bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic Antifungal Prescribing in Neonates and Children: Outcomes from the Antibiotic Resistance and Prescribing in European Children (ARPEC) Study
Authors: Lestner J. M. , Versporten A. , Doerholt K. , Warris A. , Roilides E. , Sharland M. , Bielicki J. , Goossens H.
Published: November 2014

The appropriate use of systemic antifungals is vital in the prevention and treatment of invasive fungal infection (IFI) in immunosuppressed children and neonates. This multicenter observational study describes the inpatient prescribing practice of antifungal drugs for children and neonates and identifies factors associated with prescribing variability. A single-day point prevalence study of antimicrobial use in hospitalized neonates and children was performed between October and December 2012. The data were entered through a study-specific Web-based portal using a standardized data entry protocol. Data were recorded from 17,693 patients from 226 centers. A total of 136 centers recorded data from 1,092 children and 380 neonates receiving at least one antifungal agent. The most frequently prescribed systemic antifungals were fluconazole (
n
= 355) and amphotericin B deoxycholate (
n
= 195). The most common indications for antifungal administration in children were medical prophylaxis (
n
= 325), empirical treatment of febrile neutropenia (
n
= 122), and treatment of confirmed or suspected IFI (
n
= 100 [14%]). The treatment of suspected IFI in low-birthweight neonates accounted for the majority of prescriptions in the neonatal units (
n
= 103). An analysis of variance (ANOVA) demonstrated no significant effect of clinical indication (prophylaxis or treatment of systemic or localized infection) on the total daily dose (TDD). Fewer than one-half of the patients (
n
= 371) received a TDD within the dosing range recommended in the current guidelines. Subtherapeutic doses were prescribed in 416 cases (47%). The predominance of fluconazole and high incidence of subtherapeutic doses in participating hospitals may contribute to suboptimal clinical outcomes and an increased predominance of resistant pathogenic fungi. A global consensus on antifungal dosing and coordinated stewardship programs are needed to promote the consistent and appropriate use of antifungal drugs in neonates and children.
FabH Mutations Confer Resistance to FabF-Directed Antibiotics in Staphylococcus aureus
Authors: Parsons Joshua B. , Yao Jiangwei , Frank Matthew W. , Rock Charles O.
Published: November 2014

Delineating the mechanisms for genetically acquired antibiotic resistance is a robust approach to target validation and anticipates the evolution of clinical drug resistance. This study defines a spectrum of mutations in
fabH
that render
Staphylococcus aureus
resistant to multiple natural products known to inhibit the elongation condensing enzyme (FabF) of bacterial type II fatty acid synthesis. Twenty independently isolated clones resistant to platensimycin, platencin, or thiolactomycin were isolated. All mutants selected against one antibiotic were cross-resistant to the other two antibiotics. Mutations were not detected in
fabF
, but the resistant strains harbored missense mutations in
fabH
. The altered amino acids clustered in and around the FabH active-site tunnel. The mutant FabH proteins were catalytically compromised based on the low activities of the purified enzymes, a fatty acid-dependent growth phenotype, and elevated expression of the
fabHF
operon in the mutant strains. Independent manipulation of
fabF
and
fabH
expression levels showed that the FabH/FabF activity ratio was a major determinant of antibiotic sensitivity. Missense mutations that reduce FabH activity are sufficient to confer resistance to multiple antibiotics that bind to the FabF acyl-enzyme intermediate in
S. aureus
.
Dietary Polyunsaturated Fatty Acids Increase Survival and Decrease Bacterial Load during Septic Staphylococcus aureus Infection and Improve Neutrophil Function in Mice
Authors: Svahn Sara L. , Grahnemo Louise , Pálsdóttir Vilborg , Nookaew Intawat , Wendt Karl , Gabrielsson Britt , Schéle Erik , Benrick Anna , Andersson Niklas , Nilsson Staffan , Johansson Maria E. , Jansson John-Olov
Published: November 2014

Severe infection, including sepsis, is an increasing clinical problem that causes prolonged morbidity and substantial mortality. At present, antibiotics are essentially the only pharmacological treatment for sepsis. The incidence of resistance to antibiotics is increasing; therefore, it is critical to find new therapies for sepsis.
Staphylococcus aureus
is a major cause of septic mortality. Neutrophils play an important role in the defense against bacterial infections. We have shown that a diet with high levels of dietary saturated fatty acids decreases survival in septic mice, but the mechanisms behind this remain elusive. The aim of the present study was to investigate how the differences in dietary fat composition affect survival and bacterial load after experimental septic infection and neutrophil function in uninfected mice. We found that, after
S. aureus
infection, mice fed a polyunsaturated high-fat diet (HFD-P) for 8 weeks had increased survival and decreased bacterial load during sepsis compared with mice fed a saturated high-fat diet (HFD-S), similar to mice fed a low-fat diet (LFD). Uninfected mice fed HFD-P had a higher frequency of neutrophils in bone marrow than mice fed HFD-S. In addition, mice fed HFD-P had a higher frequency of neutrophils recruited to the site of inflammation in response to peritoneal injection of thioglycolate than mice fed HFD-S. Differences between the proportion of dietary protein and carbohydrate did not affect septic survival at all. In conclusion, polyunsaturated dietary fat increased both survival and efficiency of bacterial clearance during septic
S. aureus
infection. Moreover, this diet increased the frequency and chemotaxis of neutrophils, key components of the immune response to
S. aureus
infections.
Transcriptional Profiling of Human Epithelial Cells Infected with Plasmid-Bearing and Plasmid-Deficient Chlamydia trachomatis
Authors: Porcella Stephen F. , Carlson John H. , Sturdevant Daniel E. , Sturdevant Gail L. , Kanakabandi Kishore , Virtaneva Kimmo , Wilder Hannah , Whitmire William M. , Song Lihua , Caldwell Harlan D.
Published: November 2014

Chlamydia trachomatisis an obligate intracellular epitheliotropic bacterial pathogen of humans. Infection of the eye can result in trachoma, the leading cause of preventable blindness in the world. The pathophysiology of blinding trachoma is driven by multiple episodes of reinfection of conjunctival epithelial cells, producing an intense chronic inflammatory response resulting in submucosal tissue remodeling and scarring. Recent reports have shown that infection with trachoma organisms lacking the cryptic chlamydial plasmid is highly attenuated in macaque eyes, a relevant experimental model of human trachoma infection. To better understand the molecular basis of plasmid-mediated infection attenuation and the potential modulation of host immunity, we conducted transcriptional profiling of human epithelial cells infected withC. trachomatisplasmid-bearing (A2497) and plasmid-deficient (A2497P−) organisms. Infection of human epithelial cells with either strain increased the expression of host genes coding for proinflammatory (granulocyte-macrophage colony-stimulating factor [GM-CSF], macrophage colony-stimulating factor [MCSF], interleukin-6 [IL-6], IL-8, IL-1α, CXCL1, CXCL2, CXCL3, intercellular adhesion molecule 1 [ICAM1]), chemoattraction (CCL20, CCL5, CXCL10), immune suppression (PD-L1, NFKB1B, TNFAIP3, CGB), apoptosis (CASP9, FAS, IL-24), and cell growth and fibrosis (EGR1 and IL-20) proteins. Statistically significant increases in the levels of expression of many of these genes were found in A2497-infected cells compared to the levels of expression in A2497P−-infected cells. Our findings suggest that the chlamydial plasmid plays a focal role in the host cell inflammatory response to infection and immune avoidance. These results provide new insights into the role of the chlamydial plasmid as a chlamydial virulence factor and its contributions to trachoma pathogenesis.
Pleiotropic Effects of Cell Wall Amidase LytA on Streptococcus pneumoniae Sensitivity to the Host Immune Response
Authors: Ramos-Sevillano Elisa , Urzainqui Ana , Campuzano Susana , Moscoso Miriam , González-Camacho Fernando , Domenech Mirian , Rodríguez de Córdoba Santiago , Sánchez-Madrid Francisco , Brown Jeremy S. , García Ernesto , Yuste Jose
Published: November 2014

The complement system is a key component of the host immune response for the recognition and clearance of
Streptococcus pneumoniae
. In this study, we demonstrate that the amidase LytA, the main pneumococcal autolysin, inhibits complement-mediated immunity independently of effects on pneumolysin by a complex process of impaired complement activation, increased binding of complement regulators, and direct degradation of complement C3. The use of human sera depleted of either C1q or factor B confirmed that LytA prevented activation of both the classical and alternative pathways, whereas pneumolysin inhibited only the classical pathway. LytA prevented binding of C1q and the acute-phase protein C-reactive protein to
S. pneumoniae
, thereby reducing activation of the classical pathway on the bacterial surface. In addition, LytA increased recruitment of the complement downregulators C4BP and factor H to the pneumococcal cell wall and directly cleaved C3b and iC3b to generate degradation products. As a consequence, C3b deposition and phagocytosis increased in the absence of LytA and were markedly enhanced for the
lytA ply
double mutant, confirming that a combination of LytA and Ply is essential for the establishment of pneumococcal pneumonia and sepsis in a murine model of infection. These data demonstrate that LytA has pleiotropic effects on complement activation, a finding which, in combination with the effects of pneumolysin on complement to assist with pneumococcal complement evasion, confirms a major role of both proteins for the full virulence of the microorganism during septicemia.
Accumulation of Novel Glycolipids and Ornithine Lipids in Mesorhizobium loti under Phosphate Deprivation
Authors: Diercks Hannah , Semeniuk Adrian , Gisch Nicolas , Moll Hermann , Duda Katarzyna A. , Hölzl Georg
Published: November 2014

Glycolipids are found mainly in photosynthetic organisms (plants, algae, and cyanobacteria), Gram-positive bacteria, and a few other bacterial phyla. They serve as membrane lipids and play a role under phosphate deprivation as surrogates for phospholipids.Mesorhizobium lotiaccumulates different di- and triglycosyl diacylglycerols, synthesized by the processive glycosyltransferase Pgt-Ml, and two so far unknown glycolipids, which were identified in this study by mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy asO-methyl-digalactosyl diacylglycerol (Me-DGD) and glucuronosyl diacylglycerol (GlcAD). Me-DGD is a novel glycolipid, whose synthesis depends on Pgt-Ml activity and the involvement of an unknown methyltransferase, while GlcAD is formed by a novel glycosyltransferase encoded by the open reading frame (ORF)mlr2668, using UDP-glucuronic acid as a sugar donor. Deletion mutants lacking GlcAD are not impaired in growth. Our data suggest that the different glycolipids inMesorhizobiumcan mutually replace each other. This may be an adaptation mechanism to enhance the competitiveness in natural environments. A further nonphospholipid inMesorhizobiumwas identified as a hydroxylated form of an ornithine lipid with the additional hydroxy group linked to the amide-bound fatty acid, introduced by the hydroxylase OlsD. The presence of this lipid has not been reported for rhizobia yet. The hydroxy group is placed on the C-2 position of the acyl chain as determined by NMR spectroscopy. Furthermore, the isolated ornithine lipids contained up to 80 to 90%d-configured ornithine, a stereoform so far undescribed in bacteria.
Allele Variants of Enterotoxigenic Escherichia coli Heat-Labile Toxin Are Globally Transmitted and Associated with Colonization Factors
Authors: Joffré Enrique , von Mentzer Astrid , Abd El Ghany Moataz , Oezguen Numan , Savidge Tor , Dougan Gordon , Svennerholm Ann-Mari , Sjöling Åsa
Published: November 2014

EnterotoxigenicEscherichia coli(ETEC) is a significant cause of morbidity and mortality in the developing world. ETEC-mediated diarrhea is orchestrated by heat-labile toxin (LT) and heat-stable toxins (STp and STh), acting in concert with a repertoire of more than 25 colonization factors (CFs). LT, the major virulence factor, induces fluid secretion after delivery of a monomeric ADP-ribosylase (LTA) and its pentameric carrier B subunit (LTB). A study of ETEC isolates from humans in Brazil reported the existence of natural LT variants. In the present study, analysis of predicted amino acid sequences showed that the LT amino acid polymorphisms are associated with a geographically and temporally diverse set of 192 clinical ETEC strains and identified 12 novel LT variants. Twenty distinct LT amino acid variants were observed in the globally distributed strains, and phylogenetic analysis showed these to be associated with different CF profiles. Notably, the most prevalent LT1 allele variants were correlated with major ETEC lineages expressing CS1 + CS3 or CS2 + CS3, and the most prevalent LT2 allele variants were correlated with major ETEC lineages expressing CS5 + CS6 or CFA/I. LTB allele variants generally exhibited more-stringent amino acid sequence conservation (2 substitutions identified) than LTA allele variants (22 substitutions identified). The functional impact of LT1 and LT2 polymorphisms on virulence was investigated by measuring total-toxin production, secretion, and stability using GM1–enzyme-linked immunosorbent assays (GM1-ELISA) andin silicoprotein modeling. Our data show that LT2 strains produce 5-fold more toxin than LT1 strains (P< 0.001), which may suggest greater virulence potential for this genetic variant. Our data suggest that functionally distinct LT-CF variants with increased fitness have persisted during the evolution of ETEC and have spread globally.
A Conserved Domain Is Crucial for Acceptor Substrate Binding in a Family of Glucosyltransferases
Authors: Zhu Fan , Zhang Hua , Wu Hui
Published: November 2014

Serine-rich repeat glycoproteins (SRRPs) are highly conserved in streptococci and staphylococci. Glycosylation of SRRPs is important for bacterial adhesion and pathogenesis.Streptococcus agalactiaeis the leading cause of bacterial sepsis and meningitis among newborns. Srr2, an SRRP fromS. agalactiaestrain COH1, has been implicated in bacterial virulence. Four genes (gtfA,gtfB,gtfC, and gtfD) located downstream ofsrr2share significant homology with genes involved in glycosylation of other SRRPs. We have shown previously thatgtfAandgtfBencode two glycosyltransferases, GtfA and GtfB, that catalyze the transfer of GlcNAc residues to the Srr2 polypeptide. However, the function of other glycosyltransferases in glycosylation of Srr2 is unknown. In this study, we determined that GtfC catalyzed the direct transfer of glucosyl residues to Srr2-GlcNAc. The GtfC crystal structure was solved at 2.7 Å by molecular replacement. Structural analysis revealed a loop region at the N terminus as a putative acceptor substrate binding domain. Deletion of this domain rendered GtfC unable to bind to its substrate Srr2-GlcNAc, concurrently abolished the glycosyltransferase activity of GtfC, and also altered glycosylation of Srr2. Furthermore, deletion of the corresponding regions from GtfC homologs also abolished their substrate binding and enzymatic activity, indicating that this region is functionally conserved. In summary, we have determined that GtfC is important for the glycosylation of Srr2 and identified a conserved loop region that is crucial for acceptor substrate binding from GtfC homologs in streptococci. These findings shed new mechanistic insight into this family of glycosyltransferases.
Identification of a Novel Matrix Protein That Promotes Biofilm Maturation in Vibrio fischeri
Authors: Ray Valerie A. , Driks Adam , Visick Karen L.
Published: November 2014

Bacteria form communities, termed biofilms, in which cells adhere to each other within a matrix, typically comprised of polysaccharides, proteins, and extracellular DNA. Biofilm formation by the marine bacteriumVibrio fischerirequires the Syp polysaccharide, but the involvement of matrix proteins is as yet unknown. Here we identified three genes, termedbmpA, -B, and -C(biofilmmaturationprotein), with overlapping functions in biofilm maturation. A triplebmpABCmutant, but not single or double mutants, was defective in producing wrinkled colonies, a form of biofilm. Surprisingly, the triple mutant was competent to form pellicles, another biofilm phenotype, but they generally lacked a three-dimensional architecture. Transmission electron microscopy revealed that the extracellular matrix of thebmpmutant contained electron-dense, thread-like structures that were also present in the wild type but lacking insypmutant strains. We hypothesized that thebmpmutant produces the Syp polysaccharide but fails to produce/export a distinct matrix component. Indeed, a mixture of thebmpandsypmutants produced a wrinkled colony. Finally, BmpA could be detected in cell-free supernatants from disrupted pellicles. Thus, this work identifies a new matrix protein necessary for biofilm maturation byV. fischeriand, based on the conservation ofbmp, potentially other microbes.
PapR6, a Putative Atypical Response Regulator, Functions as a Pathway-Specific Activator of Pristinamycin II Biosynthesis in Streptomyces pristinaespiralis
Authors: Dun Junling , Zhao Yawei , Zheng Guosong , Zhu Hong , Ruan Lijun , Wang Wenfang , Ge Mei , Jiang Weihong , Lu Yinhua
Published: November 2014

There are up to seven regulatory genes in the pristinamycin biosynthetic gene cluster ofStreptomyces pristinaespiralis, which infers a complicated regulation mechanism for pristinamycin production. In this study, we revealed that PapR6, a putative atypical response regulator, acts as a pathway-specific activator of pristinamycin II (PII) biosynthesis. Deletion of thepapR6gene resulted in significantly reduced PII production, and its overexpression led to increased PII formation, compared to that of the parental strain HCCB 10218. However, eitherpapR6deletion or overexpression had very little effect on pristinamycin I (PI) biosynthesis. Electrophoretic mobility shift assays (EMSAs) demonstrated that PapR6 bound specifically to the upstream region ofsnaF, the first gene of thesnaFE1E2GHIJKoperon, which is likely responsible for providing the precursor isobutyryl-coenzyme A (isobutyryl-CoA) and the intermediate C11αβ-unsaturated thioester for PII biosynthesis. A signature PapR6-binding motif comprising two 4-nucleotide (nt) inverted repeat sequences (5′-GAGG-4 nt-CCTC-3′) was identified. Transcriptional analysis showed that inactivation of thepapR6gene led to markedly decreased expression ofsnaFE1E2GHIJK. Furthermore, we found that a mutant (snaFmu) with base substitutions in the identified PapR6-binding sequence in the genome exhibited the same phenotype as that of the ΔpapR6strain. Therefore, it may be concluded that pathway-specific regulation of PapR6 in PII biosynthesis is possibly exerted via controlling the provision of isobutyryl-CoA as well as the intermediate C11αβ-unsaturated thioester.
Utilization of Host Iron Sources by Corynebacterium diphtheriae: Multiple Hemoglobin-Binding Proteins Are Essential for the Use of Iron from the Hemoglobin-Haptoglobin Complex
Authors: Allen Courtni E. , Schmitt Michael P.
Published: November 2014

The use of hemin iron byCorynebacterium diphtheriaerequires the DtxR- and iron-regulated ABC hemin transporter HmuTUV and the secreted Hb-binding protein HtaA. We recently described two surface anchored proteins, ChtA and ChtC, which also bind hemin and Hb. ChtA and ChtC share structural similarities to HtaA; however, a function for ChtA and ChtC was not determined. In this study, we identified additional host iron sources that are utilized byC. diphtheriae. We show that severalC. diphtheriaestrains use the hemoglobin-haptoglobin (Hb-Hp) complex as an iron source. We report that anhtaAdeletion mutant ofC. diphtheriaestrain 1737 is unable to use the Hb-Hp complex as an iron source, and we further demonstrate that achtA-chtCdouble mutant is also unable to use Hb-Hp iron. Single-deletion mutants ofchtAorchtCuse Hb-Hp iron in a manner similar to that of the wild type. These findings suggest that both HtaA and either ChtA or ChtC are essential for the use of Hb-Hp iron. Enzyme-linked immunosorbent assay (ELISA) studies show that HtaA binds the Hb-Hp complex, and the substitution of a conserved tyrosine (Y361) for alanine in HtaA results in significantly reduced binding.C. diphtheriaewas also able to use human serum albumin (HSA) and myoglobin (Mb) but not hemopexin as iron sources. These studies identify a biological function for the ChtA and ChtC proteins and demonstrate that the use of the Hb-Hp complex as an iron source byC. diphtheriaerequires multiple iron-regulated surface components.
Intussusception during pregnancy after laparoscopic Roux-en-Y gastric bypass
Authors: Bokslag Anouk , Jebbink Jiska , Wit Laurens De , Oudijk Martijn , Ribbert Lucie , Tahri Sabrin , Pampus Mariëlle van
Published: November 2014

In fertile women, the laparoscopic Roux-en-Y gastric bypass (LRYGB) is being increasingly performed. Pregnancy and LRYGB both give an increased risk of intussusception, which can lead to bowel necrosis, sepsis and preterm labour. We describe two pregnant women with a history of LRYGB who presented to the emergency department with non-specific abdominal pain. Both were diagnosed with intussusception. These cases illustrate that intussusception should be considered in pregnant women with a history of LRYGB who present with non-specific abdominal pain. Only MRI, CT scan or diagnostic laparoscopy is sufficient for diagnosis. Early diagnosis may prevent serious complications.
Tumour-associated osteomalacia and hypoglycaemia in a patient with prostate cancer: is Klotho involved?
Authors: Latifyan Sofiya Bedo , Vanhaeverbeek Michel , Klastersky Jean
Published: November 2014

Tumour-associated osteomalacia is a paraneoplastic syndrome caused by renal phosphate wasting, leading to severe hypophosphataemia. Excess of circulating fibroblast growth factor 23 (FGF23) is the likely cause, acting via the FGF23/α-Klotho coreceptor, a critical regulator of phosphate metabolism. The other possible effects of that complex in humans are still under investigation. We present a case of an 84-year-old Belgian man, presenting prostate cancer with bone metastases. From June 2010 to March 2013, he presented three episodes of disease progression. From January 2012, the patient developed a progressively marked dorsal kyphosis with significant hypophosphataemia. The calculated TRP (tubular reabsorption of phosphate) was decreased and the FGF23 increased. Mid-March 2013, the patient died after a profound unconsciousness due to hypoglycaemia with hypothermia. We hypothesised that the two paraneoplastic manifestations of this patient (tumour-associated osteomalacia and refractory hypoglycaemia) were due to one cause chain with two main nodes—FGF23 and its coreceptor Klotho..
Gemella morbillorumprosthetic aortic valve endocarditis
Authors: Shahani Lokesh
Published: November 2014

Gemella morbillorumis facultative anaerobic, Gram-positive cocci and are a commensal part of human flora. The reported patient in this case, with a prosthetic bovine aortic valve, presented with fever, poor dental hygiene, new cardiac murmur and signs of congestive heart failure. Blood cultures were positive for a viridans streptococcal species; however, the organism could not be further identified at our institution. Echocardiogram demonstrated a decrease in ejection fraction and vegetation attached to the prosthetic aortic valve associated with a perivalvular abscess. The patient was treated with a 6-week regimen of penicillin G with gentamicin for the first 2 weeks along with cardiac surgery. The results from the 16S rRNA gene sequencing of the viridans streptococcal species were available, which reported the organism asG. morbillorum. This case adds to the literature onG. morbillorumprosthetic valve endocarditis and provides additional evidence to consider infectious endocarditis in the setting ofG. morbillorumbacteraemia.
Diastereoselective N-quaternization of piperidines
Authors: Dunbar Christine R. , West F.G.
Published: November 2014

The study of the N-quaternization of substituted piperidines has been mostly dormant for the last 40 years, despite the demand for ammonium salts as drugs, ionic liquids, chiral catalysts or ligands, phase transfer reagents, and reagents for the Stevens and Sommelet–Hauser rearrangements. In this perspective article, the complexity of this seemingly simple reaction is studied by a summary and analysis of literature experimental results. Computational methods are applied to various literature reactions as case studies.
Nutrients and temperature interact to regulate algae and heterotrophic bacteria in an Alaskan poor fen peatland
Authors: Wyatt Kevin H. , Bange Jill S. , Fitzgibbon Andrea S. , Bernot Melody J. , Rober Allison R.
Published: November 2014

Permafrost thaw associated with warmer temperatures is expected to elevate nutrient levels in northern aquatic ecosystems, including peatlands. To evaluate these effects on algae and heterotrophic bacteria, we manipulated nutrients (nitrogen (N) and phosphorus (P)) and temperature (ambient and warmed) in a factorial design using nutrient diffusing substrates inside warming chambers in an Alaskan peatland. After 16 days, there was no effect of warming on the abundance of algae or heterotrophic bacteria in the absence of nutrient enrichment. Algal production and bacterial biomass were substantially elevated by N with and without P (NP and N, respectively), independent of warming. Warming significantly enhanced the effect of nutrient enrichment on the abundance of algae and heterotrophic bacteria compared with ambient temperatures. Rates of N fixation increased with the presence of heterocyst-forming cyanobacteria, which represented a greater proportion of algal taxonomic composition in the absence of N enrichment in both ambient and warmed conditions. Our results indicate that warmer temperatures and nutrient enrichment will elevate algal and heterotrophic metabolism in northern peatlands, and the magnitude of increase will depend on the combination of nutrients available during periods of inundation.
Pyrroloquinoline quinone ameliorates oxidative stress and lipid peroxidation in the brain of streptozotocin-induced diabetic mice
Authors: Kumar Narendra , Kar Anand
Published: November 2014

Diabetes, characterized by hyperglycemia, leads to several complications through the generation of reactive oxygen species and initiates tissue damage. Pyrroloquinoline quinone (PQQ) is believed to be a strong antioxidant, as it protects cells from oxidative damage. In this study, we elucidated the hitherto unknown potential of PQQ to ameliorate the brain damage caused by diabetes mellitus and the associated hyperglycemia-induced oxidative damage. Administration of a single dose of streptozotocin (STZ), i.e., 150 mg·(kg body mass)−1significantly enhanced the brain tissue levels of lipid peroxidation and hydroperoxidation and decreased the levels of antioxidants. It also increased the serum levels of glucose, cholesterol, and triglycerides. However, when STZ-treated animals received PQQ (20 mg·(kg body mass)−1·d−1, for 15 days), this significantly decreased the serum levels of glucose and lipid peroxidation products, and increased the activities of antioxidants in the diabetic mouse brain. These findings suggest that PQQ has the potential to ameliorate STZ-induced oxidative damage in the brain, as well as the STZ-induced diabetes.
A combination of genistein and magnesium enhances the vasodilatory effect via an eNOS pathway and BKCa current amplification
Authors: Sun Lina , Hou Yunlong , Zhao Tingting , Zhou Shanshan , Wang Xiaoran , Zhang Liming , Yu Guichun
Published: November 2014

The phytoestrogen genistein (GST) and magnesium have been independently shown to regulate vascular tone; however, their individual vasodilatory effects are limited. The aim of this study was to examine the combined effects of GST plus magnesium on vascular tone in mesenteric arteries. The effects of pretreatment with GST (0–200 μmol/L), MgCl2 (0–4.8 mmol/L) and GST plus MgCl2 on 10 μmol/L phenylephrine (PE) precontracted mesenteric arteries in rats were assessed by measuring isometric force. BKCa currents were detected by the patch clamp method. GST caused concentration- and partial endothelium-dependent relaxation. Magnesium resulted in dual adjustment of vascular tone. Magnesium-free solution eliminated the vasodilatation of GST in both endothelium-intact and denuded rings. GST (50 μmol/L) plus magnesium (4.8 mmol/L) caused stronger relaxation in both endothelium-intact and denuded rings. Pretreatment with the nitric oxide synthase (NOS) inhibitor l-N-nitroarginine methyl ester (l-NAME, 100 μmol/L) significantly inhibited the effects of GST, high magnesium, and the combination of GST and magnesium. BKCa currents were amplified to a greater extent when GST (50 μmol/L) was combined with 4.8 versus 1.2 mmol/L Mg2+. Our data suggest that GST plus magnesium provides enhanced vasodilatory effects in rat mesenteric arteries compared with that observed when either is used separately, which was related to an eNOS pathway and BKCa current amplification.
Optical computing with soliton trains in Bose–Einstein condensates
Authors: Pinsker Florian
Published: November 2014

Optical computing devices can be implemented based on controlled generation of soliton trains in single and multicomponent Bose–Einstein condensates (BEC). Our concepts utilize the phenomenon that the frequency of soliton trains in BEC can be governed by changing interactions within the atom cloud [F. Pinsker, N. G. Berloff and V. M. Pérez-García, Phys. Rev. A87, 053624 (2013), arXiv:1305.4097]. We use this property to store numbers in terms of those frequencies for a short time until observation. The properties of soliton trains can be changed in an intended way by other components of BEC occupying comparable states or via phase engineering. We elucidate, in which sense, such an additional degree of freedom can be regarded as a tool for controlled manipulation of data. Finally, the outcome of any manipulation made is read out by observing the signature within the density profile.
Chaos in a 4D dissipative nonlinear fermionic model
Authors: Aydogmus Fatma
Published: November 2014

Gursey Model is the only possible 4D conformally invariant pure fermionic model with a nonlinear self-coupled spinor term. It has been assumed to be similar to the Heisenberg's nonlinear generalization of Dirac's equation, as a possible basis for a unitary description of elementary particles. Gursey Model admits particle-like solutions for the derived classical field equations and these solutions are instantonic in character. In this paper, the dynamical nature of damped and forced Gursey Nonlinear Differential Equations System (GNDES) are studied in order to get more information on spinor type instantons. Bifurcation and chaos in the system are observed by constructing the bifurcation diagrams and Poincaré sections. Lyapunov exponent and power spectrum graphs of GNDES are also constructed to characterize the chaotic behavior.
Smoothed Particle Hydrodynamics for water wave propagation in a channel
Authors: Omidvar Pourya , Norouzi Hossein , Zarghami Ahad
Published: November 2014

In this paper, Smoothed Particle Hydrodynamics (SPH) is used to simulate the propagation of waves in an intermediate depth water channel. The major advantage of using SPH is that no special treatment of the free surface is required, which is advantageous for simulating highly nonlinear flows with possible wave breaking. The SPH method has an option of different formulations with their own advantages and drawbacks to be implemented. Here, we apply the classical and Arbitrary Lagrange–Euler (ALE) formulation for wave propagation in a water channel. The classical SPH should come with an artificial viscosity which stabilizes the numerical algorithm and increases the accuracy. Here, we will show that the use of classical SPH with an artificial viscosity may cause the waves in the channel to decay. On the other hand, we will show that using the ALE-SPH algorithm with a Riemann solver is more stable, and in addition to producing the pressure fields with much less numerical noise, the waves propagate in the channel without dissipation.
From old symmetries to new symmetries: Quarks, leptons and B-L
Authors: Mohapatra Rabindra N.
Published: November 2014

The Baryon–Lepton difference (B-L) is increasingly emerging as a possible new symmetry of the weak interactions of quarks and leptons as a way to understand the small neutrino masses. There is the possibility that current and future searches at colliders and in low energy rare processes may provide evidence for this symmetry. This paper provides a brief overview of the early developments that led to B-L as a possible symmetry beyond the standard model, and also discusses some recent developments.
Analytical determination of the QCD quark masses
Authors: Dominguez C. A.
Published: November 2014

The current status of determinations of the QCD running quark masses is reviewed. Emphasis is on recent progress on analytical precision determinations based on finite energy QCD sum rules. A critical discussion of the merits of this approach over other alternative QCD sum rules is provided. Systematic uncertainties from both the hadronic and the QCD sector have been recently identified and dealt with successfully, thus leading to values of the quark masses with unprecedented accuracy. Results currently rival in precision with lattice QCD determinations.
Zirconium metal-based MAX phases Zr2AC (A = Al, Si, P and S): A first-principles study
Authors: Nasir M. T. , Hadi M. A. , Naqib S. H. , Parvin F. , Islam A. K. M. A. , Roknuzzaman M. , Ali M. S.
Published: November 2014

We have investigated theoretical Vickers hardness, thermodynamic and optical properties of four zirconium metal-based MAX phases Zr 2 AC (A = Al , Si , P and S ) for the first time in addition to revisiting the structural, elastic and electronic properties. First-principles calculations are employed based on density functional theory (DFT) by means of the plane-wave pseudopotential method. The theoretical Vickers hardness has been estimated via the calculation of Mulliken bond populations and electronic density of states. The thermodynamic properties such as the temperature and pressure dependent bulk modulus, Debye temperature, specific heats and volume thermal expansion coefficient of all the compounds are derived from the quasi-harmonic Debye model. Further, the optical properties, e.g., dielectric functions, indices of refraction, absorption, energy loss function, reflectivity and optical conductivity of the nanolaminates have been calculated. The results are compared with available experiments and their various implications are discussed in detail. We have also shed light on the effect of different properties of Zr 2 AC as the A-group atom moves from Al to S across the periodic table.
Resonant peaks of the linear optical absorption and rectification coefficients in GaAs/GaAlAs quantum well: Combined effects of intense laser, electric and magnetic fields
Authors: Ozturk Emine , Sokmen Ismail
Published: November 2014

In this study, the resonant peaks of the linear optical absorption (OA) and rectification coefficients in GaAs/GaAlAs quantum well are calculated as dependent on the applied electric field (F), the magnetic field (B) and the laser field intensity parameter (α0). Our results show that the shape of confined potential profile, the energy levels and the dipole moment matrix elements are changed as dependent on the F, B and α0. Also, the resonant peaks of the OA and rectification coefficients depend on the applied external field effects. Therefore, the variation of the resonant peaks of these coefficients which can be appropriate for various optical modulators and infrared optical device applications can be smoothly obtained by the alteration electric, magnetic and intense laser field.
3-DIMENSIONAL NUMERICAL MODELING ON THE COMBUSTION AND EMISSION CHARACTERISTICS OF BIODIESEL IN DIESEL ENGINES
Authors: YANG WENMING , AN HUI , AMIN MAGHBOULI , LI JING
Published: November 2014

A 3-dimensional computational fluid dynamics modeling is conducted on a direct injection diesel engine fueled by biodiesel using multi-dimensional software KIVA4 coupled with CHEMKIN. To accurately predict the oxidation of saturated and unsaturated agents of the biodiesel fuel, a multicomponent advanced combustion model consisting of 69 species and 204 reactions combined with detailed oxidation pathways of methyl decenoate (C11H22O2), methyl-9-decenoate (C11H20O2) and n-heptane (C7H16) is employed in this work. In order to better represent the real fuel properties, the detailed chemical and thermo-physical properties of biodiesel such as vapor pressure, latent heat of vaporization, liquid viscosity and surface tension were calculated and compiled into the KIVA4 fuel library. The nitrogen monoxide (NO) and carbon monoxide (CO) formation mechanisms were also embedded. After validating the numerical simulation model by comparing the in-cylinder pressure and heat release rate curves with experimental results, further studies have been carried out to investigate the effect of combustion chamber design on flow field, subsequently on the combustion process and performance of diesel engine fueled by biodiesel. Research has also been done to investigate the impact of fuel injector location on the performance and emissions formation of diesel engine.
LAGRANGIAN CORRELATION AND SPECTRA IN 2D TURBULENCE
Authors: XIA HUA
Published: November 2014

Transition from chaotic flow to turbulent flow is investigated in both the Eulerian and Lagrangian frame of reference. Eulerian spectra of the kinetic energy of the flow show the development of a hierarchy of scales, generation of a broad k-5/3 spectral range in developed turbulence. In the Lagrangian frame, single particle displacement is dominant by multiple scales for the chaotic flow. In fully developed turbulence, one single scale determines the transport properties, which is related to the most persistent scale in the system, the forcing scale.
Reactive Imperative Programming with Dataflow Constraints
Authors: Demetrescu Camil , Finocchi Irene , Ribichini Andrea
Published: November 2014

Dataflow languages provide natural support for specifying constraints between objects in dynamic applications, where programs need to react efficiently to changes in their environment. In this article, we show that one-way dataflow constraints, largely explored in the context of interactive applications, can be seamlessly integrated in any imperative language and can be used as a general paradigm for writing performance-critical reactive applications that require efficient incremental computations. In our framework, programmers can define ordinary statements of the imperative host language that enforce constraints between objects stored in special memory locations designated as “reactive.” Reactive objects can be of any legal type in the host language, including primitive data types, pointers, arrays, and structures. Statements defining constraints are automatically re-executed every time their input memory locations change, letting a program behave like a spreadsheet where the values of some variables depend on the values of other variables. The constraint-solving mechanism is handled transparently by altering the semantics of elementary operations of the host language for reading and modifying objects. We provide a formal semantics and describe a concrete embodiment of our technique into C/C++, showing how to implement it efficiently in conventional platforms using off-the-shelf compilers. We discuss common coding idioms and relevant applications to reactive scenarios, including incremental computation, observer design pattern, data structure repair, and software visualization. The performance of our implementation is compared to problem-specific change propagation algorithms, as well as to language-centric approaches such as self-adjusting computation and subject/observer communication mechanisms, showing that the proposed approach is efficient in practice.
Drug Resistance or Re-Emergence? Simulating Equine Parasites
Authors: Xu Jie , Vidyashankar Anand , Nielsen Martin K.
Published: November 2014

Emerging drug resistance in parasitology and its impact on human and animal health are of serious concern. Attempts by the parasitology community to address this issue led to the introduction of so-called selective therapy where a proportion of the population is left untreated. This has led to re-emergence of parasites that have heretofore been controlled. Using stochastic simulations, this article explores the tradeoff between drug resistance and re-emergence. More importantly, the article identifies the importance of the parasite fitness parameter vector and its role in drug resistance. Suggestions for further biological work and statistical analyses are also provided.
Bringing Modern Unit Testing Techniques to Sensornets
Authors: Iwanicki Konrad , Horban Przemyslaw , Glazar Piotr , Strzelecki Karol
Published: November 2014

Unit testing, an important facet of software quality assurance, is underappreciated by wireless sensor network (sensornet) developers. This is likely because our tools lag behind the rest of the computing field. As a remedy, we present a new framework that enables modern unit testing techniques in sensornets. Although the framework takes a holistic approach to unit testing, its novelty lies mainly in two aspects. First, to boost test development, it introduces
embedded mock modules
that automatically abstract out dependencies of tested code. Second, to automate test assessment, it provides
embedded code coverage tools
that identify untested control flow paths in the code. We demonstrate that in sensornets these features pose unique problems, solving which requires dedicated support from the compiler and operating system. However, the solutions have the potential to offer substantial benefits. In particular, they reduce the unit test development effort by a few factors compared to existing solutions. At the same time, they facilitate obtaining full code coverage, compared to merely 57--72% that can be achieved with integration tests. They also allow for intercepting and reporting many classes of runtime failures, thereby simplifying the diagnosis of software flaws. Finally, they enable fine-grained management of the quality of sensornet software.
A Resource-Efficient Design for a Reversible Floating Point Adder in Quantum Computing
Authors: Nguyen Trung Duc , Van Meter Rodney
Published: November 2014

Reversible logic has applications in low-power computing and quantum computing. However, there are few existing designs for reversible floating-point adders and none suitable for quantum computation. In this article, we propose a resource-efficient reversible floating-point adder, suitable for binary quantum computation, improving the design of Nachtigal et al. [2011]. Our work focuses on improving the reversible designs of the alignment unit and the normalization unit, which are the most expensive parts. By changing a few elements of the existing algorithm, including the circuit designs of the RLZC (reversible leading zero counter) and converter, we have reduced the cost by about 68%. We also propose quantum designs adapted to use gates from fault-tolerant libraries. The
KQ
for our fault-tolerant design is almost 60 times as expensive as for a 32-bit fixed-point addition. We note that the floating-point representation makes in-place, truly reversible arithmetic impossible, requiring us to retain both inputs, which limits the sustainability of its use for quantum computation.
A Survey on Green-Energy-Aware Power Management for Datacenters
Authors: Kong Fanxin , Liu Xue
Published: November 2014

Megawatt-scale datacenters have emerged to meet the increasing demand for IT applications and services. The hunger for power brings large electricity bills to datacenter operators and causes significant impacts to the environment. To reduce costs and environmental impacts, modern datacenters, such as those of Google and Apple, are beginning to integrate renewable or green energy sources into their power supply. This article investigates the green-energy-aware power management problem for these datacenters and surveys and classifies works that explicitly consider renewable energy and/or carbon emission. Our aim is to give a full view of this problem. Hence, we first provide some basic knowledge on datacenters (including datacenter components, power infrastructure, power load estimation, and energy sources' operations), the electrical grid (including dynamic pricing, power outages, and emission factor), and the carbon market (including cap-and-trade and carbon tax). Then, we categorize existing research works according to their basic approaches used, including workload scheduling, virtual machine management, and energy capacity planning. Each category's discussion includes the description of the shared core idea, qualitative analysis, and quantitative analysis among works of this category.
Software-Defined Networking Paradigms in Wireless Networks: A Survey
Authors: Jagadeesan Nachikethas A. , Krishnamachari Bhaskar
Published: November 2014

Software-defined networking (SDN) has generated tremendous interest from both academia and industry. SDN aims at simplifying network management while enabling researchers to experiment with network protocols on deployed networks. This article is a distillation of the state of the art of SDN in the context of wireless networks. We present an overview of the major design trends and highlight key differences between them.
Supporting Novice to Expert Transitions in User Interfaces
Authors: Cockburn Andy , Gutwin Carl , Scarr Joey , Malacria Sylvain
Published: November 2014

Interface design guidelines encourage designers to provide high-performance mechanisms for expert users. However, research shows that many expert interface components are seldom used and that there is a tendency for users to persistently fail to adopt faster methods for completing their work. This article summarizes and organizes research relevant to supporting users in making successful transitions to expert levels of performance. First, we provide a brief introduction to the underlying human factors of skill acquisition relevant to interaction with computer systems. We then present our focus, which is a review of the state of the art in user interfaces that promote expertise development. The review of interface research is based around four domains of performance improvement:
intramodal improvement
that occurs as a factor of repetition and practice with a single method of interaction;
intermodal improvement
that occurs when users switch from one method to another that has a higher performance ceiling;
vocabulary extension
, in which the user broadens his or her knowledge of the range of functions available; and
task mapping
, which examines the ways in which users perform their tasks. The review emphasizes the relationship between interface techniques and the human factors that explain their relative success.