bluuebunny/crossref_metadata_2025 huggingface dataset:
Collections of Simultaneously Altered Genes as Biomarkers of Cancer Cell Drug Response
Authors: Masica David L. , Karchin Rachel
Published: January 2013

Computational analysis of cancer pharmacogenomics data has resulted in biomarkers predictive of drug response, but the majority of response is not captured by current methods. Methods typically select single biomarkers or groups of related biomarkers but do not account for response that is strictly dependent on many simultaneous genetic alterations. This shortcoming reflects the combinatorics and multiple-testing problem associated with many-body biologic interactions. We developed a novel approach, Multivariate Organization of Combinatorial Alterations (MOCA), to partially address these challenges. Extending on previous work that accounts for pairwise interactions, the approach rapidly combines many genomic alterations into biomarkers of drug response, using Boolean set operations coupled with optimization; in this framework, the union, intersection, and difference Boolean set operations are proxies of molecular redundancy, synergy, and resistance, respectively. The algorithm is fast, broadly applicable to cancer genomics data, is of immediate use for prioritizing cancer pharmacogenomics experiments, and recovers known clinical findings without bias. Furthermore, the results presented here connect many important, previously isolated observations. Cancer Res; 73(6); 1699–708. ©2012 AACR.
Measles Virus Vaccine–Infected Tumor Cells Induce Tumor Antigen Cross-Presentation by Human Plasmacytoid Dendritic Cells
Authors: Guillerme Jean-Baptiste , Boisgerault Nicolas , Roulois David , Ménager Jérémie , Combredet Chantal , Tangy Frédéric , Fonteneau Jean-François , Gregoire Marc
Published: January 2013

Purpose: Plasmacytoid dendritic cells (pDC) are antigen-presenting cells specialized in antiviral response. The measles virus vaccine is proposed as an antitumor agent to target and specifically kill tumor cells without infecting healthy cells.

Experimental Design: Here, we investigated, in vitro, the effects of measles virus vaccine–infected tumor cells on the phenotype and functions of human pDC. We studied maturation and tumor antigen cross-presentation by pDC, exposed either to the virus alone, or to measles virus vaccine–infected or UV-irradiated tumor cells.

Results: We found that only measles virus vaccine–infected cells induced pDC maturation with a strong production of IFN-α, whereas UV-irradiated tumor cells were unable to activate pDC. This IFN-α production was triggered by the interaction of measles virus vaccine single-stranded RNA (ssRNA) with TLR7. We observed that measles virus vaccine–infected tumor cells were phagocytosed by pDC. Interestingly, we showed cross-presentation of the tumor antigen NYESO-1 to a specific CD8+ T-cell clone when pDC were cocultured with measles virus vaccine–infected tumor cells, whereas pDC were unable to cross-present NYESO-1 after coculture with UV-irradiated tumor cells.

Conclusions: Altogether, our results suggest that the use of measles virus vaccine in antitumor virotherapy induces immunogenic tumor cell death, allowing pDC to mature, produce high amounts of IFN-α, and cross-present tumor antigen, thus representing a mode of recruiting these antigen-presenting cells in the immune response. Clin Cancer Res; 19(5); 1147–58. ©2012 AACR.
Phase I Study of Dovitinib (TKI258), an Oral FGFR, VEGFR, and PDGFR Inhibitor, in Advanced or Metastatic Renal Cell Carcinoma
Authors: Angevin Eric , Lopez-Martin Jose A. , Lin Chia-Chi , Gschwend Jürgen E. , Harzstark Andrea , Castellano Daniel , Soria Jean-Charles , Sen Paramita , Chang Julie , Shi Michael , Kay Andrea , Escudier Bernard
Published: January 2013

Purpose: Signaling through the fibroblast growth factor (FGF) pathway may account for tumor resistance to antiangiogenic therapies targeting the VEGF pathway. Here, dovitinib (TKI258), a potent oral inhibitor of FGF receptor, VEGF receptor (VEGFR), and platelet-derived growth factor receptor tyrosine kinases, is studied in a dose escalation trial.

Experimental Design: Patients with advanced or metastatic renal cell carcinoma (RCC) with predominant clear cell histology were treated with oral dovitinib 500 or 600 mg/day (5-days-on/2-days-off schedule).

Results: Twenty heavily pretreated patients (median 3 prior regimens) were enrolled, with 16, 11, and 12 patients having previously received at least 1: VEGFR inhibitor, mTOR inhibitor, and immunotherapy, respectively. Fifteen and 5 patients were treated in 500- and 600-mg cohorts, respectively. Three patients experienced dose-limiting toxicities: grade 2 bradycardia (500 mg), grade 4 hypertensive crisis (600 mg), and grade 3 asthenia with grade 2 nausea and vomiting (600 mg). The most common adverse events related to dovitinib were nausea (75%), diarrhea (70%), vomiting (70%), and asthenia (50%), the majority of which were mild (grade 1 or 2), with grade 3 events 5% or less (except asthenia, 15%) and only one grade 4 event (hypertensive crisis). Two patients achieved a partial response (500 mg), and 12 patients had stable disease, including 2 patients with long lasting disease stabilizations (>1 year) in the 500-mg cohort.

Conclusions: Dovitinib was tolerable and showed antitumor activity at a maximum tolerated dose of 500 mg on a 5-days-on/2-days-off schedule in heavily pretreated RCC patients. Clin Cancer Res; 19(5); 1257–68. ©2012 AACR.
Differential and Better Response to Deep Brain Stimulation of Chorea Compared to Dystonia in Huntington’s Disease
Authors: Velez-Lago Frances M. , Thompson Amanda , Oyama Genko , Hardwick Angela , Sporrer Justin M. , Zeilman Pamela , Foote Kelly D. , Bowers Dawn , Ward Herbert E. , Sanchez-Ramos Juan , Okun Michael S.
Published: January 2013

Huntington’s disease (HD) is an autosomal dominant and progressive neurodegenerative syndrome characterized by motor, cognitive and psychiatric manifestations. Chorea and dystonia are features that may be troublesome to some patients and may potentially prove unresponsive to pharmacological treatments. There are several reports on the results of globus pallidus internus deep brain stimulation (DBS) surgery for HD. In these published cases, DBS was utilized mainly to treat disabling chorea. We report our experience with 2 HD cases treated with DBS. The cases illustrate a differential response with a better outcome in the choreic presentation compared to the dystonic presentation. Additionally, DBS worsened gait features in both cases.
Epidemiology of Mammalian Hepatitis E Virus Infection
Authors: Kaba Mamadou , Moal Valérie , Gérolami René , Colson Philippe
Published: January 2013

Mammalian hepatitis E virus (HEV), the etiological agent of hepatitis E in humans, is a recently discovered infectious agent. It was identified for the first time in 1983 using electron microscopy on a faecal specimen of a person infected with non-A, non-B enterically-transmitted hepatitis. Based on retrospective and prospective studies, HEV was long described as one of the leading causes of acute viral hepatitis in tropical and subtropical countries, whereas in developed countries hepatitis E was considered an imported disease from HEV hyperendemic countries. Data from studies conducted during the past decade have greatly shifted our knowledge on the epidemiology and clinical spectrum of HEV. Recently, it has been shown that contrary to previous beliefs, hepatitis E is also an endemic disease in several developed countries, particularly in Japan and in Europe, as evidenced by reports of high anti-HEV immunoglobulin G prevalence in healthy individuals and an increasing number of non-travel-related acute hepatitis E cases. Moreover, a porcine reservoir and growing evidence of zoonotic transmission have been reported in these countries. This review summarizes the current knowledge on the epidemiology and prevention of transmission of mammalian HEV.
Pathways of Infusate Loss during Convection-Enhanced Delivery into the Putamen Nucleus
Authors: Brady Martin L. , Raghavan Raghu , Alexander Andrew , Kubota Ken , Sillay Karl , Emborg Marina E.
Published: January 2013

Background: New strategies aiming to treat Parkinson’s disease, such as delivery of trophic factors via protein infusion or gene transfer, depend upon localized intracerebral infusion, mainly into the putamen nucleus. Convection-enhanced delivery (CED) has been proposed as a method to improve intracerebral distribution of therapies. Yet analysis of controversial results during the clinical translation of these strategies suggests that intracerebral misdistribution of infusate may have affected the outcomes by limiting the amount of treatment into the target region. Objectives: This study aimed to identify possible pathways of infusate loss and their relative impact in the success of targeted CED into the postcommissural ventral putamen nucleus. Methods: Thirteen adult macaque monkeys received intraputaminal CED infusions of 100 µl of 2.0 mM gadoteridol and bromophenol blue (0.16 mg/ml) solution at a rate of 1.0 µl/min under intraoperative magnetic resonance imaging (MRI) guidance. Quantitative maps of infusate concentration were computed at 10-min intervals throughout the procedure in a 3-Tesla MRI scanner. The fraction of tracer lost from the putamen as well as the path of loss were evaluated and quantified for each infusion. Results: All injections (total 22) were successfully placed in the ventral postcommissural putamen nucleus. Four major paths of infusate loss from the putamen were observed: overflow across putamen boundaries, perivascular flow along large blood vessels, backflow along the inserted catheter and catheter tract leakage into the vacated catheter tract upon catheter removal. Overflow loss was observed within the first 30 µl of infusion in all cases. Measurable tracer loss following the path of an artery out of the putamen was observed in 15 cases, and in 8 of these cases, the loss was greater than 10% of infusate. Backflow that exited the putamen was observed in 4 cases and led to large loss of infusate (80% in 1 case) into the corona radiata. Loss into the vacated catheter tract amounted only to a few microliters. Conclusions: Our analysis demonstrates that after controlling for targeting, catheter type, infusion rate and infusate, the main issues during surgical planning are the identification of appropriate infusate volume that matches the target area, as well as mapping the regional vasculature as it may become a pathway for infusate loss. Most importantly, these results underscore the significance of presurgical planning for catheter placement and infusion, and the value of imaging guidance to ensure targeting accuracy.
The Maximum Tolerated Dose of Gamma Radiation to the Optic Nerve during Gamma Knife Radiosurgery in an Animal Study
Authors: Deng Xingli , Yang Zhiyong , Liu Ruen , Yi Meiying , Lei Deqiang , Wang Zhi , Zhao Hongyang
Published: January 2013

Background: The safety of gamma knife radiosurgery should be considered when treating pituitary adenomas. Objectives: To determine the maximum tolerated dose of radiation delivered by gamma knife radiosurgery to optic nerves. Methods: An animal model designed to establish prolonged balloon compression of the optic chiasm and parasellar region was developed to mimic the optic nerve compression caused by pituitary adenomas. Twenty cats underwent surgery to place a balloon for compression effect and 20 cats in a sham operation group received microsurgery without any treatment. The effects of gamma knife irradiation at 10–13 Gy on normal (sham operation group) and compressed (optic nerve compression group) optic nerves were investigated by pattern visual evoked potential examination and histopathology. Results: Gamma knife radiosurgery at 10 Gy had almost no effect. At 11 Gy, P100 latency was significantly prolonged and P100 amplitude was significantly decreased in compressed optic nerves, but there was little change in the normal optic nerves. Doses of 11 Gy and higher induced significant electrophysiological variations and degeneration of the myelin sheath and axons in both normal and compressed optic nerves. Conclusions: Compressed optic nerves are more sensitive to gamma knife radiosurgery than normal optic nerves. The minimum dose of gamma knife radiosurgery that causes radiation injury in normal optic nerves is 12 Gy; however, the minimum dose is 11 Gy in compressed optic nerves.
New Hemodialysis Access System
Authors: Prosl Frank , Polaschegg Hans Dietrich
Published: January 2013

A new blood access system for hemodialysis (HD) addresses the major shortcomings of current accessing techniques and helps overcome patient adversity with available choices. The system uses new methods, devices and compositions comprising several novel elements: (1) totally implanted port, elementally simple in design, small and robust with improved safety features, (2) engineered transcutaneous tissue tract (TTT) to precisely guide a tubular conduit to engage the implanted port, (3) viscoelastic gel prophylaxis for internal passages and surface interfaces of the port and TTT, (4) the tool kit aligns the TTT with the port and initiates TTT formation at the time of port placement, (5) an integrated external bloodline circuit comprising the interface between the implanted port and HD machine which can be reused for several treatment sessions. The system provides bloodless, painless, and fail-safe connections with redundant sealing along the complete blood path. It is substantially more robust than current access options and more convenient to use. TTT construct is durable, permanently aligned and fixed to the port enabling non-compromised tissue integrity during access penetration. A bullet-pointed tubular assembly enters and passes through the TTT confining the tubular device to advance towards the port and entering it to engage a solid tactually sensed stop indicating the correct position. The system may be used within a few days of port placement. The access is unobtrusive and preserves patient self-image.
Inconclusive Evidence for or against Positive Antigen Selection in the Shaping of Human Immunoglobulin E Repertoires: A Call for New Approaches
Authors: Levin Mattias , Ohlin Mats
Published: January 2013

Background: The mechanisms driving the development of immunoglobulin E (IgE) antibody repertoires are a matter of debate. Alternatives to the classical view on antibody development, involving somatic mutation and antigen-driven selection of high-affinity variants in germinal centers, have been proposed. Methods: We have re-analyzed the pattern of mutations in previously isolated and characterized human clonally unrelated IgE-encoding transcripts using the validated focused binomial methodology to find evidence in such genes of antigen-specific selection. Results: As expected there is a selection against replacement mutations in IgE framework regions. In contrast, in all examined cases but one (assessing IgE repertoires of parasite-infected individuals) there was no evidence in favor of either positive or negative selection in complementarity determining regions. Importantly, however, the validated method also failed to detect selection for replacement mutations in two, non-IgE, hypermutated antibody populations targeting tetanus toxoid and vaccinia virus, respectively. Conclusions: Current methodology is unable to define with certainty, using commonly assessed IgE repertoire sizes, whether antigen selection is or is not a major driving force in the establishment of human IgE. New approaches are needed to address this matter.
Absolute Blood Volume in Hemodialysis Patients: Why Is It Relevant, and How to Measure It
Authors: Thijssen Stephan , Kappel Franz , Kotanko Peter
Published: January 2013

Intradialytic hypotension (IDH) is the most common complication during hemodialysis and is associated with significant morbidity. It occurs as a consequence of a reduction in blood volume during ultrafiltration. Today, devices for monitoring relative blood volume (i.e. the intradialytic blood volume as a fraction of the blood volume at the start of the dialysis treatment) are routinely available and have been used to analyze the relationship between changes in relative blood volume and the occurrence of IDH in an attempt to derive critical thresholds that, when observed, would help avoid hypotensive episodes during the treatment. However, the results have been unsatisfactory in many patients. Here we illustrate the importance of absolute blood volume in hemodialysis patients, summarize the acute physiologic mechanisms involved in the preservation of adequate circulation during ultrafiltration, and outline why hemodialysis patients are often particularly vulnerable to reductions in blood volume. We then discuss the shortcomings of relative blood volume measurements, make a case for the superiority of absolute blood volume measurements, and introduce the reader to a mathematical concept that allows relative blood volume devices to be used for the estimation of absolute blood volume. Finally, we discuss the implications of absolute blood volume beyond IDH and propose a paradigm shift in the approach to dry weight attainment.
Evidence for Specific Genotype-Dependent Immune Priming in the Lophotrochozoan Biomphalaria glabrata Snail
Authors: Portela Julien , Duval David , Rognon Anne , Galinier Richard , Boissier Jérôme , Coustau Christine , Mitta Guillaume , Théron André , Gourbal Benjamin
Published: January 2013

Historically, the prevailing view in the field of invertebrate immunity was that invertebrates that do not possess acquired adaptive immunity rely on innate mechanisms with low specificity and no memory. Several recent studies have shaken this paradigm and suggested that the immune defenses of invertebrates are more complex and specific than previously thought. Mounting evidence has shown that at least some invertebrates (mainly Ecdysozoa) show high levels of specificity in their immune responses to different pathogens, and that subsequent reexposure may result in enhanced protection (recently called ‘immune priming'). Here, we investigated immune priming in the Lophotrochozoan snail species Biomphalaria glabrata, following infection by the trematode pathogen Schistosoma mansoni. We confirmed that snails were protected against a secondary homologous infection whatever the host strain. We then investigated how immune priming occurs and the level of specificity of B. glabrata immune priming. In this report we confirmed that immune priming exists and we identified a genotype-dependent immune priming in the fresh-water snail B. glabrata.
Mortality and Renal Outcome of Primary Glomerulonephritis in Korea: Observation in 1,943 Biopsied Cases
Authors: Lee Hajeong , Kim Dong Ki , Oh Kook-Hwan , Joo Kwon Wook , Kim Yon Su , Chae Dong-Wan , Kim Suhnggwon , Chin Ho Jun
Published: January 2013

Background: Previous epidemiological studies have focused on the prevalence of primary glomerulonephritis (GN), but few have explored long-term patient outcomes. This study was conducted to investigate the long-term patient and renal outcomes of primary GN. Methods: A total of 1,943 biopsy-proven primary GN patients were included. The outcomes were mortality and end-stage renal disease (ESRD) progression. The relative mortality rate was expressed by the standardized mortality ratio (SMR) and the 95% confidence interval (CI). Results: During the median follow-up of 90 months, 325 (16.7%) patients progressed to ESRD and 164 (8.4%) patients died. Patients with minimal change disease exhibited the best renal and patient outcomes, whereas those with membranoproliferative GN had the worst. IgA nephropathy patients appeared to have a good survival rate in spite of their considerable progression to ESRD, and focal segmental glomerulosclerosis patients showed poor renal and patient outcomes. Mortality was 67% higher in primary GN patients than in the age- and sex-matched general population (SMR, 1.67; 95% CI, 1.42–1.95). The difference was more prominent in women (SMR, 2.95; 95% CI, 2.27–3.77) than in men (SMR, 1.31; 95% CI, 1.07–1.60). Renal risk factors, e.g. hypertension, proteinuria and initial renal dysfunction, were all associated with higher mortality, and the relative mortality rate increased with the number of risk factors. Conclusions: In patients with primary GN, mortality is significantly higher than in the age-/sex-matched general population, especially in women. Moreover, the presence of renal risk factors is positively associated with both relative mortality and progression to ESRD.
Effects of Dialysate Flow Configurations in Continuous Renal Replacement Therapy on Solute Removal: Computational Modeling
Authors: Kim Jeong Chul , Cruz Dinna , Garzotto Francesco , Kaushik Manish , Teixeria Catarina , Baldwin Marie , Baldwin Ian , Nalesso Federico , Kim Ji Hyun , Kang Eungtaek , Kim Hee Chan , Ronco Claudio
Published: January 2013

Background/Aims: Continuous renal replacement therapy (CRRT) is commonly used for critically ill patients with acute kidney injury. During treatment, a slow dialysate flow rate can be applied to enhance diffusive solute removal. However, due to the lack of the rationale of the dialysate flow configuration (countercurrent or concurrent to blood flow), in clinical practice, the connection settings of a hemodiafilter are done depending on nurse preference or at random. Methods: In this study, we investigated the effects of flow configurations in a hemodiafilter during continuous venovenous hemodialysis on solute removal and fluid transport using computational fluid dynamic modeling. We solved the momentum equation coupling solute transport to predict quantitative diffusion and convection phenomena in a simplified hemodiafilter model. Results: Computational modeling results showed superior solute removal (clearance of urea: 67.8 vs. 45.1 ml/min) and convection (filtration volume: 29.0 vs. 25.7 ml/min) performances for the countercurrent flow configuration. Countercurrent flow configuration enhances convection and diffusion compared to concurrent flow configuration by increasing filtration volume and equilibrium concentration in the proximal part of a hemodiafilter and backfiltration of pure dialysate in the distal part. In clinical practice, the countercurrent dialysate flow configuration of a hemodiafilter could increase solute removal in CRRT. Nevertheless, while this configuration may become mandatory for high-efficiency treatments, the impact of differences in solute removal observed in slow continuous therapies may be less important. Under these circumstances, if continuous therapies are prescribed, some of the advantages of the concurrent configuration in terms of simpler circuit layout and simpler machine design may overcome the advantages in terms of solute clearance. Conclusion: Different dialysate flow configurations influence solute clearance and change major solute removal mechanisms in the proximal and distal parts of a hemodiafilter. Advantages of each configuration should be balanced against the overall performance of the treatment and its simplicity in terms of treatment delivery and circuit handling procedures.
Multifaceted Hemolytic Uremic Syndrome in Pediatrics
Authors: Nester Carla M.
Published: January 2013

Hemolytic uremic syndromes can have devastating consequences in childhood. The common feature of a microangiopathic hemolytic anemia and thrombocytopenia associated with varying degrees of renal injury often creates diagnostic confusion. The inability to arrive at a definitive diagnosis quickly can lead to a delay in initiating renal-preserving and sometimes life-saving treatment. Currently, both the treatment plan and the prognosis vary substantially according to the presumed diagnosis. The availability of anti-complement therapy makes differentiating the cause of the hemolytic uremic syndrome particularly critical. Therefore, it is imperative that consideration be given to each of the possible syndromes at presentation in order to facilitate correct diagnosis and development of an appropriate treatment strategy for both the acute phase and for the long-term care of the patient.
Sex-Specific mTOR Signaling Determines Sexual Dimorphism in Myocardial Adaptation in Normotensive DOCA-Salt Model
Authors: Gürgen Dennis , Kusch Angelika , Klewitz Robin , Hoff Uwe , Catar Rusan , Hegner Björn , Kintscher Ulrich , Luft Friedrich C. , Dragun Duska
Published: January 2013

The deoxycorticosterone acetate (DOCA)-salt mouse model exhibits adverse cardiac remodeling in male mice and cardiac protection in female mice, even when blood pressure is normalized. We hypothesized that intact mammalian target of rapamycin (mTOR) signaling is necessary for cardiac protection in females. We first tested sex differences and intracellular signaling after mTOR targeting with rapamycin in wild-type mice. Radio-telemetric blood pressure was maintained at normal for 6 weeks. Rapamycin significantly reduced left ventricular hypertrophy, preserved ejection fraction, inhibited fibrosis, and maintained capillary structure in male mice. Decreased mTORC1 and increased mTORC2 activity were detected in rapamycin-treated male mice compared with vehicle controls. In contrast, female mice developed dilative left ventricular hypertrophy, cardiac fibrosis, and capillary loss similar to DOCA-salt females lacking the estrogen receptor β (ERβ
−/−
) that we described earlier. Because rapamycin downregulated ERβ in female mice, we next studied ERβ
−/−
normotensive DOCA-salt females. Vehicle-treated wild-type females maintained their high constitutive mTORC1 and mTORC2 in response to DOCA-salt. In contrast to males, both mTORCs were decreased by rapamycin, in particular mTORC2 by 60%. ERβ
−/−
DOCA-salt females showed similar mTORC1 and mTORC2 response patterns. We suggest that ERβ-dependent regulation involves sex-specific use of mTOR signaling branches. Maintenance of both mTORC1 and mTORC2 signaling seems to be essential for adaptive cardiac remodeling in females and supports a rationale for sex-specific therapeutic strategies in left ventricular hypertrophy.
Single Nucleotide Polymorphisms in G Protein Signaling Pathway Genes in Preeclampsia
Authors: Kvehaugen Anne Stine , Melien Øyvind , Holmen Oddgeir Lingaas , Laivuori Hannele , Øian Pål , Andersgaard Alice Beathe , Dechend Ralf , Staff Anne Cathrine
Published: January 2013

Preeclampsia is a pregnancy specific disorder and a risk factor for later cardiovascular disease. The cause and detailed pathophysiology remains unknown. G protein signaling is involved in a variety of physiological processes, including blood pressure regulation. We assessed whether distributions of 3 single nucleotide polymorphisms in genes coding for components of G protein signaling pathways that have been associated with hypertension differ between women with preeclampsia and normotensive pregnant women; the G protein β3 subunit gene (
GNB3
) C825T polymorphism (rs5443), the angiotensin II type 1 receptor gene (
AGTR1
) 3′UTR A1166C polymorphism (rs5186), and the regulator of G protein signaling 2 gene (
RGS2
) 3′UTR C1114G polymorphism (rs4606). Two separate Norwegian study populations were used; a large population based study and a smaller, but clinically well-described pregnancy biobank. A descriptive study of 43 women with eclampsia was additionally included. In the population-based study, an increased odds of preeclampsia (odds ratio, 1.21; [95% confidence interval, 1.05–1.40];
P
=0.009) and recurrent preeclampsia (odds ratio, 1.43; [95% confidence interval, 1.06–1.92];,
P
=0.017) was found in women carrying the rs4606 CG or GG genotype. In early-onset preeclamptic patients with decidual spiral artery biopsies available (n=24), the rs4606 CG or GG genotype was more frequent in those with acute atherosis (resembling early stage of atherosclerosis) compared with those without: odds ratio, 15.0; (95% confidence interval, 2.02–111.2);
P
=0.004. No association was found between preeclampsia and the rs5443 or the rs5186. The genotype distribution in eclamptic women was not different from preeclamptic women. In conclusion,
RGS2
rs4606 may affect the risk and progression of preeclampsia.
Pulmonary Hypertension Secondary to Left-Heart Failure Involves Peroxynitrite-Induced Downregulation of PTEN in the Lung
Authors: Ravi Yazhini , Selvendiran Karuppaiyah , Naidu Shan K. , Meduru Sarath , Citro Lucas A. , Bognár Balázs , Khan Mahmood , Kálai Tamás , Hideg Kálmán , Kuppusamy Periannan , Sai-Sudhakar Chittoor B.
Published: January 2013

Pulmonary hypertension (PH) that occurs after left-heart failure (LHF), classified as Group 2 PH, involves progressive pulmonary vascular remodeling induced by smooth muscle cell (SMC) proliferation. However, mechanisms involved in the activation of SMCs remain unknown. The objective of this study was to determine the involvement of peroxynitrite and phosphatase-and-tensin homolog on chromosome 10 (PTEN) in vascular SMC proliferation and remodeling in the LHF-induced PH (LHF-PH). LHF was induced by permanent ligation of left anterior descending coronary artery in rats for 4 weeks. MRI, ultrasound, and hemodynamic measurements were performed to confirm LHF and PH. Histopathology, Western blot, and real-time polymerase chain reaction analyses were used to identify key molecular signatures. Therapeutic intervention was demonstrated using an antiproliferative compound, HO-3867. LHF-PH was confirmed by significant elevation of pulmonary artery pressure (mean pulmonary artery pressure/mm Hg: 35.9±1.8 versus 14.8±2.0, control;
P
<0.001) and vascular remodeling. HO-3867 treatment decreased mean pulmonary artery pressure to 22.6±0.8 mm Hg (
P
<0.001). Substantially higher levels of peroxynitrite and significant loss of PTEN expression were observed in the lungs of LHF rats when compared with control. In vitro studies using human pulmonary artery SMCs implicated peroxynitrite-mediated downregulation of PTEN expression as a key mechanism of SMC proliferation. The results further established that HO-3867 attenuated LHF-PH by decreasing oxidative stress and increasing PTEN expression in the lung. In conclusion, peroxynitrite and peroxynitrite-mediated PTEN inactivation seem to be key mediators of lung microvascular remodeling associated with PH secondary to LHF.
23
Na Magnetic Resonance Imaging-Determined Tissue Sodium in Healthy Subjects and Hypertensive Patients
Authors: Kopp Christoph , Linz Peter , Dahlmann Anke , Hammon Matthias , Jantsch Jonathan , Müller Dominik N. , Schmieder Roland E. , Cavallaro Alexander , Eckardt Kai-Uwe , Uder Michael , Luft Friedrich C. , Titze Jens
Published: January 2013

High dietary salt intake is associated with hypertension; the prevalence of salt-sensitive hypertension increases with age. We hypothesized that tissue Na
+
might accumulate in hypertensive patients and that aging might be accompanied by Na
+
deposition in tissue. We implemented
23
Na magnetic resonance imaging to measure Na
+
content of soft tissues in vivo earlier, but had not studied essential hypertension. We report on a cohort of 56 healthy control men and women, and 57 men and women with essential hypertension. The ages ranged from 22 to 90 years.
23
Na magnetic resonance imaging measurements were made at the level of the calf. We observed age-dependent increases in Na
+
content in muscle in men, whereas muscle Na
+
content did not change with age in women. We estimated water content with conventional MRI and found no age-related increases in muscle water in men, despite remarkable Na
+
accumulation, indicating water-free Na
+
storage in muscle. With increasing age, there was Na
+
deposition in the skin in both women and men; however, skin Na
+
content remained lower in women. Similarly, this sex difference was found in skin water content, which was lower in women than in men. In contrast to muscle, increasing Na
+
content was paralleled with increasing skin water content. When controlled for age, we found that patients with refractory hypertension had increased tissue Na
+
content, compared with normotensive controls. These observations suggest that
23
Na magnetic resonance imaging could have utility in assessing the role of tissue Na
+
storage for cardiovascular morbidity and mortality in longitudinal studies.
Obesity-Related Hypertension and the Role of Insulin and Leptin in High-Fat–Fed Rabbits
Authors: Lim Kyungjoon , Burke Sandra L. , Head Geoffrey A.
Published: January 2013

Feeding a high-fat diet (HFD) to rabbits results in increased blood pressure and renal sympathetic nerve activity (RSNA) and marked increases in plasma leptin and insulin. We determined the contribution of insulin and leptin signaling in the central nervous system to the increased blood pressure and RSNA during a HFD using specific antagonists. New Zealand White rabbits were implanted with an intracerebroventricular (ICV) catheter and RSNA electrode and placed on a normal or 13.5% HFD for 1 or 3 weeks. Blood pressure, heart rate, and RSNA were recorded before and for 90 minutes after ICV administration of a leptin antagonist (100 µg), insulin antagonist (0.5 U), or vehicle (50 µL) on separate days. Rabbits had higher blood pressure (+8%, +17%) and RSNA (+55%, +71%), at 1 and 3 weeks, respectively, of HFD compared with controls (n=7–11). ICV leptin antagonist reduced blood pressure by 9% and RSNA by 17% (
P
<0.001) after 3 weeks of HFD but had no effect at week 1. ICV administration of the insulin antagonist reduced blood pressure by ≈5% at both times (
P
<0.05) but there was no effect on RSNA. Leptin and insulin antagonist doses were confirmed to effectively block the pressor responses to ICV leptin and insulin, respectively. The elevation of blood pressure and RSNA induced by a HFD is predominantly mediated by central actions of leptin. Central actions of insulin contribute a smaller proportion of the hypertension but independently of RSNA.
Information Transmission Using Non-Poisson Regular Firing
Authors: Koyama Shinsuke , Omi Takahiro , Kass Robert E. , Shinomoto Shigeru
Published: January 2013

In many cortical areas, neural spike trains do not follow a Poisson process. In this study, we investigate a possible benefit of non-Poisson spiking for information transmission by studying the minimal rate fluctuation that can be detected by a Bayesian estimator. The idea is that an inhomogeneous Poisson process may make it difficult for downstream decoders to resolve subtle changes in rate fluctuation, but by using a more regular non-Poisson process, the nervous system can make rate fluctuations easier to detect. We evaluate the degree to which regular firing reduces the rate fluctuation detection threshold. We find that the threshold for detection is reduced in proportion to the coefficient of variation of interspike intervals.
Error Analysis of Coefficient-Based Regularized Algorithm for Density-Level Detection
Authors: Chen Hong , Pan Zhibin , Li Luoqing , Tang Yuanyan
Published: January 2013

In this letter, we consider a density-level detection (DLD) problem by a coefficient-based classification framework with [Formula: see text]-regularizer and data-dependent hypothesis spaces. Although the data-dependent characteristic of the algorithm provides flexibility and adaptivity for DLD, it leads to difficulty in generalization error analysis. To overcome this difficulty, an error decomposition is introduced from an established classification framework. On the basis of this decomposition, the estimate of the learning rate is obtained by using Rademacher average and stepping-stone techniques. In particular, the estimate is independent of the capacity assumption used in the previous literature.
Unexploited Gains From International Diversification: Patterns Of Portfolio Holdings Around The World
Authors: Didier Tatiana , Rigobon Roberto , Schmukler Sergio L.
Published: January 2013

Using unique data on mutual fund portfolios with different investment scopes, we study the extent of international diversification. Mutual funds invest in a surprisingly limited number of stocks—about 100. The number of holdings from a given region declines as the investment scope broadens. Moreover, unexploited gains exist from international diversification. Funds that invest globally could achieve better risk-adjusted returns by adding stocks held by more specialized funds within the same family. These findings are not driven by different sectoral allocations, lack of information or instruments, transaction costs, or different tail risks. Instead, organizational factors might play an important role.
Checklist of the Inland Fishes of El Salvador
Authors: MCMAHAN CALEB D. , MATAMOROS WILFREDO A. , ÁLVAREZ CALDERÓN FRANCISCO S. , HENRÍQUEZ WENDY YAMILETH , RECINOS H. MICHELLE , CHAKRABARTY PROSANTA , BARRAZA ENRIQUE , HERRERA NÉSTOR
Published: January 2013

The inland fish fauna of El Salvador and its distribution was originally described in 1925 by Samuel Hildebrand. That work has been the main source of information for freshwater fishes of El Salvador up to today. Based on the combination of an intensive literature review, electronic database searches, re-identification of museum specimens, and fieldwork, we hereby provide an updated checklist of the inland fishes of El Salvador. This checklist provides distributional data at the Salvadoran hydrographical and political (by department) levels. The checklist is systematically arranged at the ordinal and familial level and then alphabetically therein. The freshwater fish fauna of El Salvador includes 101 species divided into 64 genera, 29 families, and 14 orders. According to their supposed tolerance to salinity, 73% of these species are peripheral, 23% secondary, and only 4% are primary freshwater fishes. One species is endemic to the country, Amatitlania coatepeque. The low number of primary freshwater fishes and endemics is comparable to the Central American Pacific slope in particular, as well as northern Central America in general.
Identification of Long-Range Transported Haze Phenomena and Their Meteorological Features over Northeast Asia
Authors: Jo Hyun-Young , Kim Cheol-Hee
Published: January 2013

This paper presents a technique used to empirically classify operationally defined “haze” days in South Korea from 2000 to 2007 into long-range transported (LRT) and stagnant (STG) haze cases. A total of 547 haze days were classified into these two cases by tracking consecutive 6-day synoptic weather charts and air trajectories. The meteorological features associated with long-range transport of haze were identified by contrasting the values of 35 candidate meteorological parameters corresponding to the two types of haze cases. A suitable subset of synoptic variables was then chosen to diagnose the unique meteorological features of each case. The statistical test showed that geostrophic wind speed, vorticity, vorticity advection at a geopotential height of 850 hPa, and the vertical stability index of the lower atmosphere were indicated as highly effective parameters for distinguishing between the LRT and STG cases. The classification accuracies showed 93.2%, 87.8%, 85.4%, and 84.4% for these four variables, respectively. The STG case was well characterized by negative vorticity, with stable atmospheric stability conditions and weak geostrophic wind speed, that is, ~2.8 m s−1at a geopotential height of 850 hPa, whereas the LRT case had relatively strong geostrophic wind speed, >6 m s−1. For both cases, the location of the anticyclone played an important role in haze occurrence, directly and indirectly. A high pressure system led to stable STG haze with weak ventilation, resulting from upper-atmospheric subsidence. The LRT case was associated with a strong anticyclone that prevailed over southwestern China, maintaining the pressure gradient force that generated the westerly wind that was persistently conducive to downwind long-range transport of haze.
An Ensemble-Based Four-Dimensional Variational Data Assimilation Scheme. Part III: Antarctic Applications with Advanced Research WRF Using Real Data
Authors: Liu Chengsi , Xiao Qingnong
Published: January 2013

A four-dimensional ensemble-based variational data assimilation (4DEnVar) algorithm proposed in Part I of the 4DEnVar series (denoted En4DVar in Part I, but here we refer to it as 4DEnVar according to WMO conference recommendation to differentiate it from En4DVar algorithm using adjoint model) uses a flow-dependent background error covariance calculated from ensemble forecasts and performs 4DVar optimization based on an incremental approach and a preconditioning algorithm. In Part II, the authors evaluated 4DEnVar with observing system simulation experiments (OSSEs) using the Advanced Research Weather Research and Forecasting Model (ARW-WRF, hereafter WRF). The current study extends the 4DEnVar to assimilate real observations for a cyclone in the Antarctic and the Southern Ocean in October 2007. The authors performed an intercomparison of four different WRF variational approaches for the case, including three-dimensional variational data assimilation (3DVar), first guess at the appropriate time (FGAT), and ensemble-based three-dimensional (En3DVar) and four-dimensional (4DEnVar) variational data assimilations. It is found that all data assimilation approaches produce positive impacts in this case. Applying the flow-dependent background error covariance in En3DVar and 4DEnVar yields forecast skills superior to those with the homogeneous and isotropic background error covariance in 3DVar and FGAT. In addition, the authors carried out FGAT and 4DEnVar 3-day cycling and 72-h forecasts. The results show that 4DEnVar produces a better performance in the cyclone prediction. The inflation factor on 4DEnVar can effectively improve the 4DEnVar analysis. The authors also conducted a short period (10-day lifetime of the cyclone in the domain) of analysis/forecast intercomparison experiments using 4DEnVar, FGAT, and 3DVar. The 4DEnVar scheme demonstrates overall superior and robust performance.
Impacts of Assimilating Measurements of Different State Variables with a Simulated Supercell Storm and Three-Dimensional Variational Method
Authors: Ge Guoqing , Gao Jidong , Xue Ming
Published: January 2013

This paper investigates the impacts of assimilating measurements of different state variables, which can be potentially available from various observational platforms, on the cycled analysis and short-range forecast of supercell thunderstorms by performing a set of observing system simulation experiments (OSSEs) using a storm-scale three-dimensional variational data assimilation (3DVAR) method. The control experiments assimilate measurements every 5 min for 90 min. It is found that the assimilation of horizontal wind can reconstruct the storm structure rather accurately. The assimilation of vertical velocity , potential temperature , or water vapor can partially rebuild the thermodynamic and precipitation fields but poorly retrieves the wind fields. The assimilation of rainwater mixing ratio can build up the precipitation fields together with a reasonable cold pool but is unable to properly recover the wind fields. Overall, data have the greatest impact, while have the second largest impact. The impact of is the smallest. The impact of assimilation frequency is examined by comparing results using 1-, 5-, or 10-min assimilation intervals. When is assimilated every 5 or 10 min, the analysis quality can be further improved by the incorporation of additional types of observations. When are assimilated every minute, the benefit from additional types of observations is negligible, except for . It is also found that for , , and measurements, more frequent assimilation leads to more accurate analyses. For and , a 1-min assimilation interval does not produce a better analysis than a 5-min interval.
Improving sightreading accuracy: A meta-analysis
Authors: Mishra Jennifer
Published: January 2013

The purpose of this meta-analysis was to determine whether experimentally tested sightreading interventions positively influenced sightreading ability. A meta-analysis was conducted with 92 quasi-experimental research studies on sightreading (124 individual analyses) to determine the overall effect size of treatment and to examine how the effect size was influenced by treatment type, sightreading mode (sightreading/sightsinging), age and experience of sight reader, type of sightreading test, and other study design elements. The analysis revealed a small overall effect size for treatment ( d = −0.18, 95% CI [−0.24, −0.11]). Of the moderator variables, only treatment-type was significant, with treatments categorized as “Aural Training,” “Controlled Reading,” “Creative Activities,” and “Singing/Solfege” significantly and positively affecting sightreading. There was a moderately strong within-group effect size ( d = −0.48, 95% CI [−0.56, −0.40]), indicating that sightreading generally improved pre- to posttest for both control and treatment groups.
Novel chiral poly(amide-imide) nanocomposites reinforced with silicate layers and TiO2 nanoparticles based on N-trimellitylimido-l-isoleucine
Authors: Mallakpour Shadpour , Zarei Mohammad
Published: January 2013

In the present investigation, the goal was the preparation, characterization, and surface morphology of poly(amide-imide)/TiO2/oganoclay nanocomposites. At first, an optically active poly(amide-imide) was synthesized from the polymerization reaction of N-trimellitylimido-l-isoleucine diacid with 4,4′-methylenebis(3-chloro-2,6-diethylaniline). The obtained polymer and TiO2 nanoparticles were used to prepare poly(amide-imide)/TiO2 nanocomposites through ultrasonic irradiation. Then, different amounts of organoclay were added to the poly(amide-imide)/TiO2 nanocomposite system to obtain poly(amide-imide)/TiO2/oganoclay nanocomposite. The resulting hybrids materials were characterized by Fourier transform infrared spectroscopy, X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy, and thermogravimetric analysis techniques.
Numerical simulation of RTM process using the extended finite element method combined with the level set method
Authors: Jung Yeonhee , Kim Seung Jo , Han Woo-Suck
Published: January 2013

Numerical simulation for resin transfer moulding manufacturing process is attempted using the extended finite element method combined with the level set method. The level set method is used to transport the resin flow front at each time step during the mould filling. Extended finite element method allows to obtaining a good numerical precision of the resin pressure near the resin flow front, where the gradient of the pressure could be discontinuous. The enriched shape functions of extended finite element method are derived using the level set values so as to correctly describe these shape functions with the resin flow front. In addition, the position of the resin flow front at each time step is calculated by an implicit characteristic Galerkin finite element method. Some examples are presented to validate our study in comparison with analytical or experimental results and to illustrate its industrial applications.
The Politics of Accountability
Authors: Lewis Wayne D. , Young Tamara V.
Published: January 2013

Drawing on Kingdon’s multiple streams framework, this study examines how teacher education policy has gained prominence on the federal decision agenda in recent years.
Revisiting Collaborations Between Nonprofits and Businesses
Authors: Schiller Ruth S. , Almog-Bar Michal
Published: January 2013

Collaborations between nonprofits and businesses (CBNB) are a developing field of action. Much of the research deals with the business’s perspective. Usage of third sector and nonprofit management methods is a relatively new field of research. This article presents a qualitative case study of a three year collaboration between a nonprofit organization (NPO) and a pharmaceutical company that focuses on the NPO’s unique perceptions and points of view about the partnership. The findings reveal that the most crucial element affecting the success or failure of a collaboration is the added value that the business partner brings to the relationship. Furthermore, power relations suggest that weak positioning might benefit the NPO. We introduce the Fields of Action Typology of collaborations between nonprofits and businesses that adds a content layer to current classifications of CBNB and is helpful for defining and examining the benefits NPOs can derive from CBNB.