel H. , Harmer Nicholas J. , Harding Sarah V. , Fischer Gunter , Keith Karen E. , Brown Katherine A. , Sarkar-Tyson Mitali , Titball Richard W.
Published: August 2011

Macrophage infectivity potentiators (Mips) are a group of virulence factors encoded by pathogenic bacteria such as
Legionella
,
Chlamydia
, and
Neisseria
species. Mips are part of the FK506-binding protein (FKBP) family, whose members typically exhibit peptidylprolyl
cis-trans
isomerase (PPIase) activity which is inhibitable by the immunosuppressants FK506 and rapamycin. Here we describe the identification and characterization of BPSS1823, a Mip-like protein in the intracellular pathogen
Burkholderia pseudomallei
. Recombinant BPSS1823 protein has rapamycin-inhibitable PPIase activity, indicating that it is a functional FKBP. A mutant strain generated by deletion of
BPSS1823
in
B. pseudomallei
exhibited a reduced ability to survive within cells and significant attenuation
in vivo
, suggesting that BPSS1823 is important for
B. pseudomallei
virulence. In addition, pleiotropic effects were observed with a reduction in virulence mechanisms, including resistance to host killing mechanisms, swarming motility, and protease production.
Optimization of the posttranslational click modification of proteins
Authors: Vrabel Milan , Kaya Emine , Prill Stefan , Ehmke Veronika , Carell Thomas
Published: August 2011

In order to develop efficient methods that would enable the synthesis of posttranslationaly modified proteins in a site-specific manner we have adopted the orthogonal pyrrolysyl-tRNA synthetase/tRNA pair to genetically encode various pyrrolysine analogs, which we were able to insert into the yellow fluorescent protein (YFP). These experiments showed that the alkene and alkyne containing amino acids5and6are superior substrates for the pyrrolysyl-tRNA synthetase and that they can be successfully incorporated into proteins. Using the Cu(I)-catalyzed Huisgen–Meldal–Sharpless click reaction, the alkyne containing YFP was finally glycosylated with various sugars. We confirmed the presence of the modified amino acids as well as the corresponding sugar modifications by HPLC-MS/MS mass spectrometry.
SELF-DUAL CONE ANALYSIS IN CONDENSED MATTER PHYSICS
Authors: MIYAO TADAHIRO
Published: August 2011

The self-dual cone — the central object of this review — is introduced. Several operator inequalities associated with the self-dual cone are defined and mathematical properties of those are investigated. In general there are infinitely many choices of self-dual cones in a Hilbert space. Each of these lead to a distinct family of operator inequalities in the Hilbert space which enables us to analyze quantum physical models with respect to several aspects. We refer to these applications as self-dual cone analysis. The focus of this review lies on the self-dual cone analysis of models in condensed matter physics. In particular, by taking a physically proper self-dual cone, the interaction term of the Hamiltonian of the system becomes attractive from a viewpoint of our new operator inequalities. This attractive term enables us to analyze the system and various aspects of physical interest in detail. For instance, if the attractive term is ergodic, it is shown that the ground state is unique. By the uniqueness and the conservation laws, the physically symmetric state is realized as the ground state. This could be regarded as a physical order. As applications, the BCS model and the one-dimensional Fröhlich model are studied. We explain, from a viewpoint of the self-dual cone analysis, the appearance of macroscopic phase angles in the superconductors, Josephson effect and the Peierls instability.
ON THE UNRUH EFFECT IN DE SITTER SPACE
Authors: CASADIO R. , CHIODINI S. , ORLANDI A. , ACQUAVIVA G. , DI CRISCIENZO R. , VANZO L.
Published: August 2011

We give an interpretation of the temperature in de Sitter universe in terms of a dynamical Unruh effect associated with the Hubble sphere. As with the quantum noise perceived by a uniformly accelerated observer in static spacetimes, observers endowed with a proper motion can in principle detect the effect. In particular, we study a "Kodama observer" as a two-field Unruh detector for which we show the effect is approximately thermal. We also estimate the back-reaction of the emitted radiation and find trajectories associated with the Kodama vector field are stable.
SECOND-ORDER CORRECTIONS TO THE NONCOMMUTATIVE KLEIN–GORDON EQUATION WITH A COULOMB POTENTIAL
Authors: ZAIM SLIMANE , KHODJA LAMINE , DELENDA YAZID
Published: August 2011

We improve the previous study of the Klein–Gordon equation in a noncommutative space–time as applied to the hydrogen atom to extract the energy levels, by considering the second-order corrections in the noncommutativity parameter. Phenomenologically we show that noncommutativity is the source of Lamb shift corrections.
ENHANCEMENT OF COIR FIBER NORMAL INCIDENCE SOUND ABSORPTION COEFFICIENT
Authors: HOSSEINI FOULADI MOHAMMAD , NOR MOHD. JAILANI MOHD. , AYUB MD. , GHASSEM MASOMEH
Published: August 2011

Coir fiber from coconut husk is an important agricultural waste in Malaysia. The porous structure of fiber makes it an eligible material for acoustical absorption. In previous studies at Universiti Kebangsaan Malaysia, single layer coir fiber showed low acoustical absorption in medium and low frequencies; e.g. absorption coefficient of a 20 mm industrial prepared coir fiber sample was below 0.3 for frequencies less than 1.5 kHz. Current research was initiated to improve the shortcoming by mixing industrial prepared coir fiber with air gap layers. Analyzes were based on two approaches, namely; Delany–Bazley with acoustic transmission analysis (ATA) and Allard elastic model with transfer matrix analysis. Experimental measurements were conducted in impedance tube to validate the analytical results. Outcomes described that Delany–Bazley-ATA technique was an approximate solution showing overall absorption path without giving any accurate information about the peaks and resonances. Allard method took the elasticity of material into account and transfer matrices were able to characterize the whole structure as a combination of single layers. Results were close to experimental values and predicted the path and resonances very well. Further analyzes were conducted by Allard method and derived that having a fiber layer backed by an air gap was better than leaving the same gap in between that layer. The explanation was that, in the first arrangement, the sound field impacted a solid layer with higher thickness and followed a longer transmission path which caused a higher acoustical absorption. Furthermore, it was noticed that a reasonable thickness of backing air gap improved the overall sound absorption. Increase in the gap thickness produced more peaks and moved them to lower frequencies which caused better absorption in low frequencies. The cause of this phenomenon was increase in impedance of the panel due to rise in the air-gap thickness. This moved the acoustical resonances to lower frequencies and improved the sound absorption in this frequency span. Finally, it was concluded that other acoustic absorption techniques such as adding perforated plate may be combined with coir fiber-air gap structure to improve the low frequency acoustic absorption coefficient without any need to highly increase the air gap thickness.
AGENTS OF CHANGE: MODELING BIOCULTURAL EVOLUTION IN UPPER PLEISTOCENE WESTERN EURASIA
Authors: BARTON C. MICHAEL , RIEL-SALVATORE JULIEN
Published: August 2011

The complex interactions between social learning and biological change are key to understanding the human species and its origins. Yet paleoanthropological models often focus only on the evolution of the human genome and physical characters, while behavior is treated as an epiphenomenon of biological evolution. We present the results of a series of experiments that use computational models, parametrized with new archaeological data, to simulate the complex dynamics of human biocultural evolution in the changing environment of OIS (Oxygen Isotope Stage) 3 of western Eurasia (~58000–27000 ka). These experiments allow us to compare alternative trajectories of human evolution, resulting from differing combinations of socioecological behaviors and biological conditions, against the paleoanthropological record.