bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are Stocks Really Less Volatile in the Long Run?
Authors: PÁSTOR ĽUBOŠ , STAMBAUGH ROBERT F. 
Published: March 2012

ABSTRACTAccording to conventional wisdom, annualized volatility of stock returns is lower over long horizons than over short horizons, due to mean reversion induced by return predictability. In contrast, we find that stocks are substantially more volatile over long horizons from an investor's perspective. This perspective recognizes that parameters are uncertain, even with two centuries of data, and that observable predictors imperfectly deliver the conditional expected return. Mean reversion contributes strongly to reducing long‐horizon variance but is more than offset by various uncertainties faced by the investor. The same uncertainties reduce desired stock allocations of long‐horizon investors contemplating target‐date funds.
Are the Distinctions Drawn in the Debate about End-of-Life Decision Making “Principled”? If Not, How Much Does it Matter?
Authors: Kamisar Yale 
Published: March 2012

I sometimes wonder whether some proponents of physician-assisted suicide (PAS) or physician-assisted death (PAD) think they own the copyright to such catchy phrases as “death with dignity” and “a good death” so that if you are against PAS or PAD, thenyou must be againsta dignified death or a good death. If one removes the quotation marks around phrases like “aid-in-dying” or “compassionate care for the dying,” I am not opposed to such end-of-life care either. Indeed, how couldanybodybe against this type of care?I do not want to abandon dying patients anymore than Dr. Timothy Quill does. Although, unfortunately, it will not always be easy to achieve the desired result, I agree with him that it ought to be a goal of medicine “to help people die well, to help them receive a good death” — or at least “the best possible” death under the circumstances. I part company with Professor Quill, however, when he urges us to change the law in the majority of our states so that in some circumstances patients may achieve a “good death” or a “dignified” one by means of lethal drugs.
Conflicts among Multinational Ethical and Scientific Standards for Clinical Trials of Therapeutic Interventions
Authors: Kolman Jacob M. , Wray Nelda P. , Ashton Carol M. , Wenner Danielle M. , Jarman Anna F. , Brody Baruch A. 
Published: March 2012

There has been a growing concern over establishing norms that ensure the ethically acceptable and scientifically sound conduct of clinical trials. Among the leading norms internationally are the World Medical Association's Declaration of Helsinki, guidelines by the Council for International Organizations of Medical Sciences (CIOMS), the International Conference on Harmonization's standards for industry (ICH), and the CONSORT group's reporting norms (Consolidated Standards of Reporting Trials), in addition to the influential U.S. Federal Common Rule, Food and Drug Administration's (FDA) body of regulations, and information sheets by the Department of Health and Human Services. There are also many norms published at more local levels by official agencies and professional groups.Any account of international standards should cover both scientific and ethical norms at once – the two are conceptually intertwined. Recent sources recognize that “[s]cientifically unsound research on human subjects is unethical in that it exposes research subjects to risks without possible benefit.”
A short note on the horizontal and vertical movements of a whale shark, Rhincodon typus, tracked by satellite telemetry in the South China Sea
Authors: WANG Yamin , LI Wei , ZENG Xiaoguang , CUI Yunchen 
Published: March 2012

AbstractWhale sharks, a global migratory species, are often reported entangled in fishing nets in coastal areas of China. The effectiveness of conservation measures has been constrained by very limited knowledge on their movements and preferred habitats in the coastal areas of China. For the first time, we tracked the movements of 2 whale sharks by satellite telemetry in Mainland China. The tracking results of 1 whale shark revealed that it travelled in the South China Sea in a south‐eastern direction, parallel to the eastern coast of Vietnam. Total distance travelled was 1018 km, in approximately 74 days, with a mean speed of 14 km per day. It appeared to head towards the cool upwelling zones in southern Vietnam at the time of the tag's detachment. In our study, it was observed that this whale shark was a surface dweller and spent approximately 45% of its time above 10 m water depth and 90% of its time above 50 m depth. It also tended to stay in water temperatures between 27 and 30 °C, and was rarely recorded in water below 20 °C. This preliminary study indicates the importance of shallow waters as the foraging habitat for whale sharks, and has implications for their management and conservation.
Hepatitis C Virus Activates the mTOR/S6K1 Signaling Pathway in Inhibiting IRS-1 Function for Insulin Resistance
Authors: Bose Sandip K. , Shrivastava Shubham , Meyer Keith , Ray Ratna B. , Ray Ranjit 
Published: March 2012

ABSTRACT
Hepatitis C virus (HCV) infection significantly increases the prevalence of type 2 diabetes mellitus (T2DM). Insulin receptor substrate 1 (IRS-1) plays a key role in insulin signaling, thus enabling metabolic regulation in mammalian cells. We have previously shown that HCV infection modulates phosphorylation of Akt, a downstream target of IRS-1. In this study, we further examined the status of total IRS-1 and the downstream regulation of the Akt pathway in understanding mTOR/S6K1 signaling using HCV genotype 2a (clone JFH1)-infected hepatocytes. Inhibition of IRS-1 expression was observed in HCV-infected hepatocytes compared to that in a mock-infected control. The status of the tuberous sclerosis complex (TSC-1/TSC-2) was significantly decreased after HCV infection of human hepatocytes, showing a modulation of the downstream Akt pathway. Subsequent study indicated an increased level of Rheb and mTOR expression in HCV-infected hepatocytes. Interestingly, the phosphoS6K1 level was higher in HCV-infected hepatocytes, suggesting a novel mechanism for IRS-1 inhibition. Ectopic expression of TSC-1/TSC-2 significantly recovered the IRS-1 protein expression level in HCV-infected hepatocytes. Further analyses indicated that HCV core protein plays a significant role in modulating the mTOR/S6K1 signaling pathway. Proteasome inhibitor MG 132 recovered IRS-1 and TSC1/2 expression, suggesting that degradation occurred via the ubiquitin proteasome pathway. A functional consequence of IRS-1 inhibition was reflected in a decrease in GLUT4 protein expression and upregulation of the gluconeogenic enzyme PCK2 in HCV-infected hepatocytes. Together, these observations suggested that HCV infection activates the mTOR/S6K1 pathway in inhibiting IRS-1 function and perturbs glucose metabolism via downregulation of GLUT4 and upregulation of PCK2 for insulin resistance.
Mus spicilegus Endogenous Retrovirus HEMV Uses Murine Sodium-Dependent Myo-Inositol Transporter 1 as a Receptor
Authors: Tipper Christopher H. , Cingöz Oya , Coffin John M. 
Published: March 2012

ABSTRACT

We sought to determine the relationship between two recent additions to the murine leukemia virus (MLV) ecotropic subgroup:
Mus cervicolor
isolate M813 and
Mus spicilegus
endogenous retrovirus HEMV. Though divergent in sequence, the two viruses share an Env protein with similarly curtailed VRA and VRB regions, and infection by both is restricted to mouse cells. HEMV and M813 displayed reciprocal receptor interference, suggesting that they share a receptor. Expression of the M813 receptor murine sodium-dependent myo-inositol transporter 1 (mSMIT1) allowed previously nonpermissive cells to be infected by HEMV, indicating that mSMIT1 also serves as a receptor for HEMV. Our findings add HEMV as a second member to the MLV subgroup that uses mSMIT1 to gain entry into cells.
Deep Sequencing Reveals Minor Protease Resistance Mutations in Patients Failing a Protease Inhibitor Regimen
Authors: Fisher Randall , van Zyl Gert U. , Travers Simon A. A. , Kosakovsky Pond Sergei L. , Engelbrech Susan , Murrell Ben , Scheffler Konrad , Smith Davey 
Published: March 2012

ABSTRACT
Standard genotypic antiretroviral resistance testing, performed by bulk sequencing, does not readily detect variants that comprise <20% of the circulating HIV-1 RNA population. Nevertheless, it is valuable in selecting an antiretroviral regimen after antiretroviral failure. In patients with poor adherence, resistant variants may not reach this threshold. Therefore, deep sequencing would be potentially valuable for detecting minority resistant variants. We compared bulk sequencing and deep sequencing to detect HIV-1 drug resistance at the time of a second-line protease inhibitor (PI)-based antiretroviral regimen failure. Eligibility criteria were virologic failure (HIV-1 RNA load of >500 copies/ml) of a first-line nonnucleoside reverse transcriptase inhibitor-based regimen, with at least the M184V mutation (lamivudine resistance), and second-line failure of a lopinavir/ritonavir (LPV/r)-based regimen. An amplicon-sequencing approach on the Roche 454 system was used. Six patients with viral loads of >90,000 copies/ml and one patient with a viral load of 520 copies/ml were included. Mutations not detectable by bulk sequencing during first- and second-line failure were detected by deep sequencing during second-line failure. Low-frequency variants (>0.5% of the sequence population) harboring major protease inhibitor resistance mutations were found in 5 of 7 patients despite poor adherence to the LPV/r-based regimen. In patients with intermittent adherence to a boosted PI regimen, deep sequencing may detect minority PI-resistant variants, which likely represent early events in resistance selection. In patients with poor or intermittent adherence, there may be low evolutionary impetus for such variants to reach fixation, explaining the low prevalence of PI resistance.
Human Monoclonal Antibodies to Pandemic 1957 H2N2 and Pandemic 1968 H3N2 Influenza Viruses
Authors: Krause Jens C. , Tsibane Tshidi , Tumpey Terrence M. , Huffman Chelsey J. , Albrecht Randy , Blum David L. , Ramos Irene , Fernandez-Sesma Ana , Edwards Kathryn M. , García-Sastre Adolfo , Basler Christopher F. , Crowe James E. 
Published: March 2012

ABSTRACT

Investigation of the human antibody response to the 1957 pandemic H2N2 influenza A virus has been largely limited to serologic studies. We generated five influenza virus hemagglutinin (HA)-reactive human monoclonal antibodies (MAbs) by hybridoma technology from the peripheral blood of healthy donors who were born between 1950 and 1968. Two MAbs reacted with the pandemic H2N2 virus, two recognized the pandemic H3N2 virus, and remarkably, one reacted with both the pandemic H2N2 and H3N2 viruses. Each of these five naturally occurring MAbs displayed hemagglutination inhibition activity, suggesting specificity for the globular head domain of influenza virus HA. When incubated with virus, MAbs 8F8, 8M2, and 2G1 each elicited H2N2 escape mutations immediately adjacent to the receptor-binding domain on the HA globular head in embryonated chicken eggs. All H2N2-specific MAbs were able to inhibit a 2006 swine H2N3 influenza virus. MAbs 8M2 and 2G1 shared the V
H
1-69 germ line gene, but these antibodies were otherwise not genetically related. Each antibody was able to protect mice in a lethal H2N2 virus challenge. Thus, even 43 years after circulation of H2N2 viruses, these subjects possessed peripheral blood B cells encoding potent inhibiting antibodies specific for a conserved region on the globular head of the pandemic H2 HA.
Leadership competencies for medical education and healthcare professions: population-based study
Authors: Çitaku Fadil , Violato Claudio , Beran Tanya , Donnon Tyrone , Hecker Kent , Cawthorpe David 
Published: March 2012

ObjectiveTo identify and empirically investigate the dimensions of leadership in medical education and healthcare professions.DesignA population-based design with a focus group and a survey were used to identify the perceived competencies for effective leadership in medical education.SettingThe focus group, consisting of five experts from three countries (Austria n=1; Germany n=2; Switzerland n=2), was conducted (all masters of medical education), and the survey was sent to health professionals from medical schools and teaching hospitals in six countries (Austria, Canada, Germany, Switzerland, the UK and the USA).ParticipantsThe participants were educators, physicians, nurses and other health professionals who held academic positions in medical education. A total of 229 completed the survey: 135 (59.0%) women (mean age=50.3 years) and 94 (41.0%) men (mean age=51.0 years).MeasuresA 63-item survey measuring leadership competencies was developed and administered via electronic mail to participants.ResultsExploratory principal component analyses yielded five factors accounting for 51.2% of the variance: (1) social responsibility, (2) innovation, (3) self-management, (4) task management and (5) justice orientation. There were significant differences between physicians and other health professionals on some factors (Wilk's λ=0.93, p<0.01). Social responsibility was rated higher by other health professionals (M=71.09) than by physicians (M=67.12), as was innovation (health professionals M=80.83; physicians M=76.20) and justice orientation (health professionals M=21.27; physicians M=20.46).ConclusionsThe results of the principal component analyses support the theoretical meaningfulness of these factors, their coherence, internal consistency and parsimony in explaining the variance of the data. Although there are some between-group differences, the competencies appear to be stable and coherent.
Changes in the levels of thioredoxin and indoleamine-2,3-dioxygenase activity in plasma of patients with colorectal cancer treated with chemotherapy
Authors: Cavia-Saiz Monica , Muñiz Pilar , De Santiago Reyes , Herreros-Villanueva Marta , Garcia-Giron Carlos , Lopez Ana Sofia , Coma-del Corral Maria Jesus 
Published: March 2012

Increased oxidative stress and indoleamine-2,3-dioxygenase (IDO) activity have been reported in cancer, but their relationship with chemotherapy remains unknown. The aim of the present study was to examine wether the chemotherapy treatments used in colorectal cancer had an additional effect on oxidative stress and on IDO activity. Plasma samples were collected from 27 colorectal cancer patients on cytostatic treatment, 27 with cytostatic drugs plus monoclonal antibodies (cytostatic-Mabs) and 15 non-treated patients. All patients with colorectal cancer had high plasma malondialdehyde (MDA), thioredoxin (Trx) levels, and elevated IDO activity in plasma (IDOp) and in dendritic cells (IDOc). This study shows that treatment with cytostatics have an effect on oxidative stress by increasing MDA levels and by decreasing Trx levels and IDO activity. However, treatment with cytostatic-Mabs showed no effect on MDA levels but decreased Trx levels, and the IDO activity showed values similar to the healthy group. Significant correlations between plasma IDO activity and the levels of Trx (r = 0.2062, p < 0.05) and MDA (r = 0.2873, p < 0.005) were observed. Furthermore, our study suggests that IDO activity measured as kynurenine levels could be used as a marker of the response to the chemotherapy treatments, although further studies are necessary.
Time-dependent behaviour of the Bearpaw Shale in oedometric loading and unloading
Authors: Powell J. Suzanne , Take W. Andy , Siemens Greg , Remenda V.H. 
Published: March 2012

Time-dependent behaviour can have a significant influence on the compressibility characteristics of soils. However, most of the research on this topic has investigated the behaviour of soft soils. In this paper, the time-dependent behaviour of a hard clay shale (Bearpaw Shale) is investigated using both one-dimensional multi-staged loading (MSL) oedometer and constant rate of strain (CRS) oedometer consolidation tests conducted on 25.0 and 16.9 mm diameter specimens. The results show that soft clays and hard clay shales that share the same Cαe/[Formula: see text] ratio (where Cαeis the secondary compression index and [Formula: see text] is the incremental compression index) will show the same approximately 7% change in pre-consolidation pressure for an increase of one log cycle of strain rate despite the many orders of magnitude difference in pre-consolidation pressure. In the case of the Bearpaw Shale, this 7% change in pre-consolidation pressure corresponds to approximately 700 kPa. The time-dependent behaviour of the Bearpaw Shale during unloading (Cαe/[Formula: see text], where [Formula: see text] is the incremental swelling index) was observed to follow a similar ratio to that observed in compression (Cαe/[Formula: see text]). While the exact nature of the compression and swelling events that have occurred over the life of the Bearpaw Formation is not clear, the influence of secondary compression cannot be ignored for interpretation of the geological history of this deposit.
Two new one-dimensional coordination polymers containing [N(CN)2]– — Syntheses, structures, and magnetic properties of [MII(3- Bzpy)2(N(CN)2)2] (M = Mn (1) and Co (2) and 3-Bzpy = 3-benzoylpyridine)
Authors: Bao Qianqian , Ma Yutao , Zhao Qihua , Luo Yanghui , Sun Baiwang 
Published: March 2012

The structures of two one-dimensional coordination complexes, [MII(3-Bzpy)2(N(CN)2)2] (M = Mn (1) and Co (2) and 3-Bzpy = 3-benzoylpyridine), have been determined in this work. The two structures are isomorphous, crystallize in a monoclinic P21/c space group, and show almost the same crystal structure. The magnetic measurements of the two compounds (2–300 K) indicate that antiferromagnetic exchanges exist between the metal ions of the two compounds.
Forest mortality in high-elevation whitebark pine (Pinus albicaulis) forests of eastern California, USA; influence of environmental context, bark beetles, climatic water deficit, and warming
Authors: Millar Constance I. , Westfall Robert D. , Delany Diane L. , Bokach Matthew J. , Flint Alan L. , Flint Lorraine E. 
Published: March 2012

Whitebark pine ( Pinus albicaulis Engelm.) in subalpine zones of eastern California experienced significant mortality from 2007 to 2010. Dying stands were dense (mean basal area 47.5 m2/ha), young (mean 176 years), and even-age; mean stand mortality was 70%. Stands were at low elevations (mean 2993 m), on northerly aspects, and experienced warmer, drier climates relative to the regional species distribution. White pine blister rust was not observed; mountain pine beetle infestations were extensive. Ring widths were negatively correlated with climatic water deficit and positively correlated with water-year precipitation. Although trees that survived had greater growth during the 20th century than trees that died, in the 19th century trees that eventually died grew better than trees that survived, suggesting selection for genetic adaptation to current climates as a result of differential tree mortality. Air surveys (2006–2010) in the Sierra Nevada, Mt. Shasta, and Warner Mountains showed similar trends to the intensive studies. Observed mortality from air surveys was highest in the Warner Mountains (38%) and lowest in the Sierra Nevada (5%); northern aspects at lower elevations within each mountain region had the highest probabilities of mortality and dying stands had higher climatic water deficit. Scenarios for the future of whitebark pine in California are discussed.
Genetic Variation in Peroxisome Proliferator–Activated Receptor Gamma, Soy, and Mammographic Density in Singapore Chinese Women
Authors: Lee Eunjung , Hsu Chris , Van den Berg David , Ursin Giske , Koh Woon-Puay , Yuan Jian-Min , Stram Daniel O. , Yu Mimi C. , Wu Anna H. 
Published: March 2012

Abstract
Background: PPARγ is a transcription factor important for adipogenesis and adipocyte differentiation. Data from animal studies suggest that PPARγ may be involved in breast tumorigenesis, but results from epidemiologic studies on the association between PPARγ variation and breast cancer risk have been mixed. Recent data suggest that soy isoflavones can activate PPARγ. We investigated the interrelations of soy, PPARγ, and mammographic density, a biomarker of breast cancer risk in a cross-sectional study of 2,038 women who were members of the population-based Singapore Chinese Health Study Cohort.
Methods: We assessed mammographic density using a computer-assisted method. We used linear regression to examine the association between 26 tagging single-nucleotide polymorphisms (SNP) of PPARγ and their interaction with soy intake and mammographic density. To correct for multiple testing, we calculated P values adjusted for multiple correlated tests (PACT).
Results: Out of the 26 tested SNPs in the PPARγ, seven SNPs were individually shown to be statistically significantly associated with mammographic density (PACT = 0.008–0.049). A stepwise regression procedure identified that only rs880663 was independently associated with mammographic density which decreased by 1.89% per-minor allele (PACT = 0.008). This association was significantly stronger in high-soy consumers as mammographic density decreased by 3.97% per-minor allele of rs880663 in high-soy consumers (PACT = 0.006; P for interaction with lower soy intake = 0.017).
Conclusions: Our data support that PPARγ genetic variation may be important in determining mammographic density, particularly in high-soy consumers.
Impact: Our findings may help to identify molecular targets and lifestyle intervention for future prevention research. Cancer Epidemiol Biomarkers Prev; 21(4); 635–44. ©2012 AACR.