bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of an
l
-Rhamnose Synthetic Pathway in Two Nucleocytoplasmic Large DNA Viruses
Authors: Parakkottil Chothi Madhu , Duncan Garry A. , Armirotti Andrea , Abergel Chantal , Gurnon James R. , Van Etten James L. , Bernardi Cinzia , Damonte Gianluca , Tonetti Michela 
Published: June 2010

ABSTRACT

Nucleocytoplasmic large DNA viruses (NCLDVs) are characterized by large genomes that often encode proteins not commonly found in viruses. Two species in this group are
Acanthocystis turfacea
chlorella virus 1 (ATCV-1) (family
Phycodnaviridae
, genus
Chlorovirus
) and
Acanthamoeba polyphaga
mimivirus (family
Mimiviridae
), commonly known as mimivirus. ATCV-1 and other chlorovirus members encode enzymes involved in the synthesis and glycosylation of their structural proteins. In this study, we identified and characterized three enzymes responsible for the synthesis of the sugar
l
-rhamnose: two UDP-
d
-glucose 4,6-dehydratases (UGDs) encoded by ATCV-1 and mimivirus and a bifunctional UDP-4-keto-6-deoxy-
d
-glucose epimerase/reductase (UGER) from mimivirus. Phylogenetic analysis indicated that ATCV-1 probably acquired its UGD gene via a recent horizontal gene transfer (HGT) from a green algal host, while an earlier HGT event involving the complete pathway (UGD and UGER) probably occurred between a protozoan ancestor and mimivirus. While ATCV-1 lacks an epimerase/reductase gene, its
Chlorella
host may encode this enzyme. Both UGDs and UGER are expressed as late genes, which is consistent with their role in posttranslational modification of capsid proteins. The data in this study provide additional support for the hypothesis that chloroviruses, and maybe mimivirus, encode most, if not all, of the glycosylation machinery involved in the synthesis of specific glycan structures essential for virus replication and infection.
Molecular Basis of Neurovirulence of Flury Rabies Virus Vaccine Strains: Importance of the Polymerase and the Glycoprotein R333Q Mutation
Authors: Tao Lihong , Ge Jinying , Wang Xijun , Zhai Hongyue , Hua Tao , Zhao Bolin , Kong Dongni , Yang Chinglai , Chen Hualan , Bu Zhigao 
Published: June 2010

ABSTRACTThe molecular mechanisms associated with rabies virus (RV) virulence are not fully understood. In this study, the RV Flury low-egg-passage (LEP) and high-egg-passage (HEP) strains were used as models to explore the attenuation mechanism of RV. The results of our studies confirmed that the R333Q mutation in the glycoprotein (GR333Q) is crucial for the attenuation of Flury RV in mice. The R333Q mutation is stably maintained in the HEP genome background but not in the LEP genome background during replication in mouse brain tissue or cell culture. Further investigation using chimeric viruses revealed that the polymerase L gene determines the genetic stability of the GR333Qmutation during replication. Moreover, a recombinant RV containing the LEP G protein with the R333Q mutation and the HEP L gene showed significant attenuation, genetic stability, enhancement of apoptosis, and immunogenicity. These results indicate that attenuation of the RV Flury strain results from the coevolution of G and L elements and provide important information for the generation of safer and more effective modified live rabies vaccine.
The PB2 Subunit of the Influenza Virus RNA Polymerase Affects Virulence by Interacting with the Mitochondrial Antiviral Signaling Protein and Inhibiting Expression of Beta Interferon
Authors: Graef Katy M. , Vreede Frank T. , Lau Yuk-Fai , McCall Amber W. , Carr Simon M. , Subbarao Kanta , Fodor Ervin 
Published: June 2010

ABSTRACT

The PB2 subunit of the influenza virus RNA polymerase is a major virulence determinant of influenza viruses. However, the molecular mechanisms involved remain unknown. It was previously shown that the PB2 protein, in addition to its nuclear localization, also accumulates in the mitochondria. Here, we demonstrate that the PB2 protein interacts with the mitochondrial antiviral signaling protein, MAVS (also known as IPS-1, VISA, or Cardif), and inhibits MAVS-mediated beta interferon (IFN-β) expression. In addition, we show that PB2 proteins of influenza viruses differ in their abilities to associate with the mitochondria. In particular, the PB2 proteins of seasonal human influenza viruses localize to the mitochondria while PB2 proteins of avian influenza viruses are nonmitochondrial. This difference in localization is caused by a single amino acid polymorphism in the PB2 mitochondrial targeting signal. In order to address the functional significance of the mitochondrial localization of the PB2 protein
in vivo
, we have generated two recombinant human influenza viruses encoding either mitochondrial or nonmitochondrial PB2 proteins. We found that the difference in the mitochondrial localization of the PB2 proteins does not affect the growth of these viruses in cell culture. However, the virus encoding the nonmitochondrial PB2 protein induces higher levels of IFN-β and, in an animal model, is attenuated compared to the isogenic virus encoding a mitochondrial PB2. Overall this study implicates the PB2 protein in the regulation of host antiviral innate immune pathways and suggests an important role for the mitochondrial association of the PB2 protein in determining virulence.
Crystal Structure of PG16 and Chimeric Dissection with Somatically Related PG9: Structure-Function Analysis of Two Quaternary-Specific Antibodies That Effectively Neutralize HIV-1
Authors: Pancera Marie , McLellan Jason S. , Wu Xueling , Zhu Jiang , Changela Anita , Schmidt Stephen D. , Yang Yongping , Zhou Tongqing , Phogat Sanjay , Mascola John R. , Kwong Peter D. 
Published: June 2010

ABSTRACT

HIV-1 resists neutralization by most antibodies. Two somatically related human antibodies, PG9 and PG16, however, each neutralize 70 to 80% of circulating HIV-1 isolates. Here we present the structure of the antigen-binding fragment of PG16 in monoclinic and orthorhombic lattices at 2.4 and 4.0 Å, respectively, and use a combination of structural analysis, paratope dissection, and neutralization assessment to determine the functional relevance of three unusual PG9/PG16 features: N-linked glycosylation, extensive affinity maturation, and a heavy chain-third complementarity-determining region (CDR H3) that is one of the longest observed in human antibodies. Glycosylation extended off the side of the light chain variable domain and was not required for neutralization. The CDR H3 formed an axe-shaped subdomain, which comprised 42% of the CDR surface, with the axe head looming ∼20 Å above the other combining loops. Comprehensive sets of chimeric swaps between PG9 and PG16 of light chain, heavy chain, and CDR H3 were employed to decipher structure-function relationships. Chimeric swaps generally complemented functionally, with differences in PG9/PG16 neutralization related primarily to residue differences in CDR H3. Meanwhile, chimeric reversions to genomic V genes showed isolate-dependent effects, with affinity maturation playing a significant role in augmenting neutralization breadth (
P
= 0.036) and potency (
P
< 0.0001). The structural and functional details of extraordinary CDR H3 and extensive affinity maturation provide insights into the neutralization mechanism of and the elicitation pathway for broadly neutralizing antibodies like PG9 and PG16.
‘Football for Health’—a football-based health-promotion programme for children in South Africa: a parallel cohort study
Authors: Fuller Colin W , Junge Astrid , DeCelles Jeff , Donald James , Jankelowitz Ryan , Dvorak Jiri 
Published: June 2010

ObjectivesTo develop, implement and assess an interactive, football-based health education programme for children in South Africa.DesignProspective cohort study with control group.SettingTwo schools in Khayelitsha township, South Africa.Participants370 children making up two intervention groups (Grade 6: 125; Grade 7: 131) and one control group (Grade 7: 114).InterventionEleven 90 min sessions, each divided into two 45 min halves of Play Football (football skills) and Play Fair (health issues), each session focused on one specific health risk factor.Main outcome measuresHealth knowledge using a 20-item questionnaire; coaches' attitudes towards their training programme using a 10-item questionnaire and children's attitudes towards the health education programme using a six-item questionnaire.ResultsChildren in the Grade 7 intervention group showed significant (p<0.05) increases in the proportion of correct responses for nine of the 20 health knowledge questions postintervention, and these increases were maintained at 3 months postintervention. The Grade 6 intervention group showed significant increases in the proportion of correct responses for 15 of the 20 health knowledge questions postintervention. The Grade 7 control group showed a significant increase in the proportion of correct responses to one of the 20 health knowledge questions post-Play Football sessions and nine of 20 questions post-Play Fair sessions. Over 90% of the children provided positive attitude responses to the health-education programme.ConclusionsThe programme demonstrated that it was possible to implement a football-based health-education programme for children in Africa that achieved significant increases in health knowledge and that was also well received by participants.
Lateral sacral artery aneurysm of the lumbar spine: hemorrhage resulting in cauda equina syndrome
Authors: Nogueira Raul G , Kasper Ekkehard , Walcott Brian P , Nahed Brian V , Redjal Navid , Coumans Jean-Valery , Hirsch Joshua A 
Published: June 2010

ObjectiveTo describe the effective treatment of a ruptured lateral sacral artery aneurysm presenting as a spinal epidural hematoma.DesignCase report and literature review.SettingUniversity teaching hospital, neurovascular center.ParticipantA man with a history of renal allograft who presented with sudden onset low back pain.InterventionThe patient underwent emergent decompressive surgery, diagnostic angiogram and endovascular embolization.Main outcome measureObliteration of aneurysm and restoration of neurological function.ResultsSurgery resulted in decompression of the cauda equina. The patient's aneurysm was endovascularly obliterated. There was complete restoration of neurological function.ConclusionLateral sacral artery aneurysm formation and rupture is a rare cause of epidural hemorrhage and one described only in patients who have undergone renal transplantation. It may be caused by high flow from transpelvic collaterals between both internal iliac arteries. Treatment includes endovascular obliteration and may necessitate operative decompression in the setting of neurological compromise.
日出山莊輔導有濫藥習慣的青少年成效評估調查
Authors: 司徒 明旺 , 陳 志慧 , 陳 永芳 
Published: June 2010

香港基督教服務處賽馬會日出山莊 ( 下稱 ⌈日出山莊⌋ ) 於2003年3月成立, 旨在為30歲以下濫用鴉片類藥物和濫用多種藥物人士, 提供一站式的人性化戒毒治療和康復服務, 重點並不單放在解決服務使用者的濫藥問題, 並更著重在他們的成長過程中加以協助, 期望他們能更有效地處理目前與將來要面對的種種問題, 故此, 中心著力於營造一個充滿愛的治療環境及製造機會供服務使用者成長. 日出山莊於06至08年間以量化和質性的混合研究模式評估服務成效. 透過客觀的數據分析和受訪者主觀的評價, 我們印證了日出山莊的服務確能使服務使用者戒除藥癮和獲得正面成長的效果 Hong Kong Christian Service Jockey Club Lodge of Rising Sun (LRS) has commenced its operation in 2003. The centre aims at providing one-stop and humanistic drug treatment and rehabilitation service for opiate and poly-drug abusers aged under 30. The focus of the treatment method adopted by the center is not merely to solve the clients' addiction problem. Rather, it is to assist the clients in their growth process, so that they can cope with current problems as well as future problems better. All effort aims at building a loving environment and creating opportunity for clients' growth. An evaluative research, which was done from 2006 to 2008, aimed at evaluating the effectiveness of the service provided by LRS through using a quantitative-qualitative mixed mode method. The result revealed that the service users have a significant improvement in their drug problems, and growth and development after receiving humanistic service provided by LRS.
SIGWEB
Authors: Munson Ethan 
Published: June 2010

This is my penultimate Annual Report to the SIGWEB Membership and I continue to be lucky in having good news to report. As is traditional, there will also be a face-to-face SIGWEB Town Meeting on June 15 during Hypertext 2010 in Toronto, Canada.
SIGWEB is sound financially and has a solid pool of volunteers working on the SIG and its conferences. Membership has been rising recently, too. The Executive Committee is supporting a number of new initiatives including Student Travel Awards and increased communication and publicity efforts. A particularly exciting development is that SIGWEB is close to completing an agreement to be the primary sponsor of the Web Science conference series.
Phase I Dose Finding Studies of Obatoclax (GX15-070), a Small Molecule Pan-BCL-2 Family Antagonist, in Patients with Advanced Solid Tumors or Lymphoma
Authors: Hwang Jimmy J. , Kuruvilla John , Mendelson David , Pishvaian Michael J. , Deeken J.F. , Siu Lillian L. , Berger Mark S. , Viallet Jean , Marshall John L. 
Published: June 2010

Abstract
Purpose: Two phase I, single-agent studies were conducted to determine the dose and regimen of obatoclax, an antagonist of all BCL-2 antiapoptotic proteins, for evaluation in phase II trials. The two studies, GX001 and GX005, evaluated the safety and tolerability of weekly 1-hour and 3-hour infusions of obatoclax, respectively.
Experimental Design: Eligible patients in both studies were adults with solid tumor or lymphoma and performance status 0-1 for whom standard therapies were not appropriate. In the GX001 study an accelerated dose titration design was initially used with subsequent cohorts of three to six patients with 40% dose increments between levels. In the GX005 study three to six patients entered at each dose level with 40% dose increments between levels.
Results: Thirty-five patients were enrolled in studies GX001 (n = 8) and GX005 (n = 27). Clinically significant central nervous system (CNS) toxicity was observed using the 1-hour infusion schedule. The obatoclax maximum tolerated dose (MTD) in GX001 was 1.25 mg/m2 due to these infusional CNS events. The 3-hour infusion schedule studied in GX005 had improved tolerability, and the obatoclax MTD was 20 mg/m2. One patient in GX005 with relapsed non-Hodgkin's lymphoma achieved partial response of 2 months' duration, and one patient with relapsed non-Hodgkin's lymphoma had stable disease for 18 months.
Conclusions: The 1-hour infusion schedule of obatoclax was associated with neuropsychiatric dose-limiting toxicities at relatively low doses (MTD, 1.25 mg/m2). The 3-hour i.v. infusion of obatoclax administered once weekly to patients with solid tumors was better tolerated (MTD, 20 mg/m2), and evidence of clinical activity was observed. Clin Cancer Res; 16(15); 4038–45. ©2010 AACR.
Idealized Simulations of the Intertropical Convergence Zone and Its Multilevel Flows
Authors: Nolan David S. , Powell Scott W. , Zhang Chidong , Mapes Brian E. 
Published: June 2010

Abstract
A mesoscale numerical model with an idealized tropical channel environment is used to study the dynamics of intertropical convergence zones (ITCZs) and the recently identified shallow return flow (SRF) and midlevel inflow (MLI). Four idealized sea surface temperature (SST) distributions are used: a meridionally symmetric SST profile with a sharply peaked SST maximum at the equator, a similar profile with the maximum SST shifted off the equator, a cosine-shaped SST profile with zero gradient at the equator, and an idealized SST profile modeled after the observed SST of the eastern Pacific.
The simulations show that both the SRF and the MLI are robust features of the ITCZ. The prior result that the SRF is a sea-breeze-like response to surface temperature gradients is further supported, whereas the MLI is caused by the upper-level maxima in diabatic heating and vertical motion. Simulations with the SST maximum at the equator generate long-lasting, convectively coupled Kelvin waves. When the SST maximum is off the equator, the meridional circulations become highly asymmetric with strong cross-equatorial flow. Tropical cyclones are frequently generated by dynamic instability of the off-equatorial ITCZs.
The contributions of the multilevel circulations to regional budgets of mass, water, and moist static energy (MSE) are computed. About 10% of the total water transported into the ITCZ region is transported out by the SRF. The water transport of the MLI is minimal, but its mass and MSE transports are significant, accounting for about ⅓ of the mass and MSE entering the ITCZ region. Eddy fluxes are found to be a large component of the net vertically integrated transport of MSE out of the ITCZ.
Breaking of Progressive Internal Gravity Waves: Convective Instability and Shear Instability*
Authors: Liu Wei , Bretherton Francis P. , Liu Zhengyu , Smith Leslie , Lu Hao , Rutland Christopher J. 
Published: June 2010

Abstract
The breaking of a monochromatic two-dimensional internal gravity wave is studied using a newly developed spectral/pseudospectral model. The model features vertical nonperiodic boundary conditions that ensure a realistic simulation of wave breaking during the wave propagation. Isopycnal overturning is induced at a local wave steepness of sc = 0.75–0.79, which is below the conventional threshold of s = 1. Isopycnal overturning is a sufficient condition for subsequent wave breaking by convective instability. When s = sc, little primary wave energy is being transferred to high-mode harmonics. Beyond s = 1, high-mode harmonics grow rapidly. Primary wave energy is more efficiently transferred by waves of lower frequency. A local gradient Richardson number is defined as Ri = −(g/ρ0)(dρ/dz)/ζ2 to isolate convective instability (Ri ≤ 0) and wave-induced shear instability (0 &lt; Ri &lt; 0.25), where dρ/dz is the local vertical density gradient and ζ is the horizontal vorticity. Consistent with linear wave theory, the probability density function (PDF) for occurrence of convective instability has a maximum at wave phase ϕ = π/2, where the wave-induced density perturbations to the background stratification are the greatest, whereas the wave-induced shear instability has maxima around ϕ = 0 (wave trough) and ϕ = π (wave crest). Nonlinearities in the wave-induced flow broaden the phase span in PDFs of both instabilities. Diapycnal mixing in numerical simulations may be compared with that in realistic oceanic flows in terms of the Cox number. In the numerical simulations, the Cox numbers increase from 1.5 (s = 0.78) to 21.5 (s = 1.1), and the latter is in the lower range of reported values for the ocean.
Community-based Diabetes Education for Latinos
Authors: Castillo Amparo , Giachello Aida , Bates Robin , Concha Jeannie , Ramirez Vanessa , Sanchez Carlos , Pinsker Eve , Arrom Jose 
Published: June 2010

Purpose The purpose of this study was to conduct a diabetes education program delivered by community health workers (CHWs) in community settings and to evaluate its effectiveness in improving glycemic control and self-management skills in Hispanics/Latinos with type 2 diabetes. Methods Trained CHWs recruited Hispanic/Latino community residents with self-reported type 2 diabetes, implemented intervention in nonclinical locations, and collected data on diabetes knowledge, self-care behaviors, self-efficacy, depression, A1C, weight, and blood pressure. Classes applied participatory techniques and were delivered in 2-hour group sessions over 10 weeks. Two focus groups collected qualitative postintervention data. Results Seventy participants enrolled, and 47 completed pretest and posttest data. Improvements were significant for A1C (P = .001) and systolic blood pressure (P = .006). Other positive outcomes were diabetes knowledge, physical activity, spacing carbohydrates, following a healthy eating plan, and eating fruits and vegetables. Improved behaviors also included foot care, glucose self-monitoring, and medication adherence. Depressive symptoms showed a positive trend in intent-to-treat analysis (P = .07), but self-efficacy did not change significantly (P = .142). Qualitative information reported an increase in participants’ perceived competence in self-care and a positive influence of CHWs in participants’ compliance with the program. Conclusions A diabetes self-management education program for Hispanics/Latinos led by CHWs can be implemented in community settings and may effectively improve behavioral skills and glycemic control.
Science as Thinking Reason
Authors: Parrini Paolo 
Published: June 2010

AbstractThe author discusses the evolution of Heidegger's conception of science and brings out its limits as well as its possible developments. An eminent representative of contemporary thinking in the theory of knowledge, Paolo Parrini stands in a line of critical realism in the Kantian neopositivist tradition. This paper returns to and develops the lectio delivered at the award of the ‘Giulio Preti’ Prize in November 2008.
The Question of Culture: Giulio Preti's 1972 Debate with Michel Foucault Revisited
Authors: Hacking Ian 
Published: June 2010

AbstractIan Hacking sets out a parallel between Michel Foucault's thought and that of Giulio Preti based on the debate between them that took place in 1971. This is the speech given at the award of the ‘Giulio Preti’ Prize in November 2008.
Helping Children To Philosophizing: State of the Art, Live Issues, Outcomes and Proposals
Authors: Tozzi Michel 
Published: June 2010

AbstractThe author discusses in detail the basic issues related to the practice of philosophical discussions with children. He identifies and problematizes the different methods or modalities for doing philosophy with children currently practised throughout the world. He presents a series of pedagogic and didactic issues and puts forward some proposals and directions for the future that might allow us to facilitate philosophy-oriented discussions with children.
Procoagulant platelets: are they necrotic?
Authors: Jackson Shaun P. , Schoenwaelder Simone M. 
Published: June 2010

AbstractApoptosis and necrosis represent distinct cell death processes that regulate mammalian development, physiology and disease. Apoptosis characteristically leads to the silent destruction and removal of cells in the absence of an inflammatory response. In contrast, necrotic cell death can induce physiologic inflammatory responses linked to tissue defense and repair. Although anucleate, platelets undergo programmed cell death, with apoptosis playing an important role in clearing effete platelets from the circulation. While it has long been recognized that procoagulant platelets exhibit characteristic features of dying cells, recent studies have demonstrated that platelet procoagulant function can occur independent of apoptosis. A growing body of evidence suggest that the biochemical, morphologic and functional changes underlying agonist-induced platelet procoagulant function are broadly consistent with cell necrosis, raising the possibility that distinct death pathways regulate platelet function and survival. In this article, we will discuss the mechanisms underlying apoptotic and necrotic cell death pathways and examine the evidence linking these pathways to the platelet procoagulant response. We will also discuss the potential contribution of these pathways to the platelet storage lesion and propose a simplified nomenclature to describe procoagulant platelets.