bluuebunny/crossref_metadata_2025 huggingface dataset:
NUMERICAL INVESTIGATION OF THE INTERACTION MECHANISM OF TWO BUBBLES
Authors: WANG HAN , ZHANG ZHEN-YU , YANG YONG-MING , ZHANG HUI-SHENG
Published: February 2010

In the frame of inviscid and incompressible fluids without taking into consideration of surface tension effects, the axisymmetric evolution of two buoyancy-driven bubbles in an infinite and initially stationary liquid are investigated numerically by VOF method. The numerical experiments are performed for two bubbles with same size, with the following one being half of the leading one, and with the leading one being half of the following one, and for different bubble distances. The ratio of gas density to liquid density is 0.001. It is found by numerical experiment that when the distance between the two bubbles is greater than or equal to one and half of the bigger bubble radius, the interaction is very weak and the two bubbles evolute like isolated ones rising in an infinite liquid. When the two bubbles come closer, the leading bubble itself evolutes like an isolated one rising in an infinite liquid. However, due to the smaller distance between the two bubbles, large pressure gradient forms in the liquid region near the top of the following bubble, which causes the upward stretch of its top part no matter what sizes of the two bubbles are. When the distance between the two bubbles is less than or equal to three-tenth of the bigger bubble radius, before the liquid jet behind the leading bubble fully developed, the top part of the following bubble has already been sucked into the leading one, giving a pear-like shape. Soon after the following bubble merges with the leading one. It is also found that for the smaller bubble, its transition to toroidal is always faster than that of the bigger one because of its smaller size. The mechanism of the above phenomena has been analyzed numerically.
DIFFERENTIATING THE PROTEIN CODING AND NONCODING RNA SEGMENTS OF DNA USING SHANNON ENTROPY
Authors: MAZAHERI P. , SHIRAZI A. H. , SAEEDI N. , REZA JAFARI G. , SAHIMI MUHAMMAD
Published: February 2010

The complexity of DNA sequences is evaluated in order to differentiate between protein-coding and noncoding RNA segments. The method is based on computing the Shannon entropy of the sequences. By comparing the entropy of the original sequence with that of its shuffled one, we identify the source of the difference between the two segments and their relative contributions to the sequence. To demonstrate the method, the DNA sequences of the bacterium Clostridium difficile 630(G + C = 29.1%) and Bdellovibrio bacteriovorus(G + C = 50.6%) are analyzed, which are representatives of bacteria with unbalanced and balanced nucleotide content, respectively. It is shown that in both bacteria, regardless of nucleotide content, ΔrS — the relative difference of the two entropies — is significantly greater in protein-coding regions, when compared with noncoding RNA segments.
MODELING THE SINOATRIAL NODE BY CELLULAR AUTOMATA WITH IRREGULAR TOPOLOGY
Authors: MAKOWIEC DANUTA
Published: February 2010

The role of irregularity in intercellular connections is studied in the first natural human pacemaker called the sinoatrial node by modeling with the Greenberg–Hastings cellular automata. Facts from modern physiology about the sinoatrial node drive modeling. Heterogeneity between cell connections is reproduced by a rewiring procedure applied to a square lattice. The Greenberg–Hastings rule, representing the intrinsic cellular dynamics, is modified to imitate self-excitation of each pacemaker cell. Moreover, interactions with nearest neighbors are changed to heterogeneous ones by enhancing horizontal connections. Stationary states of the modeled system emerge as self-organized robust oscillatory states. Since the sinoatrial node role relies on a single cell cyclic activity, properties of single cells are studied. It appears that the strength and diversity of cellular oscillations depend directly on properties of intrinsic cellular dynamics. But these oscillations also depend on the underlying topology. Moderate nonuniformity of intercellular connections are found vital for proper function of the sinoatrial node, namely, for producing robust oscillatory states that are able to respond effectively to the autonomic system control.
SCALING LIMITS FOR TIME-FRACTIONAL DIFFUSION-WAVE SYSTEMS WITH RANDOM INITIAL DATA
Authors: LIU GI-REN , SHIEH NARN-RUEIH
Published: February 2010

Let w (x, t) := (u, v)(x, t), x ∈ ℝ3, t > 0, be the ℝ2-valued spatial-temporal random field w = (u, v) arising from a certain two-equation system of time-fractional linear partial differential equations of reaction-diffusion-wave type, with given random initial data u(x,0), ut(x,0), and v(x,0), vt(x,0). We discuss the scaling limit, under proper homogenization and renormalization, of w(x,t), subject to suitable assumptions on the random initial conditions. Since the component fields u,v depend on the interactions present within the system, we employ a certain stochastic decoupling method to tackle this component dependence. The work shows, in particular, the various non-Gaussian scenarios proposed in [4, 13, 17] and the references therein, for the single diffusion type equations, in classical or in fractional time/space derivatives, can be studied for the two-equation system, in a significant way.
FRACTIONAL LÉVY PROCESSES AND NOISES ON GEL′FAND TRIPLE
Authors: HUANG ZHIYUAN , LÜ XUEBIN , WAN JIANPING
Published: February 2010

In this paper, we construct a class of infinitely divisible distributions on Gel′fand triple. Based on this construction, we define Lévy processes on Gel′fand triple and give their Lévy–Itô decompositions. Then, we construct the general Lévy white noises on Gel′fand triple. By using the Riemann–Liouville fractional integral method, we define the general fractional Lévy noises on Gel′fand triple and investigate their distribution properties.
CDK inhibitor p21 is prosurvival in adriamycin-induced podocyte injury, in vitro and in vivo
Authors: Marshall Caroline B. , Krofft Ron D. , Pippin Jeffrey W. , Shankland Stuart J.
Published: February 2010

In response to injury, the highly specialized and terminally differentiated glomerular visceral epithelial cell, or podocyte, may undergo several cell fates, including dedifferentiation and proliferation, persistent cell cycle arrest, hypertrophy, apoptosis, or necrosis. Common to these potential outcomes of injury is their ultimate regulation at the level of the cell cycle. There is now a large body of literature confirming the importance of cell cycle regulatory proteins in the cellular response to injury. Although CDK inhibitor p21 levels increase in podocytes following injury, the role of p21 is unclear in focal segmental glomerulosclerosis (FSGS), in part because its function depends heavily on the cytotoxic stimulus and the cellular context. Adriamycin (ADR) is a podocyte toxin used to induce experimental FSGS. The purpose of this study was to define the role of p21 in ADR-induced podocyte injury. BALB/c mice, a strain carrying the recessive ADR susceptibility gene, were backcrossed against c57B6 p21−/− mice to yield a 12th generation BALB/c p21−/− strain. Experimental FSGS was induced by injection of ADR 12 mg/kg × 2 doses ( n = 8/group), with mice killed at 1, 2, 8, and 11 wk. Diseased p21−/− mice demonstrated worse albuminuria, more widespread glomerulosclerosis, and higher blood urea nitrogen compared with diseased p21+/+ mice. In diseased p21−/− mice vs. p21+/+ mice, apoptosis [measured by TdT-mediated dUTP nick end labeling (TUNEL) assay] was increased, and podocyte number (measured by WT-1 immunostaining) was decreased. To validate these findings in vitro, we utilized differentiated mouse podocytes, p21−/− and p21+/+, exposed to 0.125 μg/ml ADR. Apoptosis, measured by Hoechst 33342 staining and TUNEL assay, was greater in cultured p21−/− podocytes compared with p21+/+ podocytes. Reconstitution of p21 via retroviral transfection rescued the p21−/− podocytes from apoptosis. We conclude that p21 is prosurvival in the podocyte's response to ADR-induced injury. Ongoing studies are defining the mechanisms of this protective effect as it relates to DNA damage and apoptosis.
Dehydration-induced increase in aquaporin-2 protein abundance is blocked by nonsteroidal anti-inflammatory drugs
Authors: Baggaley Erin , Nielsen Søren , Marples David
Published: February 2010

It is now well established that the antidiuretic response to vasopressin is modulated by changes in aquaporin-2 (AQP2) expression in response to hydration status. While vasopressin itself is one signal driving expression, other signals also play a part. In this study, we planned to investigate whether prostaglandins, known to modulate AQP2 trafficking, may play a role in this process. Male Wistar rats were kept in metabolic cages, with either free access to water and food, or were given 15 g of food gelled with water, such that they were fluid restricted or fluid loaded. The effects of oral administration of two structurally different NSAIDs, indomethacin and ibuprofen, and a COX-2-selective NSAID, meloxicam, on urine output and AQP2 expression were investigated in kidneys removed under terminal anesthesia. All the NSAIDs decreased AQP2 expression significantly in water-restricted rats but did not significantly alter PGE excretion. In water-loaded rats, the effects were less marked, and meloxicam had no significant effect. Consistent with this, ibuprofen prevented the increase in AQP2 expression seen in response to dehydration. These results demonstrate that NSAIDs decrease AQP2 protein abundance, particularly during adaptation during dehydration. This may be of particular significance in older and critically ill patients, who are prone to dehydration.
Wegener Granulomatosis Revealed by Pleural Effusion
Authors: Toffart Anne-Claire , Arbib François , Lantuejoul Sylvie , Roux Jean-François , Bland Vincent , Ferretti Gilbert , Diab Samia
Published: February 2010

Pulmonary signs are common in Wegener's granulomatosis (WG). However, an initial presentation including pleural effusion has not been described. We describe a case of WG in which pleural effusion was the first clinical manifestation. A 45-year-old man with dorsal pain presented with pleural thickening and effusion, and a visible nodule on a thoracic scan. A dense chronic inflammatory infiltrate was obtained by pleural biopsy and an open lung biopsy revealed necrotizing granulomatous vasculitis. Serologies were positive for antineutrophil cytoplasmic antibodies and antiproteinase 3 antibodies. A diagnosis of WG was conducted and the patient was started on cyclophosphamide and methylprednisolone as an initial treatment, with a favorable evolution. Although pleural effusion is rarely described in WG, this pathology must be considered in the presence of this clinical manifestation.
A Patient with an Unusual Cause Right Lower Quadrant Pain and Vomiting: Pyelonephritis of an Ectopic Right Kidney Masquerading as Acute Appendicitis
Authors: Lossius Michele N. , Araya Carlos E. , Henry Dwayne D. , Neiberger Richard E.
Published: February 2010

An adolescent female presented with one day of abdominal pain and clinical findings of acute appendicitis. CT scan revealed an ectopic right kidney with changes of acute pyelonephritis. This paper underscores the importance of imaging the right pelvis prior to surgical intervention in suspected cases of acute appendicitis in children.
Carbon Flux of Down Woody Materials in Forests of the North Central United States
Authors: Woodall C. W.
Published: February 2010

Across large scales, the carbon (C) flux of down woody material (DWM) detrital pools has largely been simulated based on forest stand attributes (e.g., stand age and forest type). The annual change in forest DWM C stocks and other attributes (e.g., size and decay class changes) was assessed using a forest inventory in the north central United States to provide an empirical assessment of strategic-scale DWM C flux. Using DWM inventory data from the USDA Forest Service's Forest Inventory and Analysis program, DWM C stocks were found to be relatively static across the study region with an annual flux rate not statistically different from zero. Mean C flux rates across the study area were 0.25, 0.12, 0.01, and 0.04 (Mg/ha/yr) for standing live trees, standing dead trees, coarse woody debris, and fine woody debris, respectively. Flux rates varied in their both magnitude and status (emission/sequestration) by forest types, latitude, and DWM component size. Given the complex dynamics of DWM C flux, early implementation of inventory remeasurement, and relatively low sample size, numerous future research directions are suggested.
Moderate or Supranormal Folic Acid Supplementation Does Not Exert a Protective Effect for Homocysteinemia and Methylation Markers in Growing Rats
Authors: Partearroyo T. , Úbeda N. , Alonso-Aperte E. , Varela-Moreiras G.
Published: February 2010

Background/Aims: Folic acid (FA) deficiency/supplementation effects seem to be dependent on age group and/or physiological status. The aim was to evaluate changes associated with rapid growth in relation to methionine metabolism in rats. Methods: Four groups (n = 10 each) of male Sprague Dawley rats (5 weeks old) were on diets that varied in their FA content: 0 mg FA/kg diet (deficient), 2 mg FA/kg diet (control), 8 mg FA/kg diet (moderate supplementation), 40 mg FA/kg diet (supranormal supplementation). Animals were fed ad libitum for 30 days. Biomarkers of methionine metabolism and antioxidant status were evaluated. Results: Serum total homocysteine concentration increased (p < 0.01) in FA deficient animals, with no differences between the supplemented groups. The hepatic ‘methylation ratio’ (S-adenosylmethionine/S-adenosylhomocysteine) of the FA content groups reached similar values, which were significantly higher compared to the deficient group. The brain ‘methylation ratio’, however, remained unmodified independently of FA content in the diet. FA deficiency induced hepatic DNA hypomethylation, and supranormal FA supplementation exerted the most protective effect (p < 0.01). Serum folate levels increased according to FA dietary level, whereas no differences were seen for vitamin B12 and vitamin B6. Conclusions: FA deficiency compromises methionine metabolism whereas supplementation does not show an additional positive effect compared to the control diet in growing animals.
Suicide in Different Cultures: A Thematic Comparison of Suicide Notes From Turkey and the United States
Authors: Leenaars Antoon A. , Sayin Aslıhan , Candansayar Selçuk , Leenaars Lindsey , Akar Taner , Demirel Birol
Published: February 2010

Suicide is a global concern, hence, cross-cultural research ought to be central; yet, there is a paucity of cross-cultural study in suicidology. A thematic or theoretical-conceptual analysis of 60 suicide notes drawn from Turkey and the United States, matched for age and sex, was undertaken, based on Leenaars’s empirical-based multidimensional model of suicide. The results suggested that there were more culturally common factors than specific differences; yet, not consistent with previous cross-cultural studies of suicide notes, differences emerged in Turkey notes expressing more indirect and veiled communications (indirect expressions). Specifically, Turkish notes expressed that there may be more reasons to the act than the person writes. It was concluded that the model may be applicable to suicide in both countries, but also much greater cross-cultural study is warranted on specific cultural risk factors. A question raised is whether the findings are related to collectivism versus individualism.
Culture and Interpersonal Conflict Resolution Styles: Role of Acculturation
Authors: Kim-Jo Tina , Benet-Martínez Verónica , Ozer Daniel J.
Published: February 2010

This study explored the role of acculturation and bicultural identity processes in the interpersonal conflict resolution preferences of monoculturals (Koreans and European Americans) and biculturals (Korean Americans). Koreans and European Americans differed in their conflict resolution styles in a manner congruent with individualism-collectivism theory. Korean Americans displayed a complex bicultural pattern of conflict resolution: They endorsed “competing” (a traditionally individualistic style) more than Koreans and similar to European Americans, while also endorsing “avoidance” (a traditionally collectivistic style) more than both European Americans and Koreans. The authors discuss the results in light of biculturalism and cultural encapsulation theories.
Properties of Natural Rubber Filled with Ultra Fine Acrylate Rubber Powder
Authors: Sae-Oui Pongdhorn , Sirisinha Chakrit , Hatthapanit Kannika
Published: February 2010

Properties of natural rubber (NR) filled with various loadings of ultra-fine vulcanized acrylate rubber powder (ACMP) were investigated. ACMP loading was varied from 0 to 20 phr and, after compounding, the compound properties were determined. Results reveal that increasing ACMP loading leads to improved processability, as evidenced by the reduction of both mixing energy and Mooney viscosity. ACMP, however, has negative effect on cure, that is, both scorch time and optimum cure time are prolonged while the state of cure is reduced with increasing ACMP loading. Due to the reinforcing effect of the fine ACMP particles, both modulus and hardness are found to increase consecutively with increasing ACMP loading. The tensile strength is also found to improve with increasing ACMP loading up to 10 phr. However, due to the cure retardation effect and the high thermoplastic nature, the presence of ACMP causes deterioration of elasticity. As ACMP is highly polar and fully saturated, the addition of ACMP enhances the resistance to oil and thermal aging of the NR vulcanizate. Significant improvement of thermal aging resistance is found when 10 phr or more of ACMP is added.
The education of racial perception
Authors: Monahan Michael
Published: February 2010

This article argues for the practice of the ‘education of racial perception’ as a critical component of any struggle against racial oppression (and for a liberated humanity generally). Taking the phenomenological ontology suggested by Linda Alcoff’s recent book Visible Identities, I argue that the project of educating our racial perception is a way to critically assess the way in which our perception of race both conditions and is conditioned by a racialized social world. By learning more about and ultimately challenging this relation we affirm our responsibility and agency in the face of an oppressive status quo.
The Effects of Troops to Teachers on Student Achievement: One State’s Study
Authors: Nunnery John , Kaplan Leslie , Owings William A. , Pribesh S.
Published: February 2010

This study examined approximately 6,500 Florida students’ reading and mathematics performance when taught by a sample of teachers who obtained their teaching credentials through the Troops to Teachers program. Results indicated that students served by Troops teachers performed about equally well in reading and achieved a small but statistically significant advantage in mathematics when compared with all teachers but achieved substantially and statistically significantly higher in both reading and mathematics when compared with teachers matched by subject and teaching experience.
Reorganizing Leaders’ Time: Does It Create Better Schools for Students?
Authors: Walker Jan
Published: February 2010

Effective schools research gave birth to a new role for principals: instructional leader. Recent studies have suggested the relationship between strong school instructional leadership and higher student achievement. Skeptics question whether the principal’s job is realistic and reasonable, with its emphasis on instructional leadership, multiple managerial responsibilities, and conflicting time demands. A more crucial question is, can the job allow the principal more time for instructional pursuits to provide greater impact on student learning? The answer to which this article explores.
Differences in Depression, Posttraumatic Stress Disorder, and Lifetime Trauma Exposure in Formerly Abused Women With Mild Versus Moderate to Severe Chronic Pain
Authors: Humphreys Janice , Cooper Bruce A. , Miaskowski Christine
Published: February 2010

Although associations between intimate partner violence, chronic pain, depression, posttraumatic stress disorder (PTSD), and lifetime trauma exposure are well known, previous studies are limited by their recruitment of women from shelters. These relationships were explored with a community-based sample of formerly abused women ( N = 84). Seventy-seven percent of women reported pain of >" xbd="604" xhg="581" ybd="1721" yhg="1685"/>3 months duration, and 75% had moderate to severe pain. Based on logistic regression analysis, women with moderate to severe chronic pain were significantly less likely to be employed, had more depressive symptoms, and were in the abusive relationship longer than women in mild chronic pain. Both pain severity groups had equally high levels of depressive and PTSD symptoms and multiple trauma exposures. Findings document the persistence of significant symptomatology in formerly abused women.
Preliminary Construction of a Service Provider—Informed Domestic Violence Research Agenda
Authors: Murray Christine E. , Welch Metoka L.
Published: February 2010

This article presents the results of a statewide survey of domestic violence (DV) service providers that focused on the needs, background characteristics, and opinions of service providers related to research. The survey included an examination of service providers’ motivation for working in the field, research background and training, and perceptions of research as well as the topics they believe are important for researchers to study, the resources they consult to learn about DV, and their suggestions to help researchers learn more about the nature of their work. The results are integrated into a preliminary agenda for future DV research that accounts for the needs and insight of service providers.
Family policy and fertility: fathers’ and mothers’ use of parental leave and continued childbearing in Norway and Sweden
Authors: Duvander Ann-Zofie , Lappegård Trude , Andersson Gunnar
Published: February 2010

In the Nordic countries, gender equality is an explicit policy goal. For example, Norway and Sweden both offer paid parental leave for approximately one year following childbirth with earnings-related benefits and with certain periods reserved exclusively for the father. In this study, we examine the relationship between fathers’ and mothers’ use of parental leave and continued childbearing among couples in Norway and Sweden. The two countries offer largely similar family policies, but differ concerning family policy context. While Sweden has a consistent policy concerning gender relations, Norway has more ambiguous family policies giving incentives both to gender equality and childrearing at home. Our study is based on event-history analyses of Nordic register data and shows that fathers’ parental leave use is positively associated with continued childbearing in both Norway and Sweden, for both one- and two-child couples. The association is stronger in Norway. For two-child families, a long period of leave for the mother is positively associated with a third birth. It seems as if the two-child family is highly compatible with the combination of work and family life, but that in families who choose to have more children, the mother often seems to have a weaker work orientation.
Non-Linear Elastic Bodies Exhibiting Limiting Small Strain
Authors: Rajagopal K.R.
Published: February 2010

In this paper we develop a constitutive model for describing the elastic response of solids that does not stem from either classical Cauchy or Green elasticity. In contrast to the classical theory, we show that it is possible to obtain a constitutive model wherein the linearized strain is related to the stress in a non-linear manner. The specific choice that we make allows for the stress to be arbitrarily large while the strain remains small (consistent with the assumption used in the linearization of the non-linear strain) or below some limiting value. Such models are worth investigating in detail as they have relevance to problems involving cracks as well as other problems wherein one finds strain singularities within the classical theory of linearized elasticity, and to models that exhibit limited stretch.
Pharmacist Approach to Geriatrics
Authors: Hutchison Lisa C.
Published: February 2010

Pharmacists have traditionally focused on the appropriate use of medications to enhance the functional status of the elderly patient. However, in the proper provision of pharmaceutical care, the influence of lifestyle factors on the use and misuse of medications cannot be ignored. The pharmacist collaborates with other members of the health care team to ensure that drugs are dosed according to known changes occurring with age such as pharmacokinetic and pharmacodynamic alterations. Also, medications that may decrease cognitive function, impair gait/balance, or reduce sensory stimulation must be avoided. The appropriate use of medications can improve the functional status and reduce morbidity in the elderly patient, and drug adherence issues should be addressed to ensure that the elderly patient can receive the optimal benefit from his or her medication regimen. Pharmacists, in collaboration with physicians and other health care providers, can help to ensure that a comprehensive approach to patient care occurs, one that involves medications, diet, and exercise as it embraces the mind, body, and spirit.
Effect of hydrogen on microstructure evolution and tensile properties of TC21 alloy
Authors: Zhang X. M. , Zhao Y. Q. , Zeng W. D.
Published: February 2010

Hydrogen can be used as a temporary element to refine microstructure and improve workability of titanium alloys. In this article, the influence of hydrogen on the microstructure evolution and tensile properties of TC21 alloy is investigated. The microstructure observation reveals that the FCC hydrides δ precipitate firstly at the grainboundaries of primary α phases in TC21 alloy with hydrogen contents above 0·319 wt-. These hydrides which block the grains deformation reduce both the strength and ductility at room temperature. With increasing hydrogen contents, the elevated temperature strength decreases first and then increases, while the ductility behaves the contrary. These are resulted from the interaction of hydrogen induced softening and hardening.
Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms
Authors: Quintás-Cardama Alfonso , Vaddi Kris , Liu Phillip , Manshouri Taghi , Li Jun , Scherle Peggy A. , Caulder Eian , Wen Xiaoming , Li Yanlong , Waeltz Paul , Rupar Mark , Burn Timothy , Lo Yvonne , Kelley Jennifer , Covington Maryanne , Shepard Stacey , Rodgers James D. , Haley Patrick , Kantarjian Hagop , Fridman Jordan S. , Verstovsek Srdan
Published: February 2010

Constitutive JAK2 activation in hematopoietic cells by the JAK2V617F mutation recapitulates myeloproliferative neoplasm (MPN) phenotypes in mice, establishing JAK2 inhibition as a potential therapeutic strategy. Although most polycythemia vera patients carry the JAK2V617F mutation, half of those with essential thrombocythemia or primary myelofibrosis do not, suggesting alternative mechanisms for constitutive JAK-STAT signaling in MPNs. Most patients with primary myelofibrosis have elevated levels of JAK-dependent proinflammatory cytokines (eg, interleukin-6) consistent with our observation of JAK1 hyperactivation. Accordingly, we evaluated the effectiveness of selective JAK1/2 inhibition in experimental models relevant to MPNs and report on the effects of INCB018424, the first potent, selective, oral JAK1/JAK2 inhibitor to enter the clinic. INCB018424 inhibited interleukin-6 signaling (50% inhibitory concentration [IC50] = 281nM), and proliferation of JAK2V617F+ Ba/F3 cells (IC50 = 127nM). In primary cultures, INCB018424 preferentially suppressed erythroid progenitor colony formation from JAK2V617F+ polycythemia vera patients (IC50 = 67nM) versus healthy donors (IC50 > 400nM). In a mouse model of JAK2V617F+ MPN, oral INCB018424 markedly reduced splenomegaly and circulating levels of inflammatory cytokines, and preferentially eliminated neoplastic cells, resulting in significantly prolonged survival without myelosuppressive or immunosuppressive effects. Preliminary clinical results support these preclinical data and establish INCB018424 as a promising oral agent for the treatment of MPNs.
CNV Workshop: an integrated platform for high-throughput copy number variation discovery and clinical diagnostics
Authors: Gai Xiaowu , Perin Juan C , Murphy Kevin , O'Hara Ryan , D'arcy Monica , Wenocur Adam , Xie Hongbo M , Rappaport Eric F , Shaikh Tamim H , White Peter S
Published: February 2010

Background

Recent studies have shown that copy number variations (CNVs) are frequent in higher eukaryotes and associated with a substantial portion of inherited and acquired risk for various human diseases. The increasing availability of high-resolution genome surveillance platforms provides opportunity for rapidly assessing research and clinical samples for CNV content, as well as for determining the potential pathogenicity of identified variants. However, few informatics tools for accurate and efficient CNV detection and assessment currently exist.

Results

We developed a suite of software tools and resources (CNV Workshop) for automated, genome-wide CNV detection from a variety of SNP array platforms. CNV Workshop includes three major components: detection, annotation, and presentation of structural variants from genome array data. CNV detection utilizes a robust and genotype-specific extension of the Circular Binary Segmentation algorithm, and the use of additional detection algorithms is supported. Predicted CNVs are captured in a MySQL database that supports cohort-based projects and incorporates a secure user authentication layer and user/admin roles. To assist with determination of pathogenicity, detected CNVs are also annotated automatically for gene content, known disease loci, and gene-based literature references. Results are easily queried, sorted, filtered, and visualized via a web-based presentation layer that includes a GBrowse-based graphical representation of CNV content and relevant public data, integration with the UCSC Genome Browser, and tabular displays of genomic attributes for each CNV.

Conclusions

To our knowledge, CNV Workshop represents the first cohesive and convenient platform for detection, annotation, and assessment of the biological and clinical significance of structural variants. CNV Workshop has been successfully utilized for assessment of genomic variation in healthy individuals and disease cohorts and is an ideal platform for coordinating multiple associated projects.

Availability and Implementation

Available on the web at: http://sourceforge.net/projects/cnv
Cluster randomized trial in smoking cessation with intensive advice in diabetic patients in primary care. ITADI Study
Authors: Roig Lydia , Perez Santiago , Prieto Gemma , Martin Carlos , Advani Mamta , Armengol Angelina , Roura Pilar , Maria Manresa Josep , Briones Elena ,   ITADI Study Group
Published: February 2010

Background

It is a priority to achieve smoking cessation in diabetic smokers, given that this is a group of patients with elevated cardiovascular risk. Furthermore, tobacco has a multiplying effect on micro and macro vascular complications. Smoking abstinence rates increase as the intensity of the intervention, length of the intervention and number and diversity of contacts with the healthcare professional during the intervention increases. However, there are few published studies about smoking cessation in diabetics in primary care, a level of healthcare that plays an essential role in these patients. Therefore, the aim of the present study is to evaluate the effectiveness of an intensive smoking cessation intervention in diabetic patients in primary care.

Methods/Design

Cluster randomized trial, controlled and multicentric. Randomization unit: Primary Care Team. Study population: 546 diabetic smokers older than 14 years of age whose disease is controlled by one of the primary care teams in the study. Outcome Measures: Continuous tobacco abstinence (a person who has not smoked for at least six months and with a CO level of less than 6 ppm measured by a cooximeter) , evolution in the Prochaska and DiClemente's Transtheoretical Model of Change, number of cigarettes/day, length of the visit. Point of assessment: one- year post- inclusion in the study. Intervention: Brief motivational interview for diabetic smokers at the pre-contemplation and contemplation stage, intensive motivational interview with pharmacotherapy for diabetic smokers in the preparation-action stage and reinforcing intevention in the maintenance stage. Statistical Analysis: A descriptive analysis of all variables will be done, as well as a multilevel logistic regression and a Poisson regression. All analyses will be done with an intention to treatment basis and will be fitted for potential confounding factors and variables of clinical importance. Statistical packages: SPSS15, STATA10 y HLM6.

Discussion

The present study will try to describe the profile of a diabetic smoker who receives the most benefit from an intensive intervention in primary care. The results will be useful for primary care professionals in their usual clinical practice.

Trial Registration

Clinical Trials.gov Identifier: NCT00954967
Compliance with a three-day course of artesunate-mefloquine combination and baseline anti-malarial treatment in an area of Thailand with highly multidrug resistant falciparum malaria
Authors: Congpuong Kanungnit , Bualombai Pongwit , Banmairuroi Vick , Na-Bangchang Kesara
Published: February 2010

Background

Artemisinin-based combination therapy (ACT) is presently recommended by the World Health Organization as first-line treatment for uncomplicated Plasmodium falciparum malaria in several countries, as a mean of prolonging the effectiveness of first-line malaria treatment regimens. A three-day course of artesunate-mefloquine (4 mg/kg body weight once daily for three consecutive days, plus 15 and 10 mg/kg body weight mefloquine on the first and second days) has been adopted by Malaria Control Programme of Thailand as first-line treatment for uncomplicated falciparum malaria all over the country since 2008. The gametocytocydal anti-malarial drug primaquine is administered at the dose of 30 mg (0.6 mg/kg) on the last day. The aim of the present study was to assess patient compliance of this combination regimen when applied to field condition.

Methods

A total of 240 patients (196 males and 44 females) who were attending the malaria clinics in Mae-Sot, Tak Province and presenting with symptomatic acute uncomplicated falciparum malaria, with no reappearance of Plasmodium vivax parasitaemia during follow-up were included into the study. The first dose of the treatment was given to the patients under direct supervision. All patients were given the medication for self-treatment at home and were requested to come back for follow-up on day 3 of the initial treatment. Baseline (day 0) and day 3 whole blood mefloquine and plasma primaquine concentrations were determined by high performance liquid chromatography.

Results

Two patients had recrudescence on days 28 and 35. The Kaplan-Meier estimate of the 42-day efficacy rate of this combination regimen was 99.2% (238/240). Based on whole blood mefloquine and plasma primaquine concentrations on day 3 of the initial treatment, compliance with mefloquine and primaquine in this three-day artesunate-mefloquine combination regimen were 96.3% (207/215), and 98.5% (197/200), respectively. Baseline mefloquine and primaquine levels were observed in 24 and 16% of the patients.

Conclusion

The current first-line treatment and a three-day combination regimen of artesunate-mefloquine provides excellent patient compliance with good efficacy and tolerability in the treatment of highly multidrug resistance falciparum malaria. Previous treatment with mefloquine and primaquine were common in this area.
Unscheduled expression of CDC25B in S-phase leads to replicative stress and DNA damage
Authors: Bugler Béatrix , Schmitt Estelle , Aressy Bernadette , Ducommun Bernard
Published: February 2010

Background

CDC25B phosphatase is a cell cycle regulator that plays a critical role in checkpoint control. Up-regulation of CDC25B expression has been documented in a variety of human cancers, however, the relationships with the alteration of the molecular mechanisms that lead to oncogenesis still remain unclear. To address this issue we have investigated, in model cell lines, the consequences of unscheduled and elevated CDC25B levels.

Results

We report that increased CDC25B expression leads to DNA damage in the absence of genotoxic treatment. H2AX phosphorylation is detected in S-phase cells and requires active replication. We also report that CDC25B expression impairs DNA replication and results in an increased recruitment of the CDC45 replication factor onto chromatin. Finally, we observed chromosomal aberrations that are also enhanced upon CDC25B expression.

Conclusion

Overall, our results demonstrate that a moderate and unscheduled increase in CDC25B level, as observed in a number of human tumours, is sufficient to overcome the S-phase checkpoint efficiency thus leading to replicative stress and genomic instability.
Roles for common MLL/COMPASS subunits and the 19S proteasome in regulating CIITA pIV and MHC class II gene expression and promoter methylation
Authors: Koues Olivia I , Mehta Ninad T , Truax Agnieszka D , Dudley R Kyle , Brooks Jeanne K , Greer Susanna F
Published: February 2010

Background

Studies indicate that the 19S proteasome contributes to chromatin reorganization, independent of the role the proteasome plays in protein degradation. We have previously shown that components of the 19S proteasome are crucial for regulating inducible histone activation events in mammalian cells. The 19S ATPase Sug1 binds to histone-remodeling enzymes, and in the absence of Sug1, a subset of activating epigenetic modifications including histone H3 acetylation, H3 lysine 4 trimethylation and H3 arginine 17 dimethylation are inhibited at cytokine-inducible major histocompatibilty complex (MHC)-II and class II transactivator (CIITA) promoters, implicating Sug1 in events required to initiate mammalian transcription.

Results

Our previous studies indicate that H3 lysine 4 trimethylation at cytokine-inducible MHC-II and CIITA promoters is dependent on proteolytic-independent functions of 19S ATPases. In this report, we show that multiple common subunits of the mixed lineage leukemia (MLL)/complex of proteins associated with Set I (COMPASS) complexes bind to the inducible MHC-II and CIITA promoters; that overexpressing a single common MLL/COMPASS subunit significantly enhances promoter activity and MHC-IIHLA-DRAexpression; and that these common subunits are important for H3 lysine 4 trimethylation at MHC-II and CIITA promoters. In addition, we show that H3 lysine 27 trimethylation, which is inversely correlated with H3 lysine 4 trimethylation, is significantly elevated in the presence of diminished 19S ATPase Sug1.

Conclusion

Taken together, these experiments suggest that the 19S proteasome plays a crucial role in the initial reorganization of events enabling the relaxation of the repressive chromatin structure surrounding inducible promoters.
Insulin-treated diabetes is not associated with increased mortality in critically ill patients
Authors: Vincent Jean-Louis , Preiser Jean-Charles , Sprung Charles L , Moreno Rui , Sakr Yasser
Published: February 2010

Introduction

This was a planned substudy from the European observational Sepsis Occurrence in Acutely ill Patients (SOAP) study to investigate the possible impact of insulin-treated diabetes on morbidity and mortality in ICU patients.

Methods

The SOAP study was a cohort, multicenter, observational study which included data from all adult patients admitted to one of 198 participating ICUs from 24 European countries during the study period. For this substudy, patients were classified according to whether or not they had a known diagnosis of insulin-treated diabetes mellitus. Outcome measures included the degree of organ dysfunction/failure as assessed by the sequential organ failure assessment (SOFA) score, the occurrence of sepsis syndromes and organ failure in the ICU, hospital and ICU length of stay, and all cause hospital and ICU mortality.

Results

Of the 3147 patients included in the SOAP study, 226 (7.2%) had previously diagnosed insulin-treated diabetes mellitus. On admission, patients with insulin-treated diabetes were older, sicker, as reflected by higher simplified acute physiology system II (SAPS II) and SOFA scores, and more likely to be receiving hemodialysis than the other patients. During the ICU stay, more patients with insulin-treated diabetes required renal replacement therapy (hemodialysis or hemofiltration) than other patients. There were no significant differences in ICU or hospital lengths of stay or in ICU or hospital mortality between patients with or without insulin-treated diabetes. Using a Cox proportional hazards regression analysis with hospital mortality censored at 28-days as the dependent factor, insulin-treated diabetes was not an independent predictor of mortality.

Conclusions

Even though patients with a history of insulin-treated diabetes are more severely ill and more likely to have renal failure, insulin-treated diabetes is not associated with increased mortality in ICU patients.
HIV DNA in circulating monocytes as a mechanism to dementia and other HIV complications
Authors: Valcour Victor G , Shiramizu Bruce T , Shikuma Cecilia M
Published: February 2010

Failure of potent antiretroviral therapy to eradicate this HIV reservoir may be responsible for the continued occurence of dementia in HIV-infected individuals.

It is broadly accepted that HIV DNA in lymphoid and myeloid cells persists despite combination antiretroviral therapy. Recognized as the Achilles heel to HIV eradication, the role of these peripheral reservoirs in HIV morbidity is less well developed. The burden of HIV DNA in peripheral mononuclear cells is linked to HIV disease outcomes such as time to AIDS diagnosis, survival, and CD4 T-lymphocyte counts. Monocytes are a minor HIV DNA reservoir, and the burden of HIV DNA in these cells appears to be linked to dementia, suggesting that residual infection in this subset is linked to tissue-related HIV complications. Since monocytes are likely involved in trafficking virus to the brain, there is a strong mechanistic link underlying this discovery. Herein, we summarize our current understanding of monocyte HIV DNA and central nervous system dysfunction in humans. We present a model to understand these relationships and suggest possible treatment approaches to be tested.
Intestinal and Hepatic Cholesterol Carriers in Diabetic Psammomys obesus
Authors: Levy Emile , Lalonde Geneviève , Delvin Edgard , Elchebly Mounib , Précourt Louis P. , Seidah Nabil G. , Spahis Schohraya , Rabasa-Lhoret Rémi , Ziv Ehud
Published: February 2010

Insulin resistance and type 2 diabetes (T2D) are characterized by hyperlipidemia. The aim of the present study was to elucidate whether T2D contributes to abnormal cholesterol (CHOL) homeostasis. Experiments were carried out in the small intestine and liver of Psammomys obesus, a model of nutritionally induced T2D. Our results show that diabetic animals exhibited a lower intestinal CHOL uptake, which was associated with a decrease in 1) the gene and protein expression of Niemann-Pick C1 like 1 that plays a pivotal role in CHOL incorporation in the enterocytes; and 2) mRNA of ATP-binding cassette transporters (ABC)A1 that mediates CHOL efflux from intestinal cells to apolipoprotein A-I and high-density lipoprotein. No changes were observed in the other intestinal transporters scavenger receptor-class B type I (SR-BI) and annexin 2. On the other hand, in diabetic animals, a significant mRNA decrease was noticed in intestinal ABCG5 and ABCG8 responsible for the secretion of absorbed CHOL back into the lumen. Furthermore, jejunal PCSK9 protein was diminished and low-density lipoprotein receptor was raised, along with a significant down-regulation in jejunal 3-hydroxy-3-methylglutaryl-coenzyme A reductase in P. obesus with T2D. Finally, among the transcription factors tested, only an increase in liver X receptors α and a decrease in peroxisome proliferator-activated receptors δ/β mRNAs were detected in the intestine. In the liver, there was 1) an augmentation in the protein mass of Niemann-Pick C1 like 1, SR-BI, and annexin 2; 2) an up-regulation of SR-BI mRNA; 3) a fall in ABCG8 protein content as well as in ABCG5 and ABCA1 mRNA; and 4) an augmentation in liver X receptors α and peroxisome proliferator-activated receptors β/δ mRNA, together with a drop in sterol regulatory element binding protein-2 protein. Our findings show that the development in P. obesus with T2D modifies the whole intraenterocyte and hepatocyte machinery responsible for CHOL homeostasis.
The prophylactic effects of platelet-leucocyte gel in osteomyelitis
Authors: Jia W.-T. , Zhang C.-Q. , Wang J.-Q. , Feng Y. , Ai Z.-S.
Published: February 2010

Platelet-leucocyte gel (PLG), a new biotechnological blood product, has hitherto been used primarily to treat chronic ulcers and to promote soft-tissue and bone regeneration in a wide range of medical fields. In this study, the antimicrobial efficacy of PLG against Staphylococcus aureus (ATCC 25923) was investigated in a rabbit model of osteomyelitis. Autologous PLG was injected into the tibial canal after inoculation with Staph. aureus. The prophylactic efficacy of PLG was evaluated by microbiological, radiological and histological examination. Animal groups included a treatment group that received systemic cefazolin and a control group that received no treatment.

Treatment with PLG or cefazolin significantly reduced radiological and histological severity scores compared to the control group. This result was confirmed by a significant reduction in the infection rate and the number of viable bacteria. Although not comparable to cefazolin, PLG exhibited antimicrobial efficacy in vivo and therefore represents a novel strategy to prevent bone infection in humans.