bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of Large Conformational Changes and Autoproteolysis in the Maturation of a T=4 Virus Capsid
Authors: Matsui Tsutomu , Lander Gabriel , Johnson John E. 
Published: November 2008

ABSTRACT

Nudaurelia capensis ω virus
-like particles have been characterized as a 480-Å procapsid and a 410-Å capsid, both with T=4 quasisymmetry. Procapsids transition to capsids when pH is lowered from 7.6 to 5.0. Capsids undergo autoproteolysis at residue 570, generating the 74-residue C-terminal polypeptide that remains with the particle. Here we show that the particle size becomes smaller under conditions between pH 6.8 and 6.0 without activating cleavage and that the particle remains at an intermediate size when the pH is carefully maintained. At pH 5.8, cleavage is very slow, becoming detectable only after 9 h. The optimum pH for cleavage is 5.0 (half-life, ∼30 min), with a significant reduction in the cleavage rate at pH values below 5. We also show that lowering the pH is required only to make the virus particles compact and to presumably form the active site for autoproteolysis but not for the chemistry of cleavage. The cleavage reaction proceeds at pH 7.0 after ∼10% of the subunits cleave at pH 5.0. Employing the virion crystal structure for reference, we investigated the role of electrostatic repulsion of acidic residues in the pH-dependent large conformational changes. Three mutations of Glu to Gln that formed procapsids showed three different phenotypes on maturation. One, close to the threefold and quasithreefold symmetry axes and far from the cleavage site, did not mature at pH 5, and electron cryomicroscopy reconstruction showed that it was intermediate in size between those of the procapsid and capsid; one near the cleavage site exhibited a wild-type phenotype; and a third, far from the cleavage site, resulted in cleavage of 50% of the subunits after 4 h, suggesting quasiequivalent specificity of the mutation.
Virus-Encoded B7-2 Costimulation Molecules Enhance the Protective Capacity of a Replication-Defective Herpes Simplex Virus Type 2 Vaccine in Immunocompetent Mice
Authors: Vagvala Sri P. , Thebeau Lydia G. , Wilson Saydra R. , Morrison Lynda A. 
Published: November 2008

ABSTRACTHerpes simplex virus 2 (HSV-2) and, to a lesser extent, HSV-1 cause the majority of sexually transmitted genital ulcerative disease. No effective prophylactic vaccine is currently available. Replication-defective HSV stimulates immune responses in animals but produces no progeny virus, making it potentially useful as a safe form of live vaccine against HSV. Because it does not replicate and spread in the host, however, replication-defective virus may have relatively limited capacity to solicit professional antigen presentation. We previously demonstrated that in mice devoid of B7-1 and B7-2 costimulation molecules, replication-defective HSV-2 encoding B7-1 or B7-2 induces stronger immune responses and protection against HSV-2 challenge than immunization with replication-defective virus alone. Here, we vaccinated wild-type mice fully competent to express endogenous B7 costimulation molecules with replication-defective HSV-2 or replication-defective virus encoding B7-2 and compared their capacities to protect against vaginal HSV-2 infection and disease. Replication-defective virus encoding B7-2 induced more IFN-γ-producing CD4 T cells than did replication-defective virus alone. Immunization with B7-2-expressing virus decreased challenge virus replication in the vaginal mucosa, genital and neurological disease, and mortality more effectively than did immunization with the parental replication-defective virus. Prior immunization with B7-expressing, replication-defective virus also effectively suppressed infection of the nervous system compared to immunization with the parental virus. Thus, B7 costimulation molecules expressed at the site of HSV infection can enhance vaccine efficacy even in a fully immunocompetent host.
Factors Associated with the Development of Cross-Reactive Neutralizing Antibodies during Human Immunodeficiency Virus Type 1 Infection
Authors: Sather D. Noah , Armann Jakob , Ching Lance K. , Mavrantoni Angeliki , Sellhorn George , Caldwell Zachary , Yu Xuesong , Wood Blake , Self Steve , Kalams Spyros , Stamatatos Leonidas 
Published: November 2008

ABSTRACT
The characterization of the cross-reactive, or heterologous, neutralizing antibody responses developed during human immunodeficiency virus type 1 (HIV-1) infection and the identification of factors associated with their generation are relevant to the development of an HIV vaccine. We report that in healthy HIV-positive, antiretroviral-naïve subjects, the breadth of plasma heterologous neutralizing antibody responses correlates with the time since infection, plasma viremia levels, and the binding avidity of anti-Env antibodies. Anti-CD4-binding site antibodies are responsible for the exceptionally broad cross-neutralizing antibody responses recorded only in rare plasma samples. However, in most cases examined, antibodies to the variable regions and to the CD4-binding site of Env modestly contributed in defining the overall breadth of these responses. Plasmas with broad cross-neutralizing antibody responses were identified that targeted the gp120 subunit, but their precise epitopes mapped outside the variable regions and the CD4-binding site. Finally, although several plasmas were identified with cross-neutralizing antibody responses that were not directed against gp120, only one plasma with a moderate breadth of heterologous neutralizing antibody responses contained cross-reactive neutralizing antibodies against the 4E10 epitope, which is within the gp41 transmembrane subunit. Overall, our study indicates that more than one pathway leads to the development of broad cross-reactive neutralizing antibodies during HIV infection and that the virus continuously escapes their action.
The use of narcotic analgesics in terminal illness
Authors: Twycross Robert G 
Published: November 2008

To answer some of the questions surrounding the medicinal use of narcotic analgesics in advanced cancer, a group of 500 patients admitted to St Christopher's Hospice was reviewed. To achieve and maintain pain relief many of the patients received diamorphine (heroin) regularly every four hours. Almost all the patients received a phenothiazine concurrently; other drugs were prescribed when indicated. It was concluded that: 1) Although most patients receive parenteral diamorphine during the last 12 to 24 hours, the majority can be maintained on oral medication until this time. 2) There is no single optimal dose of diamorphine. 3) Psychological dependence does not occur. 4) Physical dependence may develop but does not prevent the downward adjustment of the dose of diamorphine when considered clinically feasible. 5) Tolerance is not a practical problem. 6) The prescription of diamorphine does not, by itself, lead to impairment of mental faculties.Also discussed are: 1) the psychobiological nature of pain; 2) the rational use of analgesics; 3) the need for further research; 4) the importance of the doctor's attitude.
Is geriatrics the answer to the problem of old age?
Authors: Millard P H 
Published: November 2008

Two doctors attempt to answer this question, one a specialist in geriatric medicine, the other a psychiatrist interested in the psychiatric problems of the elderly and the old. Both, however, come to the same general conclusion: attitudes of the doctors themselves and of society must be changed. These attitudes can determine not only whether an old person lives or dies but how he lives. Old people should not have to survive in mentally suspended animation with all objectives gone but should be helped to achieve the goal of an independent life until death in their own homes.The third paper in this miniature symposium is provided by David Hobman, of Age Concern, who amplifies the specialist views of the first two writers in his discussion of attitudes to the elderly in modern society. He hints, however, that these may shortly change as the elderly become a sophisticated and powerful lobby which governments are forced to heed.
The diagnosis of brain death
Authors: Jennett Bryan 
Published: November 2008

No apologies are needed for returning to the subject of brain death and its definition. There has been so much public discussion that it is important for public confidence that the issues should be clarified. In the following two contributions - one from a professor of neurosurgery and the other from a lawyer - an attempt is made to convince doctors (if that is needed) and lay people alike that what appears to be a new bogy is not one at all but a confusion of thought arising from the use of new technology to treat brain-damaged patients. This, however, might not be the view of Mr Skegg(Journal of medical ethics, 2, 190)who, fearful of the situation, has argued for a statutory definition of death.Professor Jennett discusses the findings of a conference of the Royal Colleges of the United Kingdom which met to try and remove uncertainty surrounding the diagnosis of brain death. In his view the Colleges' document is to be welcomed for `its authority and its practicality' and `should lead to more humane medical practice'. Mr Kennedy, from a legal position, comes to the same conclusion, that with a good code of practice, as advocated by the Royal Colleges, no legislation is called for.
Strikes and the National Health Service: Some legal and ethical issues
Authors: Dworkin Gerald 
Published: November 2008

This paper is sadly opportune. The general public is angry and bewildered if not hurt by the variety of strikes which are brought more or less forcibly to their attention. People used to understand what lay behind a strike - a demand for more pay, better conditions - but today a political element often intrudes, and it is this that worries those who ask themselves whether this or that dispute is either lawful or morally acceptable.Professor Dworkin, a lawyer, first sets out the legal issues surrounding strikes and then advances the ethical arguments, closely relating them to the legal framework. The most interesting part of the paper, however, may well be that devoted to the moral obligation of example, in particular the example to be set by members of the medical profession and by all those caring for the sick. As public attitudes to industrial disputes `become dulled and quiescent' it is absolutely necessary that there should be a reappraisal of the moral standards of the past which coincide with a respect for the law. In the last century the term `anomie' was used to describe a `society which has shaken off its former restraints such as religion, respect for law and order and a definite moral code as to what is right and wrong'. We are living in that sort of society today, and one need not be a professional `ethicist' to recognize the signs, and hopefully, to work for the return of `ethical' values.
Medical migration and world health
Authors: Fraser Alan G 
Published: November 2008

Everyone knows that British doctors are emigrating and that other doctors, mostly from the third world, are immigrating to Britain. Also everyone thinks that he knows the reasons why. However, the Edinburgh Medical Group thought the various reasons for this medical migration should be examined more closely, and held a symposium (Chairman, Professor A S Duncan, Professor Emeritus of Medical Education in the University of Edinburgh) to examine the causes for medical migration at the present time.Medical teaching and practice is still basically as it has been developed in the West and so overseas doctors trained in Britain take with them not only the medical knowledge and skills but also the attitudes of the West when they return to their own countries. Consequently they wish to settle in the towns and practise as consultants when the real medical problems in many of the developing countries are those of a rural population needing health care rather than treatment in what have been called `disease palaces'. As speakers made clear, a new responsibility must fall on those training doctors from overseas in the British medical schools to fit them not for the dream world of the sophisticated medical scene but for the realities of working in often badly equipped clinics and dealing with common conditions such as malnutrition and other problems of maternity and child health.The symposium also included discussions as to why British doctors wished to emigrate. Money seemed to be the most compelling motive, but opportunities were being limited for their migration for economic and political reasons.Finally, a look at the whole of the medical scene in Britain: perhaps the standard sought in Britain both by the doctor and the patient is too high and too individualistic. Events will show if this be true.
DETERMINING THE PRINCIPLES UNDERLYING PERFORMANCE VARIATION IN CSP HEURISTICS
Authors: WALLACE RICHARD J. 
Published: November 2008

This paper develops the idea that variable ordering heuristics for CSPs can be characterised in terms of a small number of distinguishable actions or strategies, and that while specific heuristics may be classified differently depending on the problem type, the basic actions that determine their classification are the same. These strategies can be described as building up contention and propagating effects to future, uninstantiated variables. The propagation-of-effects type of action is related to the "simplification hypothesis" of Hooker and Vinay, but since this is only one of two independent actions, this work gives a more complete account of the basis of heuristic performance. The basic technique uses factor analysis to simplify the set of correlations between performance scores for a particular set of problems. The present work shows that the results of this analysis are robust, and that amenability of a problem to one or the other kind of heuristic action is also a robust effect. This approach also elucidates the effectiveness of modern adaptive heuristics by showing that they balance the two kinds of heuristic action, which is known to enhance performance. The two heuristic actions are distinguished by descriptive measures such as depth of failure and depth at which a problem becomes tractable, that reflect differences in rapidity of effects with respect to search depth. Other experiments indicate that the effectiveness of propagation-of-effects depends on the degree to which nonadjacent assignments can interact in the future part of the problem. Extensions to structured problems suggest that the theoretical analysis can be generalised, although the factor analysis of performance becomes more complicated due to the interaction of the basic actions with specific parts of the problem. This work contributes to the goals of explaining heuristic performance and putting heuristic selection on a rational basis.
Algorithm 887
Authors: Chen Yanqing , Davis Timothy A. , Hager William W. , Rajamanickam Sivasankaran 
Published: November 2008

CHOLMOD is a set of routines for factorizing sparse symmetric positive definite matrices of the form
A
or
AA
T
, updating/downdating a sparse Cholesky factorization, solving linear systems, updating/downdating the solution to the triangular system
Lx
=
b
, and many other sparse matrix functions for both symmetric and unsymmetric matrices. Its supernodal Cholesky factorization relies on LAPACK and the Level-3 BLAS, and obtains a substantial fraction of the peak performance of the BLAS. Both real and complex matrices are supported. CHOLMOD is written in ANSI/ISO C, with both C and MATLAB
TM
interfaces. It appears in MATLAB 7.2 as x = A\b when A is sparse symmetric positive definite, as well as in several other sparse matrix functions.
ScaleFFS
Authors: Jung Dawoon , Kim Jaegeuk , Kim Jin-Soo , Lee Joonwon 
Published: November 2008

NAND flash memory has become one of the most popular storage media for mobile multimedia systems. A key issue in designing storage systems for mobile multimedia systems is handling large-capacity storage media and numerous large files with limited resources such as memory. However, existing flash file systems, including JFFS2 and YAFFS in particular, exhibit many limitations in addressing the storage capacity of mobile multimedia systems.
In this article, we design and implement a scalable flash file system, called ScaleFFS, for mobile multimedia systems. ScaleFFS is designed to require only a small fixed amount of memory space and to provide fast mount time, even if the file system size grows to more than tens of gigabytes. The measurement results show that ScaleFFS can be instantly mounted regardless of the file system size, while achieving the same write bandwidth and up to 22% higher read bandwidth compared to JFFS2.
Puffing Style and Human Exposure Minimally Altered by Switching to a Carbon-Filtered Cigarette
Authors: Rees Vaughan W. , Wayne Geoffrey Ferris , Connolly Gregory N. 
Published: November 2008

AbstractObjective: Potential Reduced Exposure tobacco Products (PREP) are intended to lower human exposure to toxic constituents of tobacco smoke, but rigorous clinical evaluations are required to assess such claims. The present study assessed human smoking behavior and short-term exposure to a new carbon-filtered PREP, Marlboro UltraSmooth (MUS). Two MUS prototypes with filter carbon loads of 120 and 180 mg were compared with low and ultralow-yield conventional cigarettes.Methods: After a 48-hour baseline period, 32 adult Marlboro Lights smokers were switched in a counterbalanced order, to MUS and Marlboro Ultra Lights for 48 hours each. Measures of smoking topography, subjective response, change in cardiac response, and carbon monoxide boost were obtained under supervised test conditions on separate days. After each test, topography measures were obtained via a 48-hour free smoking phase for each brand. Salivary cotinine was measured at the end of each 48-hour period.Results: Although MUS was generally smoked in a style similar to conventional cigarettes, compensatory smoking was observed with 1 MUS prototype (P = 0.003). Carbon monoxide boost was lower for MUS compared with Marlboro Lights, but salivary cotinine and cardiac function measures after smoking of MUS did not vary from conventional brands.Conclusions: Smoking MUS produced few differences in smoking topography and exposure compared with conventional low and ultralow-yield cigarettes. Results suggest that the manner in which MUS is smoked by humans is unlikely in the short term to reduce exposure among smokers who switch from a conventional brand. (Cancer Epidemiol Biomarkers Prev 2008;17(11):2995–3003)
Self-report versus Medical Records for Assessing Cancer-Preventive Services Delivery
Authors: Ferrante Jeanne M. , Ohman-Strickland Pamela , Hahn Karissa A. , Hudson Shawna V. , Shaw Eric K. , Crosson Jesse C. , Crabtree Benjamin F. 
Published: November 2008

Abstract
Accurate measurement of cancer-preventive behaviors is important for quality improvement, research studies, and public health surveillance. Findings differ, however, depending on whether patient self-report or medical records are used as the data source. We evaluated concordance between patient self-report and medical records on risk factors, cancer screening, and behavioral counseling among primary care patients. Data from patient surveys and medical records were compared from 742 patients in 25 New Jersey primary care practices participating at baseline in SCOPE (supporting colorectal cancer outcomes through participatory enhancements), an intervention trial to improve colorectal cancer screening in primary care offices. Sensitivity, specificity, and rates of agreement describe concordance between self-report and medical records for risk factors (personal or family history of cancer, smoking), cancer screening (breast, cervical, colorectal, prostate), and counseling (cancer screening recommendations, diet or weight loss, exercise, smoking cessation). Rates of agreement ranged from 41% (smoking cessation counseling) to 96% (personal history of cancer). Cancer screening agreement ranged from 61% (Pap and prostate-specific antigen) to 83% (colorectal endoscopy) with self-report rates greater than medical record rates. Counseling was also reported more frequently by self-report (83% by patient self-report versus 34% by medical record for smoking cessation counseling). Deciding which data source to use will depend on the outcome of interest, whether the data is used for clinical decision making, performance tracking, or population surveillance; the availability of resources; and whether a false positive or a false negative is of more concern. (Cancer Epidemiol Biomarkers Prev 2008;17(11):2987–94)
Vitamin D Status and the Risk of Lung Cancer: A Cohort Study in Finland
Authors: Kilkkinen Annamari , Knekt Paul , Heliövaara Markku , Rissanen Harri , Marniemi Jukka , Hakulinen Timo , Aromaa Arpo 
Published: November 2008

Abstract
Experimental data support the suppressing effect of vitamin D on lung carcinogenesis, but epidemiologic evidence is limited. The aim of the present study was to evaluate whether serum 25-hydroxyvitamin D [25(OH)D] level is associated with the risk of lung cancer in a prospective cohort study in Finland. 25(OH)D levels were measured by RIA from serum collected at baseline (1978-1980) from 6,937 men and women. During a maximum follow-up of 24 years, 122 lung cancers were identified. After adjustment for potential confounders, no overall significant association between vitamin D and lung cancer risk was observed [relative risk (RR) for the highest versus lowest tertile, 0.72; 95% confidence interval (95% CI), 0.43-1.19; Ptrend = 0.22]. There was a statistically significant interaction between vitamin D and sex (P = 0.02) and age (P = 0.02): serum 25(OH)D level was inversely associated with lung cancer incidence for women (RR, 0.16; 95% CI, 0.04-0.59; Ptrend &lt; 0.001) and younger participants (RR, 0.34; 95% CI, 0.13-0.90; Ptrend = 0.04) but not for men (RR, 1.03; 95% CI, 0.59-1.82; Ptrend = 0.81) or older individuals (RR, 0.92; 95% CI, 0.50-1.70; Ptrend = 0.79). In conclusion, although there was no overall association between vitamin D and lung cancer risk, women and young participants with a higher level of vitamin D were observed to have a lower lung cancer risk. Although experimental data support the suppressing effect of vitamin D on the development of lung cancer, large epidemiologic studies from different populations with repeated measurements of vitamin D are warranted to confirm this finding. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3274–8)