bluuebunny/crossref_metadata_2025 huggingface dataset:
Agent‐Based Modeling to Simulate Contamination Events and Evaluate Threat Management Strategies in Water Distribution Systems
Authors: Zechman Emily M.
Published: January 2011

In the event of contamination of a water distribution system, decisions must be made to mitigate the impact of the contamination and to protect public health. Making threat management decisions while a contaminant spreads through the network is a dynamic and interactive process. Response actions taken by the utility managers and water consumption choices made by the consumers will affect the hydraulics, and thus the spread of the contaminant plume, in the network. A modeling framework that allows the simulation of a contamination event under the effects of actions taken by utility managers and consumers will be a useful tool for the analysis of alternative threat mitigation and management strategies. This article presents a multiagent modeling framework that combines agent‐based, mechanistic, and dynamic methods. Agents select actions based on a set of rules that represent an individual's autonomy, goal‐based desires, and reaction to the environment and the actions of other agents. Consumer behaviors including ingestion, mobility, reduction of water demands, and word‐of‐mouth communication are simulated. Management strategies are evaluated, including opening hydrants to flush the contaminant and broadcasts. As actions taken by consumer agents and utility operators affect demands and flows in the system, the mechanistic model is updated. Management strategies are evaluated based on the exposure of the population to the contaminant. The framework is designed to consider the typical issues involved in water distribution threat management and provides valuable analysis of threat containment strategies for water distribution system contamination events.
Lesion border detection in dermoscopy images using dynamic programming
Authors: Abbas Qaisar , Celebi M. Emre , Fondón García Irene , Rashid Muhammad
Published: January 2011

Background/purpose: Automated border detection is an important and challenging task in the computerized analysis of dermoscopy images. However, dermoscopic images often contain artifacts such as illumination, dermoscopic gel, and outline (hair, skin lines, ruler markings, and blood vessels). As a result, there is a need for robust methods to remove artifacts and detect lesion borders in dermoscopy images.

Methods: This automated method consists of three main steps: (1) preprocessing, (2) edge candidate point detection, and (3) tumor outline delineation. First, algorithms to reduce artifacts were used. Second, a least‐squares method (LSM) was performed to acquire edge points. Third, dynamic programming (DP) technique was used to find the optimal boundary of the lesion. Statistical measures based on dermatologist‐drawn borders were utilized as ground‐truth to evaluate the performance of the proposed method.

Results: The method is tested on a total of 240 dermoscopic images: 30 benign melanocytic, 50 malignant melanomas, 50 basal cell carcinomas, 20 Merkel cell carcinomas, 60 seborrheic keratosis, and 30 atypical naevi. We obtained mean border detection error of 8.6%, 5.04%, 9.0%, 7.02%, 2.01%, and 3.24%, respectively.

Conclusions: The results demonstrate that border detection combined with artifact removal increases sensitivity and specificity for segmentation of lesions in dermoscopy images.
Evaluation of photoaging in facial skin by multiphoton laser scanning microscopy
Authors: Sugata Keiichi , Osanai Osamu , Sano Tomohiko , Takema Yoshinori
Published: January 2011

Background/purpose: It has been reported that autofluorescence (AF) and second harmonic generation (SHG) generated in the upper dermis are related with skin photoaging. In this study, we assessed the photoaging of facial skin exposed to daily sunlight using in vivo multiphoton laser microscopy to measure AF and SHG.

Methods: The intensities of AF and SHG in the upper dermis of cheek skin of 56 healthy volunteers aged 20–69 years were measured using a commercially available multiphoton laser microscope (DermaInspect®). Correlations between the photo‐signals and volunteer age were calculated.

Results: The intensity of SHG and the SHG‐to‐AF aging index of dermis (SAAID) correlated significantly with age (r=−0.48, −0.67, respectively).

Conclusion: Our results suggest that SHG and the SAAID index are useful indicators of facial skin aging in vivo.
Counselling of a couple faced with a prenatal diagnosis of Klinefelter syndrome
Authors: Girardin Céline M , Van Vliet Guy
Published: January 2011

When a prenatal diagnosis of Klinefelter syndrome (KS) is made, a couple is faced with an unfamiliar and unexpected diagnosis. The aim of this article is to give clues to prenatal counselling in this situation. The information provided to couples facing a prenatal diagnosis of KS should ideally be based on longitudinal studies of unselected individuals, including those diagnosed prenatally. Indeed, there are several reasons to think that the phenotype of individuals diagnosed prenatally is globally less severe than in those diagnosed postnatally.

Based on these studies, the evidence to be explained to couples to help them make an informed decision about the pregnancy is the following: except for rather tall height, generally normal appearance throughout life; increased risk of learning disabilities; spontaneous puberty, reduced testicular size, usual need for testosterone supplementation from adolescence onward; increased risk of gynecomastia; sexual orientation similar to the general male population; infertility, but with the possibility of having biological offspring with assisted reproductive techniques.

In this article, we review the evidence about the phenotype of KS according to the circumstances of diagnosis and its use in counselling couples faced with a prenatal diagnosis of this common condition.

Conclusion:  Cohort studies including individuals with KS diagnosed prenatally are still lacking.
Human papillomavirus 16 E7 protein inhibits interferon‐γ‐mediated enhancement of keratinocyte antigen processing and T‐cell lysis
Authors: Zhou Fang , Leggatt Graham R. , Frazer Ian H.
Published: January 2011

Infection of epithelium with human papillomavirus (HPV) 16 is generally prolonged, suggesting an ineffective virus‐specific immune response, and prolonged infection promotes anogenital cancer. To determine whether poor antigen presentation by HPV‐infected keratinocytes (KCs) contributes to prolonged HPV infection, KCs and KCs expressing HPV 16 E7 protein (E7‐KCs) were compared for susceptibility to T‐cell‐mediated lysis directed to ovalbumin (OVA) processed for presentation by the KCs. Interferon (IFN)‐γ efficiently enhanced susceptibility to lysis of KCs presenting OVA, but not of E7‐KCs similarly presenting OVA. E7‐KCs also exhibited impaired IFN‐γ‐induced upregulation of transcription of major histocompatibility complex class I antigen processing and presentation‐associated genes, and of membrane SIINFEKL–H‐2Kb complexes. Thus, expression of HPV 16 E7 protein in KCs may inhibit enhancement by IFN‐γ of KC sensitivity to T‐cell lysis, by impairing antigen presentation.
Toxin Genes Profiles and Toxin Production Ability of Bacillus cereus Isolated from Clinical and Food Samples
Authors: Kim Jung‐Beom , Kim Jai‐Moung , Cho Seung‐Hak , Oh Hyuk‐Soo , Choi Na Jung , Oh Deog‐Hwan
Published: January 2011

Abstract:  Bacillus cereus can cause diarrheal and emetic type of food poisoning but little study has been done on the main toxins of food poisoning caused by B. cereus in Korea. The objective of this study is to characterize the toxin gene profiles and toxin‐producing ability of 120 B. cereus isolates from clinical and food samples in Korea. The detection rate of nheABC, hblCDA, entFM, and cytK enterotoxin gene among all B. cereus strains was 94.2, 90.0, 65.8, and 52.5%, respectively. The ces gene encoding emetic toxin was not detected in all strains. Bacillus cereus strains carried at least 1 of the 8 enterotoxin genes were classified into 12 groups according to the presence or absence of 8 virulence genes. The 3 major patterns, I (nheABC, hblCDA, entFM, and cytK gene), II (nheABC, hblCDA and entFM gene), and VI (nheABC and hblCDA gene), accounted for 79.2% of all strains (95 out of 120 B. cereus isolates). Non‐hemolytic enterotoxin (NHE) and hemolysin BL (HBL) enterotoxins were produced by 107 and 100 strains, respectively. Our finding revealed that NHE and HBL enterotoxins encoded by nhe and hbl genes were the major toxins among B. cereus tested in this study and enterotoxic type of B. cereus was predominant in Korea.
Safety Evaluations on Ethanolic Extract of Red Cabbage (Brassica oleracea L.) in Mice
Authors: Thounaojam Menaka C. , Jadeja Ravirajsinh N. , Sankhari Jayanta M. , Devkar Ranjitsinh V. , Ramachandran A.V.
Published: January 2011

Abstract:  The present study has carried out safety evaluations on an ethanolic extract of red cabbage (RC) leaves in terms of acute and subchronic oral toxicity tests as per Organisation for Economic Cooperation and Development (OECD) guidelines in Swiss albino mice. Single‐dose administration of RC extract (1000, 2000, 3000, 4000, or 5000 mg/kg body weight) to Swiss albino mice did not manifest toxicity or any significant adverse behavioral alterations. Chronic administration of RC extract (1000, 2000, and 3000 mg/kg body weight) for 28 d also did not register any significant alterations in fluid intake, organ weights, plasma lipid profile, plasma creatine kinase‐MB, lactate dehydrogenase, aspartate transaminase, alanine transaminase, creatinine, electrolytes, and calcium levels, and the total blood count showed a nonsignificant change. However, significant reduction in body‐weight gain, food intake, red blood cell count, and hemoglobin content along with higher alkaline phosphatase, bilirubin, and urea levels was observed in mice treated with 3000 mg/kg body weight for 28 d. Since there was no mortality up to a dose of 5000 mg/kg body weight, 50% lethal dose (LD50) could not be determined, and hence, it can be assumed that, LD50 of RC extract is >5000 mg/kg. No observable adverse effect level dose of the RC extract was found to be 2000 mg/kg body weight. Hence, consumption of RC extract for various medicinal purposes is safe.

Practical Application:  RC is a popularly consumed foodstuff that has been ubiquitously reported to exert medicinal properties. It is mandatory to understand the highest permissible consumption limit of any food supplement to avoid toxicity. This study establishes the safe dose of RC. These results can be of relevance for the scientific fraternity as well as laymen who consume this vegetable or its phytochemical preparation.
Growth Inhibition of Foodborne Pathogens by Kimchi Prepared with Bacteriocin‐Producing Starter Culture
Authors: Chang Ji Yoon , Chang Hae Choon
Published: January 2011

Abstract:  Kimchi (starter kimchi) was prepared with Leuconostoc citreum GJ7, a bacteriocin producer, with the objective of preventing growth and/or survival of foodborne pathogens such as Escherichia coli O157:H7, Salmonella Typhi, and Staphylococcus aureus. Numbers of the pathogens inoculated to 5.41 to 5.63 log CFU/mL into the filtrate of freshly made starter kimchi remained stable for the first 12 h of incubation at 10 °C. Reductions of 2.69, 2.88, and 3.42 log CFU/mL were observed 48 h after inoculation with E. coli O157:H7, S. Typhi, and S. aureus, respectively. Use of the bacteriocin‐producing starter culture for kimchi fermentation significantly reduced the numbers of pathogens in the filtrate. Reductions of 3.85, 4.45, and 5.19 log CFU/mL were observed 48 h after inoculation for E. coli O157:H7, S. Typhi, and S. aureus, respectively. Presumably, the antimicrobial activity came from the ingredients of kimchi such as sulfur‐containing compounds, low pH (approximately pH 4.5) produced by the conversion of sugars into organic acids and the bacteriocins potentially produced by lactic acid bacteria (LAB), such as kimchicin GJ7. Together, these data suggest that addition of a starter culture capable of producing bacteriocins could serve as a strategy to protect the fermented product from delivering pathogens upon consumption and that the kimchi filtrate itself may be used as a food preservative.

Practical Application:  The adaptation of the starter fermentation into kimchi induced a faster die off of the pathogens as compared to natural fermentation. The in situ bateriocin‐production by Leuc. citreum GJ7 in kimchi would act with antimicrobial kimchi ingredients in a synergistic manner to protect the fermented product from delivering pathogens upon consumption.
Phytochemical Composition and Biological Activity of 8 Varieties of Radish (Raphanus sativus L.) Sprouts and Mature Taproots
Authors: Hanlon Paul R. , Barnes David M.
Published: January 2011

Abstract:  Radishes (Raphanus sativus L.) are members of the cruciferous vegetable family that contain many classes of biologically active phytochemicals. This study determined the phytochemical composition of the sprouts and mature taproots of 8 radish varieties. Radish sprouts contained significantly greater concentrations of glucosinolates (3.8‐fold) and isothiocyanates (8.2‐fold) than the mature radish taproot and also contained significantly greater concentrations of phenolics (on average 6.9‐fold). The anthocyanin concentrations of the mature radish taproot were significantly greater than in the sprouts of red, pink, and purple varieties. The primary anthocyanidins present in the red and pink radish varieties were pelargonidin and delphinidin, while the primary anthocyanidin in the purple radish variety was cyanidin. Radish sprouts were between 9‐ and 59‐fold more potent than the corresponding mature taproot at activating the antioxidant response element (ARE) in a stably transfected hepatoma cell line. The ARE activity of the radish sprouts and mature taproots was significantly correlated with the total isothiocyanate concentration of the radishes.

Practical Application:  Understanding the influence variety and developmental stage has on the biological activity of cruciferous vegetables provides important information for further studies examining the in vivo effects of radish treatment and foundation for providing recommendations to reduce the risk of chronic disease through dietary intervention.
Logistic response models with item interactions
Authors: Revuelta Javier
Published: January 2011

Items that are clustered according to shared content may violate the principle of conditional independence commonly used in item response theory. This paper investigates the capabilities of a logistic item response model in relation to locally dependent item responses. The model includes main effect and interaction parameters that are computed as linear functions of the latent trait. The paper explains the interpretation of the parameters, the maximum likelihood estimation algorithm, the information matrix and some results concerning parameter identifiability. The problem of over‐fitting the data is addressed in a simulation study, and two real data examples are described to illustrate the approach, one from the context of a sample survey and the other from ability testing using testlets.
Heat Transfer Properties and Energy-Exergy Efficiency in a Finned Cross-Flow Heat Recovery Unit
Authors: Kotcioglu Isak , Cansiz Ahmet
Published: January 2011

In this study, a cross-flow heat recovery-exchanger system operating with unmixed fluids was manufactured and tested. The thermodynamic analysis of the system was presented via determining the variations of exergy loss with Reynolds number. The analysis also included the effects of convergent and divergent plate-type winglets on heat transfer properties of the designed system. Experimental tests consisted of temperature and pressure drop measurements for the Reynolds numbers (3000 and 12,000) according to the working conditions of the boiler, fan, preheater, and reheater. The effects of inlet conditions of the working fluids on the heat transfer characteristics were correlated via entropy generation number and exergy loss. The variation of the effectiveness with the number of transfer unit of heat recovery unit was calculated and discussed in terms of literature.
Optimization of Annular Cylindrical and Spherical Fins in an Internal Combustion Engine Under Realistic Conditions
Authors: Illán Fernando , Alarcón Mariano
Published: January 2011

The heat transfer from cylinder to air of a two-stroke internal combustion finned engine has been simulated. For this purpose, a 2D model of the block and head has been done. Starting from the geometry of a real engine, annular cylindrical and spherical symmetric walls to fins has been used to obtain an equivalent simplified geometry, where the heat transfer rate is the same as that in the real engine. The cylinder body, cylinder head (both provided with fins), and piston have been numerically analyzed and optimized in order to minimize engine dimensions. The maximum temperature admissible at the hottest point of the engine has been adopted as the limiting condition. An engine temperature map has been presented as additional information. Cyclically variable inner cylinder conditions (thermodynamic, thermal, and chemical) proceed from a previous work; convective and radiative inner boundary conditions and convective external conditions have also been taken into account in this work. A network simulation model has been used as the numerical tool in the analysis presented.
A Biological Solution to a Fundamental Distributed Computing Problem
Authors: Afek Yehuda , Alon Noga , Barad Omer , Hornstein Eran , Barkai Naama , Bar-Joseph Ziv
Published: January 2011

Modeling of development in the fruit fly yields an algorithm useful in designing wireless communication networks.
The Structure of Human 5-Lipoxygenase
Authors: Gilbert Nathaniel C. , Bartlett Sue G. , Waight Maria T. , Neau David B. , Boeglin William E. , Brash Alan R. , Newcomer Marcia E.
Published: January 2011

Substitution of a destabilizing sequence has allowed crystallization of a key enzyme of the inflammatory response.
Light-Driven Changes in Energy Metabolism Directly Entrain the Cyanobacterial Circadian Oscillator
Authors: Rust Michael J. , Golden Susan S. , O’Shea Erin K.
Published: January 2011

Cyanobacterial circadian clock components are directly coupled to the metabolic status of the cell through interactions with adenine nucleotides.
Suppression of Avian Influenza Transmission in Genetically Modified Chickens
Authors: Lyall Jon , Irvine Richard M. , Sherman Adrian , McKinley Trevelyan J. , Núñez Alejandro , Purdie Auriol , Outtrim Linzy , Brown Ian H. , Rolleston-Smith Genevieve , Sang Helen , Tiley Laurence
Published: January 2011

Transgenic birds expressing a short hairpin RNA that blocks viral polymerase hinder influenza transmission.
Changing the Culture of Science Education at Research Universities
Authors: Anderson W. A. , Banerjee U. , Drennan C. L. , Elgin S. C. R. , Epstein I. R. , Handelsman J. , Hatfull G. F. , Losick R. , O'Dowd D. K. , Olivera B. M. , Strobel S. A. , Walker G. C. , Warner I. M.
Published: January 2011

Universities must better recognize, reward, and support the efforts of researchers who are also excellent and dedicated teachers.
Electron Vortex Beams with High Quanta of Orbital Angular Momentum
Authors: McMorran Benjamin J. , Agrawal Amit , Anderson Ian M. , Herzing Andrew A. , Lezec Henri J. , McClelland Jabez J. , Unguris John
Published: January 2011

Diffraction holograms are used to create electron vortex beams that should enable higher-resolution imaging.
Fermilab to End Its Quest for Higgs Particle This Year
Authors: Cho Adrian
Published: January 2011

Officials at the U.S. Department of Energy, which funds Fermi National Accelerator Laboratory, informed lab officials this week that DOE cannot come up with the extra $35 million per year to keep the Tevatron atom smasher going beyond September.
Why Loneliness Is Hazardous to Your Health
Authors: Miller Greg
Published: January 2011

New research suggests that chronic loneliness can cause changes in the cardiovascular, immune, and nervous systems.
Tectonic Blow Ended Mountain Building, Fired Up Volcanoes
Authors: Kerr Richard A.
Published: January 2011

Fifty-five million years ago, Siletzia arrived on North American shores with nary a bump. But the 500-kilometer-wide chunk of drifting oceanic plate had far-reaching geologic effects across the continent's western third, according to a presentation at the meeting.
Interference of Vaccination against Bluetongue Virus Serotypes 1 and 8 with Serological Diagnosis of Small-Ruminant Lentivirus Infection
Authors: Valas Stephen , Le Ven Alain , Croise Benoit , Maquigneau Maud , Perrin Cécile
Published: January 2011

The effects of the recent vaccinations against bluetongue virus serotype 1 (BTV-1) and BTV-8 in Europe on the reliability of enzyme-linked immunosorbent assays (ELISAs) currently used for diagnosis of small-ruminant lentivirus (SRLV) infection were examined. Primary vaccination against BTV-8 in goats induced an increase in reactivity that did not exceed 3 months in a whole-virus indirect ELISA and a competitive ELISA based on the gp135 glycoprotein. Subsequent BTV-1/8 vaccination extended the time scale of false-positive reactivity for up to 6 months. These results are of relevance for SRLV-monitoring programs.
Early Immune Markers Associated withMycobacterium aviumsubsp.paratuberculosisInfection in a Neonatal Calf Model
Authors: Stabel J. R. , Robbe-Austerman S.
Published: January 2011

The objective of this study was to observe early markers of cell-mediated immunity in naïve calves infected withMycobacterium aviumsubsp.paratuberculosisand how expression of these markers evolved over the 12-month period of infection. Groups for experimental infection included control (noninfected), oral (infected orally withM. aviumsubsp.paratuberculosisstrain K-10), oral/DXM (pretreatment with dexamethasone before oral inoculation), intraperitoneal (i.p.) inoculation, and oral/M (oral inoculation with mucosal scrapings from a cow with clinical disease) groups. One of the earliest markers to emerge was antigen-specific gamma interferon (IFN-γ). Only i.p. inoculated calves had detectable antigen-specific IFN-γ responses at 7 days, with responses of the other infection groups becoming detectable at 90 and 120 days. All infection groups maintained robust IFN-γ responses for the remainder of the study. At 1 month, calves in the oral and oral/M groups had higher antigen-stimulated interleukin-10 (IL-10) levels than calves in the other treatment groups, but IL-10 secretion declined by 12 months for all calves. T-cell activation markers such as CD25, CD26, CD45RO, and CD5 were significantly upregulated in infected calves compared to noninfected controls. Oral inoculation of calves resulted in significantly increased antigen-specific lymphocyte proliferation at 9 and 12 months, as well as inducible nitric oxide synthase (iNOS) secretion at 6 and 12 months. These results demonstrate that infection of naïve calves withM. aviumsubsp.paratuberculosisinvoked early immunologic responses characterized by robust antigen-specific IFN-γ responses and induction of CD25 and CD45RO expression on T-cell subsets. These were followed by antigen-specific lymphocyte proliferation, iNOS secretion, and expression of CD26 and CD5brightmarkers in the latter part of the 12-month study.
Pathogenicity and Immunogenicity of a Mutant Strain of
Listeria monocytogenes
in the Chicken Infection Model
Authors: Yin Yuelan , Tian Debin , Jiao Hongmei , Zhang Chenju , Pan Zhiming , Zhang Xiaoming , Wang Xiaobo , Jiao Xinan
Published: January 2011

Listeria monocytogenes
has been exploited as a vaccine carrier based upon its ability to induce a strong cell-mediated immune response. At present, the safety of live, attenuated
L. monocytogenes
vaccines in patients is being studied in clinical trials.
L. monocytogenes
is also an attractive vaccine vector for use in poultry; however, the pathogenicity and immunogenicity of this organism in poultry remain to be fully elucidated. In this study, we investigated the pathogenicity and immunogenicity of an
actA
- and
plcB
-deficient
L. monocytogenes
strain, yzuLM4Δ
actA
/
plcB
, and its wild-type parent strain, yzuLM4, in an avian infection model. The results showed that the wild-type strain could infect ISA brown chickens, causing serious tissue disruptions, including various degrees of degeneration, necrotic lesions, and inflammatory cell infiltration in the liver, spleen, heart, and kidney. However, the mutant strain showed reduced virulence in embryonated eggs compared with that of the parent strain (the 50% lethal dose [LD
50
] was 3 logs higher). The mutant strain also showed low virulence in chickens and was rapidly eliminated by the host. There were no obvious pathological changes in tissue sections, but the mutant strain still retained the ability to stimulate high levels of antibody against the protein listeriolysin O (LLO). Booster immunization with the mutant strain led to rapid bacterial clearance from the livers and spleens of chickens challenged by the intramuscular route or the oral route. Collectively, our data suggest that the wild-type serotype 1/2a
L. monocytogenes
strain can cause serious disease in chickens but the mutant strain with a deletion of the
actA
and
plcB
genes is less virulent but induces a strong immune response. This mutant strain of
L. monocytogenes
is therefore a promising candidate as a safe and effective vector for the delivery of heterologous antigens to prevent zoonosis and infectious disease in poultry.
Full Serotype- and Group-Specific NS1 Capture Enzyme-Linked Immunosorbent Assay for Rapid Differential Diagnosis of Dengue Virus Infection
Authors: Ding Xixia , Hu Dongmei , Chen Yue , Di Biao , Jin Jing , Pan Yuxian , Qiu Liwen , Wang Yadi , Wen Kun , Wang Ming , Che Xiaoyan
Published: January 2011

Dengue virus (DENV), a member of the
Flavivirus
family, has four distinct serotypes (DENV serotype 1 [DENV1], DENV2, DENV3, and DENV4) that require differentiation for the effective prevention of morbid disease. Early and rapid differentiation between flaviviruses remains challenging. Full assays combining four individual, serotype-specific and one group-specific nonstructural protein 1 (NS1) antigen capture enzyme-linked immunosorbent assays (ELISAs) based on monoclonal antibodies (MAbs) against DENV NS1 were developed and validated. The sensitivities and specificities of the full NS1 ELISAs were evaluated with viral cultures and dengue acute-phase sera. Four serotype-specific NS1 ELISAs displayed high specificities for the detection and differentiation of appropriate serotypes. The group-specific NS1 ELISA was broadly reactive with the four dengue virus serotypes. None of the NS1 ELISAs displayed cross-reactivity with the other flaviviruses or samples from febrile patients with non-dengue virus infections. The full serotype- and group-specific MAb-based NS1 capture ELISAs may provide tools for the early detection and typing of dengue infection, which is preferable to reverse transcriptase PCR (RT-PCR) for the rapid differential diagnosis of dengue virus infection in the field.
Identification of Surrogates and Correlates of Protection in Protective Immunity againstMycobacterium bovisInfection Induced in Neonatal Calves by Vaccination withM. bovisBCG Pasteur andM. bovisBCG Danish
Authors: Hope J. C. , Thom M. L. , McAulay M. , Mead E. , Vordermeier H. M. , Clifford D. , Hewinson R. G. , Villarreal-Ramos B.
Published: January 2011

Vaccination of neonatal calves withMycobacterium bovisbacillus Calmette-Guérin (BCG) induces a significant degree of protection against infection with virulentM. bovis, the causative agent of bovine tuberculosis (bTB). We compared two strains of BCG, Pasteur and Danish, in order to confirm that the current European human vaccine strain (BCG Danish) induced protective immunity in calves, and we assessed immune responses to determine correlates of protection that could assist future vaccine evaluation in cattle. Both vaccine strains induced antigen (purified protein derivate [PPD])-specific gamma interferon (IFN-γ) in whole-blood cultures. These responses were not significantly different for BCG Pasteur and BCG Danish and peaked at week 2 to 4 postvaccination. Vaccination with either BCG Danish or BCG Pasteur induced significant protection against bTB, with reductions in both lesion score and bacteriological burden evident in both groups of vaccinated calves compared with nonvaccinated control calves. Measurement of IFN-γ-expressing T lymphocytes postvaccination and postchallenge revealed both correlates and surrogates of protective efficacy. The frequency of central memory T lymphocytes present at 12 weeks postvaccination (at the time ofM. bovischallenge) correlated significantly with protection. Conversely, the number of IFN-γ-expressing effector T cells present afterM. bovischallenge was correlated with disease. These results demonstrate that vaccination of neonatal calves with either BCG Pasteur or BCG Danish induces protective immune responses against TB. In addition, we show that measurement of antigen-specific T lymphocyte populations may provide a reliable means for identifying protective vaccine candidates.
Human Bocavirus as the Cause of a Life-Threatening Infection
Authors: Uršič Tina , Steyer Andrej , Kopriva Silvester , Kalan Gorazd , Krivec Uroš , Petrovec Miroslav
Published: January 2011

Human bocavirus is a recently described respiratory pathogen. A case of a life-threatening human bocavirus infection of a previously healthy pediatric patient is described. An initial clinical presentation of acute bronchiolitis developed into an extremely severe course of disease characterized by pneumothorax, pneumomediastinum, and acute respiratory failure with pronounced air-leak syndrome.
Rotavirus Replication Requires a Functional Proteasome for Effective Assembly of Viroplasms
Authors: Contin R. , Arnoldi F. , Mano M. , Burrone O. R.
Published: January 2011

The ubiquitin-proteasome system has been shown to play an important role in the replication cycle of different viruses. In this study, we describe a strong impairment of rotavirus replication upon inhibition of proteasomal activity. The effect was evidenced at the level of accumulation of viral proteins, viral RNA, and yield of infective particles. Kinetic studies revealed that the early steps of the replicative cycle following attachment, entry, and uncoating were clearly more sensitive to proteasome inhibition. We ruled out a direct inhibition of the viral polymerase activities and stability of viral proteins and found that the crucial step that was impaired by blocking proteasome activity was the assembly of new viroplasms. This was demonstrated by using chemical inhibitors of proteasome and by gene silencing using small interfering RNAs (siRNAs) specific for different proteasomal subunits and for the ubiquitin precursor RPS27A. In addition, we show that the effect of proteasome inhibition on virus infection is not due to increased levels of beta interferon (IFN-β).
Hepatitis B Virus X Protein Enhances Cisplatin-Induced Hepatotoxicity via a Mechanism Involving Degradation of Mcl-1
Authors: Hu Liang , Chen Lei , Li Liang , Sun HanYong , Yang GuangZhen , Chang YanXin , Tu QianQian , Wu MengChao , Wang HongYang
Published: January 2011

Hepatitis B virus X protein (HBx) is implicated in the pathogenesis of hepatitis B virus (HBV)-associated liver diseases. However, whether HBx has the ability to disturb the susceptibility of hepatocytes to common chemotherapeutic agents remains incompletely understood. Here we demonstrate that HBx enhances cisplatin-induced hepatotoxicity by a mechanism involving degradation of Mcl-1, an antiapoptotic member of the Bcl-2 family. Ectopic expression of HBx sensitized hepatocytes to cisplatin-induced apoptosis, which was accompanied by a marked downregulation of Mcl-1 but not of Bcl-2 or Bcl-xL. Overexpression of Mcl-1 prevented HBx-induced proapoptotic and proinflammatory effects during cisplatin treatment bothin vitroandin vivo. HBx-induced dysregulation of Mcl-1 resulted mainly from posttranslational degradation rather than transcription repression. Moreover, a caspase-3 inhibitor effectively abrogated HBx-enhanced Mcl-1 degradation and cell death. Importantly, antioxidants blocked activation of caspase-3 and acceleration of Mcl-1 loss, as well as cell death, in HBx-expressing hepatocytes upon cisplatin exposurein vitroandin vivo. Collectively, these data implicate oxidative stress-dependent caspase-3-mediated degradation of Mcl-1 as a mechanism contributing to HBx-mediated sensitization of cisplatin-induced hepatotoxicity. A combination of cisplatin and antioxidants might provide more advantage than cisplatin alone in the treatment of cancer patients with chronic HBV infection.
Regulation of the Human Papillomavirus Type 18 E6/E6AP Ubiquitin Ligase Complex by the HECT Domain-Containing Protein EDD
Authors: Tomaić Vjekoslav , Pim David , Thomas Miranda , Massimi Paola , Myers Michael P. , Banks Lawrence
Published: January 2011

Human papillomavirus (HPV) E6 oncoproteins target many cellular proteins for ubiquitin-mediated proteasomal degradation. In the case of p53, this is mediated principally by the E6AP ubiquitin ligase. Several studies have reported that E6 can target certain of its substrates in an apparently E6AP-independent fashion and that several of these substrates vary in the degree to which they are degraded by E6 at different stages of malignancy. To more fully understand the regulation of the E6AP/E6 proteolytic targeting complex, we performed a mass spectroscopic analysis of HPV type 18 (HPV-18) E6 protein complexes and identified the HECT domain-containing ubiquitin ligase EDD as a new HPV-18 E6 binding partner. We show that EDD can interact independently with both E6 and E6AP. Furthermore, EDD appears to regulate E6AP expression levels independently of E6, and loss of EDD stimulates the proteolytic activity of the E6/E6AP complex. Conversely, higher levels of EDD expression protect a number of substrates from E6-induced degradation, partly as a consequence of lower levels of E6 and E6AP expression. Intriguingly, reduction in EDD expression levels in HPV-18-positive HeLa cells enhances cell resistance to apoptotic and growth arrest stimuli. These studies suggest that changes in the levels of EDD expression during different stages of the viral life cycle or during malignancy could have a profound effect upon the ability of E6 to target various substrates for proteolytic degradation and thereby directly influence the development of HPV-induced malignancy.
Recombinant Sendai Viruses Expressing Fusion Proteins with Two Furin Cleavage Sites Mimic the Syncytial and Receptor-Independent Infection Properties of Respiratory Syncytial Virus
Authors: Rawling Joanna , Cano Olga , Garcin Dominique , Kolakofsky Daniel , Melero José A.
Published: January 2011

Cell entry by paramyxoviruses requires fusion between viral and cellular membranes. Paramyxovirus infection also gives rise to the formation of multinuclear, fused cells (syncytia). Both types of fusion are mediated by the viral fusion (F) protein, which requires proteolytic processing at a basic cleavage site in order to be active for fusion. In common with most paramyxoviruses, fusion mediated by Sendai virus F protein (FSeV) requires coexpression of the homologous attachment (hemagglutinin-neuraminidase [HN]) protein, which binds to cell surface sialic acid receptors. In contrast, respiratory syncytial virus fusion protein (FRSV) is capable of fusing membranes in the absence of the viral attachment (G) protein. Moreover, FRSVis unique among paramyxovirus fusion proteins since FRSVpossesses two multibasic cleavage sites, which are separated by an intervening region of 27 amino acids. We have previously shown that insertion of both FRSVcleavage sites in FSeVdecreases dependency on the HN attachment protein for syncytium formation in transfected cells. We now describe recombinant Sendai viruses (rSeV) that express mutant F proteins containing one or both FRSVcleavage sites. All cleavage-site mutant viruses displayed reduced thermostability, with double-cleavage-site mutants exhibiting a hyperfusogenic phenotype in infected cells. Furthermore, insertion of both FRSVcleavage sites in FSeVreduced dependency on the interaction of HN with sialic acid for infection, thus mimicking the unique ability of RSV to fuse and infect cells in the absence of a separate attachment protein.
Superparamagnetic Nanoparticle Capture of Prions for Amplification
Authors: Miller Michael B. , Supattapone Surachai
Published: January 2011

Prion diseases are associated with the presence of PrP
Sc
, a disease-associated misfolded conformer of the prion protein. We report that superparamagnetic nanoparticles bind PrP
Sc
molecules efficiently and specifically, permitting magnetic separation of prions from a sample mixture. Captured PrP
Sc
molecules retain the activity to seed protein misfolding cyclic amplification (PMCA) reactions, enabling the rapid concentration of dilute prions to improve detection. Furthermore, superparamagnetic nanoparticles clear contaminated solutions of PrP
Sc
. Our findings suggest that coupling magnetic nanoparticle capture with PMCA could accelerate and improve prion detection. Magnetic nanoparticles may also be useful for developing a nontoxic prion decontamination method for biologically derived products.
Histone Demethylase JMJD2A Regulates Kaposi's Sarcoma-Associated Herpesvirus Replication and Is Targeted by a Viral Transcriptional Factor
Authors: Chang Pei-Ching , Fitzgerald Latricia D. , Hsia Datsun A. , Izumiya Yoshihiro , Wu Chun-Yi , Hsieh Wen-Ping , Lin Su-Fang , Campbell Mel , Lam Kit S. , Luciw Paul A. , Tepper Clifford G. , Kung Hsing-Jien
Published: January 2011

The switch between the latency and lytic cycles of Kaposi's sarcoma-associated herpesvirus (KSHV) is accompanied by specific alterations of histone codes. Recently, comprehensive analysis of histone modifications of KSHV showed the deposition of H3K27me3 across the KSHV genome with two specific regions occupied by the heterochromatin marker H3K9me3. Here, we show that knockdown of JMJD2A, an H3K9me3 demethylase, attenuates viral titers, whereas its overexpression increases KSHV reactivation. JMJD2A is localized in regions of latent viral chromosomes that are deficient in the H3K9me3 mark, indicating that JMJD2A may be responsible for the low level of this mark on viral chromatin. The presence of JMJD2A on the latent genome maintains H3K9 in unmethylated form and signals the readiness of specific sets of viral genes to be reactivated. The demethylase activity of JMJD2A is important for KSHV reactivation, because a demethylase-deficient mutant cannot restore the JMJD2A knockdown phenotype. Interestingly, we found that the KSHV encoded K-bZIP associated with JMJD2A, resulting in the inhibition of demethylase activity of JMJD2A both
in vivo
and
in vitro
. Inhibition of JMJD2A by K-bZIP is likely due to a physical interaction which blocks substrate accessibility. A consequence of such an inhibition is increasing global levels of H3K9me3 and gene silencing. Consistently, K-bZIP overexpression resulted in a repression of ∼80% of the ≥2-fold differentially regulated genes compared to results for the uninduced control cells. The consequences of K-bZIP targeting JMJD2A during viral replication will be discussed. To our knowledge, this is the first description of a viral product shown to be a potent inhibitor of a host cellular histone demethylase.
High oesophageal web formation in association with heterotopic gastric mucosa (the gastric inlet patch): a small case series
Authors: Ainley Eric J
Published: January 2011

Background

Upper oesophageal webs or rings have rarely been reported in association with heterotopic gastric mucosa (HGM).

Objective

To describe the finding of oesophageal webs in association with HGM.

Design

Small case series.

Setting

Patients presenting with dysphagia to an open access hospital dysphagia clinic.

Patients

Six cases were found.

Interventions

Symptomatic improvement is demonstrated with oesophageal dilatation in symptomatic patients.

Main outcome measurements

Symptomatic improvement.

Results

The six cases which are described here demonstrate that a web or ring exactly matches the distribution of the heterotopic mucosa, can occur at both proximal and distal squamo-columnar junctions and the inlet patches may be multiple with multiple rings. A radiological double web sign is described.

Limitations

A rare condition with a small number of patients.

Conclusions

Effective treatment can be by oesophageal dilatation and acid suppression. The cause of web formation is thought to be due to heterotopic acid production and is analogous to the Schatzki ring.
SPACE PARTITIONING STRATEGIES FOR INDOOR WLAN POSITIONING WITH CASCADE-CONNECTED ANN STRUCTURES
Authors: BORENOVIĆ MILOŠ , NEŠKOVIĆ ALEKSANDAR , BUDIMIR DJURADJ
Published: January 2011

Position information in indoor environments can be procured using diverse approaches. Due to the ubiquitous presence of WLAN networks, positioning techniques in these environments are the scope of intense research. This paper explores two strategies for space partitioning when utilizing cascade-connected Artificial Neural Networks (ANNs) structures for indoor WLAN positioning. A set of cascade-connected ANN structures with different space partitioning strategies are compared mutually and to the single ANN structure. The benefits of using cascade-connected ANNs structures are shown and discussed in terms of the size of the environment, number of subspaces and partitioning strategy. The optimal cascade-connected ANN structures with space partitioning show up to 50% decrease in median error and up to 12% decrease in the average error with respect to the single ANN model. Finally, the single ANN and the optimal cascade-connected ANN model are compared against other well-known positioning techniques.
RECURSIVE DISCRIMINANT REGRESSION ANALYSIS TO FIND HOMOGENEOUS GROUPS
Authors: GARCÍA-CUESTA ESTEBAN , GALVÁN INÉS M. , DE CASTRO ANTONIO J.
Published: January 2011

The main motivation of this paper is to propose a method to extract the output structure and find the input data manifold that best represents that output structure in a multivariate regression problem. A graph similarity viewpoint is used to develop an algorithm based on LDA, and to find out different output models which are learned as an input subspace. The main novelty of the algorithm is related with finding different structured groups and apply different models to fit better those structures. Finally, the proposed method is applied to a real remote sensing retrieval problem where we want to recover the physical parameters from a spectrum of energy.
ON THE VOLUME CONJECTURE FOR CABLES OF KNOTS
Authors: LE THANG T. Q. , TRAN ANH T.
Published: January 2011

We establish the volume conjecture for (m, 2)-cables of the figure 8 knot, when m is odd. For (m, 2)-cables of general knots where m is even, we show that the limit in the volume conjecture depends on the parity of the color (of the Kashaev invariant). There are many cases when the volume conjecture for cables of the figure 8 knot is false if one considers all the colors, but holds true if one restricts the colors to a subset of the set of positive integers.
A 3-MANIFOLD COMPLEXITY VIA IMMERSED SURFACES
Authors: AMENDOLA GENNARO
Published: January 2011

We define an invariant, which we call surface-complexity, of closed 3-manifolds by means of Dehn surfaces. The surface-complexity of a manifold is a natural number measuring how much the manifold is complicated. We prove that it fulfils interesting properties: it is subadditive under connected sum and finite-to-one on ℙ2-irreducible manifolds. Moreover, for ℙ2-irreducible manifolds, it equals the minimal number of cubes in a cubulation of the manifold, except for the sphere S3, the projective space ℝℙ3 and the lens space L4,1, which have surface-complexity zero. We will also give estimations of the surface-complexity by means of triangulations, Heegaard splittings, surgery presentations and Matveev complexity.
PRIME KNOTS WITH ARC INDEX UP TO 11 AND AN UPPER BOUND OF ARC INDEX FOR NON-ALTERNATING KNOTS
Authors: JIN GYO TAEK , PARK WANG KEUN
Published: January 2011

Every knot can be embedded in the union of finitely many half planes with a common boundary line in such a way that the portion of the knot in each half plane is a properly embedded arc. The minimal number of such half planes is called the arc index of the knot. We have identified all prime knots with arc index up to 11. We also proved that the crossing number is an upperbound of arc index for non-alternating knots. As a result the arc index is determined for prime knots up to twelve crossings.
VARIATIONAL STRUCTURE OF THE OPTIMAL ARTIFICIAL DIFFUSION METHOD FOR THE ADVECTION–DIFFUSION EQUATION
Authors: NAKSHATRALA K. B. , VALOCCHI A. J.
Published: January 2011

In this research note, we provide a variational basis for the optimal artificial diffusion method, which has been a cornerstone in developing many stabilized methods. The optimal artificial diffusion method produces exact nodal solutions when applied to one-dimensional (1D) problems with constant coefficients and forcing function. We first present a variational principle for a multi-dimensional advective-diffusive system, and then derive a new stable weak formulation. When applied to 1D problems with constant coefficients and forcing function, this resulting weak formulation will be equivalent to the optimal artificial diffusion method. We present representative numerical results to corroborate our theoretical findings.
THE FINITENESS OF COMPUTING THE ULTRAMETRIC MAHLER MEASURE
Authors: SAMUELS CHARLES L.
Published: January 2011

Recent work of Fili and the author examines an ultrametric version of the Mahler measure, denoted M∞(α) for an algebraic number α. We show that the computation of M∞(α) can be reduced to a certain search through a finite set. Although it is an open problem to record the points of this set in general, we provide some examples where it is reasonable to compute and our result can be used to determine M∞(α).
SPECIAL VALUES OF L-FUNCTIONS ON GSp4 × GL2 AND THE NON-VANISHING OF SELMER GROUPS
Authors: BROWN JIM
Published: January 2011

In this paper, we show how one can use an inner product formula of Heim giving the inner product of the pullback of an Eisenstein series from Sp10 to Sp 2 × Sp 4 × Sp 4 with a new-form on GL2 and a Saito–Kurokawa lift to produce congruences between Saito–Kurokawa lifts and non-CAP forms. This congruence is in part controlled by the L-function on GSp 4 × GL 2. The congruence is then used to produce nontrivial torsion elements in an appropriate Selmer group, providing evidence for the Bloch–Kato conjecture.