bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Novel Multiantigenic Vaccine Candidates with Pan-HLA Coverage against Mycobacterium tuberculosis
Authors: Kovjazin Riva , Shitrit David , Preiss Rachel , Haim Ilanit , Triezer Lev , Fuks Leonardo , Nader Abdel Rahman , Raz Meir , Bardenstein Ritta , Horn Galit , Smorodinsky Nechama I. , Carmon Lior
Published: January 2013

The low protection by the bacillus Calmette-Guérin (BCG) vaccine and existence of drug-resistant strains require better anti-Mycobacterium tuberculosisvaccines with a broad, long-lasting, antigen-specific response. Using bioinformatics tools, we identified five 19- to 40-mer signal peptide (SP) domain vaccine candidates (VCs) derived fromM. tuberculosisantigens. All VCs were predicted to have promiscuous binding to major histocompatibility complex (MHC) class I and II alleles in large geographic territories worldwide. Peripheral mononuclear cells (PBMC) from healthy naïve donors and tuberculosis patients exhibited strong proliferation that correlated positively with Th1 cytokine secretion only in healthy naïve donors. Proliferation to SP VCs was superior to that to antigen-matched control peptides with similar length and various MHC class I and II binding properties. T-cell lines induced to SP VCs from healthy naïve donors had increased CD44high/CD62L+activation/effector memory markers and gamma interferon (IFN-γ), but not interleukin-4 (IL-4), production in both CD4+and CD8+T-cell subpopulations. T-cell lines from healthy naïve donors and tuberculosis patients also manifested strong, dose-dependent, antigen-specific cytotoxicity against autologous VC-loaded orM. tuberculosis-infected macrophages. Lysis ofM. tuberculosis-infected targets was accompanied by high IFN-γ secretion. Various combinations of these five VCs manifested synergic proliferation of PBMC from selected healthy naïve donors. Immunogenicity of the best three combinations, termed Mix1, Mix2, and Mix3 and consisting of 2 to 5 of the VCs, was then evaluated in mice. Each mixture manifested strong cytotoxicity againstM. tuberculosis-infected macrophages, while Mix3 also manifested a VC-specific humoral immune response. Based on these results, we plan to evaluate the protection properties of these combinations as an improved tuberculosis subunit vaccine.
Targeting the “Cytokine Storm” for Therapeutic Benefit
Authors: D'Elia Riccardo V. , Harrison Kate , Oyston Petra C. , Lukaszewski Roman A. , Clark Graeme C.
Published: January 2013

Inflammation is the body's first line of defense against infection or injury, responding to challenges by activating innate and adaptive responses. Microbes have evolved a diverse range of strategies to avoid triggering inflammatory responses. However, some pathogens, such as the influenza virus and the Gram-negative bacteriumFrancisella tularensis, do trigger life-threatening “cytokine storms” in the host which can result in significant pathology and ultimately death. For these diseases, it has been proposed that downregulating inflammatory immune responses may improve outcome. We review some of the current candidates for treatment of cytokine storms which may prove useful in the clinic in the future and compare them to more traditional therapeutic candidates that target the pathogen rather than the host response.
Helicobacter canis Bacteremia in a Patient with Fever of Unknown Origin
Authors: Abidi Maheen Z. , Wilhelm Mark P. , Neff Jadee L. , Hughes John G. , Cunningham Scott A. , Patel Robin
Published: January 2013

A 57-year-old woman with common variable immune deficiency and liver failure of unknown etiology presented with recurrent fevers over a 5-month period. She was found to haveHelicobacter canisbacteremia. Immunocompromised hosts with exposure to cats or dogs may be at risk for infection with this organism, which may be challenging to diagnose.
Point-Counterpoint: Quantitative Cultures of Bronchoscopically Obtained Specimens Should Be Performed for Optimal Management of Ventilator-Associated Pneumonia
Authors: Baselski Vickie , Klutts J. Stacey , Baselski Vickie , Klutts J. Stacey
Published: January 2013

Ventilator-associated pneumonia (VAP) is a leading cause of health care-associated infection. It has a high rate of attributed mortality, and this mortality is increased in patients who do not receive appropriate empirical antimicrobial therapy. As a result of the overuse of broad-spectrum antimicrobials such as the carbapenems, strains of
Acinetobacter
,
Enterobacteriaceae
, and
Pseudomonas aeruginosa
susceptible only to polymyxins and tigecycline have emerged as important causes of VAP. The need to accurately diagnose VAP so that appropriate discontinuation or de-escalation of antimicrobial therapy can be initiated to reduce this antimicrobial pressure is essential. Practice guidelines for the diagnosis of VAP advocate the use of bronchoalveolar lavage (BAL) fluid obtained either bronchoscopically or by the use of a catheter passed through the endotracheal tube. The CDC recommends that quantitative cultures be performed on these specimens, using ≥10
4
CFU/ml to designate a positive culture (
http://www.cdc.gov/nhsn/TOC_PSCManual.html
, accessed 30 October 2012). However, there is no consensus in the clinical microbiology community as to whether these specimens should be cultured quantitatively, using the aforementioned designated bacterial cell count to designate infection, or by a semiquantitative approach. We have asked Vickie Baselski, University of Tennessee Health Science Center, who was the lead author on one of the seminal papers on quantitative BAL fluid culture, to explain why she believes that quantitative BAL fluid cultures are the optimal strategy for VAP diagnosis. We have Stacey Klutts, University of Iowa, to advocate the semiquantitative approach.
Mandarin Fish Caveolin 1 Interaction with Major Capsid Protein of Infectious Spleen and Kidney Necrosis Virus and Its Role in Early Stages of Infection
Authors: Jia Kun-Tong , Wu Yan-Yan , Liu Zhao-Yu , Mi Shu , Zheng Yi-Wen , He Jian , Weng Shao-Ping , Li Shengwen Calvin , He Jian-Guo , Guo Chang-Jun
Published: January 2013

Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the genus
Megalocytivirus
from the family
Iridoviridae
. ISKNV is one of the major agents that cause mortality and economic losses to the freshwater fish culture industry in Asian countries, particularly for mandarin fish (
Siniperca chuatsi
). In the present study, we report that the interaction of mandarin fish caveolin 1 (mCav-1) with the ISKNV major capsid protein (MCP) was detected by using a virus overlay assay and confirmed by pulldown assay and coimmunoprecipitation. This interaction was independent of the classic caveolin 1 scaffolding domain (CSD), which is responsible for interacting with several signaling proteins and receptors. Confocal immunofluorescence microscopy showed that ISKNV MCP colocalized with mCav-1 in the perinuclear region of virus-infected mandarin fish fry (MFF-1) cells, which appeared as soon as 4 h postinfection. Subcellular fractionation analysis showed that ISKNV MCP was associated with caveolae in the early stages of viral infection. RNA interference silencing of mCav-1 did not change virus-cell binding but efficiently inhibited the entry of virions into the cell. Taken together, these results suggested that mCav-1 plays an important role in the early stages of ISKNV infection.
Neuraminidase-Inhibiting Antibody Is a Correlate of Cross-Protection against Lethal H5N1 Influenza Virus in Ferrets Immunized with Seasonal Influenza Vaccine
Authors: Rockman Steven , Brown Lorena E. , Barr Ian G. , Gilbertson Brad , Lowther Sue , Kachurin Anatoly , Kachurina Olga , Klippel Jessica , Bodle Jesse , Pearse Martin , Middleton Deborah
Published: January 2013

In preparing for the threat of a pandemic of avian H5N1 influenza virus, we need to consider the significant delay (4 to 6 months) necessary to produce a strain-matched vaccine. As some degree of cross-reactivity between seasonal influenza vaccines and H5N1 virus has been reported, this was further explored in the ferret model to determine the targets of protective immunity. Ferrets were vaccinated with two intramuscular inoculations of trivalent inactivated split influenza vaccine or subcomponent vaccines, with and without adjuvant, and later challenged with a lethal dose of A/Vietnam/1203/2004 (H5N1) influenza virus. We confirmed that vaccination with seasonal influenza vaccine afforded partial protection against lethal H5N1 challenge and showed that use of either AlPO
4
or Iscomatrix adjuvant with the vaccine resulted in complete protection against disease and death. The protection was due exclusively to the H1N1 vaccine component, and although the hemagglutinin contributed to protection, the dominant protective response was targeted toward the neuraminidase (NA) and correlated with sialic acid cleavage-inhibiting antibody titers. Purified heterologous NA formulated with Iscomatrix adjuvant was also protective. These results suggest that adjuvanted seasonal trivalent vaccine could be used as an interim measure to decrease morbidity and mortality from H5N1 prior to the availability of a specific vaccine. The data also highlight that an inducer of cross-protective immunity is the NA, a protein whose levels are not normally monitored in vaccines and whose capacity to induce immunity in recipients is not normally assessed.
Nipah Virus Entry and Egress from Polarized Epithelial Cells
Authors: Lamp Boris , Dietzel Erik , Kolesnikova Larissa , Sauerhering Lucie , Erbar Stephanie , Weingartl Hana , Maisner Andrea
Published: January 2013

Highly pathogenic Nipah virus (NiV) infections are transmitted via airway secretions and urine, commonly via the respiratory route. Epithelial surfaces represent important replication sites in both primary and systemic infection phases. NiV entry and spread from polarized epithelial cells therefore determine virus entry and dissemination within a new host and influence virus shedding via mucosal surfaces in the respiratory and urinary tract. To date, there is no knowledge regarding the entry and exit sites of NiV in polarized epithelial cells. In this report, we show for the first time that NiV can infect polarized kidney epithelial cells (MDCK) from both cell surfaces, while virus release is primarily restricted to the apical plasma membrane. Substantial amounts of basolateral infectivity were detected only after infection with high virus doses, at time points when the integrity of the cell monolayer was largely disrupted as a result of cell-to-cell fusion. Confocal immunofluorescence analyses of envelope protein distribution at early and late infection stages suggested that apical virus budding is determined by the polarized sorting of the NiV matrix protein, M. Studies with stably M-expressing and with monensin-treated cells furthermore demonstrated that M protein transport is independent from the glycoproteins, implying that the M protein possesses an intrinsic apical targeting signal.
N-Terminal Phosphorylation of Phosphoprotein of Vesicular Stomatitis Virus Is Required for Preventing Nucleoprotein from Binding to Cellular RNAs and for Functional Template Formation
Authors: Chen Longyun , Zhang Shengwei , Banerjee Amiya K. , Chen Mingzhou
Published: January 2013

The phosphoprotein (P) of vesicular stomatitis virus (VSV) plays essential roles in viral RNA synthesis. It associates with nascent nucleoprotein (N) to form N
0
-P (free of RNAs), thereby preventing the N from binding to cellular RNAs and maintaining the N in a viral genomic RNA encapsidation-competent form for transcription and replication. The contributions of phosphorylation of P to transcription and replication have been studied intensively, but a concrete mechanism of action still remains unclear. In this study, using a VSV minigenome system, we demonstrated that a mutant of P lacking N-terminal phosphorylation (P3A), in which the N-terminal phosphate acceptor sites are replaced with alanines (S60/A, T62/A, and S64/A), does not support transcription and replication. However, results from protein interaction assays showed that P3A self-associates and interacts with N and the large protein (L) as efficiently as P does. Furthermore, purified recombinant P3A from Sf21 cells supported transcription in an
in vitro
transcription reconstitution assay. We also proved that P3A is not distributed intranuclearly
in vivo
. CsCl gradient centrifugation showed that P3A is incapable of preventing N from binding to cellular RNAs and therefore prevents functional template formation. Taken together, our results demonstrate that N-terminal phosphorylation is indispensable for P to prevent N from binding to nonviral RNAs and to maintain the N-specific encapsidation of viral genomic RNA for functional template formation.
Evolution of CD8
+
T Cell Responses after Acute PARV4 Infection
Authors: Simmons Ruth , Sharp Colin , Levine Jordana , Bowness Paul , Simmonds Peter , Cox Andrea , Klenerman Paul
Published: January 2013

PARV4 is a small DNA human virus that is strongly associated with hepatitis C virus (HCV) and HIV infections. The immunologic control of acute PARV4 infection has not been previously described. We define the acute onset of PARV4 infection and the characteristics of the acute-phase and memory immune responses to PARV4 in a group of HCV- and HIV-negative, active intravenous drug users. Ninety-eight individuals at risk of blood-borne infections were tested for PARV4 IgG. Gamma interferon enzyme-linked immunosorbent spot assays, intracellular cytokine staining, and a tetrameric HLA-A2–peptide complex were used to define the T cell populations responding to PARV4 peptides in those individuals who acquired infection during the study. Thirty-five individuals were found to be PARV4 seropositive at the end of the study, eight of whose baseline samples were found to be seronegative. Persistent and functional T cell responses were detected in the acute infection phase. These responses had an active, mature, and cytotoxic phenotype and were maintained several years after infection. Thus, PARV4 infection is common in individuals exposed to blood-borne infections, independent of their HCV or HIV status. Since PARV4 elicits strong, broad, and persistent T cell responses, understanding of the processes responsible may prove useful for future vaccine design.
Respiratory Syncytial Virus Polymerase Can Initiate Transcription from Position 3 of the Leader Promoter
Authors: Tremaglio Chadene Z. , Noton Sarah L. , Deflubé Laure R. , Fearns Rachel
Published: January 2013

The mechanisms by which the respiratory syncytial virus (RSV) RNA-dependent RNA polymerase (RdRp) initiates mRNA transcription and RNA replication are poorly understood. A previous study, using an RSV minigenome, suggested that the leader (Le) promoter region at the 3′ end of the genome has two initiation sites, one at position +1, opposite the 3′ terminal nucleotide of the genome, and a second site at position +3, at a sequence that closely resembles the gene start (GS) signal of the RSV L gene. In this study, we show that the +3 initiation site of the Le is utilized with apparently high frequency in RSV-infected cells and yields small RNA transcripts that are heterogeneous in length but mostly approximately 25 nucleotides (nt) long. Experiments with an
in vitro
assay in which RSV RNA synthesis was reconstituted using purified RdRp and an RNA oligonucleotide showed that nt 1 to 14 of the Le promoter were sufficient to signal initiation from +3 and that the RdRp could access the +3 initiation site without prior initiation at +1. In a minigenome assay, nucleotide substitutions within the Le to increase its similarity to a GS signal resulted in more-efficient elongation of the RNA initiated from position +3 and a reduction in RNA initiated from the NS1 gene start signal at +45. Taken together, these data suggest a new model for initiation of sequential transcription of the RSV genes, whereby the RdRp initiates the process from a gene start-like sequence at position +3 of the Le.
Neuroattenuation of Vesicular Stomatitis Virus through Picornaviral Internal Ribosome Entry Sites
Authors: Ammayappan Arun , Nace Rebecca , Peng Kah-Whye , Russell Stephen J.
Published: January 2013

Vesicular stomatitis virus (VSV) is potent and a highly promising agent for the treatment of cancer. However, translation of VSV oncolytic virotherapy into the clinic is being hindered by its inherent neurotoxicity. It has been demonstrated that selected picornaviral internal ribosome entry site (IRES) elements possess restricted activity in neuronal tissues. We therefore sought to determine whether the picornavirus IRES could be engineered into VSV to attenuate its neuropathogenicity. We have used IRES elements from human rhinovirus type 2 (HRV2) and foot-and-mouth disease virus (FMDV) to control the translation of the matrix gene (M), which plays a major role in VSV virulence.
In vitro
studies revealed slowed growth kinetics of IRES-controlled VSVs in most of the cell lines tested. However,
in vivo
studies explicitly demonstrated that IRES elements of HRV2 and FMDV severely attenuated the neurovirulence of VSV without perturbing its oncolytic potency.
Detection of Receptor-Induced Glycoprotein Conformational Changes on Enveloped Virions by Using Confocal Micro-Raman Spectroscopy
Authors: Lu Xiaonan , Liu Qian , Benavides-Montano Javier A. , Nicola Anthony V. , Aston D. Eric , Rasco Barbara A. , Aguilar Hector C.
Published: January 2013

Conformational changes in the glycoproteins of enveloped viruses are critical for membrane fusion, which enables viral entry into cells and the pathological cell-cell fusion (syncytia) associated with some viral infections. However, technological capabilities for identifying viral glycoproteins and their conformational changes on actual enveloped virus surfaces are generally scarce, challenging, and time-consuming. Our model, Nipah virus (NiV), is a syncytium-forming biosafety level 4 pathogen with a high mortality rate (40 to 75%) in humans. Once the NiV attachment glycoprotein (G) (NiV-G) binds the cell receptor ephrinB2 or -B3, G triggers conformational changes in the fusion glycoprotein (F) that result in membrane fusion and viral entry. We demonstrate that confocal micro-Raman spectroscopy can, within minutes, simultaneously identify specific G and F glycoprotein signals and receptor-induced conformational changes in NiV-F on NiV virus-like particles (VLPs). First, we identified reproducible G- and F-specific Raman spectral features on NiV VLPs containing M (assembly matrix protein), G, and/or F or on NiV/vesicular stomatitis virus (VSV) pseudotyped virions via second-derivative transformations and principal component analysis (PCA). Statistical analyses validated our PCA models. Dynamic temperature-induced conformational changes in F and G or receptor-induced target membrane-dependent conformational changes in F were monitored in NiV pseudovirions
in situ
in real time by confocal micro-Raman spectroscopy. Advantageously, Raman spectroscopy can identify specific protein signals in relatively impure samples. Thus, this proof-of-principle technological development has implications for the rapid identification and biostability characterization of viruses in medical, veterinary, and food samples and for the analysis of virion glycoprotein conformational changes
in situ
during viral entry.
Insights into Head-Tailed Viruses Infecting Extremely Halophilic Archaea
Authors: Pietilä Maija K. , Laurinmäki Pasi , Russell Daniel A. , Ko Ching-Chung , Jacobs-Sera Deborah , Butcher Sarah J. , Bamford Dennis H. , Hendrix Roger W.
Published: January 2013

Extremophilic archaea, both hyperthermophiles and halophiles, dominate in habitats where rather harsh conditions are encountered. Like all other organisms, archaeal cells are susceptible to viral infections, and to date, about 100 archaeal viruses have been described. Among them, there are extraordinary virion morphologies as well as the common head-tailed viruses. Although approximately half of the isolated archaeal viruses belong to the latter group, no three-dimensional virion structures of these head-tailed viruses are available. Thus, rigorous comparisons with bacteriophages are not yet warranted. In the present study, we determined the genome sequences of two of such viruses of halophiles and solved their capsid structures by cryo-electron microscopy and three-dimensional image reconstruction. We show that these viruses are inactivated, yet remain intact, at low salinity and that their infectivity is regained when high salinity is restored. This enabled us to determine their three-dimensional capsid structures at low salinity to a ∼10-Å resolution. The genetic and structural data showed that both viruses belong to the same T-number class, but one of them has enlarged its capsid to accommodate a larger genome than typically associated with a T=7 capsid by inserting an additional protein into the capsid lattice.
A case presentation of a pulmonary complication of ulcerative colitis
Authors: Talwar Ambika , Kunst Heinke , Ngatchu Theodore , Trotter Simon
Published: January 2013

We present the case of a 25-year-old Afro-Caribbean man with a longstanding history of ulcerative colitis and primary sclerosing cholangitis. The patient presented to clinic and reported pleuritic-type chest pain. A routine chest radiograph requested from the clinic revealed an incidental right middle zone opacity in the right lung. A subsequent high-resolution CT showed multiple lung nodules. The patient also had a positive cytoplamic anti-neutrophil cytoplasmic antibody (cANCA) and proteinase 3 antibodies. Bronchoscopy was inconclusive. A video-assisted thoracoscopic surgery biopsy was then taken. The histology revealed changes suggestive of bronchiolitis obliterans organising pneumonia. The pulmonary manifestations of inflammatory bowel disease are poorly characterised. Our literature search has revealed cases hypothesising that immune system dysregulation could display pulmonary complications of ulcerative colitis. The aetiology is thought to be related to the treatment with mesalazine. However, our patient also had a positive vasculitic screen. Previous cases have resolved with supportive management or steroid therapy.
The role of positron emission tomography/CT in hypoxic ischaemic encephalopathy in children
Authors: Koc Zehra Pinar , Balcı Tansel Ansal , Akarsu Saadet , Unal Kemal
Published: January 2013

The role of positron emission tomography/CT (PET/CT) in diagnosis and follow-up of newborns with hypoxic ischaemic encephalopathy has been documented before; however, this is the first presentation of elder children with both diagnostic and follow-up PET/CT results as far as we know.
Multidisciplinary management of ornithine transcarbamylase (OTC) deficiency in pregnancy: essential to prevent hyperammonemic complications
Authors: Lamb Stephanie , Aye Christina Yi Ling , Murphy Elaine , Mackillop Lucy
Published: January 2013

Ornithine transcarbamylase (OTC) deficiency is the most common inborn error in the metabolism of the urea cycle with an incidence of 1 in 14 000 live births. Pregnancy can trigger potentially fatal hyperammonemic crises. We report a successful pregnancy in a 29-year-old primiparous patient with a known diagnosis of OTC deficiency since infancy. Hyperammonemic complications were avoided due to careful multidisciplinary management which included a detailed antenatal, intrapartum and postnatal plan. Management principles include avoidance of triggers, a low-protein diet and medications which promote the removal of nitrogen by alternative pathways. Triggers include metabolic stress such as febrile illness, particularly gastroenteritis, fasting and any protein loading. In our case the patient, in addition to a restricted protein intake, was prescribed sodium benzoate 4 g four times a day, sodium phenylbutyrate 2 g four times a day and arginine 500 mg four times a day to aid excretion of ammonia and reduce flux through the urea cycle.
Visual impairment and posterior cortical atrophy preceding rapid progressive dementia
Authors: Müller Kai Ivar , Bekkelund Svein Ivar
Published: January 2013

Posterior cortical atrophy (PCA), also known as Benson's disease, has been previously reported as a variant of Alzheimer's disease (AD). We present a clinical picture and MRI findings of a patient with PCA who developed early right-sided homonymous haemianopia and marked atrophy of parieto-occipital regions of the brain before a cognitive decline appeared. This case demonstrates that PCA may appear with advanced brain atrophy at the onset of focal visual deficits before the development of progressive dementia, and adds to the knowledge of dementias with rapid progression.
Walking unsteadily: a case of acute cerebellar ataxia
Authors: Simonetta Federico , Christou Fotini , Vandoni Riccardo E , Nierle Thomas
Published: January 2013

Acute cerebellar ataxia is an infrequent neurological syndrome in adults especially if complicated by additional neurological deficits. We report the case of a 69-year-old woman who presented with sudden onset of left facial droop, dizziness, slurred speech and impaired balance. Her medical history included paroxysmal atrial fibrillation and a sigmoid diverticular abscess treated with ciprofloxacin and metronidazole. Cranial computed tomographic angiography and MRI showed no signs of acute ischaemia or haemorrhage but demonstrated symmetrically distributed lesions in the cerebellar dentate nuclei. A diagnosis of metronidazole-induced encephalopathy was suspected. Metronidazole was stopped and the patient completely recovered. Metronidazole is a commonly prescribed medication. Clinicians should be aware of the clinical and radiological presentation of metronidazole-induced encephalopathy so that this serious but completely reversible condition can be promptly diagnosed.
Paraneoplastic pemphigus presenting with a single oral lesion
Authors: Gissi Davide Bartolomeo , Bernardi Antonio , D'Andrea Mariangela , Montebugnoli Lucio
Published: January 2013

Paraneoplastic pemphigus (PNP) is recognised in most cases after diagnosis of malignant and benign haematological tumours. PNP usually presents with severe and diffuse oral ulcerations, ocular lesions, lichen planus-like skin lesions and frequently genital ulcerations. We describe the uncommon case of a patient unaware of any neoplasia with a unique ulcerated oral lesion with histological (acantholysis of the basal epithelial layer,necrotic keratinocytesand pronounced regenerative hyperplasia) and immunofluorescent (direct immunofluorescence test exhibited immunoglobulin IgG, fibrinogen and C3 deposition in intercellular areas and along the basement membrane; indirect immunofluorescence test performed on rat bladder showed bright fluorescence) features suggestive of PNP. Diagnosis of PNP was strengthened by the subsequent discovery of monoclonal gammopathy. The reported case is quite unusual if we consider the clinical appearance of the oral lesions and the patient's negative medical history. Following serological examinations, the patient proved to have monoclonal gammopathy of undetermined significance (MGUS), one of the most common premalignant plasma cell disorders.
Role of a TehA homolog inVibrio choleraeC6706 antibiotic resistance and intestinal colonization
Authors: Pei Bin , Wang Yuning , Katzianer David S. , Wang Hui , Wu Hui , Zhong Zengtao , Zhu Jun
Published: January 2013

Vibrio cholerae is the causative agent of the devastating diarrheal disease cholera. A number of regulatory pathways are involved in V. cholerae pathogenesis and antibiotic resistance. For example, there are over 40 LysR-family proteins in the V. cholerae genome, but most of their functions are unknown. In this study, we examine the role of VC2323 (TehAVc) and its divergently transcribed LysR-family regulator VC2324 (TehRVc) in V. cholerae pathogenesis. We found that in V. cholerae C6706, the expression of tehAVcis dependent on TehRVc. VC2323 (TehAVc), homologous to the Escherichia coli tellurite resistance protein (TehAEc), differs from TehAEcin that TehAVchas no noticeable role in tellurite resistance but instead contributes to chloramphenicol resistance. Interestingly, both tehAVcand tehRVcmutants were defective in colonization of infant mice. Though the expression of a key virulence gene tcpA was not affected in either of these mutants, tehAVcmutants failed to attach to mouse intestinal surfaces in the presence of crude bile, suggesting a new role of the TehAVc–TehRVcpair in V. cholerae pathogenesis.
Modeling xenobiotic susceptibility to hepatotoxicity using an in vitro oxidative stress inflammation model
Authors: MacAllister Stephanie L. , Maruf Abdullah A. , Wan Luke , Chung Erin , O'Brien Peter
Published: January 2013

Evidence suggests xenobiotic exposure during periods of inflammation can increase an individual's susceptibility to toxicity. The present study aimed to validate an in-vitro inflammatory model to identify compounds that increase hepatotoxicity during inflammation. Using freshly isolated hepatocytes exposed to a low nontoxic flow of H2O2 using glucose (G) and glucose oxidase (GO) and supplementing it with either peroxidase or Fe(II), the effects of inflammation on 2 classes of drugs known to cause hepatotoxicity were examined: nitroaromatics (nimesulide, nilutamide, flutamide) and aromatic amines (clozapine, thioridazine). Co-incubation with G/GO and the nitroaromatics increased toxicity that was further increased when peroxidase was present. While the aromatic amines did not increase cytotoxicity with G/GO alone, they demonstrated significant increases in cytotoxicity when incubated with peroxidase+G/GO. Liver injury is commonly observed with alcohol abusers; therefore, the effects of inflammation on ethanol, and its metabolite acetaldehyde, were observed. Both ethanol and acetaldehyde increased cytotoxicity, which was further increased when Fe(II) was present. These results implicate H2O2, a cellular mediator of inflammation, as a potential risk factor for hepatotoxicity. A H2O2-enhanced hepatocyte-system in the presence of peroxidase or Fe(II) may prove useful for a more robust screening of xenobiotics for assessing potential toxicity associated with inflammation.
APPLICATION OF NEW DECISION MAKING MODEL BASED ON MODIFIED COST-BENEFIT ANALYSIS — A CASE STUDY: BELGRADE TRAMWAY TRANSIT
Authors: POPOVIC VLADIMIR M. , VASIC BRANKO M. , LAZOVIC TATJANA M. , GRBOVIC ALEKSANDAR M.
Published: January 2013

Tramway transit has an important place within the public transportation system of Belgrade. However, due to the very unfavorable age structure, the bad condition of tramway tracks and infrastructure, as well as the maintenance system that require significant advancement, Belgrade tramways are in very bad repair, so the transport requirements are not properly met. The principal task of the analysis presented in this paper is to recognize and estimate the justifiability of investment into various solutions for revitalization of Belgrade tramway rolling stock. We have chosen a somewhat different from usual approach to decision making, that is, applied a combination of cost-benefit, life-cycle cost and multi-criteria analysis.
TRANSIT TIME DISTRIBUTION AND MOBILITY IN MONTE CARLO SIMULATIONS OF THE GAUSSIAN DISORDER MODEL
Authors: KIM SUNIL , YEO JOONHYUN , IM CHAN
Published: January 2013

We study the distribution of transit times in Monte Carlo simulations of the Gaussian disorder model (GDM). The GDM is one of the most successful models to describe the charge transport in random organic materials. The transit time is the time it takes for a charge carrier to travel across a sample. We find that the distribution of transit times over many charge carriers and over different realizations of Gaussian energies shows a heavy tail in the long time limit at low temperatures. This heavy tail can be described by a power law with an exponent that depends on temperature. This sets a limitation on the calculation of mobility of charge carriers using an average transit time at low temperatures. We discuss the implication of these results on dispersive transport.
THE RATIONAL SOLUTIONS TO A GENERALIZED RICCATI EQUATION AND THEIR APPLICATION
Authors: LIU QING , SHEN SHI-YAO , WANG ZI-HUA
Published: January 2013

Based on the rational solutions to a generalized Riccati equation, a new method which is called as rational function method is proposed. We apply this method to solve the coupled mKdV equations and derive a set of rational solutions. This method is also available for seeking their solutions to other NLPDEs. It shows that the rational function method is more universal and powerful than the auxiliary Riccati equation method.
NON-MSF A-WAVELETS FROM A-WAVELET SETS
Authors: SHUKLA NIRAJ K.
Published: January 2013

Generalizing the result of Bownik and Speegle [Approximation Theory X: Wavelets, Splines and Applications, Vanderbilt University Press, pp. 63–85, 2002], we provide plenty of non-MSF A-wavelets with the help of a given A-wavelet set. Further, by showing that the dimension function of the non-MSF A-wavelet constructed through an A-wavelet set W coincides with the dimension function of W, we conclude that the non-MSF A-wavelet and the A-wavelet set through which it is constructed possess the same nature as far as the multiresolution analysis is concerned. Some examples of non-MSF d-wavelets and non-MSF A-wavelets are also provided. As an illustration we exhibit a pathwise connected class of non-MSF non-MRA wavelets sharing the same wavelet dimension function.
IMAGE DISPARITY ESTIMATION BASED ON FRACTIONAL DUAL-TREE COMPLEX WAVELET TRANSFORM: A MULTI-SCALE APPROACH
Authors: KUMAR SANOJ , KUMAR SANJEEV , RAMAN BALASUBRAMANIAN , SUKAVANAM N.
Published: January 2013

In this paper, an efficient multi-scale image disparity estimation algorithm is proposed which estimates the local displacements needed to align different regions between a pair of images. This phase-based approach is based on fractional dual-tree complex wavelet transform (FrDTCWT). In the proposed FrDTCWT, initially we obtained the fractional Fourier transform of the image. We decomposed the fractional transformed image by dual-tree complex wavelet transform into real and imaginary parts. The complex analytic signal is obtained from the real-valued function which is obtained from this FrDTCWT. The FRDTCWT inherits the excellent mathematical properties of DTCWT and FrFT. Phase and amplitude of the image are computed from the complex analytic signal. The disparity is estimated as the optical flow using the phase difference method. The efficiency of the proposed algorithm is carried out by different experiments on synthetic as well as on realistic image sequences.
CONSISTENT SAMPLING WITH MULTI-, PRE- AND POST-FILTERINGS
Authors: HIRABAYASHI AKIRA , KWON KIL HYUN , LEE JAEKYU
Published: January 2013

We consider the approximate consistent sampling process in the space L2(ℝ) of signals of finite energy, where multi-, pre- and post-filters [Formula: see text] and [Formula: see text] are from L2(ℝ). We take {(f * hi)(qk)| 1 ≤ i ≤ M, k ∈ ℤ} as measurements(or generalized samples) of an input signal f and then seek its consistent approximation [Formula: see text] in the reconstruction space V(Φ), which is a shift-invariant subspace of L2(ℝ) generated by N post-filters [Formula: see text]. Here [Formula: see text] is a rational number and the consistency means that f and [Formula: see text] have the same measurements. We find equivalent conditions for the existence of such consistent approximation in L2(ℝ) together with some relevant properties such as performance analysis.
A COMPARATIVE STUDY OF PHENOMENOLOGICAL MODELS OF MR BRAKE BASED ON NEURAL NETWORKS APPROACH
Authors: PAWLUS WITOLD , KARIMI HAMID REZA
Published: January 2013

In this paper a full-scale commercially available magnetorheological (MR) brake installed in a semi-active suspension (SAS) system is modeled and simulated. Two well-known phenomenological hysteresis models are explored: Bouc–Wen and Dahl ones. In particular, influence of their parameters on the response is evaluated and assessed. The next step is to introduce the artificial neural networks and discuss their application in the field of systems identification. Subsequently, two feedforward neural networks are created and trained to estimate parameters characterizing each of the MR damper models described. The semi-active suspension (SAS) system equipped with a MR brake is described and the detailed procedure for acquisition of the reference data used in the models validation stage is elaborated. The models outputs obtained by simulating them with the values of coefficients as identified by the networks are compared to each other as well as to the reference experimental data. Thanks to that, the comparative analysis between the suggested vibration suppression models and the full-scale MR brake is done and it is concluded which of the discussed models has a better performance. The usability of neural networks in the field of parameters estimation of the mathematical models of the real world phenomena is described as well. The novelty of the presented methodology is the application of artificial intelligence methods to estimate model parameters of a MR brake utilized in a SAS system. The results of this approach have a strong potential to be successfully implemented in the area of model-based control of semi-active vibration suppression systems.
FLUX SYNTHESIS OF Na0.44MnO2 NANORIBBONS AND THEIR ELECTROCHEMICAL PROPERTIES FOR Na-ION BATTERIES
Authors: ZHAO LIWEI , NI JIANGFENG , WANG HAIBO , GAO LIJUN
Published: January 2013

Well-crystallized Na0.44MnO2 is readily synthesized via a facile NaCl -flux reaction at 850°C for 5 h. The Na0.44MnO2 material exhibits a well-defined nanoribbon structure with dimension of 50–100 nm in thickness and 200–500 nm in width. Electrochemical properties of as-prepared Na0.44MnO2 are thoroughly investigated on assembled nonaqueous Na0.44MnO2 // Na cells using cyclic voltammetry, galvanostatic test, and electrochemical impedance spectroscopy. The results show that the Na0.44MnO2 nanoribbon material can deliver a high capacity of 106 mAh g-1 with stable cycling performance over 40 cycles. In addition, it exhibits a favorable rate capability, delivering a capacity of 90 mAh g-1 at a rate of 1 C. The high capacity retention combined with acceptable rate capability makes the Na0.44MnO2 a promising electrode material for advanced Na -ion batteries.
Demo hour
Authors: Brock Anke , Truillet Philippe , Oriola Bernard , Picard Delphine , Jouffrais Christophe , Wintergerst Götz , Jagodzinski Ron , Giles Peter , Choi Sangwon , Gu Jiseong , Han Jaehyun , Heo Seongkook , Kim Sunjun , Lee Geehyuk , Ronchi Gloria , Benghi Claudio
Published: January 2013

Demo Hour highlights new prototypes and projects that exemplify innovation and novel forms of interaction.

Leah Maestri, Editor
Deception detection for the tangled web
Authors: Vartapetiance Anna , Gillam Lee
Published: January 2013

Deception is a reasonably common part of daily life that society sometimes demonstrates a degree of acceptance of, and occasionally people are very willing to be deceived. But can a computer identify deception and distinguish it from that which is not deceptive?

We explore deception in various guises, differentiating it from lies, and highlighting the influence of medium and message in both deception and its detection. Our investigations to date have uncovered disagreements relating to the measurements of such cues, and variations in interpretations, as could be problematic in building a deception detection system.
Moving Contact Lines: Scales, Regimes, and Dynamical Transitions
Authors: Snoeijer Jacco H. , Andreotti Bruno
Published: January 2013

The speed at which a liquid can move over a solid surface is strongly limited when a three-phase contact line is present, separating wet from dry regions. When enforcing large contact line speeds, this leads to the entrainment of drops, films, or air bubbles. In this review, we discuss experimental and theoretical progress revealing the physical mechanisms behind these dynamical wetting transitions. In this context, we discuss microscopic processes that have been proposed to resolve the moving–contact line paradox and identify the different dynamical regimes of contact line motion.
Gating of maxi channels observed from pseudo-phase portraits
Authors: Parsons Sean P. , Huizinga Jan D.
Published: January 2013

Phase space has been used to visualize and analyze the dynamic behavior of stochastic and chaotic systems. We applied this concept to maxi channels recorded from excised inside-out patches of in situ interstitial cells of Cajal. Pseudo-phase portraits of channel current were fairly homogeneous from patch to patch. They showed three main peaks, α, β, and γ, in increasing conductance. These represented single or near aggregated states. The α-peak was the closed state. The β-peak was small, consisting of a single conductance state, or in some cases two (a doublet). The β-peak state(s) had a long lifetime and displayed a characteristic behavior of frequent short transitions to γ but not to α. It was always preceded by a short series of α/γ-transitions. The γ-peak was the largest and consisted of a large number of conductance states with fast state transitions, sometimes to the extent of causing a diffusive-type behavior. Phase portraits allowed us to construct a provisional gating scheme for the maxi channel and suggest that further analysis of recordings in higher dimensional phase space and with related techniques may be promising.
Dietary protein digestion and absorption are impaired during acute postexercise recovery in young men
Authors: van Wijck Kim , Pennings Bart , van Bijnen Annemarie A. , Senden Joan M. G. , Buurman Wim A. , Dejong Cornelis H. C. , van Loon Luc J. C. , Lenaerts Kaatje
Published: January 2013

Previously, we demonstrated that exercise can cause small intestinal injury, leading to loss of gut barrier function. The functional consequences of such exercise-induced intestinal injury on subsequent food digestion and absorption are unclear. The present study determined the impact of resistance-type exercise on small intestinal integrity and in vivo dietary protein digestion and absorption kinetics. Twenty-four young males ingested 20 g specifically produced intrinsically l-[1-13C]phenylalanine-labeled protein at rest or after performing a single bout of resistance-type exercise. Continuous intravenous infusions with l-[ring-2H5]phenylalanine were employed, and blood samples were collected regularly to assess in vivo protein digestion and absorption kinetics and to quantify plasma levels of intestinal fatty-acid binding protein (I-FABP) as a measure of small intestinal injury. Plasma I-FABP levels were increased after exercise by 35%, reaching peak values of 344 ± 53 pg/ml compared with baseline 254 ± 31 pg/ml ( P < 0.05). In resting conditions, I-FABP levels remained unchanged. Dietary protein digestion and absorption rates were reduced during postexercise recovery when compared with resting conditions ( P < 0.001), with average peak exogenous phenylalanine appearance rates of 0.18 ± 0.04 vs. 0.23 ± 0.03 mmol phenylalanine·kg lean body mass−1·min−1, respectively. Plasma I-FABP levels correlated with in vivo rates of dietary protein digestion and absorption ( r S = −0.57, P < 0.01). Resistance-type exercise induces small intestinal injury in healthy, young men, causing impairments in dietary protein digestion and absorption kinetics during the acute postexercise recovery phase. To the best of our knowledge, this is first evidence that shows that exercise attenuates dietary protein digestion and absorption kinetics during acute postexercise recovery.
Hypoxic effects on sympathetic vasomotor outflow and blood pressure during exercise with inspiratory resistance
Authors: Katayama Keisho , Yamashita Shin , Ishida Koji , Iwamoto Erika , Koike Teruhiko , Saito Mitsuru
Published: January 2013

The purpose of the present study was to clarify the influence of inspiratory resistive breathing during exercise under hypoxic conditions on muscle sympathetic nerve activity (MSNA) and blood pressure (BP). Six healthy males completed this study. The subjects performed a submaximal exercise test using a cycle ergometer in a semirecumbent position under normoxic [inspired oxygen fraction (FiO2) = 0.21] and hypoxic (FiO2 = 0.12–0.13) conditions. The subjects carried out two 10-min exercises at 40% peak oxygen uptake [spontaneous breathing for 5 min and voluntary breathing with inspiratory resistance for 5 min (breathing frequency: 60 breaths/min, inspiratory and expiratory times were set at 0.5 s each)]. MSNA was recorded via microneurography of the right median nerve at the elbow. A progressive increase in MSNA burst frequency (BF) during leg-cycling exercise with inspiratory resistance in normoxia and hypoxia were accompanied by an augmentation of BP. The increased MSNA BF and mean arterial BP (MBP) during exercise with inspiratory resistive breathing in hypoxia (MSNA BF, 55.7 ± 1.4 bursts/min, MBP, 134.3 ± 6.6 mmHg) were higher than those in normoxia (MSNA BF, 39.2 ± 1.8 bursts/min, MBP, 123.6 ± 4.5 mmHg). These results suggest that an enhancement of inspiratory muscle activity under hypoxic condition leads to large increases in muscle sympathetic vasomotor outflow and BP during dynamic leg exercise.
Renal redox response to normal pregnancy in the rat
Authors: Cunningham Mark W. , Sasser Jennifer M. , West Crystal A. , Baylis Chris
Published: January 2013

Normal pregnancy involves increased renal sodium reabsorption, metabolism, and oxygen consumption, which can cause increased oxidative stress (OS). OS can decrease nitric oxide (NO) bioavailability and cause pregnancy complications. In this study we examined the NO synthases (NOS) and redox state in the kidney cortex and aorta in early (E), mid (M), and late (L) pregnant (P) ( days 3, 12, 20) and 2–4 days postpartum (PP) rats compared with virgin rats (V). Protein abundance of endothelial NOS (eNOS) was unchanged and neuronal NOS (nNOS)α fell at LP in the kidney cortex. Kidney cortex nNOSβ was elevated at MP, LP, and PP. No changes in aortic NOS isoforms were observed. Kidney cortex nitrotyrosine (NT) abundance decreased in EP, MP, and PP, whereas aortic NT increased in EP, MP, and PP. The NADPH oxidase subunit p22phox decreased in the kidney cortex at EP while aortic p22phox increased in EP and LP. No changes in kidney cortex NADPH-dependent superoxide production or hydrogen peroxide levels were noted. Kidney cortex cytosolic (CuZn) superoxide dismutase (SOD) was unchanged, while mitochondrial SOD decreased at EP and extracellular SOD decreased at MP and LP in the kidney cortex. Despite falls in abundance of kidney cortex SODs, total antioxidant capacity (TAC) was elevated in EP, MP, and PP in the kidney cortex. Aortic CuZn SOD deceased at PP, while the other aortic SODs and aortic TAC did not change. Data from this study suggest that the kidney cortex is protected from OS during normal rat pregnancy via an increase in antioxidant activity.