bluuebunny/crossref_metadata_2025 huggingface dataset:
Ablation of ghrelin receptor in leptin-deficient ob/ob mice has paradoxical effects on glucose homeostasis when compared with ablation of ghrelin in ob/ob mice
Authors: Ma Xiaojun , Lin Yuezhen , Lin Ligen , Qin Guijun , Pereira Fred A. , Haymond Morey W. , Butte Nancy F. , Sun Yuxiang
Published: June 2012

The orexigenic hormone ghrelin is important in diabetes because it has an inhibitory effect on insulin secretion. Ghrelin ablation in leptin-deficient ob/ob ( Ghrelin−/−: ob/ ob) mice increases insulin secretion and improves hyperglycemia. The physiologically relevant ghrelin receptor is the growth hormone secretagogue receptor (GHS-R), and GHS-R antagonists are thought to be an effective strategy for treating diabetes. However, since some of ghrelin's effects are independent of GHS-R, we have utilized genetic approaches to determine whether ghrelin's effect on insulin secretion is mediated through GHS-R and whether GHS-R antagonism indeed inhibits insulin secretion. We investigated the effects of GHS-R on glucose homeostasis in Ghsr-ablated ob/ ob mice ( Ghsr−/−: ob/ ob). Ghsr ablation did not rescue the hyperphagia, obesity, or insulin resistance of ob/ ob mice. Surprisingly, Ghsr ablation worsened the hyperglycemia, decreased insulin, and impaired glucose tolerance. Consistently, Ghsr ablation in ob/ ob mice upregulated negative β-cell regulators (such as UCP-2, SREBP-1c, ChREBP, and MIF-1) and downregulated positive β-cell regulators (such as HIF-1α, FGF-21, and PDX-1) in whole pancreas; this suggests that Ghsr ablation impairs pancreatic β-cell function in leptin deficiency. Of note, Ghsr ablation in ob/ ob mice did not affect the islet size; the average islet size of Ghsr−/−: ob/ ob mice is similar to that of ob/ ob mice. In summary, because Ghsr ablation in leptin deficiency impairs insulin secretion and worsens hyperglycemia, this suggests that GHS-R antagonists may actually aggravate diabetes under certain conditions. The paradoxical effects of ghrelin ablation and Ghsr ablation in ob/ob mice highlight the complexity of the ghrelin-signaling pathway.
Tissue-specific mRNA expression patterns reveal a coordinated metabolic response associated with genetic selection for milk production in cows
Authors: Weikard R. , Goldammer T. , Brunner R. M. , Kuehn C.
Published: June 2012

The molecular mechanisms regulating the physiological adaptation of tissues important for nutrient partitioning and metabolism in lactating cows are still not completely understood. The aim of our study was to identify tissue-specific regulatory mechanisms necessary to accommodate metabolic changes associated with different genetic potential for milk performance. For this purpose, we analyzed mRNA expression of genes involved in energy metabolism of segregating F2beef type cows with a combined genetic dairy and beef background (Charolais × German Holstein cross, CH×GH) in contrast to purebred German Holstein (GH) dairy cows. Three groups of cows differing in milk performance were examined using quantitative real-time PCR in liver, mammary gland, and skeletal muscle. Our results describe substantial tissue-specific differences in mRNA transcription profiles between cow groups in relation to their genetic potential for milk performance and highlight genes exhibiting specific, partially yet-unknown functions in dairy and beef type cows, e.g., upregulation of PCK2 transcripts in the mammary gland and FBP2 transcripts in skeletal muscle of dairy cows. Noticeably, PCCA and PPARGC1A mRNA abundance varied significantly across experimental groups in all three tissues, pointing to potential key gene functions in the metabolic adaptation relative to divergent milk production performance. Correlations of mRNA expression levels to milk performance traits indicate that gene transcriptional processes may play a regulatory role in liver, mammary gland, and skeletal muscle to enable cows with different genetic potential for milk performance to cope with metabolic lactation-associated challenges.
Synthesis of a New Potential Conjugated TAT‐Peptide‐Chitosan Nanoparticles Carrier via Disulphide Linkage
Authors: Katas Haliza , Nik Dzulkefli Nik Nur Shamiha , Sahudin Shariza
Published: June 2012

Chitosan and TAT peptide have been widely investigated as delivery systems for various biomolecules such as plasmid DNA, oligonucleotides, and siRNAs. Conjugation of chitosan with TAT‐peptide was therefore expected to produce a carrier with enhanced ability to facilitate cellular uptake. In this study, chitosan nanoparticles (CNs) were prepared by ionic gelation method prior to conjugation with TAT‐peptide via disulphide linkage (CN‐TAT). The conjugation was performed at various TAT‐peptide‐to‐chitosan weight ratios ranging from 0.008 : 1 to 0.125 : 1. siRNA as a model biomolecule was loaded by adsorption onto the CN‐TAT. Nanosize range particles were produced with a size range of less than 700 nm depending on TAT‐peptide concentration used. HPLC and Raman spectrometry analysis revealed that TAT‐peptide was successfully conjugated to the CN via disulphide linkage. siRNA loading efficiency for CN‐TAT was 93%  ±0.01. In vitro cytotoxicity studies showed that CN‐TAT has relatively low toxicity. In conclusion, TAT conjugated onto CN via disulphide linkage was successfully synthesized, and its low cytoxicity demonstrates a potential for its use as a vector for biomolecules.
Immune Responses to RHAMM in Patients with Acute Myeloid Leukemia after Chemotherapy and Allogeneic Stem Cell Transplantation
Authors: Casalegno-Garduño R. , Meier C. , Schmitt A. , Spitschak A. , Hilgendorf I. , Rohde S. , Hirt C. , Freund M. , Pützer B. M. , Schmitt M.
Published: June 2012

Leukemic blasts overexpress immunogenic antigens, so-called leukemia-associated antigens like the receptor for hyaluronan acid-mediated motility (RHAMM). Persistent RHAMM expression and decreasing CD8+T-cell responses to RHAMM in the framework of allogeneic stem cell transplantation or chemotherapy alone might indicate the immune escape of leukemia cells. In the present study, we analyzed the expression of RHAMM in 48 patients suffering from acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Furthermore, we correlated transcripts with the clinical course of the disease before and after treatment. Real-time quantitative reverse transcriptase polymerase chain reaction was performed from RNA of peripheral blood mononuclear cells. T cell responses against RHAMM were assessed by tetramer staining (flow cytometry) and enzyme-linked immunospot (ELISPOT) assays. Results were correlated with the clinical outcome of patients. The results of the present study showed that almost 60% of the patients were RHAMM positive; specific T-cells recognizing RHAMM could be detected, but they were nonfunctional in terms of interferon gamma or granzyme B release as demonstrated by ELISPOT assays. Immunotherapies like peptide vaccination or adoptive transfer of RHAMM-specific T cells might improve the immune response and the outcome of AML/MDS patients.
Oral Verrucous Carcinoma Mimicking a Chronic Candidiasis: A Case Report
Authors: Garcia Natália Galvão , Oliveira Denise Tostes , Hanemann João Adolfo Costa , Pereira Alessandro Antônio Costa
Published: June 2012

Verrucous carcinoma has a special propensity to mimic benign lesions of the oral cavity. A case of the oral verrucous carcinoma in maxillary alveolar ridge, extending to buccal vestibule, cheek, and labial mucosa, which was diagnosed and initially treated as chronic candidiasis, is presented. Clinical, histopathological, and therapeutic considerations related to diagnosis of the verrucous carcinoma in the oral cavity are discussed.
Multiple Approaches to Investigate the Transport and Activity-Dependent Release of BDNF and Their Application in Neurogenetic Disorders
Authors: Hartmann David , Drummond Jana , Handberg Erik , Ewell Sharday , Pozzo-Miller Lucas
Published: June 2012

Studies utilizing genetic and pharmacological manipulations in rodent models and neuronal cultures have revealed myriad roles of brain-derived neurotrophic factor (BDNF). Currently, this knowledge of BDNF function is being translated into improvement strategies for several debilitating neurological disorders in which BDNF abnormalities play a prominent role. Common among the BDNF-related disorders are irregular trafficking and release of mature BDNF (mBDNF) and/or its prodomain predecessor, proBDNF. Thus, investigating the conditions required for proper trafficking and release of BDNF is an essential step toward understanding and potentially improving these neurological disorders. This paper will provide examples of disorders related to BDNF release and serve as a review of the techniques being used to study the trafficking and release of BDNF.
Control and Synchronization of the Fractional‐Order Lorenz Chaotic System via Fractional‐Order Derivative
Authors: Zhou Ping , Ding Rui
Published: June 2012

The unstable equilibrium points of the fractional‐order Lorenz chaotic system can be controlled via fractional‐order derivative, and chaos synchronization for the fractional‐order Lorenz chaotic system can be achieved via fractional‐order derivative. The control and synchronization technique, based on stability theory of fractional‐order systems, is simple and theoretically rigorous. The numerical simulations demonstrate the validity and feasibility of the proposed method.
A Coupled System of Nonlinear Fractional Differential Equations with Multipoint Fractional Boundary Conditions on an Unbounded Domain
Authors: Wang Guotao , Ahmad Bashir , Zhang Lihong
Published: June 2012

This paper investigates the existence of solutions for a coupled system of nonlinear fractional differential equations with m‐point fractional boundary conditions on an unbounded domain. Some standard fixed point theorems are applied to obtain the main results. The paper concludes with two illustrative examples.
Impact of HMGB1/TLR Ligand Complexes on HIV-1 Replication: Possible Role for Flagellin during HIV-1 Infection
Authors: Nowak Piotr , Abdurahman Samir , Lindkvist Annica , Troseid Marius , Sönnerborg Anders
Published: June 2012

Objective. We hypothesized that HMGB1 in complex with bacterial components, such as flagellin, CpG-ODN, and LPS, promotes HIV-1 replication. Furthermore, we studied the levels of antiflagellin antibodies during HIV-1-infection.Methods. Chronically HIV-1-infected U1 cells were stimulated with necrotic extract/recombinant HMGB1 in complex with TLR ligands or alone. HIV-1 replication was estimated by p24 antigen in culture supernatants 48–72 hours after stimulation. The presence of systemic anti-flagellin IgG was determined in 51 HIV-1-infected patients and 19 controls by immunoblotting or in-house ELISA.Results. Flagellin, LPS, and CpG-ODN induced stronger HIV-1 replication when incubated together with necrotic extract or recombinant HMGB1 than activation by any of the compounds alone. Moreover, the stimulatory effect of necrotic extract was inhibited by depletion of HMGB1. Elevated levels of anti-flagellin antibodies were present in plasma from HIV-1-infected patients and significantly decreased during 2 years of antiretroviral therapy.Conclusions. Our findings implicate a possible role of HGMB1-bacterial complexes, as a consequence of microbial translocation and cell necrosis, for immune activation in HIV-1 pathogenesis. We propose that flagellin is an important microbial product, that modulates viral replication and induces adaptive immune responsesin vivo.
Adaptive Control for Nonlinear Systems with Time-Varying Control Gain
Authors: Rincon Alejandro , Angulo Fabiola
Published: June 2012

We propose a scheme for nonlinear plants with time-varying control gain and time-varying plant coefficients, on the basis of a plant model consisting of a Brunovsky-type model with polynomials as approximators. We develop an adaptive robust control scheme for this plant, under the following assumptions: (i) the plant terms involve time-varying but bounded coefficients, being its upper bound unknown; (ii) the control gain is unknown, not necessarily bounded, and only its signum is known. To achieve robustness, we use a combination of robustifying control inputs and dead zone-type update laws. We apply this methodology to the speed control of a permanent magnet synchronous motor (PMSM), and we achieve proper tracking results.
The Role of Arg13 in Protein Phosphatase M tPphA from Thermosynechococcus elongatus
Authors: Su Jiyong , Forchhammer Karl
Published: June 2012

A highly conserved arginine residue is close to the catalytic center of PPM/PP2C-type protein phosphatases. Different crystal structures of PPM/PP2C homologues revealed that the guanidinium side chain of this arginine residue can adopt variable conformations and may bind ligands, suggesting an important role of this residue during catalysis. In this paper, we randomly mutated Arginine 13 of tPphA, a PPM/PP2C-type phosphatase from Thermosynechococcus elongatus, and obtained 18 different amino acid variants. The generated variants were tested towards p-nitrophenyl phosphate and various phosphopeptides. Towards p-nitrophenyl phosphate as substrate, twelve variants showed 3–7 times higher Km values than wild-type tPphA and four variants (R13D, R13F, R13L, and R13W) completely lost activity. Strikingly, these variants were still able to dephosphorylate phosphopeptides, although with strongly reduced activity. The specific inability of some Arg-13 variants to hydrolyze p-nitrophenyl phosphate highlights the importance of additional substrate interactions apart from the substrate phosphate for catalysis. The properties of the R13 variants indicate that this residue assists in substrate binding.
Economic Analysis of Different Nuclear Fuel Cycle Options
Authors: Ko Won Il , Gao Fanxing
Published: June 2012

An economic analysis has been performed to compare four nuclear fuel cycle options: a once-through cycle (OT), DUPIC recycling, thermal recycling using MOX fuel in a pressurized water reactor (PWR-MOX), and sodium fast reactor recycling employing pyroprocessing (Pyro-SFR). This comparison was made to suggest an economic competitive fuel cycle for the Republic of Korea. The fuel cycle cost (FCC) has been calculated based on the equilibrium material flows integrated with the unit cost of the fuel cycle components. The levelized fuel cycle costs (LFCC) have been derived in terms of mills/kWh for a fair comparison among the FCCs, and the results are as follows: OT 7.35 mills/kWh, DUPIC 9.06 mills/kWh, PUREX-MOX 8.94 mills/kWh, and Pyro-SFR 7.70 mills/kWh. Due to unavoidable uncertainties, a cost range has been applied to each unit cost, and an uncertainty study has been performed accordingly. A sensitivity analysis has also been carried out to obtain the break-even uranium price (215$/kgU) for the Pyro-SFR against the OT, which demonstrates that the deployment of the Pyro-SFR may be economical in the foreseeable future. The influence of pyrotechniques on the LFCC has also been studied to determine at which level the potential advantages of Pyro-SFR can be realized.
Chronic and Recurrent Depression in Primary Care: Socio-Demographic Features, Morbidity, and Costs
Authors: McMahon Elaine M. , Buszewicz Marta , Griffin Mark , Beecham Jennifer , Bonin Eva-Maria , Rost Felicitas , Walters Kate , King Michael
Published: June 2012

Background. Major depression is often chronic or recurrent and is usually treated within primary care. Little is known about the associated morbidity and costs. Objectives. To determine socio-demographic characteristics of people with chronic or recurrent depression in primary care and associated morbidity, service use, and costs. Method. 558 participants were recruited from 42 GP practices in the UK. All participants had a history of chronic major depression, recurrent major depression, or dysthymia. Participants completed questionnaires including the BDI-II, Work and Social Adjustment Scale, Euroquol, and Client Service Receipt Inventory documenting use of primary care, mental health, and other services. Results. The sample was characterised by high levels of depression, functional impairment, and high service use and costs. The majority (74%) had been treated with an anti-depressant, while few had seen a counsellor (15%) or a psychologist (3%) in the preceding three months. The group with chronic major depression was most depressed and impaired with highest service use, whilst those with dysthymia were least depressed, impaired, and costly to support but still had high morbidity and associated costs. Conclusion. This is a patient group with very significant morbidity and high costs. Effective interventions to reduce both are required.
Urinary TWEAK Level as a Marker of Lupus Nephritis Activity in 46 Cases
Authors: Xuejing Zhu , Jiazhen Tan , Jun Li , Xiangqing Xu , Shuguang Yuan , Fuyou Liu
Published: June 2012

Objective. This study is designed to observe the urinary tumor necrosis factor-like weak inducer of apoptosis (TWEAK) levels in patients with lupus nephritis (LN) and to identify new biomarker of lupus nephritis activity.Methods. Study subjects were 46 cases of patients with LN (including 34 of active cases) who underwent routine renal biopsy. Activity and chronicity indexes of LN were assessed using pathological criteria proposed by Hill et al. in 2000. Urinary TWEAK (uTWEAK) level and Monocyte chemoattractant protein-1 (MCP-1) level were detected by ELISA.Results.Urinary TWEAK level was significantly higher in active LN group than in non-active LN group. Correlation analysis showed that urinary TWEAK levels were significantly correlated with activity index (r=0.825,P<0.01), glomerular activity index (r=  0.754,P<0.01), and tubulointerstitial qualitative activity index (r=0.751,P<0.01), while not significant correlated with chronicity Index (P>0.05). The association between urinary TWEAK levels and urinary MCP-1 levels were significant in active LN group (r=0.809,P<0.01) but not significant in non-active LN group (P>0.05).Conclusions. uWEAK levels were correlated with all active indexes of LN, suggesting its potential role as novel biomarker of active lupus nephritis.
Hematological- and Neurological-Expressed Sequence 1 Gene Products in Progenitor Cells during Newt Retinal Development
Authors: Goto Tatsushi , Tokunaga Fumio , Hisatomi Osamu
Published: June 2012

Urodele amphibians such as Japanese common newts have a remarkable ability to regenerate their injured neural retina, even as adults. We found that hematological- and neurological-expressed sequence 1 (Hn1) gene was induced in depigmented retinal pigment epithelial (RPE) cells, and its expression was maintained at later stages of newt retinal regeneration. In this study, we investigated the distribution of the HN1 protein, the product of the Hn1 gene, in the developing retinas. Our immunohistochemical analyses suggested that the HN1 protein was highly expressed in an immature retina, and the subcellular localization changed during this retinogenesis as observed in newt retinal regeneration. We also found that the expression of Hn1 gene was not induced in mouse after retinal removal. Our results showed that Hn1 gene can be useful for detection of undifferentiated and dedifferentiated cells during both newt retinal development and regeneration.
Wheat Gluten-Laminated Paperboard with Improved Moisture Barrier Properties: A New Concept Using a Plasticizer (Glycerol) Containing a Hydrophobic Component (Oleic Acid)
Authors: Cho Sung-Woo , Blomfeldt Thomas O. J. , Halonen Helena , Gällstedt Mikael , Hedenqvist Mikael S.
Published: June 2012

This paper presents a novel approach to reduce the water vapor transmission rate (WVTR) and water absorbance of wheat gluten/paperboard laminates by introducing a hydrophobic component (oleic acid (OA)) into the hydrophilic plasticizer (glycerol). Whereas the paperboard showed immeasurably high WVTR, the laminate with gluten/glycerol yielded finite values. More importantly, by incorporating 75 wt.% OA into the plasticizer, the WVTR and water absorbance were reduced by, respectively, a factor of three and 1.5–2. Of particular interest was that the mechanical properties were not changing dramatically between 0 and 50 wt.% OA. The results showed clear benefits of combining a gluten film with paperboard. Whereas the paperboard provided toughness, the WG layer contributed with improved moisture barrier properties. In addition, WVTR indicated that the paperboard reduced the swelling of the outer gluten/glycerol layer in moist conditions; a free standing gluten/glycerol film would yield infinite, rather than finite, WVTR values.
Optimal PMU Placement with Uncertainty Using Pareto Method
Authors: Ketabi A. , Nosratabadi S. M. , Sheibani M. R.
Published: June 2012

This paper proposes a method for optimal placement of Phasor Measurement Units (PMUs) in state estimation considering uncertainty. State estimation has first been turned into an optimization exercise in which the objective function is selected to be the number of unobservable buses which is determined based on Singular Value Decomposition (SVD). For the normal condition, Differential Evolution (DE) algorithm is used to find the optimal placement of PMUs. By considering uncertainty, a multiobjective optimization exercise is hence formulated. To achieve this, DE algorithm based on Pareto optimum method has been proposed here. The suggested strategy is applied on the IEEE 30‐bus test system in several case studies to evaluate the optimal PMUs placement.
Exergy Analysis in Hydrogen‐Air Detonation
Authors: Rouboa Abel , Silva Valter , Couto Nuno
Published: June 2012

The main goal of this paper is to analyze the exergy losses during the shock and rarefaction wave of hydrogen‐air mixture. First, detonation parameters (pressure, temperature, density, and species mass fraction) are calculated for three cases where the hydrogen mass fraction in air is 1.5%, 2.5%, and 5%. Then, exergy efficiency is used as objective criteria of performance evaluation. A two‐dimensional computational fluid dynamic code is developed using Finite volume discretization method coupled with implicit scheme for the time discretization (Euler system equations). A seven‐species and five‐step global reactions mechanism is used. Implicit total variation diminishing (TVD) algorithm, based on Riemann solver, is solved. The typical diagrams of exergy balances of hydrogen detonation in air are calculated for each case. The energy balance shows a successive conversion of kinetic energy, and total enthalpy, however, does not indicate consequent losses. On the other hand, exergy losses increase with the augment of hydrogen concentration in air. It obtained an exergetic efficiency of 77.2%, 73.4% and 69.7% for the hydrogen concentrations of 1.5%, 2.5%, and 5%, respectively.
Periurethral Smooth Muscle Tumor of Undetermined Malignant Potential
Authors: Hsieh Jessica , Collins Sarah , Morosky Christopher M.
Published: June 2012

Smooth muscle tumors of undermined malignant potential (STUMP) are atypical smooth muscle tumors. The majority of these tumors are of uterine origin. We report the first known periurethral STUMP. Complete surgical resection is recommended for all cases of STUMP. They can recur in the form of STUMP or leiomyosarcoma.
CXCR2 in Acute Lung Injury
Authors: Konrad F. M. , Reutershan J.
Published: June 2012

In pulmonary inflammation, recruitment of circulating polymorphonuclear leukocytes is essential for host defense and initiates the following specific immune response. One pathological hallmark of acute lung injury and acute respiratory distress syndrome is the uncontrolled transmigration of neutrophils into the lung interstitium and alveolar space. Thereby, the extravasation of leukocytes from the vascular system into the tissue is induced by chemokines that are released from the site of inflammation. The most relevant chemokine receptors of neutrophils are CXC chemokine receptor (CXCR) 1 and CXCR2. CXCR2 is of particular interest since several studies implicate a pivotal role of this receptor in development and promotion of numerous inflammatory disorders. CXCR2 gets activated by ELR+chemokines, including MIP-2, KC (rodents) and IL-8 (human). Since multiple ELR+CXC chemokines act on both receptors—CXCR1 and CXCR2—a pharmacologic agent blocking both receptors seems to be advantageous. So far, several CXCR1/2 antagonists have been developed and have been tested successfully in experimental studies. A newly designed CXCR1 and CXCR2 antagonist can be orally administered and was for the first time found efficient in humans. This review highlights the role of CXCR2 in acute lung injury and discusses its potential as a therapeutic target.
An Approximation of Ultra‐Parabolic Equations
Authors: Ashyralyev Allaberen , Yılmaz Serhat
Published: June 2012

The first and second order of accuracy difference schemes for the approximate solution of the initial boundary value problem for ultra‐parabolic equations are presented. Stability of these difference schemes is established. Theoretical results are supported by the result of numerical examples.
Parallel Motion Simulation of Large‐Scale Real‐Time Crowd in a Hierarchical Environmental Model
Authors: Wang Xin , Zhang Jianhua , Scalia Massimo
Published: June 2012

This paper presents a parallel real‐time crowd simulation method based on a hierarchical environmental model. A dynamical model of the complex environment should be constructed to simulate the state transition and propagation of individual motions. By modeling of a virtual environment where virtual crowds reside, we employ different parallel methods on a topological layer, a path layer and a perceptual layer. We propose a parallel motion path matching method based on the path layer and a parallel crowd simulation method based on the perceptual layer. The large‐scale real‐time crowd simulation becomes possible with these methods. Numerical experiments are carried out to demonstrate the methods and results.
Evaluation of the Morphology and Osteogenic Potential ofTitania‐Based Electrospun Nanofibers
Authors: Wang Xiaokun , Zhu Jingxian , Yin Ling , Liu Shize , Zhang Xin , Ao Yingfang , Chen Haifeng
Published: June 2012

Submicron‐scale titania‐based ceramic fibers with various compositions have been prepared by electrospinning. The as‐prepared nanofibers were heat‐treated at 700°C for 3 h to obtain pure inorganic fiber meshes. The results show that the diameter and morphology of the nanofibers are affected by starting polymer concentration and sol‐gel composition. The titania and titania‐silica nanofibers had the average diameter about 100–300 nm. The crystal phase varied from high‐crystallized rutile‐anatase mixed crystal to low‐crystallized anatase with adding the silica addition. The morphology and crystal phase were evaluated by SEM and XRD. Bone‐marrow‐derived mesenchymal stem cells were seeded on titania‐silica 50/50 fiber meshes. Cell number and early differentiation marker expressions were analyzed, and the results indicated osteogenic potential of the titania‐silica 50/50 fiber meshes.
Diosgenin Induces Apoptosis in HepG2 Cells through Generation of Reactive Oxygen Species and Mitochondrial Pathway
Authors: Kim Dae Sung , Jeon Byoung Kook , Lee Young Eun , Woo Won Hong , Mun Yeun Ja
Published: June 2012

Diosgenin, a naturally occurring steroid saponin found abundantly in legumes and yams, is a precursor of various synthetic steroidal drugs. Diosgenin is studied for the mechanism of its action in apoptotic pathway in human hepatocellular carcinoma cells. Based on DAPI staining, diosgenin-treated cells manifested nuclear shrinkage, condensation, and fragmentation. Treatment of HepG2 cells with 40 μM diosgenin resulted in activation of the caspase-3, -8, -9 and cleavage of poly-ADP-ribose polymerase (PARP) and the release of cytochromec.In the upstream, diosgenin increased the expression of Bax, decreased the expression of Bid and Bcl-2, and augmented the Bax/Bcl-2 ratio. Diosgenin-induced, dose-dependent induction of apoptosis was accompanied by sustained phosphorylation of JNK, p38 MAPK and apoptosis signal-regulating kinase (ASK)-1, as well as generation of the ROS. NAC administration, a scavenger of ROS, reversed diosgene-induced cell death. These results suggest that diosgenin-induced apoptosis in HepG2 cells through Bcl-2 protein family-mediated mitochndria/caspase-3-dependent pathway. Also, diosgenin strongly generated ROS and this oxidative stress might induce apoptosis through activation of ASK1, which are critical upstream signals for JNK/p38 MAPK activation in HepG2 cancer cells.
Predictors and Prognostic Value of Myocardial Injury During Transcatheter Aortic Valve Implantation
Authors: Yong Ze Yie , Wiegerinck Esther M. A. , Boerlage-van Dijk Kirsten , Koch Karel T. , Vis Marije M. , Bouma Berto J. , Henriques José P. S. , Cocchieri Riccardo , Piek Jan J. , de Mol Bas A. J. M. , Baan Jan
Published: June 2012

Background—

Myocardial injury is a common complication during cardiac surgery and percutaneous coronary intervention and is associated with postprocedural cardiovascular morbidity and mortality. Limited data have been reported about the occurrence of myocardial damage associated with transcatheter aortic valve implantation (TAVI). Therefore, our purpose was to investigate the incidence, predictors, and prognostic value of myocardial injury during TAVI.

Methods and Results—

We studied 119 patients (aged 81±8 years; 47 male) who had undergone a TAVI with the Medtronic-CoreValve bioprosthesis. Serum creatine kinase-MB (CK-MB) and cardiac troponin T (cTnT) levels were measured before and after the procedure.
Myocardial injury
was defined as a postprocedural increase of CK-MB and/or cTnT level >5 times the upper reference limit. After TAVI, the incidence of myocardial injury was 17%, which was independently predicted by procedural duration (in minutes) (odds ratio [OR], 1.04; 95% CI, 1.01–1.06), preprocedural β-blocker use (OR, 0.12; 95% CI, 0.03–0.45), peripheral arterial disease (OR, 6.36; 95% CI, 1.56–25.87), and prosthesis depth (in millimeters) (OR, 1.31; 95% CI, 1.08–1.59). The 30-day mortality after TAVI was 13% and was independently predicted by myocardial injury (OR, 8.54; 95% CI, 2.17–33.52), preprocedural hospitalization (OR, 9.36; 95% CI, 2.55–34.38), and left ventricular mass index (in g/m
2
) (OR, 1.02; 95% CI, 1.00–1.03).

Conclusions—

After transcatheter aortic valve implantation, serum levels of both CK-MB and cTnT increase, reflecting the occurrence of periprocedural myocardial injury. A longer procedural duration, the absence of β-blocker use, peripheral arterial disease, and a deeper prosthesis insertion are associated with myocardial injury. Together with preprocedural hospitalization and left ventricular mass, myocardial injury is an independent predictor for 30-day mortality after TAVI.
Prolonged Clopidogrel Use After Bare Metal and Drug-Eluting Stent Placement
Authors: Faxon David P. , Lawler Elizabeth , Young Melissa , Gaziano Michael , Kinlay Scott
Published: June 2012

Background—

Current guidelines recommend combining clopidogrel with aspirin for up to 1 year after coronary stenting, but the value of clopidogrel beyond this time is uncertain.

Methods and Results—

We evaluated all patients in the Veterans Administration healthcare system receiving either drug-eluting or bare metal stents from 2002 to 2006. The Veterans Administration National Patient Care and Pharmacy databases were used to extract patient characteristics, duration of clopidogrel use, and outcomes for up to 4 years after the index procedure. We used Cox proportional hazards to estimate hazard ratios for death, myocardial infarction, revascularization, and bleeding from a 12-month landmark after stenting that excluded patients with events within the first 12 months. Of 42 254 patients, 29 175 met the study inclusion criteria. Compared with ≤12 months of clopidogrel, prolonged clopidogrel (>12 months) was associated with a lower adjusted risk of death for both drug-eluting stents (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.61, 0.82;
P
<0.01) and bare metal stents (HR, 0.85; 95% CI, 0.76, 0.96;
P
=0.01) as well as for death and myocardial infarction but was unrelated to stroke or major bleeding. The effect of prolonged clopidogrel on death or myocardial infarction was significantly greater among patients receiving drug-eluting (HR, 0.70; 95% CI, 0.64, 0.84) compared with bare metal stents (HR, 0.88; 95% CI, 0.79, 0.98; interaction
P
=0.024).

Conclusions—

Patients receiving clopidogrel beyond 12 months had a lower risk of death or myocardial infarction compared patients receiving clopidogrel ≤12 months. The risk reduction was greater for drug-eluting stents. These data support longer durations of dual antiplatelet therapy for patients receiving a stent, particularly for those receiving a drug-eluting stent.
Atmosphere Response Time Scales Estimated from AOGCM Experiments
Authors: Olivié D. J. L. , Peters G. P. , Saint-Martin D.
Published: June 2012

The global-mean surface air temperature response of the climate system to a specific radiative forcing shows characteristic time scales. Identifying these time scales and their corresponding amplitudes (climate sensitivity) allows one to approximate the response to arbitrary radiative forcings. The authors estimate these time scales for a set of atmosphere–ocean general circulation models (AOGCMs) based on relatively short integrations of 100–300 yr for some idealized forcings. Two modes can be clearly distinguished but a large spread in time scales and climate sensitivities exists among the AOGCMs. The analysis herein also shows that different factors influence the mode estimates. The value and uncertainty of the smallest time scale estimate is significantly lower when based on step scenarios than gradual scenarios; the uncertainty on the climate sensitivity of the slow mode can only be reduced significantly by performing longer AOGCM simulations; and scenarios with only a monotonically increasing forcing do not easily permit the climate sensitivity and the response time for the slow mode to be disentangled. Finally, climate sensitivities can be estimated more accurately than response times.
On the Use of Emulators with Extreme and Highly Nonlinear Geophysical Simulators
Authors: Tokmakian Robin , Challenor Peter , Andrianakis Yiannis
Published: June 2012

Gaussian process emulators are a powerful tool for understanding complex geophysical simulators, including oceanic and atmospheric general circulation models. Concern has been raised about their ability to emulate complex nonlinear systems. For the first time, using the simple Stommel model, the way in which emulators can reasonably represent the full sampling space of an extreme nonlinear, bimodal system is illustrated. This simple example also shows how an emulator can help to elucidate interactions between parameters. The ideas are further illustrated with a second, more realistic, intermediate complex climate simulator. The paper describes what is meant by an emulator, the methodology of emulators, how emulators can be assessed, and why they are useful. It is shown how simple emulators can be useful to explore the parameter space (initial conditions, process parameters, and boundary conditions) of complex computer simulators, such as ocean and climate general circulation models, even when simulator outcomes contain steps in the response.
Use of Underwater Gliders for Acoustic Data Retrieval from Subsurface Oceanographic Instrumentation and Bidirectional Communication in the Deep Ocean
Authors: Send Uwe , Regier Lloyd , Jones Brent
Published: June 2012

Many fixed oceanographic instruments and observing systems are deployed in the water column or on the seafloor for extended periods of time without any expression at the sea surface. To routinely communicate with such subsurface instruments in the deep ocean, here a system is presented that uses underwater gliders and commercially available acoustic modems for this task and its use is demonstrated with subsurface moorings and inverted echo sounders plus bottom pressure sensor (PIES). One recent glider mission spent 31 days in data retrieval dives, capturing 2 MB of error-free subsurface data. To acquire this volume, a total of 2.65 MB (including all retransmissions) were sent, with a success rate of 75%. A model for the energy usage of each phase of modem function was derived from laboratory measurements. While the model predicts that the glider would expend 0.21 J to acquire each data byte, the actual consumption of the glider in the field is 0.49 J byte−1. The inefficiency is due to overhead associated with establishment of the acoustic link and with the resending of data that is received with errors. Including all the time for negotiating the acoustic link and for the retransmission of erroneous data, the net data throughput are around 3 bytes s−1 in spite of the modem operating at 140 to 600 baud. Even with these limitations, the technique has shown to be useful and is being utilized routinely in a research project in the California Current to obtain data from horizontal distances up to 7 km from an instrument at depths up to 4000 m, transferring on average 6 kB of data in a day of acoustic communications.
A Scale-Aware Anticipated Potential Vorticity Method: On Variable-Resolution Meshes
Authors: Chen Qingshan , Gunzburger Max , Ringler Todd
Published: June 2012

A scale-aware formulation of the anticipated potential vorticity method (APVM), previously derived for quasi-uniform unstructured grids, is evaluated on multiresolution grids. Comparison is made to the original, nonscale-aware formulation of the APVM. Numerical experiments are performed using the shallow-water standard test case 5. The scale awareness of the new formulation is demonstrated by the following observations: (i) the range of optimal values for the single parameter of the new formulation is much less sensitive to grid resolution than that of the original formulation; (ii) within the optimal parameter range, the new formulation is able to maintain proper dissipation across scales and is thus able to produce better results in terms of errors in the potential enstrophy spectrum curves; and (iii) the new formulation is robust in that a single optimal parameter obtained for a specific grid can be safely used on other grids as well.
A Modified Flood Severity Assessment for Enhanced Decision Support: Application to the Boscastle Flash Flood of 2004
Authors: Murray S. J. , Smith A. D. , Phillips J. C.
Published: June 2012

A modified flash flood severity assessment is presented, based on scoring a set of factors according to their potential for generating extreme catchment-scale flooding. Improvements are made to the index through incorporation of parameter uncertainties, managing data absence, and clearer graphical communication. The motive for proposing these changes is to better inform flood managers during the development of a flash flood that may require an emergency response. This modified decision-support system is demonstrated for the Boscastle flood of 2004 and other historical floods in the United Kingdom. For Boscastle, the extreme nature of the flood is underestimated, which is likely to be due to the lack of sophistication in weighting flood parameters. However, the proposed amendments are able to rapidly reflect the reliability of a catchment severity rating, which may further enhance this technique as a decision-support tool alongside radar observations of localized storms.
The co-evolution of cosmopolitan and national statehood – Preliminary theoretical considerations on the historical evolution of constitutionalism
Authors: Brunkhorst Hauke
Published: June 2012

The article claims that we should not just look towards a utopian future in fulfilling a claim about realization of a cosmopolitan, non-national world order. Already during antiquity the idea of a transcendent universal order took on a differentiated form at the same time as there happened to be institutionalization. Since the legal revolution of the long 12th century, this duality has been constitutional and has had a hierarchical structure. However, not only was the invention legal, it was also organizational; hence, the modern political, legal and organizational powers emerged long before the more celebrated state-building processes of the 16th and 17th centuries. The point is that the order was both political and cosmopolitan, institutional and universal. The nation-state was an exception compared with this long and widespread legacy of cosmopolitan power. But the universality of subjective rights was re-institutionalized according to principles that excluded inequalities. This was set in motion even before the UN Charter, not just with the ideas of 1789 but also institutionalized in Roosevelt’s New Deal together with the social and political rights that were institutionalized specifically as a consequence of the World Wars and the political claims that followed.
Obstacles to a world state in the shadow of the world market
Authors: Jessop Bob
Published: June 2012

This article explores the obstacles to the development and operation of a world state that are rooted in functional differentiation of modern societies, the ecological dominance of the broadly capitalist world market, and the inherent tendencies of all forms of governance to fail. It also highlights the challenges to the temporal as well as territorial sovereignty of states, whatever their scale of operation, due to the acceleration as well as globalization of social relations. Combining insights from Niklas Luhmann and Karl Marx, the article develops some novel arguments about multi-spatial metagovernance as an alternative approach to the problems posed by a world state as the guarantor of global social order.
The Impact of Numeracy Ability and Technology Skills on Older Adults’ Performance of Health Management Tasks Using a Patient Portal
Authors: Taha Jessica , Sharit Joseph , Czaja Sara J.
Published: June 2012

Patient portals, which allow patients to access their health record via the Internet, are becoming increasingly widespread and are expected to be used by diverse consumer populations. In addition to technology skills, numeracy skills are also likely to be critical to performing health management tasks, as much of the data contained in the portal are numeric. This study examined how factors such as Internet experience, numeracy, and education impacted the performance of common tasks using a simulated patient portal among a sample of older adults. In addition, information was gathered on the ability of older adults to estimate their numeracy skills. Results indicated that numeracy and Internet experience had a significant impact on their ability to perform the tasks and that older adults tended to overestimate their numeracy skills. Results from this study can help to identify interventions that may enhance the usability of patient portals for older adults.
Do African American Women Require Fewer Calories to Maintain Weight?
Authors: Brewer LaPrincess C. , Miller Edgar R. , Appel Lawrence J. , Anderson Cheryl A. M.
Published: June 2012

Background:

The high prevalence of obesity in African American (AA) women may result, in part, from a lower resting metabolic rate (RMR) than non‐AA women. If true, AA women should require fewer calories than non‐AA women to maintain weight. Our objective was to determine in the setting of a controlled feeding study, if AA women required fewer calories than non‐AA women to maintain weight.

Materials and Methods:

This analysis includes 206 women (73% AA), aged 22–75 years, who participated in the Dietary Approaches to Stop Hypertension (DASH) trial—a multicenter, randomized, controlled, feeding study comparing the effects of 3 dietary patterns on blood pressure in individuals with prehypertension or stage 1 hypertension. After a 3‐week run‐in, participants were randomized to 1 of 3 dietary patterns for 8 weeks. Calorie intake was adjusted during feeding to maintain stable weight. The primary outcome of this analysis was average daily calorie (kcal) intake during feeding.

Results:

AA women had higher baseline weight and body mass index than non‐AA women (78.4 vs 72.4 kg, P < .01; 29.0 vs 27.6 kg/m2, P < .05, respectively). During intervention feeding, mean (SD) kcal was 2168 (293) in AA women and 2073 (284) in non‐AA women. Mean intake was 94.7 kcal higher in AA women than in non‐AA women (P < .05). After adjustment for potential confounders, there was no difference in caloric intake between AA and non‐AA women (Δ = −2.8 kcal, P = .95).

Conclusion:

These results do not support the view that AA women are at greater risk for obesity because they require fewer calories to maintain weight.
To the Other Side of the Neglected Brain
Authors: Koch Giacomo , Veniero Domenica , Caltagirone Carlo
Published: June 2012

The human brain is characterized by the lateralization of cognitive functions. Multiple lines of evidence suggest the deployment of visuospatial attention is controlled by a frontoparietal network, with a right hemisphere dominance. Among cortical areas included in the network, the right posterior parietal cortex (PPC) has been proposed to be a crucial node and has also been implicated on clinical grounds. Here, the authors provide an overview of the existent literature giving evidence to a functional asymmetry of the parietal cortices in directing visuospatial attention, focusing on those studies seeking to characterize the causal role of PPC, applying transcranial magnetic stimulation and its combination with imaging techniques, such as electroencephalography and fMRI. First, the role of PPC and how this region exerts its control over remote areas of both hemispheres is discussed. The second part discusses studies involving neglect patients shedding light on the complex interplay between left and right PPC, strongly supporting the hemispheric rivalry theory. Finally, studies demonstrating changes of neglect disorders following the manipulation of the unaffected hemisphere activation will be discussed.
The key role of repeated DNAs in sex chromosome evolution in two fish species with ZW sex chromosome system
Authors: de Bello Cioffi Marcelo , Kejnovský Eduard , Marquioni Vinicius , Poltronieri Juliana , Molina Wagner Franco , Diniz Débora , Bertollo Luiz Antonio Carlos
Published: June 2012

Despite substantial progress, there are still several gaps in our knowledge about the process of sex chromosome differentiation. The degeneration of sex-specific chromosome in some species is well documented, but it is not clear if all species follow the same evolutionary pathway. The accumulation of repetitive DNA sequences, however, is a common feature. To better understand this involvement, fish species emerge as excellent models because they exhibit a wide variety of sex chromosome and sex determining systems. Besides, they have much younger sex chromosomes compared to higher vertebrates, making it possible to follow early steps of differentiation. Here, we analyzed the arrangement of 9 repetitive DNA sequences in the W chromosomes of 2 fish species, namely Leporinus reinhardti and Triportheus auritus, which present well-differentiated ZZ/ZW sex system, but differ in respect to the size of the sex-specific chromosome. Both W chromosomes are almost fully heterochromatic, with accumulation of repeated DNAs in their heterochromatic regions. We found that microsatellites have strongly accumulated on the large W chromosome of L. reinhardti but not on the reduced-size W chromosome of T. auritus and are therefore important players of the W chromosome expansion. The present data highlight that the evolution of the sex chromosomes can diverge even in the same type of sex system, with and without the degeneration of the specific-sex chromosome, being more dynamic than traditionally appreciated.