bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Arginine Switch in the Species B Adenovirus Knob Determines High-Affinity Engagement of Cellular Receptor CD46
Authors: Persson B. David , Müller Steffen , Reiter Dirk M. , Schmitt Benedikt B. T. , Marttila Marko , Sumowski Chris Vanessa , Schweizer Sabine , Scheu Ulrike , Ochsenfeld Christian , Arnberg Niklas , Stehle Thilo 
Published: November 2008

ABSTRACTAdenoviruses (Ads) are icosahedral, nonenveloped viruses with a double-stranded DNA genome. The 51 known Ad serotypes exhibit profound variations in cell tropism and disease types. The number of observed Ad infections is steadily increasing, sometimes leading to fatal outcomes even in healthy individuals. Species B Ads can cause kidney infections, hemorrhagic cystitis, and severe respiratory infections, and most of them use the membrane cofactor protein CD46 as a cellular receptor. The crystal structure of the human Ad type 11 (Ad11) knob complexed with CD46 is known; however, the determinants of CD46 binding in related species B Ads remain unclear. We report here a structural and functional analysis of the Ad11 knob, as well as the Ad7 and Ad14 knobs, which are closely related in sequence to the Ad11 knob but have altered CD46-binding properties. The comparison of the structures of the three knobs, which we determined at very high resolution, provides a platform for understanding these differences and allows us to propose a mechanism for productive high-affinity engagement of CD46. At the center of this mechanism is an Ad knob arginine that needs to switch its orientation in order to engage CD46 with high affinity. Quantum chemical calculations showed that the CD46-binding affinity of Ad11 is significantly higher than that of Ad7. Thus, while Ad7 and Ad14 also bind CD46, the affinity and kinetics of these interactions suggest that these Ads are unlikely to use CD46 productively. The proposed mechanism is likely to determine the receptor usage of all CD46-binding Ads.
VP22 of Herpes Simplex Virus 1 Promotes Protein Synthesis at Late Times in Infection and Accumulation of a Subset of Viral mRNAs at Early Times in Infection
Authors: Duffy Carol , Mbong Ekaette F. , Baines Joel D. 
Published: November 2008

ABSTRACT

VP22, encoded by the U
L
49 gene, is one of the most abundant proteins of the herpes simplex virus 1 (HSV-1) tegument. In the present study we show VP22 is required for optimal protein synthesis at late times in infection. Specifically, in the absence of VP22, viral proteins accumulated to wild-type levels until ∼6 h postinfection. At that time, ongoing synthesis of most viral proteins dramatically decreased in the absence of VP22, whereas protein stability was not affected. Of the individual proteins we assayed, VP22 was required for optimal synthesis of the late viral proteins gE and gD and the immediate-early protein ICP0 but did not have discernible effects on accumulation of the immediate-early proteins ICP4 or ICP27. In addition, we found VP22 is required for the accumulation of a subset of mRNAs to wild-type levels at early, but not late, times in infection. Specifically, the presence of VP22 enhanced the accumulation of gE and gD mRNAs until ∼9 h postinfection, but it had no discernible effect at later times in infection. Also, VP22 did not significantly affect ICP0 mRNA at any time in infection. Thus, the protein synthesis and mRNA phenotypes observed with the U
L
49-null virus are separable with regard to both timing during infection and the genes affected and suggest separate roles for VP22 in enhancing the accumulation of viral proteins and mRNAs. Finally, we show that VP22's effects on protein synthesis and mRNA accumulation occur independently of mutations in genes encoding the VP22-interacting partners VP16 and vhs.
Problems in deceptive medical procedures: an ethical and legal analysis of the administration of placebos
Authors: Simmons Beth 
Published: November 2008

The use of placebos in therapy or research poses ethical questions. What are the benefits and the costs in ethical terms of condoning deception of the patient or subject? What does the deception mean for the patient's or subject's right to give informed consent to his treatment?Doctors are rightly expected to disclose to their patient facts which would in their judgement best enable him to give informed consent to treatment. On occasion, the degree of this disclosure may be limited by the need to avoid hazarding the success of treatment of an unstable patient whose condition threatens his life, but doctors should have no right to withhold information just to prevent a patient refusing consent to therapy. No such limitation should apply in experiments wherefulldisclosure must operate to enable the subject to give his informed consent.The potential medical benefits for the patient of placebo therapy have to be weighed against all the ethical costs of the deception and dishonesty involved, including the longer term repercussions on doctor/patient trust: similar ethical costs may arise in experiments involving the use of placebos without disclosure of this as a possibility to the subject. Deception is ethically degrading to both parties not only being a breach of trust, but denying the moral autonomy of the patient or subject to make his own choice.The writer concludes that placebos should be used only with full disclosure and consent whether in therapy or in research, and that this need not impede the success of either.
USES OF A SMALL FIELD VALUE WHICH FALLS FROM A METASTABLE MAXIMUM OVER COSMOLOGICAL TIMES
Authors: BARSHAY SAUL , KREYERHOFF GEORG 
Published: November 2008

We consider a small, metastable maximum vacuum expectation value b0 of order of a few eV, for a pseudoscalar Goldstone-like field, which is related to the scalar inflaton field ϕ in an idealized model of a cosmological, spontaneously-broken chiral symmetry. The b field allows for relating semi-quantitatively three distinct quantities in a cosmological context. (a) A very small, residual vacuum energy density or effective cosmological constant of [Formula: see text], for λ ~ 3×10-14, the same as an empirical inflaton self-coupling. (b) A tiny neutrino mass, less than b0. (c) A possible small variation downward of the proton to electron mass ratio over cosmological time. The latter arises from the motion downward of the b field over cosmological time, toward a nonzero value. Such behavior is consistent with an equation of motion. We argue that hypothetical b quanta, potentially inducing new long-range forces, are absent, because of negative, effective squared mass in an equation of motion for b-field fluctuations. The assumed flatness of a potential maximum involves a small inverse-time parameter μ ≪ 1/t0, where t0 is the present age of the universe.
ESTABLISHING LOGICAL RULES FROM EMPIRICAL DATA
Authors: PFALTZ JOHN L. 
Published: November 2008

We review a method of generating logical rules, or axioms, from empirical data. This method, using closed set properties of formal concept analysis, has been previously described and tested on rather large sets of deterministic data. In spite of the fact that formal concept techniques have been used to prune frequent set data mining results, frequency and/or statistical significance are totally irrelevant to this method. It is strictly logical and deterministic. The contribution of this paper is a completely new extension of this method to create implications involving numeric inequalities. That is, numerical inequalities such as "age > 39" can be treated as logical predicates that have been extracted from the data itself and not postulated apriori.
CGMN Revisited
Authors: Gordon Dan , Gordon Rachel 
Published: November 2008

Given a linear system
Ax
=
b
, one can construct a related “normal equations” system
AA
T
y
=
b, x
=
A
T
y
. Björck and Elfving have shown that the SSOR algorithm, applied to the normal equations, can be accelerated by the conjugate gradient algorithm (CG). The resulting algorithm, called CGMN, is error-reducing and in theory it always converges even when the equation system is inconsistent and/or nonsquare. SSOR on the normal equations is equivalent to the Kaczmarz algorithm (KACZ), with a fixed relaxation parameter, run in a double (forward and backward) sweep on the original equations. CGMN was tested on nine well-known large and sparse linear systems obtained by central-difference discretization of elliptic convection-diffusion partial differential equations (PDEs). Eight of the PDEs were strongly convection-dominated, and these are known to produce very stiff systems with large off-diagonal elements. CGMN was compared with some of the foremost state-of-the art Krylov subspace methods: restarted GMRES, Bi-CGSTAB, and CGS. These methods were tested both with and without various preconditioners. CGMN converged in all the cases, while none of the preceding algorithm/preconditioner combinations achieved this level of robustness. Furthermore, on varying grid sizes, there was only a gradual increase in the number of iterations as the grid was refined. On the eight convection-dominated cases, the initial convergence rate of CGMN was better than all the other combinations of algorithms and preconditioners, and the residual decreased monotonically. The CGNR algorithm was also tested, and it was as robust as CGMN, but slower.
Social Determinants of Black-White Disparities in Breast Cancer Mortality: A Review
Authors: Gerend Mary A. , Pai Manacy 
Published: November 2008

Abstract
Despite the recent decline in breast cancer mortality, African American women continue to die from breast cancer at higher rates than do White women. Beyond the fact that breast cancer tends to be a more biologically aggressive disease in African American than in White women, this disparity in breast cancer mortality also reflects social barriers that disproportionately affect African American women. These barriers hinder cancer prevention and control efforts and modify the biological expression of disease. The present review focuses on delineating social, economic, and cultural factors that are potentially responsible for Black-White disparities in breast cancer mortality. This review was guided by the social determinants of health disparities model, a model that identifies barriers associated with poverty, culture, and social injustice as major causes of health disparities. These barriers, in concert with genetic, biological, and environmental factors, can promote differential outcomes for African American and White women along the entire breast cancer continuum, from screening and early detection to treatment and survival. Barriers related to poverty include lack of a primary care physician, inadequate health insurance, and poor access to health care. Barriers related to culture include perceived invulnerability, folk beliefs, and a general mistrust of the health care system. Barriers related to social injustice include racial profiling and discrimination. Many of these barriers are potentially modifiable. Thus, in addition to biomedical advancements, future efforts to reduce disparities in breast cancer mortality should address social barriers that perpetuate disparities among African American and White women in the United States. (Cancer Epidemiol Biomarkers Prev 2008;17(11):2913–23)
Cardiovascular Medication Use and Risk for Colorectal Cancer
Authors: Boudreau Denise M. , Koehler Elizabeth , Rulyak Stephen J. , Haneuse Sebastien , Harrison Robert , Mandelson Margaret T. 
Published: November 2008

Abstract
Objective: To evaluate the association between lipid-lowering agents, antihypertensive medications, and colorectal cancer risk. We hypothesized a reduction in colorectal cancer risk with 3-hydroxy-3-methylglutaryl coA reductase inhibitors (statins) and angiotensin-converting enzyme inhibitors.
Methods: We conducted a case-control study at Group Health Cooperative, an integrated delivery system in Washington State. Incident colorectal cancer cases diagnosed between January 1, 2000, and December 31, 2003, were identified from the western Washington Surveillance, Epidemiology, and End Results cancer registry. Controls were matched by age, sex, and duration of enrollment. Data on medication use and potential confounders were obtained from health plan records. We estimated odds ratios and 95% confidence intervals (95% CI) using multivariate conditional logistic regression.
Results: Risk for colorectal cancer was not associated with use of statins (odds ratio, 1.02; 95% CI, 0.65-1.59), other lipid-lowering agents (odds ratio, 1.31; 95% CI, 0.70-2.47), angiotensin-converting enzyme inhibitors (odds ratio, 0.98; 95% CI, 0.67-1.43), calcium channel blockers (odds ratio, 1.06; 95% CI, 0.72-1.55), or diuretics (odds ratio, 1.00; 95% CI, 0.70-1.44). Risk did not differ by duration of medication use, including long-term use.
Conclusions: Risk for colorectal cancer was not reduced by use of statins or angiotensin-converting enzyme inhibitors. Other lipid-lowering and antihypertensive medications were also not associated with colorectal cancer risk. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3076–80)
Unintended Effects of Emphasizing Disparities in Cancer Communication to African-Americans
Authors: Nicholson Robert A. , Kreuter Matthew W. , Lapka Christina , Wellborn Rachel , Clark Eddie M. , Sanders-Thompson Vetta , Jacobsen Heather M. , Casey Chris 
Published: November 2008

Abstract
Little is known about how minority groups react to public information that highlights racial disparities in cancer. This double-blind randomized study compared emotional and behavioral reactions to four versions of the same colon cancer (CRC) information presented in mock news articles to a community sample of African-American adults (n = 300). Participants read one of four articles that varied in their framing and interpretation of race-specific CRC mortality data, emphasizing impact (CRC is an important problem for African-Americans), two dimensions of disparity (Blacks are doing worse than Whites and Blacks are improving, but less than Whites), or progress (Blacks are improving over time). Participants exposed to disparity articles reported more negative emotional reactions to the information and were less likely to want to be screened for CRC than those in other groups (both P &lt; 0.001). In contrast, progress articles elicited more positive emotional reactions and participants were more likely to want to be screened. Moreover, negative emotional reaction seemed to mediate the influence of message type on individuals wanting to be screened for CRC. Overall, these results suggest that the way in which disparity research is reported in the medium can influence public attitudes and intentions, with reports about progress yielding a more positive effect on intention. This seems especially important among those with high levels of medical mistrust who are least likely to use the health care system and are thus the primary target of health promotion advertising. (Cancer Epidemiol Biomarkers Prev 2008;17(11):2946–53)
The Influence of Tumor Necrosis Factor-α −308 G/A and IL-6 −174 G/C on Pain and Analgesia Response in Lung Cancer Patients Receiving Supportive Care
Authors: Reyes-Gibby Cielito C. , El Osta Badi , Spitz Margaret R. , Parsons Henrique , Kurzrock Razelle , Wu Xifeng , Shete Sanjay , Bruera Eduardo 
Published: November 2008

Abstract
Introduction: We previously showed that select cytokine gene polymorphisms are a significant predictor for pain reported at initial presentation in 446 white patients newly diagnosed with non–small cell lung cancer. This follow-up study explores the extent to which polymorphisms in tumor necrosis factor-α (TNF- α-308 G/A), interleukin (IL)-6 −174G/C, and IL-8 −251T/A could explain variability in pain and analgesic response among those patients (n = 140) subsequently referred for pain treatment.
Methods: Pain severity (0, no pain; 10, worst pain) was assessed at initial consultation and at follow-up visit. The total dose of opioids at the time of first-follow up visit (30 days postconsult) was converted to an equivalent dose of parenteral morphine.
Results: Forty-one percent (57 of 140) of the patients reported severe pain (score &gt;7/10) at initial consultation (mean, 5.5), which significantly decreased to 25% (mean, 4) at first follow-up visit (McNemar = P &lt; 0.001). Polymorphisms in TNF and IL-6 were significantly associated with pain severity (for TNF GG, 4.12; GA, 5.38; AA, 5.50; P = 0.04) and with morphine equivalent daily dose (IL-6 GG, 69.61; GC, 73.17; CC, 181.67; P = 0.004), respectively. Adjusting for demographic and clinical variables, variant alleles in TNFα −308 G/A remained significantly associated with pain severity (b = 0.226; P = 0.036) and carriers of the IL-6 −174C/C genotypes required 4.7 times higher dose of opioids for pain relief (odds ratio, 4.7; 95% confidence interval, 1.2;15.0) relative to GG and GC genotypes.
Conclusions: We provide preliminary evidence of the influence of cytokine genes on pain and response to analgesia in lung cancer patients. Additional studies are needed to validate our findings. The long-term application is to tailored pain therapies. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3262–7)
Recent Trends in Black-White Disparities in Cancer Mortality
Authors: DeLancey John Oliver L. , Thun Michael J. , Jemal Ahmedin , Ward Elizabeth M. 
Published: November 2008

Abstract
Despite decreases in overall cancer death rates across all racial and ethnic groups since the early 1990s, racial disparities in cancer mortality persist. We examined temporal trends in Black-White disparities in cancer mortality from all sites combined, smoking-related cancers (lung and a group including oral cavity, pharynx, larynx, esophagus, pancreas, bladder, and kidney), and sites affected, or potentially affected by screening and treatment (breast, prostate, colon/rectum). Death rates, rate differences, and rate ratios comparing Blacks to Whites from 1975 through 2004 were based on mortality data from the National Center for Health Statistics. The Black-White disparity in overall cancer death rates narrowed from the early 1990s through 2004, especially in men. This reduction was driven predominantly by more rapid decreases in mortality from tobacco-related cancers in Black men than White men. In contrast, racial disparities in mortality from cancers potentially affected by screening and treatment increased over most of the interval since 1975. Coordinated efforts to improve early detection and treatment for all segments of the population are essential to eliminate racial disparities in cancer mortality. (Cancer Epidemiol Biomarkers Prev 2008;17(11):2908–12)
Altered Gene Expression Profiles Define Pathways in Colorectal Cancer Cell Lines Affected by Celecoxib
Authors: Fatima Naheed , Yi Ming , Ajaz Sadia , Stephens Robert M. , Stauffer Stacey , Greenwald Peter , Munroe David J. , Ali Iqbal Unnisa 
Published: November 2008

Abstract
It is well established that celecoxib, a selective inhibitor of cyclooxygenase-2 (COX-2) and a tested chemopreventive agent, has several COX-2–independent activities. In an attempt to better understand COX-2–independent molecular mechanisms underlying the chemopreventive activity of celecoxib, we did global transcription profiling of celecoxib-treated COX-2–positive and COX-2–deficient colorectal cancer cell lines. Celecoxib treatment resulted in significantly altered expression levels of over 1,000 to 3,000 transcripts in these cell lines, respectively. A pathway/functional analysis of celecoxib-affected transcripts, using Gene Ontology and Biocarta Pathways and exploring biological association networks, revealed that celecoxib modulates expression of numerous genes involved in a variety of cellular processes, including metabolism, cell proliferation, apoptotic signaling, cell cycle check points, lymphocyte activation, and signaling pathways. Among these processes, cell proliferation and apoptotic signaling consistently ranked as the highest-scoring Gene Ontology terms and Biocarta Pathways in both COX-2 expresser and nonexpresser cell lines. Altered expression of many of the genes by celecoxib was confirmed by quantitative PCR and at the protein level by Western blotting. Many novel genes emerged from our analysis of global transcription patterns that were not previously reported to be affected by celecoxib. In the future, in-depth work on selected genes will determine if these genes may serve as potential molecular targets for more effective chemopreventive strategies. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3051–61)
20 Years into the Gambia Hepatitis Intervention Study: Assessment of Initial Hypotheses and Prospects for Evaluation of Protective Effectiveness Against Liver Cancer
Authors: Viviani Simonetta , Carrieri Patrizia , Bah Ebrima , Hall Andrew J. , Kirk Gregory D. , Mendy Maimuna , Montesano Ruggero , Plymoth Amelie , Sam Omar , Van der Sande Marianne , Whittle Hilton , Hainaut Pierre ,   The Gambia Hepatitis Intervention Study
Published: November 2008

Abstract
Primary hepatocellular carcinoma is the commonest cancer in The Gambia. The Gambia Hepatitis Intervention Study (GHIS) was established in 1986 to evaluate the protective effectiveness of infant hepatitis B immunization in the prevention of chronic liver disease, particularly, hepatocellular carcinoma and cirrhosis later in adult life. This program was designed based on a series of assumptions. Here, we used data from observational and epidemiologic studies developed since 1986 to examine the validity of these assumptions. We found that (a) hepatitis B vaccine coverage was 15% more than originally assumed, (b) protection against hepatitis B virus (HBV) infection was not dependent on the number of vaccine doses received, (c) perinatal infection with HBV was of negligible importance, and (d) the HBV attributable risk of hepatocellular carcinoma at age &lt;50 was 70% to 80%, lower than initially assumed. Based on these data, the final outcome of the GHIS should be measurable from 2017, sooner than originally assumed. The GHIS strategy takes into account-specific patterns of virus epidemiology and natural history of hepatocellular carcinoma in Africa and provides a model for integrating and evaluating new vaccines into the Expanded Programme of Immunization of sub-Saharan African countries. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3216–24)