bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sirtuin 1 Retards Hyperphosphatemia-Induced Calcification of Vascular Smooth Muscle Cells
Authors: Takemura Aya , Iijima Katsuya , Ota Hidetaka , Son Bo-Kyung , Ito Yuki , Ogawa Sumito , Eto Masato , Akishita Masahiro , Ouchi Yasuyoshi 
Published: July 2011

Objective—
Arterial calcification is associated with cardiovascular disease as a complication of advanced atherosclerosis. Aged vascular cells manifest some morphological features of a senescent phenotype. Recent studies have demonstrated that mammalian sirtuin 1 (SIRT1), a histone deacetylase, is an exciting target for cardiovascular disease management. Here, we investigated the role of SIRT1 in a calcification model of vascular smooth muscle cells (SMCs).

Methods and Results—
In adenine-induced renal failure rats with hyperphosphatemia, massive calcification was induced in the aortic media. Senescence-associated β-galactosidase (SAβ-gal) activity, a marker of cellular senescence, in medial SMCs was significantly increased, and its induction was positively associated with the degree of calcification. In cultured SMCs, inorganic phosphate (Pi) stimulation dose-dependently increased SAβ-gal-positive cells, and Pi-induced senescence was associated with downregulation of SIRT1 expression, leading to p21 activation. The activation via SIRT1 downregulation was blunted by inhibition of Pi cotransporter. Activation of SIRT1 by resveratrol significantly reduced the senescence-associated calcification. Conversely, SIRT1 knockdown by small interfering RNA accelerated the Pi-induced SMC senescence and subsequent calcification. In addition, SIRT1 knockdown induced phenotypic change from a differentiated state to osteoblast-like cells. The senescence-related SMC calcification was completely prevented by p21 knockdown. In addition to Pi-induced premature senescence, SMCs with replicative senescence were also more sensitive to Pi-induced calcification compared with young SMCs, and this finding was attributable to augmented p21 expression.

Conclusion—
SIRT1 plays an essential role in preventing hyperphosphatemia-induced arterial calcification via inhibition of osteoblastic transdifferentiation. In addition, Pi-induced SMC calcification may be associated with both premature and replicative cellular senescence.
Roles of SST Anomalies on the Wintertime Turbulent Heat Fluxes in the Kuroshio–Oyashio Confluence Region: Influences of Warm Eddies Detached from the Kuroshio Extension
Authors: Sugimoto Shusaku , Hanawa Kimio 
Published: July 2011

Abstract
Variations of turbulent heat fluxes (sum of sensible and latent heat fluxes) in the North Pacific during 16 winters from December 1992/February 1993 to December 2007/February 2008 are investigated because the months from December to February correspond to the period having peak winter conditions in the atmosphere field. Turbulent heat fluxes are calculated from the bulk formula using daily variables [surface wind speed, surface air specific humidity, surface air temperature, and sea surface temperature (SST)] of the objectively analyzed air–sea flux (OAFlux) dataset and bulk coefficients based on the Tropical Ocean and Global Atmosphere Coupled Ocean–Atmosphere Response Experiment (TOGA COARE) bulk flux algorithm 3.0. The winter turbulent heat fluxes over the Kuroshio–Oyashio Confluence Region (KOCR; 142°–150°E, 35°–40°N) have the largest temporal variances in the North Pacific. The relative contributions among observed variables in SST, surface air temperature, and surface wind speed causing turbulent heat flux variations in the KOCR are assessed quantitatively by performing simple experiments using combinations of two types of variables: raw daily data and daily climatological data. Results show that SST is primarily responsible for the turbulent heat flux variations—a huge amount of heat is released in the state of the positive SST anomaly. Using the datasets of satellite-derived SST and sea surface height with high spatial and temporal resolutions, it is found that the SST anomalies in the KOCR are formed through activities of the anticyclonic (warm) eddies detached northward from the Kuroshio Extension; SSTs take positive (negative) anomalies when more (less) anticyclonic eddies are distributed there, associated with a more convoluted (straight) Kuroshio Extension path.
Seasonal Modulation of Tropical Intraseasonal Oscillations on Tropical Cyclone Geneses in the Western North Pacific
Authors: Huang Ping , Chou Chia , Huang Ronghui 
Published: July 2011

Abstract
The seasonal modulation of tropical intraseasonal oscillation (TISO) on tropical cyclone (TC) geneses over the western North Pacific Ocean (WNP) is investigated in three periods of the WNP TC season: May–June (MJ), July–September (JAS), and October–December (OND). The modulation of the TISO–TC geneses over the WNP is strong in MJ, while it appears weaker in JAS and OND. In MJ, TISO propagates northward via two routes, the west route through the South China Sea and the east route through the WNP monsoon trough region, which are two clustering locations of TC geneses. TISO can synchronously influence most TC geneses over these two regions. In JAS, however, the modulation is out of phase between the monsoon trough region and the East Asian summer monsoon region, as well as the WNP subtropical high region, as a result of further northward propagation of TISO and scattered TC geneses. The TISO–TC genesis modulation in each individual region is comparable to that in MJ, although the modulation over the entire WNP in JAS appears weaker. In OND, TISO has a stronger influence on TC geneses west than east of 150°E because TISO decays and its convection center located at the equator is out of the TC genesis region when propagating eastward into east of 150°E. Midlevel relative humidity is the primary contribution to the modulations of TISO on the genesis environment, while vorticity could contribute to the modulation over the subtropics in JAS.
Application of the Marsupial Paradigm to Tropical Cyclone Formation from Northwestward-Propagating Disturbances
Authors: Wang Zhuo , Dunkerton Timothy J. , Montgomery Michael T. 
Published: July 2011

Abstract
A wave-tracking algorithm is developed for northwestward-propagating waves that, on occasion, play a role in tropical cyclogenesis over the western oceans. To obtain the Lagrangian flow structure, the frame of reference is translated obliquely at the same propagation speed with the precursor disturbance. Trajectory analysis suggests that streamlines in the obliquely translated frame of reference can be used to approximate flow trajectories. The algorithm was applied to Super Typhoon Nakri (2008), Tropical Cyclone Erika (2009), and a few other examples. Diagnoses of meteorological analyses and satellite-derived moisture and precipitation fields show that the marsupial framework for tropical cyclogenesis in tropical easterly waves is relevant also for northwestward-propagating disturbances as are commonly observed in the tropical western Atlantic, the Gulf of Mexico, and the western North Pacific. Finally, it is suggested that analysis of the global model data and satellite observations in the marsupial framework can provide useful guidance on early tropical cyclone advisories.
The Response of the Tropospheric Circulation to Water Vapor–Like Forcings in the Stratosphere
Authors: Tandon Neil F. , Polvani Lorenzo M. , Davis Sean M. 
Published: July 2011

Abstract
An idealized, dry general circulation model is used to examine the response of the tropospheric circulation to thermal forcings that mimic changes in stratospheric water vapor (SWV). It is found that SWV-like cooling in the stratosphere produces a poleward-shifted, strengthened jet and an expanded, weakened Hadley cell. This response is shown to be almost entirely driven by cooling located in the extratropical lower stratosphere; when cooling is limited to the tropical stratosphere, it generates a much weaker and qualitatively opposite response. It is demonstrated that these circulation changes arise independently of any changes in tropopause height, are insensitive to the detailed structure of the forcing function, and are robust to model resolution. The responses are quantitatively of the same order as those due to well-mixed greenhouse gases, suggesting a potentially significant contribution of SWV to past and future changes in the tropospheric circulation.
Sensitivity of a Simulated Squall Line to Horizontal Resolution and Parameterization of Microphysics
Authors: Bryan George H. , Morrison Hugh 
Published: July 2011

Abstract
Idealized simulations of the 15 May 2009 squall line from the Second Verification of the Origins of Rotation in Tornadoes Experiment (VORTEX2) are evaluated in this study. Four different microphysical setups are used, with either single-moment (1M) or double-moment (2M) microphysics, and either hail or graupel as the dense (rimed) ice species. Three different horizontal grid spacings are used: Δx = 4, 1, or 0.25 km (with identical vertical grids). Overall, results show that simulated squall lines are sensitive to both microphysical setup and horizontal resolution, although some quantities (i.e., surface rainfall) are more sensitive to Δx in this study. Simulations with larger Δx are slower to develop, produce more precipitation, and have higher cloud tops, all of which are attributable to larger convective cells that do not entrain midlevel air. The highest-resolution simulations have substantially more cloud water evaporation, which is partly attributable to the development of resolved turbulence. For a given Δx, the 1M simulations produce less rain, more intense cold pools, and do not have trailing stratiform precipitation at the surface, owing to excessive rainwater evaporation. The simulations with graupel as the dense ice species have unrealistically wide convective regions. Comparison against analyses from VORTEX2 data shows that the 2M setup with hail and Δx = 0.25 km produces the most realistic simulation because (i) this simulation produces realistic distributions of reflectivity associated with convective, transition, and trailing stratiform regions, (ii) the cold pool properties are reasonably close to analyses from VORTEX2, and (iii) relative humidity in the cold pool is closest to observations.
Effect of Gender and Sports on the Risk of Full-Thickness Articular Cartilage Lesions in Anterior Cruciate Ligament–Injured Knees
Authors: Røtterud Jan Harald , Sivertsen Einar A. , Forssblad Magnus , Engebretsen Lars , Årøen Asbjørn 
Published: July 2011

Background: The presence of an articular cartilage lesion in anterior cruciate ligament–injured knees is considered a predictor of osteoarthritis. Purpose: This study was undertaken to evaluate risk factors for full-thickness articular cartilage lesions in anterior cruciate ligament–injured knees, in particular the role of gender and the sport causing the initial injury. Study Design: Cohort study (prognosis); Level of evidence, 2. Methods: Primary unilateral anterior cruciate ligament reconstructions prospectively registered in the Swedish and the Norwegian National Knee Ligament Registry during 2005 through 2008 were included (N = 15 783). Logistic regression analyses were used to evaluate risk factors for cartilage lesions. Results: A total of 1012 patients (6.4%) had full-thickness cartilage lesions. The median time from injury to surgery was 9 months (range, 0 days-521 months). Male patients had an increased odds of full-thickness cartilage lesions compared with females (odds ratio = 1.22; 95% confidence interval, 1.04-1.42). In males, team handball had an increase in the odds of full-thickness cartilage lesions compared with soccer (odds ratio = 2.36; 95% confidence interval, 1.33-4.19). Among female patients, no sport investigated showed a significant decrease or increase in the odds of full-thickness cartilage lesions. The odds of a full-thickness cartilage lesion increased by 1.006 (95% confidence interval, 1.005-1.008) for each month elapsed from time of injury until anterior cruciate ligament reconstruction when all patients were considered, while time from injury to surgery did not affect the odds significantly in those patients reconstructed within 1 year of injury (odds ratio = 0.98; 95% confidence interval, 0.95-1.02). Previous surgery increased the odds of having a full-thickness cartilage lesion (odds ratio = 1.40; 95% confidence interval, 1.21-1.63). One year of increasing patient age also increased the odds (odds ratio = 1.05; 95% confidence interval, 1.05-1.06). Conclusion: Male gender is associated with an increased risk of full-thickness articular cartilage lesions in anterior cruciate ligament–injured knees. Male team handball players had an increased risk of full-thickness lesions. No other sports investigated were found to have significant effect on the risk in either gender. Furthermore, age, previous surgery, and time from injury to surgery exceeding 12 months are risk factors for full-thickness cartilage lesions.
Oral fingolimod (FTY720) in relapsing multiple sclerosis: impact on health-related quality of life in a phase II study
Authors: Montalban X , Comi G , O’Connor P , Gold SM , de Vera A , Eckert B , Kappos L 
Published: July 2011

Background: Health-related quality of life (HRQoL) worsens with multiple sclerosis (MS) relapses and disease progression. Common symptoms including depression and fatigue may contribute to poor HRQoL. Objectives: To report exploratory analyses assessing the impact of fingolimod (FTY720) on HRQoL and depression in a phase II study of relapsing MS. Methods: The Hamburg Quality of Life Questionnaire in MS (HAQUAMS) and Beck Depression Inventory second edition (BDI-II) scores were assessed during a 6-month, placebo-controlled study and optional extension. Results: HAQUAMS total score improved with fingolimod and worsened with placebo. Mean score change from baseline to month 6 was −0.02 with fingolimod 1.25 mg ( p < 0.05 versus placebo), −0.01 with fingolimod 5.0 mg and + 0.12 with placebo. Categorical data supported a clinically important effect of fingolimod on HRQoL. Fingolimod 1.25 mg was also beneficial over placebo in the fatigue/thinking HAQUAMS sub-domain ( p < 0.05 versus placebo). Change in mean BDI-II scores from baseline to month 6 and the proportion of patients with BDI-II scores indicative of clinical depression favored fingolimod 1.25 mg over placebo ( p < 0.05 for both). At month 4, mean BDI-II and HAQUAMS total scores appeared to be maintained in fingolimod-treated patients. Conclusion: Fingolimod 1.25 mg may improve HRQoL and depression at 6 onths compared with placebo in patients with relapsing MS.
Monitoring the quality of conduct of clinical trials: a survey of current practices
Authors: Morrison Briggs W , Cochran Chrissy J , White Jennifer Giangrande , Harley Joan , Kleppinger Cynthia F , Liu An , Mitchel Jules T , Nickerson David F , Zacharias Cynthia R , Kramer Judith M , Neaton James D 
Published: July 2011

Background There is a little empirical evidence to determine which, if any, monitoring practices best achieve the goals of trial monitoring set forth in ICH E6 under the variable circumstances of different clinical trial settings. Purpose The purpose of this project was to describe current methods of monitoring clinical trials and to explore the rationale for the use of those methods. Methods An electronic survey of known monitoring practices was developed and sent to over 200 organizations involved in conducting clinical research. The survey collected information on institutional demographics, methods of overall study oversight, use of risk-based monitoring and factors that influence assessments of risk, and details on quality assurance and monitoring practices. Results Seventy-nine organizations completed the survey; our analysis included the 65 organizations that indicated they perform clinical trials. Data from the survey indicate that a wide variety of monitoring practices are currently being employed. Eighty-three percent of respondents use centrally available data to evaluate site performance, but only 12% of respondents always or frequently used centralized monitoring to replace on-site visits. Eighty-seven percent of respondents indicated that they always performed on-site visits. This varied by type of organization, with 31% of academic coordinating centers/cooperative groups/government organizations always performing on-site monitoring visits versus 84% of other organizations. The rationale for using a specific monitoring approach does not appear to be based on empirical evidence. Fifty-four percent of respondents stated that ‘usual practice’ determined the frequency with which they conducted on-site monitoring visits. Limitations The overall response rate to our survey was only 30%; thus, we may not have captured the full variance of current monitoring practices, and our responding sample may not be representative. Conclusion These findings underscore the necessity of research to provide an evidence base for monitoring practice.
The development and description of the comparison group in the Look AHEAD trial
Authors:   The Look AHEAD Research Group
Published: July 2011

Background Despite more lifestyle intervention trials, there is little published information on the development of the comparison group intervention. This article describes the comparison group intervention, termed Diabetes Support and Education Intervention and its development for the Action for HEAlth in Diabetes (Look AHEAD) trial. Look AHEAD, a randomized, controlled, multicenter trial, was designed to determine whether an Intensive Lifestyle Intervention to reduce weight and increase physical activity reduces cardiovascular morbidity and mortality in overweight volunteers with type 2 diabetes compared to the Diabetes Support and Education Intervention. The Diabetes Support and Education Committee was charged with developing the Diabetes Support and Education Intervention with the primary aim of participant retention. Purpose The objectives were to design the Diabetes Support and Education Intervention sessions, standardize delivery across the 16 clinics, review quality and protocol adherence and advise on staffing and funding. Methods Following a mandatory session on basic diabetes education, three optional sessions were offered on nutrition, physical activity, and support yearly for 4 years. For each session, guidelines, objectives, activities, and a resource list were created. Conclusions Participant evaluations were very positive with hands on experiences being the most valuable. Retention so far at years 1 and 4 has been excellent and only slightly lower in the Diabetes Support and Education Intervention arm. The comparison group plays an important role in the success of a clinical trial. Understanding the effort needed to develop and implement the comparison group intervention will facilitate its implementation in future lifestyle intervention trials, particularly multicenter trials. Retention rates may improve by developing the comparison intervention simultaneously with the lifestyle intervention.
How I conduct a comprehensive chronic graft-versus-host disease assessment
Authors: Carpenter Paul A. 
Published: July 2011

Abstract
Since the National Institutes of Health Chronic Graft-Versus-Host Disease (cGVHD) Consensus Project in 2005, a need has emerged to evaluate cGVHD more methodically, not only to make a cGVHD diagnosis, but also to accurately classify individual organ and global organ severity, at baseline and in follow-up so that subjects participating in clinical trials may reliably be assigned an accurate response category irrespective of the evaluator. Even for patients not enrolled on a clinical trial, periodic complete cGVHD assessments can allow subtle manifestations to be detected, monitored carefully, and/or treated early with the goal of hopefully avoiding progression to highly morbid, difficult to treat, and quite often irreversible forms of cGVHD. Early feedback has been that the National Institutes of Health approach to diagnosis classification, staging, and response, as well as other new assessment tools, are too detailed and overly complex. This article tries to address many of these issues by describing how I conduct a comprehensive cGVHD assessment using a streamlined and reliable method that I use regularly within the constraints of a busy clinic.
Amino-terminal extension present in the methionine aminopeptidase type 1c of Mycobacterium tuberculosis is indispensible for its activity
Authors: Kanudia Pavitra , Mittal Monica , Kumaran Sangaralingam , Chakraborti Pradip K 
Published: July 2011

Abstract

Background
Methionine aminopeptidase (MetAP) is a ubiquitous enzyme in both prokaryotes and eukaryotes, which catalyzes co-translational removal of N-terminal methionine from elongating polypeptide chains during protein synthesis. It specifically removes the terminal methionine in all organisms, if the penultimate residue is non-bulky and uncharged. The MetAP action for exclusion of N-terminal methionine is mandatory in 50-70% of nascent proteins. Such an activity is required for proper sub cellular localization, additional processing and eventually for the degradation of proteins.

Results
We cloned genes encoding two such metalloproteases (Mt MetAP1a and Mt MetAP1c) present in Mycobacterium tuberculosis and expressed them as histidine-tagged proteins in Escherichia coli. Although they have different substrate preferences, for Met-Ala-Ser, we found, Mt MetAP1c had significantly high enzyme turnover rate as opposed to Mt MetAP1a. Circular dichroism spectroscopic studies as well as monitoring of enzyme activity indicated high temperature stability (up to 50°C) of Mt MetAP1a compared to that of the Mt MetAP1c. Modelling of Mt MetAP1a based on Mt MetAP1c crystal structure revealed the distinct spatial arrangements of identical active site amino acid residues and their mutations affected the enzymatic activities of both the proteins. Strikingly, we observed that 40 amino acid long N-terminal extension of Mt MetAP1c, compared to its other family members, contributes towards the activity and stability of this enzyme, which has never been reported for any methionine aminopeptidase. Furthermore, mutational analysis revealed that Val-18 and Pro-19 of Mt MetAP1c are crucial for its enzymatic activity. Consistent with this observation, molecular dynamic simulation studies of wild-type and these variants strongly suggest their involvement in maintaining active site conformation of Mt MetAP1c.

Conclusion
Our findings unequivocally emphasized that N-terminal extension of Mt MetAP1c contributes towards the functionality of the enzyme presumably by regulating active site residues through "action-at-a-distance" mechanism and we for the first time are reporting this unique function of the enzyme.