bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of multilevel sequentially semiseparable preconditioners on computational fluid dynamics benchmark problems using Incompressible Flow and Iterative Solver Software
Authors: Qiu Yue , van Gijzen Martin B. , van Wingerden Jan‐Willem , Verhaegen Michel , Vuik Cornelis
Published: March 2015

This paper studies a new preconditioning technique for sparse systems arising from discretized partial differential equations in computational fluid dynamics problems. This preconditioning technique exploits the multilevel sequentially semiseparable (MSSS) structure of the system matrix. MSSS matrix computations give a data‐sparse way to approximate theLUfactorization of a sparse matrix from discretized partial differential equations in linear computational complexity with respect to the problem size. In contrast to the standard block diagonal and block upper‐triangular preconditioners, we exploit the global MSSS structure of the 2×2 block system from the discretized Stokes equation and linearized Navier‐Stokes equation. This avoids approximating the Schur complement explicitly, which is a big advantage over standard block preconditioners. Through numerical experiments on standard computational fluid dynamics benchmark problems in Incompressible Flow and Iterative Solver Software, we show the performance of the MSSS preconditioners. They indicate that the global MSSS preconditioner not only yields mesh size independent convergence but also gives viscosity parameter and Reynolds number independent convergence. Compared with the algebraic multigrid (AMG) method and the geometric multigrid (GMG) method for block preconditioners, the MSSS preconditioning technique is more robust than both the AMG method and GMG method, and considerably faster than the AMG method. Copyright © 2015 John Wiley & Sons, Ltd.
Stage‐structured population systems with temporally periodic delay
Authors: Wu Xiaotian , Magpantay Felicia Maria G. , Wu Jianhong , Zou Xingfu
Published: March 2015

For some ectotherms such as Ixodes scapularis, a vector of Lyme disease, changes in temperature are believed to affect the interstadial development time and hence give rise to a time‐periodic delay due to seasonality in the population dynamics described by a stage‐structured population growth model. Here, we develop a formulation linking the chronological delay with multiple stage‐specific interstadial delays. We also present a definition for the basic reproductive ratio for such a system, develop a simple algorithm to compute it, and show that the results regarding the stability of the zero solution are consistent with those from computing the dominant Floquet multiplier. Numerical simulations also show that the threshold value for the population persistence or extinction depends not only on the mean but also on the amplitude and phase of the periodic development delays. Copyright © 2015 John Wiley & Sons, Ltd.
Interventions that may reduce depressive symptoms among prostate cancer patients: a systematic review and meta‐analysis
Authors: Newby Timothy A. , Graff Julie N. , Ganzini Linda K. , McDonagh Marian S.
Published: March 2015

Objective

Prostate cancer patients are at increased risk of depression yet there is no standard intervention to address this. The purpose of this meta‐analysis is to examine the efficacy of interventions in reducing depressive symptoms in men with prostate cancer.

Methods

Searches for studies were conducted in four databases and by hand. Randomized controlled trials of any intervention relative to control for depression in prostate cancer patients at any stage of their cancer treatment were included.

Results

We identified 11 studies that randomized men with prostate cancer to either an intervention meant to improve some aspect of quality of life or control and reported depressive symptoms scores before and after the intervention or control condition. Two of these were not used in our meta‐analysis either for concerns about quality or for lack of depression scores. The interventions identified in the remaining nine articles were exercise (four), information (three), psychotherapy or peer support (three), massage therapy (one), and medication (one). Several publications included more than one type of intervention. A meta‐analysis of all studies showed that an intervention of some types significantly improved depressive symptom scores relative to the control condition (improvement in depression score by −0.86 unit (95% CI: −1.42, −0.31)). Isolating the peer support/psychotherapy studies also showed significant improvement (improvement in depression score by −1.09 unit (95% CI: −2.05, −0.13)).

Conclusion

Treatments to improve depressive symptoms in men with prostate cancer may be effective, with the best evidence supporting the use of peer support/psychotherapy. Copyright © 2015 John Wiley & Sons, Ltd.
Investigation on Plasma‐Driven Methane Dry Reforming in a Self‐Triggered Spark Reactor
Authors: Shapoval Volodymyr , Marotta Ester
Published: March 2015

The performance of methane dry reforming in a self‐triggered spark discharge reactor is evaluated in terms of conversion of reagents, yield and selectivity of desired products (syngas), and energy efficiency. The effects of feed gas composition (CO2:CH4 ratio), flow rate and input electrical power were investigated. The process performance is very good: under the best experimental conditions (CO2:CH4 of 1:1 at 100 mL · min−1, input power of 20 W) conversion (71% for CH4 and 65% for CO2), selectivity (78% for H2 and 86% for CO), and energy efficiency (2.3–2.4 mmol · kJ−1) are all quite high. The formation of ethane, ethylene, and acetylene was also detected and analyzed as a function of the CO2:CH4 ratio. As the CO2:CH4 ratio is decreased below 1, the conversion of both CH4 and CO2 slightly increases, but the yield in syngas decreases favoring the formation of C2 hydrocarbons and the appearance of carbon deposits. Increasing the CO2:CH4 ratio from 0.5 to 1.5 has virtually no effect on the reagents conversion and on H2 production but promotes the formation of CO and reduces that of C2 hydrocarbons. The best CO2:CH4 was determined to be 1.0 considering also the lowest formation of water as byproduct and the optimal discharge stability.
State selection in Markov models for panel data with application to psoriatic arthritis
Authors: Thom Howard H. Z. , Jackson Christopher H. , Commenges Daniel , Sharples Linda D.
Published: March 2015

Markov multistate models in continuous‐time are commonly used to understand the progression over time of disease or the effect of treatments and covariates on patient outcomes. The states in multistate models are related to categorisations of the disease status, but there is often uncertainty about the number of categories to use and how to define them. Many categorisations, and therefore multistate models with different states, may be possible. Different multistate models can show differences in the effects of covariates or in the time to events, such as death, hospitalisation, or disease progression. Furthermore, different categorisations contain different quantities of information, so that the corresponding likelihoods are on different scales, and standard, likelihood‐based model comparison is not applicable.

We adapt a recently developed modification of Akaike's criterion, and a cross‐validatory criterion, to compare the predictive ability of multistate models on the information which they share. All the models we consider are fitted to data consisting of observations of the process at arbitrary times, often called ‘panel’ data. We develop an implementation of these criteria through Hidden Markov models and apply them to the comparison of multistate models for the Health Assessment Questionnaire score in psoriatic arthritis. This procedure is straightforward to implement in the R package ‘msm’. Copyright © 2015 John Wiley & Sons, Ltd.
Establishing Criteria for Human Mesenchymal Stem Cell Potency
Authors: Samsonraj Rebekah M. , Rai Bina , Sathiyanathan Padmapriya , Puan Kia Joo , Rötzschke Olaf , Hui James H. , Raghunath Michael , Stanton Lawrence W. , Nurcombe Victor , Cool Simon M.
Published: March 2015

This study sought to identify critical determinants of mesenchymal stem cell (MSC) potency using in vitro and in vivo attributes of cells isolated from the bone marrow of age- and sex-matched donors. Adherence to plastic was not indicative of potency, yet capacity for long-term expansion in vitro varied considerably between donors, allowing the grouping of MSCs from the donors into either those with high-growth capacity or low-growth capacity. Using this grouping strategy, high-growth capacity MSCs were smaller in size, had greater colony-forming efficiency, and had longer telomeres. Cell-surface biomarker analysis revealed that the International Society for Cellular Therapy (ISCT) criteria did not distinguish between high-growth capacity and low-growth capacity MSCs, whereas STRO-1 and platelet-derived growth factor receptor alpha were preferentially expressed on high-growth capacity MSCs. These cells also had the highest mean expression of the mRNA transcripts TWIST-1 and DERMO-1. Irrespective of these differences, both groups of donor MSCs produced similar levels of key growth factors and cytokines involved in tissue regeneration and were capable of multilineage differentiation. However, high-growth capacity MSCs produced approximately double the volume of mineralized tissue compared to low-growth capacity MSCs when assessed for ectopic bone-forming ability. The additional phenotypic criteria presented in this study when combined with the existing ISCT minimum criteria and working proposal will permit an improved assessment of MSC potency and provide a basis for establishing the quality of MSCs prior to their therapeutic application. Stem Cells  2015;33:1878–1891
Unipotent Megakaryopoietic Pathway Bridging Hematopoietic Stem Cells and Mature Megakaryocytes
Authors: Nishikii Hidekazu , Kanazawa Yosuke , Umemoto Terumasa , Goltsev Yury , Matsuzaki Yu , Matsushita Kenji , Yamato Masayuki , Nolan Garry P. , Negrin Robert , Chiba Shigeru
Published: March 2015

Recent identification of platelet/megakaryocyte-biased hematopoietic stem/repopulating cells requires revision of the intermediate pathway for megakaryopoiesis. Here, we show a unipotent megakaryopoietic pathway bypassing the bipotent megakaryocyte/erythroid progenitors (biEMPs). Cells purified from mouse bone marrow by CD42b (GPIbα) marking were demonstrated to be unipotent megakaryocytic progenitors (MKPs) by culture and transplantation. A subpopulation of freshly isolated CD41+ cells in the lineage Sca1+cKit+ (LSK) fraction (subCD41+LSK) differentiated only into MKP and mature megakaryocytes in culture. Although CD41+LSK cells as a whole were capable of differentiating into all myeloid and lymphoid cells in vivo, they produced unipotent MKP, mature megakaryocytes, and platelets in vitro and in vivo much more efficiently than Flt3+CD41−LSK cells, especially at the early phase after transplantation. In single cell polymerase chain reaction and thrombopoietin (TPO) signaling analyses, the MKP and a fraction of CD41+LSK, but not the biEMP, showed the similarities in mRNA expression profile and visible TPO-mediated phosphorylation. On increased demand of platelet production after 5-FU treatment, a part of CD41+LSK population expressed CD42b on the surface, and 90% of them showed unipotent megakaryopoietic capacity in single cell culture and predominantly produced platelets in vivo at the early phase after transplantation. These results suggest that the CD41+CD42b+LSK are straightforward progenies of megakaryocytes/platelet-biased stem/repopulating cells, but not progenies of biEMP. Consequently, we show a unipotent/highly biased megakaryopoietic pathway interconnecting stem/repopulating cells and mature megakaryocytes, the one that may play physiologic roles especially in emergency megakaryopoiesis. Stem Cells 2015;33:2196–2207
PI3kα and STAT1 Interplay Regulates Human Mesenchymal Stem Cell Immune Polarization
Authors: Mounayar Marwan , Kefaloyianni Eirini , Smith Brian , Solhjou Zhabiz , Maarouf Omar H. , Azzi Jamil , Chabtini Lola , Fiorina Paolo , Kraus Morey , Briddell Robert , Fodor William , Herrlich Andreas , Abdi Reza
Published: March 2015

The immunomodulatory capacity of mesenchymal stem cells (MSCs) is critical for their use in therapeutic applications. MSC response to specific inflammatory cues allows them to switch between a proinflammatory (MSC1) or anti-inflammatory (MSC2) phenotype. Regulatory mechanisms controlling this switch remain to be defined. One characteristic feature of MSC2 is their ability to respond to IFNγ with induction of indoleamine 2,3-dioxygenase (IDO), representing the key immunoregulatory molecule released by human MSC. Here, we show that STAT1 and PI3Kα pathways interplay regulates IFNγ-induced IDO production in MSC. Chemical phosphoinositide 3-kinase (PI3K) pan-inhibition, PI3Kα-specific inhibition or shRNA knockdown diminished IFNγ-induced IDO production. This effect involved PI3Kα-mediated upregulation of STAT1 protein levels and phosphorylation at Ser727. Overexpression of STAT1 or of a constitutively active PI3Kα mutant failed to induce basal IDO production, but shifted MSC into an MSC2-like phenotype by strongly enhancing IDO production in response to IFNγ as compared to controls. STAT1 overexpression strongly enhanced MSC-mediated T-cell suppression. The same effect could be induced using short-term pretreatment of MSC with a chemical inhibitor of the counter player of PI3K, phosphatase and tensin homolog. Finally, downregulation of STAT1 abrogated the immunosuppressive capacity of MSC. Our results for the first time identify critical upstream signals for the induced production of IDO in MSCs that could be manipulated therapeutically to enhance their immunosuppressive phenotype. Stem Cells  2015;33:1892–1901
Continuous Non-Cell Autonomous Reprogramming to Generate Retinal Ganglion Cells for Glaucomatous Neuropathy
Authors: Parameswaran Sowmya , Dravid Shashank Manohar , Teotia Pooja , Krishnamoorthy Raghu R. , Qiu Fang , Toris Carol , Morrison John , Ahmad Iqbal
Published: March 2015

Glaucoma, where the retinal ganglion cells (RGCs) carrying the visual signals from the retina to the visual centers in the brain are progressively lost, is the most common cause of irreversible blindness. The management approaches, whether surgical, pharmacological, or neuroprotective do not reverse the degenerative changes. The stem cell approach to replace dead RGCs is a viable option but currently faces several barriers, such as the lack of a renewable, safe, and ethical source of RGCs that are functional and could establish contacts with bona fide targets. To address these barriers, we have derived RGCs from the easily accessible adult limbal cells, reprogrammed to pluripotency by a non-nucleic acid approach, thus circumventing the risk of insertional mutagenesis. The generation of RGCs from the induced pluripotent stem (iPS) cells, also accomplished non-cell autonomously, recapitulated the developmental mechanism, ensuring the predictability and stability of the acquired phenotype, comparable to that of native RGCs at biochemical, molecular, and functional levels. More importantly, the induced RGCs expressed axonal guidance molecules and demonstrated the potential to establish contacts with specific targets. Furthermore, when transplanted in the rat model of ocular hypertension, these cells incorporated into the host RGC layer and expressed RGC-specific markers. Transplantation of these cells in immune-deficient mice did not produce tumors. Together, our results posit retinal progenitors generated from non-nucleic acid-derived iPS cells as a safe and robust source of RGCs for replacing dead RGCs in glaucoma. Stem Cells  2013;33:1743–1758
Multipotent Caudal Neural Progenitors Derived from Human Pluripotent Stem Cells That Give Rise to Lineages of the Central and Peripheral Nervous System
Authors: Denham Mark , Hasegawa Kouichi , Menheniott Trevelyan , Rollo Ben , Zhang Dongcheng , Hough Shelley , Alshawaf Abdullah , Febbraro Fabia , Ighaniyan Samiramis , Leung Jessie , Elliott David A. , Newgreen Donald F. , Pera Martin F. , Dottori Mirella
Published: March 2015

The caudal neural plate is a distinct region of the embryo that gives rise to major progenitor lineages of the developing central and peripheral nervous system, including neural crest and floor plate cells. We show that dual inhibition of the glycogen synthase kinase 3β and activin/nodal pathways by small molecules differentiate human pluripotent stem cells (hPSCs) directly into a preneuroepithelial progenitor population we named “caudal neural progenitors” (CNPs). CNPs coexpress caudal neural plate and mesoderm markers, and, share high similarities to embryonic caudal neural plate cells in their lineage differentiation potential. Exposure of CNPs to BMP2/4, sonic hedgehog, or FGF2 signaling efficiently directs their fate to neural crest/roof plate cells, floor plate cells, and caudally specified neuroepithelial cells, respectively. Neural crest derived from CNPs differentiated to neural crest derivatives and demonstrated extensive migratory properties in vivo. Importantly, we also determined the key extrinsic factors specifying CNPs from human embryonic stem cell include FGF8, canonical WNT, and IGF1. Our studies are the first to identify a multipotent neural progenitor derived from hPSCs, that is the precursor for major neural lineages of the embryonic caudal neural tube. Stem Cells  2015;33:1759–1770
How Can Book Reading Close the Word Gap? Five Key Practices From Research
Authors: Snell Emily K. , Hindman Annemarie H. , Wasik Barbara A.
Published: March 2015

Vocabulary development is critical for children's ability to learn to read and their success at school. Vocabulary has also been identified as a key factor in the achievement gap, with children from low‐income families knowing significantly fewer words when they enter school. Although book reading has long been celebrated as an effective way for teachers to introduce children to vocabulary words, teachers have received little specific guidance about exactly which strategies are most effective for teaching children words. In this paper, we review the literature on book reading‐focused vocabulary interventions for preschool‐ and kindergarten‐aged children. Findings suggest that teachers should focus on five strategies that boost word learning through book reading, including defining words, discussing and asking questions about the words, rereading books, retelling books, and designing classroom activities that allow children to hear and use new vocabulary throughout the day.
Three Cadmium(II) Coordination Polymers based on Mixed 1,2‐Naphthalenedicarboxylate and Bis(pyridyl) Co‐ligands: Structural Diversities and Photoluminescent Properties
Authors: Chen Min , Zhao Hui , Wang Zhuo‐Wei , Liu Chun‐Sen
Published: March 2015

Hydrothermal reactions of Cd(OAc)2·2H2O with 1,2‐naphthalic anhydride in the absence/presence of different rigid/flexible bis(pyridyl) co‐ligands, produce three distinct coordination polymers, namely [Cd(ndc)]n (1), {[Cd5(ndc)4(bpp)2(OH)2](H2O)4}n (2), and [Cd5(ndc)4(bpy)2(OH)2]n (3) [ndc = 1,2‐naphthalenedicarboxylate, bpp = 1,3‐bis(4‐pyridyl)propane, and bpy = 4,4′‐bipyridine]. Complex 1 contains dinuclear [Cd2O2] clusters as secondary building units (SBUs) and shows a two‐dimensional (2D) kgd network. Complexes 2 and 3 possess one‐dimensional (1D) chains based on pentanuclear [Cd5(μ3‐OH)2(COO)2] units as SBUs, which are further extended to afford 2D sql sheet via flexible bpp in 2 and three‐dimensional (3D) pcu network via rigid bpy in 3, respectively. The structural diversities indicate that the bis(pyridyl) co‐ligands with different flexibility play a key role on the formation of the final supramolecular structures. The complexes were characterized by X‐ray crystallographic, IR, elemental, thermal stability, and powder X‐ray diffraction analyses. In addition, the photoluminescent properties in solid state were also investigated.
Comprehensive review of the detection methods for synthetic cannabinoids and cathinones
Authors: Namera Akira , Kawamura Maho , Nakamoto Akihiro , Saito Takeshi , Nagao Masataka
Published: March 2015

A number of N-alkyl indole or indazole-3-carbonyl analogs, with modified chemical structures, are distributed throughout the world as synthetic cannabinoids. Like synthetic cannabinoids, cathinone analogs are also abused and cause serious problems worldwide. Acute deaths caused by overdoses of these drugs have been reported. Various analytical methods that can cope with the rapid changes in chemical structures are required for routine analysis and screening of these drugs in seized and biological materials for forensic and clinical purposes. Although many chromatographic methods to analyze each drug have been published, there are only a few articles summarizing these analytical methods. This review presents the various colorimetric detections, immunochemical assays, gas chromatographic–mass spectrometric methods, and liquid chromatographic–mass spectrometric methods proposed for the analysis of synthetic cannabinoids and cathinones.
Cardiac Findings and Events Observed in an Open-Label Clinical Trial of Tafamidis in Patients with non-Val30Met and non-Val122Ile Hereditary Transthyretin Amyloidosis
Authors: Damy Thibaud , Judge Daniel P. , Kristen Arnt V. , Berthet Karine , Li Huihua , Aarts Janske
Published: March 2015

A phase 2, open-label study in 21 patients with non-Val30Met and non-Val122Ile hereditary transthyretin amyloidosis showed that tafamidis (20 mg daily for 12 months) stabilized these transthyretin variants. We assessed cardiac amyloid infiltration and cardiac abnormalities in this same study population. At baseline, median age was 64.3 years, 11 patients were in NYHA class II, 13 had conduction abnormalities, 14 N-terminal pro-hormone brain natriuretic peptide concentrations >300 pg/ml, and 17 interventricular septal thickness >12 mm. Mean (SD) left ventricular ejection fraction was 60.3 % (9.96). Patients with normal heart rate variability increased from 4/19 at baseline to 8/19 at month 12 (p < 0.05). Cardiac biomarkers remained stable. Although four patients had increases in interventricular septal thickness ≥2 mm, the remainder had stable septal wall thickness. There were no clinically relevant changes in mean echocardiographic/electrocardiographic variables and no safety concerns.
Structural stability and functional remodeling of high‐density lipoproteins
Authors: Gursky Olga
Published: March 2015

Lipoproteins are protein–lipid nanoparticles that transport lipids in circulation and are central in atherosclerosis and other disorders of lipid metabolism. Apolipoproteins form flexible structural scaffolds and important functional ligands on the particle surface and direct lipoprotein metabolism. Lipoproteins undergo multiple rounds of metabolic remodeling that is crucial to lipid transport. Important aspects of this remodeling, including apolipoprotein dissociation and particle fusion, are mimicked in thermal or chemical denaturation and are modulated by free energy barriers. Here we review the biophysical studies that revealed the kinetic mechanism of lipoprotein stabilization and unraveled its structural basis. The main focus is on high‐density lipoprotein (HDL). An inverse correlation between stability and functions of various HDLs in cholesterol transport suggests the functional role of structural disorder. A mechanism for the conformational adaptation of the major HDL proteins, apoA‐I and apoA‐II, to the increasing lipid load is proposed. Together, these studies help understand why HDL forms discrete subclasses separated by kinetic barriers, which have distinct composition, conformation and functional properties. Understanding these properties may help improve HDL quality and develop novel therapies for cardiovascular disease.
The effects of prenatal undernutrition and postnatal high‐fat diet on hypothalamic Kiss1 mRNA and serum leptin levels
Authors: Iwasa Takeshi , Matsuzaki Toshiya , Munkhzaya Munkhsaikhan , Tungalagsuvd Altankhuu , Yamasaki Mikio , Kuwahara Akira , Yasui Toshiyuki , Irahara Minoru
Published: March 2015

Prenatal undernutrition and postnatal overnutrition increase the risk of some metabolic disorders in adulthood, and hypothalamic leptin resistance makes an important contribution to these effects. Leptin plays important roles in the maintenance of reproductive function, and its actions might be partially mediated by kisspeptin, which is a potent positive regulator of gonadotropin‐releasing hormone. In this study, the effects of prenatal undernutrition and postnatal overnutrition on reproductive parameters and sexual maturation during the peripubertal period were evaluated. Rats subjected to prenatal undernutrition (IUGR) and fed a postnatal high‐fat diet (HFD) (n = 7) exhibited 40% higher serum leptin levels and 30% lower hypothalamic Kiss1 (the gene encoding kisspeptin) mRNA levels than those subjected to prenatal undernutrition (IUGR) and fed a normal diet (n = 7). No such HFD‐induced postnatal alterations were observed in the rats fed a normal diet during the prenatal period (control) (n = 7 per group). Although the consumption of the HFD did not affect the serum luteinizing hormone levels or body weight of the IUGR or control rats, it did promote vaginal opening in both groups (evaluated in 14 rats per group). These findings indicate that hypothalamic leptin resistance might occur in IUGR‐HFD rats, but these changes do not influence downstream effectors of the reproductive endocrinological system. They also suggest that the relationships between nutritional conditions, body weight, reproductive factors, and sexual maturation are complex.
Establish a perioperative check forum for peripheral intravenous access to prevent the occurrence of phlebitis
Authors: Chiu Po‐Chun , Lee Ya‐Hui , Hsu Hung‐Te , Feng Yu‐Tung , Lu I‐Cheng , Chiu Shun‐Li , Cheng Kuang‐I
Published: March 2015

The prevalence of intravenous (IV) catheter‐related infections is 0.5 per 1000 device days, and these infections cause tenderness, erythema, swelling and phlebitis. Catheter‐related bloodstream infections (CRBSI) may independently increase hospital costs and length of stay; the aim of the study was to set up a standard operating procedure (SOP) for the maintenance of peripheral vein catheter patency and the prevention of IV catheter‐related complications. This is a retrospective study, enrolling patients who received anesthesia between April 2010 and January 2011. The study included 1 month of pretest phase, and 3 months each of “notification” phase, “observation” phase and “end” phase, respectively. The cannulations were set up by surgical ward nurses following the SOP on establishing peripheral intravenous catheter in our hospital. The cannulation sites were then examined before surgery and postoperatively by registered nurse anesthetists using the Baxter Scale. We also tried to set up a feedback circuit to let ward nurses know about the IV patency rate. As a result, 14,682 patients were enrolled in the study. The incidence of IV therapy‐related adverse events was 0.78% in the notification phase, 0.43% in the observation phase, and 0.13% in the end phase. Overall IV therapy‐related events declined significantly (p < 0.01), and the presence of phlebitis was associated with age (p < 0.05). An SOP established to assess IV patency through a checklist can reduce phlebitis and improve quality. The checklist increases ward nurses' and nurse anesthetists' awareness of IV patency, and the feedback circuit substantially reduces IV event rate.
Instability of a dinucleotide repeat in the 3′‐untranslated region (UTR) of the microsomal prostaglandin E synthase‐1 (mPGES‐1) gene in microsatellite instability‐high (MSI‐H) colorectal carcinoma
Authors: Cherukuri Durga Prasad , Deignan Joshua L. , Das Kingshuk , Grody Wayne W. , Herschman Harvey
Published: March 2015

DNA mismatch‐repair gene mutations, with consequent loss of functional protein expression, result in microsatellite instability (MSI). Microsatellite sequences are found in coding regions and in regulatory regions of genes (i.e., 5′‐UTRs and 3′‐UTRs). In addition to being a surrogate marker of defective mismatch repair, deletion or insertion microsatellite sequences can dysregulate gene expression in MSI‐H (microsatellite instability‐high) tumors. The microsomal prostaglandin E synthase‐1 (mPGES‐1) gene product, mPGES‐1, participates in prostaglandin E2 (PGE2) production. Moreover, mPGES‐1 is often overexpressed in human colorectal tumors, and is thought to contribute to progression of these tumors. Here we identified a dinucleotide repeat, (GT)24, in the mPGES‐1 gene 3′ untranslated region (3′‐UTR), and analyzed its mutation frequencies in MSI‐H and microsatellite stable (MSS) tumors. The (GT)24 repeat exhibited instability in all MSI‐H tumors examined (14), but not in any of the MSS tumors (13). In most cases, (GT)24 repeat instability resulted in insertion of additional GT units. We also determined mPGES‐1 mRNA levels in MSI‐H and MSS colorectal cancer cell lines. Three of four previously designated “MSI‐H” cell lines showed higher mPGES‐1 mRNA levels compared to MSS cell lines; correlations between elevated mPGES‐1 mRNA levels and microsatellite (GT)24 repeat characteristics are present for all six cell lines. Our results demonstrate that mPGES‐1 is a target gene of defective mismatch repair in human colorectal cancer, with functional consequence.
Hitting the right spot: Mechanism of action of OPB‐31121, a novel and potent inhibitor of the Signal Transducer and Activator of Transcription 3 (STAT3)
Authors: Brambilla Lara , Genini Davide , Laurini Erik , Merulla Jessica , Perez Laurent , Fermeglia Maurizio , Carbone Giuseppina M. , Pricl Sabrina , Catapano Carlo V.
Published: March 2015

STAT3 is a key element in many oncogenic pathways and, like other transcription factors, is an attractive target for development of novel anticancer drugs. However, interfering with STAT3 functions has been a difficult task and very few small molecule inhibitors have made their way to the clinic. OPB‐31121, an anticancer compound currently in clinical trials, has been reported to affect STAT3 signaling, although its mechanism of action has not been unequivocally demonstrated. In this study, we used a combined computational and experimental approach to investigate the molecular target and the mode of interaction of OPB‐31121 with STAT3. In parallel, similar studies were performed with known STAT3 inhibitors (STAT3i) to validate our approach. Computational docking and molecular dynamics simulation (MDS) showed that OPB‐31121 interacted with high affinity with the SH2 domain of STAT3. Interestingly, there was no overlap of the OPB‐31121 binding site with those of the other STAT3i. Computational predictions were confirmed by in vitro binding assays and competition experiments along with site‐directed mutagenesis of critical residues in the STAT3 SH2 domain. Isothermal titration calorimetry experiments demonstrated the remarkably high affinity of OPB‐31121 for STAT3 with Kd (10 nM) 2–3 orders lower than other STAT3i. Notably, a similar ranking of the potency of the compounds was observed in terms of inhibition of STAT3 phosphorylation, cancer cell proliferation and clonogenicity. These results suggest that the high affinity and efficacy of OPB‐31121 might be related to the unique features and mode of interaction of OPB‐31121 with STAT3. These unique characteristics make OPB‐31121 a promising candidate for further development and an interesting lead for designing new, more effective STAT3i.
Early Anti-Coagulation after Ischemic Stroke due to Atrial Fibrillation is Safe and Prevents Recurrent Stroke
Authors: Hahn Christopher , Hill Michael D.
Published: March 2015

Background: Patients with acute cardio-embolic stroke from atrial fibrillation (AF) are at risk for recurrence with up to 50% of recurrent stroke occurring within two weeks of the index event. Anti-coagulation with heparinoids within 48 hours of stroke has been shown to increase risk of symptomatic intracranial hemorrhage (ICH) with no clear benefit on early stroke recurrence. Methods: This study was a retrospective chart review of consecutive patients who were admitted to the stroke service at the Foothills Medical Centre between 2009 and 2011. All patients with an acute stroke with a cardio-embolic etiology and a diagnosis of atrial fibrillation were reviewed. We hypothesized that anti-coagulation within two weeks of stroke, appropriately begun because of a diagnosis of AF, decreased rates of recurrent stroke without causing an increase in rates of symptomatic ICH. Results: Between 2009-2011, 324 patients were identified with cardio-embolic stroke secondary to AF. Within two weeks of stroke onset 61.4% (199/324) of patients were therapeutic on anti-coagulation. Patients who were anti-coagulated had a smaller median index stroke volume (3.2 ml vs 18.4 ml). Three (0.9%) patients suffered a clinically significant ICH. Recurrent stroke occurred in 11 patients (3.4%) within the two-week period. Therapeutic anti-coagulation within two weeks of initial stroke was associated with a decreased risk of recurrent stroke (RR 0.1, 95% CI 0.03-0.64). Conclusions: Anti-coagulation within two weeks of acute stroke in patients with AF appears to be safe among patients with smaller infarcts and prevents early recurrent infarction.
Influence ofNRGNrs12807809 polymorphism on symptom severity in individuals with schizophrenia in the Han population but not the Zhuang population of south China
Authors: Su Li , Long Jianxiong , Pan Runde , Xie Xinfeng , Mao Xixiang , Zhou Yang , Chen Qiang , Wei Bo
Published: March 2015

Background

NRGNis one of the most promising candidate genes for schizophrenia based on function and position. Therefore, this study aimed to examine the genetic association of this polymorphism with schizophrenia in the Zhuang and Han populations of south China.

Subjects and methods

A total of 282 patients (188 Han and 94 Zhuang) and 282 healthy subjects (188 Han and 94 Zhuang) were recruited. Of these, 246 schizophrenia patients underwent an assessment of psychotic symptoms using the Positive and Negative Syndrome Scale (PANSS). A TaqMan genotyping assay method was used to determine the genotypes.

Results

We did not find a significant association of rs12807809 polymorphism with schizophrenia in the total pooled samples, or in the separate ethnic groups. However, in Han schizophrenia patients, quantitative data analyses showed that the CC genotype of the rs12807809 polymorphism was associated with PANSS aggression subscale score and activation subscale score. Furthermore, carriers of the C allele of rs12807809 polymorphism among Han schizophrenia patients had higher scores of general, activation, depression, aggression, and global symptoms than the T allele carriers.

Conclusion

In conclusion rs12807809 polymorphism may not contribute to the risk of schizophrenia but influence the clinical symptoms of schizophrenia in the Han population.
Origination, extinction, invasion, and extirpation components of the brachiopod latitudinal biodiversity gradient through the Phanerozoic Eon
Authors: Powell Matthew G. , Moore Brandi R. , Smith Travis J.
Published: March 2015

The geographic distribution of brachiopod genus occurrences over the Phanerozoic shows that secular declines in origination and extinction rates were paralleled by increases in invasion and extirpation rates. Origination and extinction rates declined in two phases, the first from the Cambrian to latest Permian Periods and the second from the latest Permian Period to the present, which were accompanied by concomitant increases in invasion and extirpation rates. In addition to the temporal correlation, an inverse correlation was also weakly evident among time-averaged latitudinal gradients of rates. Compared with faunas at higher latitudes, low-latitude faunas experienced higher origination and extinction rates, and lower invasion and extirpation rates. We suggest that progressive increases in migration ability lowered origination and extinction rates because species that were better equipped to track a preferred habitat, for example, by the ability to disperse larvae over large distances, were less likely to evolve or become extinct in response to local environmental changes. The two phases were separated by the end-Permian mass extinction, which reset to high levels the origination and extinction rates of a taxonomically and ecologically altered global brachiopod fauna. Our data also allow us to quantify the relative contributions of origination, extinction, invasion, and extirpation to regional diversity (quantified as 10° latitudinal zones) more generally. Overall, invasion and extirpation explained slightly more variation in diversity than in situ origination and extinction. The four variables usually occurred in combinations that maintained rather than altered the shape of the latitudinal diversity gradient. For most of the Phanerozoic Eon, the gradient was not the product of continuous renewal, but rather existed as a holdover from a previous interval.
“Courts of Conscience”: Local Law, the Baptists, and Church Schism in Kentucky, 1780–1840
Authors: Perry Jeffrey Thomas
Published: March 2015

This article examines how religious controversy affected antebellum Kentucky's legal culture and helped construct the relationship between church and state. It incorporates legal theory to broaden conceptions of law and argues that Baptist churches served as important legal sites for their communities. More than simply punishing moral transgressions, churches litigated disputes that under common law and within county courts would be considered criminal or civil law. By acknowledging that individuals produced law outside of state institutions, the article illuminates a more complex and fluid trans-Appalachian legal culture, one in which church members and non-members alike possessed a capacious vision of law. During the late 1820s and 1830s, Kentucky Baptists faced years of discord emanating from Alexander Campbell's “Reformation.” Amidst a religious backdrop of doctrinal controversy and schism, afflicted churches witnessed a decline of disciplinary activities as individuals' ceased to envision their churches as sites for neutral dispute resolution. The failure of church courts to contain internal dissension and curtail schism led to contentious court battles over rights to local meetinghouses. As judges reviewed church disciplinary records and litigants debated religious doctrine at the courthouse, these church property disputes highlight the process of redefining church-state relations in the post-establishment era.
The Pentecostalization of Christian Zionism
Authors: Williams Joseph
Published: March 2015

This essay highlights U.S. pentecostals' and charismatics' cultivation of more experiential forms of identification with Jews and with Israel that in turn played a crucial role in the global growth of Christian Zionism. Already at the turn of the twentieth century, key figures experimented with “Judeo-centric” forms of ritual and dress, merging eschatological concerns inherited from nineteenth-century Protestantism with British Israelite ideas equating Anglo-Saxons with the lost tribes of Israel. In subsequent decades these racial notions were pushed to the fringes of the pentecostal movement, but the intense sense of identification with Israel remained. Building on the emergent mythology in the midcentury U.S. of a shared “Judeo-Christian tradition,” adherents increasingly stressed their religious and cultural (as opposed to racial) connections with God's “chosen people.” And by the late twentieth century, the 1960s counterculture, a burgeoning emphasis on the therapeutic, and growing religious diversity all facilitated pentecostals' and charismatics' renewed experimentation with “exotic” Israel-themed rituals. Significantly, believers' appropriation of Jewish-based religious practices and identities transcended nationalistic categories, and reinforced post-American sensibilities in important respects. As such, U.S.-based evangelists and broadcast ministries were able to disseminate pentecostalized expressions of Christian Zionism well beyond North America, and help catalyze a transnational, global movement.
‘Home and the World’: Cosmopolitan, transnational identities of courtly Indian women in the late imperialzenana
Authors: JHALA ANGMA D.
Published: March 2015

This article examines the cosmopolitan world of the colonialzenanathrough the marriages of two mid-twentieth-century royal Indian women, Maharani Brijraj Kumari of Dhrangadhra and Maharani Krishna Kumari of Jodhpur. In particular, it analyses the close connection betweenzenanawomen's education and emergent adolescent sexuality. These women ordinarily began their studies in mixed-gender classrooms with their brothers and male cousins as children. As they neared the age of menarche, girls were extracted from the formal schoolroom and undertook instruction in household management and childcare in preparation for their expected roles as wives and mothers. Despite being prematurely cut off from the childhood classroom, women's educational backgrounds (in both Western and Indic forms of knowledge) and future learning potential remained an important part of their postmarital identity. Young, anglicized Indian men increasingly desired wives who reflected the modernity that they hoped to represent as imperial subjects and were encouraged to adopt by British advisors and tutors. They required wives who would not wearpardahand thus reflect more Western ideals of companionate marriages of friendship, yet simultaneously live in gender-segregated palace quarters, uphold traditional kinship networks, perform religious duties, and engage in the maintenance of a large polygamous household. Definitions of sex, marriage, and domesticity were increasingly cross-cultural and pan-historical in nature, incorporating aspects both of the ‘modern’ and the ‘traditional’, the Indic and the European, the regional and the transnational.
Coaxial propagation of Laguerre–Gaussian (LG) and Gaussian beams in a plasma
Authors: Misra Shikha , Mishra Sanjay K. , Brijesh P.
Published: March 2015

This paper investigates the non-linear coaxial (or coupled mode) propagation of Laguerre–Gaussian (LG) (in particular L01 mode) and Gaussian electromagnetic (em) beams in a homogeneous plasma characterized by ponderomotive and relativistic non-linearities. The formulation is based on numerical solution of non-linear Schrödinger wave equation under Jeffreys–Wentzel–Kramers–Brillouin approximation, followed by paraxial approach applicable in the vicinity of intensity maximum of the beams. A set of coupled differential equations for spot size (beam width) and phase evolution with space corresponding to coupled mode has been derived and numerically solved to determine the propagation dynamics. Using focusing equation a critical condition describing the self-trapped (i.e., spatial soliton) mode of laser beam propagation in the plasma has been discussed; as a consequence oscillatory focusing/defocusing of the beams in coupled mode propagation have been analyzed and presented graphically. As an important outcome, significant enhancement in the intensity of LG beam is noticed when it is coupled with the Gaussian mode.
Dementia and the population health approach: promise, pitfalls and progress. An Australian perspective
Authors: Travers Catherine , Lie David , Martin-Khan Melinda
Published: March 2015

The increasing prevalence of dementia in Australia (and worldwide) over the next few decades poses enormous social, health and economic challenges. In the absence of a cure, strategies to prevent, delay the onset of, or reduce the impact of dementia are required to contain a growing disease burden, and health and care costs. A population health approach has the potential to substantially reduce the impact of dementia. Internationally, many countries have started to adopt population health strategies that incorporate elements of dementia prevention. The authors examine some of the elements of such an approach and barriers to its implementation.

International dementia frameworks and strategies were reviewed to identify options utilized for a population health approach to dementia.

Internationally and nationally, dementia frameworks are being developed that include population health approaches. Most of the frameworks identified included early diagnosis and intervention, and increasing community awareness as key objectives, while several included promotion of the links between a healthy lifestyle and reduced risk for dementia.

A poor evidence base (especially for illness prevention), diagnostic and technical limitations, and policy and implementation issues are significant barriers in maximizing the promise of population health approaches in this area.

The review and analysis of the population health approach to dementia will inform national and jurisdictional policy development.
Musique Concrète Today: Its reach, evolution of concepts and role in musical thought
Authors: Teruggi Daniel
Published: March 2015

Musique concrète has become a well-known word and concept. The history of the concept permits us to understand how it evolved and how its inventor, Pierre Schaeffer, felt about it and its impact. The terms have gone through several transformations, the main one being that into the term acousmatique, which implied a change of perspective in the reach of the concept. Today musique concrète is an active concept, not generally applied to describe contemporary musical creation, however embedded in musical thought and theory.
Collagen Structure Deterioration in the Skin of Patients with Pelvic Organ Prolapse Determined by Atomic Force Microscopy
Authors: Kotova Svetlana L. , Timashev Peter S. , Guller Anna E. , Shekhter Anatoly B. , Misurkin Pavel I. , Bagratashvili Victor N. , Solovieva Anna B.
Published: March 2015

We used atomic force microscopy (AFM) to diagnose pathological changes in the extracellular matrix (ECM) of skin connective tissue in patients with pelvic organ prolapse (POP). POP is a common condition affecting women that considerably decreases the patients’ quality of life. Deviations from normal morphology of the skin ECM from patients with POP occur including packing and arrangement of individual collagen fibers and arrangement of collagen fibrils. The nanoindentation study revealed significant deterioration of the mechanical properties of collagen fibril bundles in the skin of POP patients as compared with the skin of healthy subjects. Changes in the skin ECM appeared to correlate well with changes in the ECM of the pelvic ligament tissue associated with POP. AFM data on the ECM structure of normal and pathologically altered connective tissue were in agreement with results of the standard histological study on the same clinical specimens. Thus, AFM and related techniques may serve as independent or complementary diagnostic tools for tracking POP-related pathological changes of connective tissue.