bluuebunny/crossref_metadata_2025 huggingface dataset:
Thioacetamide-induced liver injury: protective role of genistein
Authors: Saleh Dalia O. , Abdel Jaleel Gehad A. Raheem , El-Awdan Sally A. , Oraby Fatma , Badawi Manal
Published: October 2014

This study aimed to investigate the possible protective effects of genistein (GEN), a phytoestrogen, on the liver injury induced in rats by thioacetamide (TTA; 200.0 mg·(kg body mass)–1; administered 3 times a week by intraperitoneal injection). GEN (0.5, 1.0, or 2.0 mg·(kg body mass)–1; by subcutaneous injection) was concurrently administered on a daily basis for 8 weeks, and its effects were evaluated 24 h after the administration of the last dose. The results from this study revealed that TTA-induced liver injury was associated with massive changes in the serum levels of liver biomarkers, oxidative stress markers, and liver inflammatory cytokines. Treatment of TAA-induced liver injury in rats with GEN decreased the elevated serum levels of aspartate aminotransferase, alanine aminotransferase, and total and direct bilirubin, and increased the serum level of albumin. GEN also restored the liver levels of malondialdehyde and reduced glutathione, as well as tumor necrosis factor-alpha, interleukin-6, and their modulator nuclear factor kappa-light-chain-enhancer of activated B cells. From our results, it can be concluded that GEN attenuates the liver injury-induced in rats with TAA, and this hepatoprotective role is attributed to its anti-inflammatory and antioxidant properties.
Molecular systematics of the South American rodent Calomys laucha (Cricetidae: Sigmodontinae), a reservoir of the Laguna Negra hantavirus
Authors: González-Ittig Raúl E. , Kandel Narayan , Levis Silvana , Calderón Gladys , Salazar-Bravo Jorge , Gardenal Cristina N.
Published: October 2014

The small vesper mouse (Calomys laucha (Fischer, 1814)) (Cricetidae: Sigmodontinae) ranges widely in Brazil, Uruguay, Paraguay, Argentina, and Bolivia. The species is the reservoir of the Laguna Negra hantavirus (LNV) in Paraguay but not in Argentina, where it is one of the most abundant rodents in agro-pastoral ecosystems. To answer the question if the nominal species C. laucha constitutes a single genetic unit or if it presents genetic discontinuities that may relate to hosting LNV, we sequenced the cytochrome b (cyt b) gene of specimens from throughout the range of the distribution of the species. Phylogenetic analyses revealed two well-supported clades. Twenty-two sequences from Argentina, Paraguay, and Bolivia grouped in clade A, but three sequences from Uruguay and Brazil clustered in a quite divergent clade B. The genetic distance between the two groups is 5.75%. No significant differences between Argentinean, Paraguayan, and Bolivian specimens assigned to C. laucha were detected. The restricted distribution of LNV associated to C. laucha in central Paraguay could be explained by a “natural nidality” phenomenon.
Thermodynamic structure of field equations near apparent horizon for radiating black holes
Authors: Papnoi Uma , Govender Megan , Ghosh Sushant G.
Published: October 2014

We study the intriguing analogy between gravitational dynamics of the horizon and thermodynamics for the case of nonstationary radiating spherically symmetric black holes both in four dimensions and higher dimensions. By defining all kinematical parameters of nonstationary radiating black holes in terms of null vectors, we demonstrate that it is possible to interpret the Einstein field equations near the apparent horizon in the form of a thermodynamical identity T dS = dE+P dV.
The SUR2B subunit of rat vascular KATP channel is targeted by miR-9a-3p induced by prolonged exposure to methylglyoxal
Authors: Li Shan-Shan , Wu Yang , Jin Xin , Jiang Chun
Published: October 2014

ATP-sensitive K+ (KATP) channels regulate plasma membrane excitability. The Kir6.1/SUR2B isoform of KATP channels is expressed in vascular smooth muscles and plays an important role in vascular tone regulation. This KATP channel is targeted by several reactive species. One of them is methylglyoxal (MGO), which is overly produced with persistent hyperglycemia and contributes to diabetic vascular complications. We have previously found that MGO causes posttranscriptional inhibition of the KATP channel, aggravating vascular tone regulation. Here we show evidence for the underlying molecular mechanisms. We screened microRNA databases and found several candidates. Of them, miR-9a-3p, increased its expression level by ∼240% when the cultured smooth muscle cell line was exposed to micromolar concentrations of MGO. Treatments with exogenous miR-9a-3p downregulated the SUR2B but not Kir6.1 mRNA. Antisense nucleotides of miR-9a-3p alleviated the effects of MGO. Quantitative PCR showed that the targeting sites of the miR-9a-3p were likely to be in the coding region of SUR2B. The effects of miR-9a-3p were mostly eliminated when the potential targeting site in SUR2B was site-specifically mutated. Our functional assays showed that KATP currents were impaired by miR-9a-3p induced with MGO treatment. These results suggest that MGO exposure raises the expression of miR-9a-3p, which subsequently downregulates the SUR2B mRNA, compromising KATP channel function in vascular smooth muscle.
Caffeine exposure alters cardiac gene expression in embryonic cardiomyocytes
Authors: Fang Xiefan , Mei Wenbin , Barbazuk William B. , Rivkees Scott A. , Wendler Christopher C.
Published: October 2014

Previous studies demonstrated that in utero caffeine treatment at embryonic day (E) 8.5 alters DNA methylation patterns, gene expression, and cardiac function in adult mice. To provide insight into the mechanisms, we examined cardiac gene and microRNA (miRNA) expression in cardiomyocytes shortly after exposure to physiologically relevant doses of caffeine. In HL-1 and primary embryonic cardiomyocytes, caffeine treatment for 48 h significantly altered the expression of cardiac structural genes ( Myh6, Myh7, Myh7b, Tnni3), hormonal genes ( Anp and BnP), cardiac transcription factors ( Gata4, Mef2c, Mef2d, Nfatc1), and microRNAs (miRNAs; miR208a, miR208b, miR499). In addition, expressions of these genes were significantly altered in embryonic hearts exposed to in utero caffeine. For in utero experiments, pregnant CD-1 dams were treated with 20–60 mg/kg of caffeine, which resulted in maternal circulation levels of 37.3–65.3 μM 2 h after treatment. RNA sequencing was performed on embryonic ventricles treated with vehicle or 20 mg/kg of caffeine daily from E6.5-9.5. Differential expression (DE) analysis revealed that 124 genes and 849 transcripts were significantly altered, and differential exon usage (DEU) analysis identified 597 exons that were changed in response to prenatal caffeine exposure. Among the DE genes identified by RNA sequencing were several cardiac structural genes and genes that control DNA methylation and histone modification. Pathway analysis revealed that pathways related to cardiovascular development and diseases were significantly affected by caffeine. In addition, global cardiac DNA methylation was reduced in caffeine-treated cardiomyocytes. Collectively, these data demonstrate that caffeine exposure alters gene expression and DNA methylation in embryonic cardiomyocytes.
Properly timed exposure to central ANG II prevents behavioral sensitization and changes in angiotensin receptor expression
Authors: Santollo Jessica , Whalen Philip E. , Speth Robert C. , Clark Stewart D. , Daniels Derek
Published: October 2014

Previous studies show that the angiotensin type 1 receptor (AT1R) is susceptible to rapid desensitization, but that more chronic treatments that stimulate ANG II lead to sensitization of several responses. It is unclear, however, if the processes of desensitization and sensitization interact. To test for differences in AT1R expression associated with single or repeated injections of ANG II, we measured AT1R mRNA in nuclei that control fluid intake of rats given ANG II either in a single injection or divided into three injections spaced 20 min apart. Rats given a single injection of ANG II had more AT1R mRNA in the subfornical organ (SFO) and the periventricular tissue surrounding the anteroventral third ventricle (AV3V) than did controls. The effect was not observed, however, when the same cumulative dose of ANG II was divided into multiple injections. Behavioral tests found that single daily injections of ANG II sensitized the dipsogenic response to ANG II, but a daily regimen of four injections did not cause sensitization. Analysis of125I-Sar1-ANG II binding revealed a paradoxical decrease in binding in the caudal AV3V and dorsal median preoptic nucleus after 5 days of single daily injections of ANG II; however, this effect was absent in rats treated for 5 days with four daily ANG II injections. Taken together, these data suggest that a desensitizing treatment regimen prevents behavior- and receptor-level effects of repeated daily ANG II.
Repression of let-7 by transforming growth factor-β1-induced Lin28 upregulates collagen expression in glomerular mesangial cells under diabetic conditions
Authors: Park Jung Tak , Kato Mitsuo , Lanting Linda , Castro Nancy , Nam Bo Young , Wang Mei , Kang Shin-Wook , Natarajan Rama
Published: October 2014

Accumulation of mesangial extracellular matrix (ECM) proteins such as collagen type 1-α2(Col1a2) and collagen type 4-α1(Col4a1) is a key feature of diabetic nephropathy (DN). Transforming growth factor (TGF)-β1plays important roles in ECM accumulation in DN, and evidence shows a mediatory role for microRNAs. In the present study, we found that microRNA let-7 family members (let-7b/c/d/g/i) were downregulated in TGF-β-treated mouse mesangial cells (MMCs) along with upregulation of Col1a2 and Col4a1. Ectopic expression of let-7b in TGF-β-treated MMCs attenuated Col1a2 and Col4a1 upregulation. Conversely, let-7b inhibitors increased Col1a2 and Col4a1 levels. Cotransfection of MMCs with mouse Col1a2 or Col4a1 3′-untranslated region luciferase constructs and let-7b inhibitors increased luciferase activity. However, constructs with let-7 target site mutations were unresponsive to TGF-β. TGF-β-induced 3′-untranslated region activity was attenuated by let-7b mimics, suggesting that Col1a2 and Col4a1 are direct targets of let-7b. In addition, Lin28b, a negative regulator of let-7 biogenesis, was upregulated in TGF-β-treated MMCs. Luciferase assays showed that the Lin28b promoter containing the Smad-binding element (SBE) responded to TGF-β, which was abolished in constructs without SBE. Chromatin immunoprecipitation assays showed TGF-β-induced enrichment of Smad2/3 at the Lin28b promoter, together suggesting that Lin28b is transcriptionally induced by TGF-β through SBE. Furthermore, let-7b levels were decreased, whereas Lin28b, Col1a2, and Col4a1 levels were increased, in glomeruli of diabetic mice compared with nondiabetic control mice, demonstrating the in vivo relevance of this Lin28/let-7/collagen axis. These results identify Lin28 as a new TGF-β target gene and suggest a novel role for the Lin28/let-7 pathway in controlling TGF-β-induced collagen accumulation in DN.
Reward feedback accelerates motor learning
Authors: Nikooyan Ali A. , Ahmed Alaa A.
Published: October 2014

Recent findings have demonstrated that reward feedback alone can drive motor learning. However, it is not yet clear whether reward feedback alone can lead to learning when a perturbation is introduced abruptly, or how a reward gradient can modulate learning. In this study, we provide reward feedback that decays continuously with increasing error. We asked whether it is possible to learn an abrupt visuomotor rotation by reward alone, and if the learning process could be modulated by combining reward and sensory feedback and/or by using different reward landscapes. We designed a novel visuomotor learning protocol during which subjects experienced an abruptly introduced rotational perturbation. Subjects received either visual feedback or reward feedback, or a combination of the two. Two different reward landscapes, where the reward decayed either linearly or cubically with distance from the target, were tested. Results demonstrate that it is possible to learn from reward feedback alone and that the combination of reward and sensory feedback accelerates learning. An analysis of the underlying mechanisms reveals that although reward feedback alone does not allow for sensorimotor remapping, it can nonetheless lead to broad generalization, highlighting a dissociation between remapping and generalization. Also, the combination of reward and sensory feedback accelerates learning without compromising sensorimotor remapping. These findings suggest that the use of reward feedback is a promising approach to either supplement or substitute sensory feedback in the development of improved neurorehabilitation techniques. More generally, they point to an important role played by reward in the motor learning process.
On Perturbations of Generators ofC0-Semigroups
Authors: Adler Martin , Bombieri Miriam , Engel Klaus-Jochen
Published: October 2014

We present a perturbation result for generators ofC0-semigroups which can be considered as an operator theoretic version of the Weiss-Staffans perturbation theorem for abstract linear systems. The results are illustrated by applications to the Desch-Schappacher and the Miyadera-Voigt perturbation theorems and to unbounded perturbations of the boundary conditions of a generator.
Development and Statistical Optimisation of Buspirone Hydrochloride Buccoadhesive Films
Authors: Nagaich Upendra , Chaudhary Vandana , Nagaich Jaya
Published: October 2014

The aim of the present study was to prepare unidirectional buccal films of buspirone hydrochloride by solvent casting technique. Hydroxypropylmethylcellulose (HPMC K15M) and Eudragit RL-100 were used as polymers in different proportion. Polyethylene glycol 400 and sodium lauryl sulphate were used as plasticizer and permeation enhancer, respectively, in different concentration. In the formulation, total amount of polymer (X1) and percentage of HPMC K15M (X2) were kept as independent variables. Afterwards, statistically optimized process was carried out and two optimized formulations (OF1 and OF2) were developed. The observed results of optimized formulation were showed a greater degree of percentage of similarity with predicted values. The stability studies showed that there was no significant change found in physicochemical properties, in-vitro release, and ex-vivo diffusion studies.
Effect of Chitosan Loading on the Morphological, Thermal, and Mechanical Properties of Diglycidyl Ether of Bisphenol A/Hexamethylenediamine Epoxy System
Authors: Satheesh B. , Tshai K. Y. , Warrior N. A.
Published: October 2014

The effect of chitosan filled diglycidyl ether of bisphenol A (DGEBA) epoxy system were investigated using the thermal, mechanical, and morphological properties. The mixing ratio of resin/hardener was kept constant while the chitosan of 1.0, 2.5, 5.0, 7.5, and 10 weight percentage (wt%) was incorporated into the system. The thermal stability and the transition behaviour of the chitosan filled epoxy system were analysed through a differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and Fourier transform infrared spectroscopy (FTIR) while atomic force microscope (AFM) and scanning electron microscopy (SEM) were used to investigate the morphology. It was observed that the additive tends to agglomerate, with the formation of clear phase separation, when the chitosan content increases above 5 wt%. At lower chitosan loading (2.5 wt% and below), relatively uniform dispersion of the additive can be achieved. The thermal stability of the system increases with chitosan loading while the mechanical tensile strength is compromised.
LPS- and LTA-Induced Expression of IL-6 and TNF-αin Neonatal and Adult Blood: Role of MAPKs and NF-κB
Authors: Koch Lutz , Frommhold David , Buschmann Kirsten , Kuss Navina , Poeschl Johannes , Ruef Peter
Published: October 2014

As nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) seem to be critical mediators in the inflammatory response, we studied the effects of lipopolysaccharide (LPS) and lipoteichoic acid (LTA) on (a) the activation of NF-κB and MAPKs and (b) the expression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) with or without the specific inhibitors of these intracellular signal transduction pathways in neonatal cord and adult blood. TNF-αand IL-6 concentrations showed a sharp increase in the supernatants of cord and adult whole blood after stimulation. TNF-αconcentrations were significantly higher, whereas IL-6 concentrations were tendentially lower in adult blood after stimulation. Stimulation with LPS or LTA resulted in a significantly decreased activation of p38 MAPK in neonatal compared with adult blood. Although LTA failed to induce additional ERK1/2 phosphorylation, LPS stimulation mediated the moderately increased levels of activated ERK1/2 in neonatal monocytes. The addition of the p38 MAPK inhibitor SB202190 significantly decreased IL-6 and TNF-αproduction upon LPS or LTA stimulation. Furthermore, the inhibition of ERK1/2 was able to reduce LPS-stimulated TNF-αproduction in neonatal blood. We conclude that p38 MAPK as well as ERK1/2 phosphorylation is crucially involved in LPS activation and could explain the differences in early cytokine response between neonatal and adult blood.
Levenberg-Marquardt Method for the Eigenvalue Complementarity Problem
Authors: Chen Yuan-yuan , Gao Yan
Published: October 2014

The eigenvalue complementarity problem (EiCP) is a kind of very useful model, which is widely used in the study of many problems in mechanics, engineering, and economics. The EiCP was shown to be equivalent to a special nonlinear complementarity problem or a mathematical programming problem with complementarity constraints. The existing methods for solving the EiCP are all nonsmooth methods, including nonsmooth or semismooth Newton type methods. In this paper, we reformulate the EiCP as a system of continuously differentiable equations and give the Levenberg-Marquardt method to solve them. Under mild assumptions, the method is proved globally convergent. Finally, some numerical results and the extensions of the method are also given. The numerical experiments highlight the efficiency of the method.
Linear Discrete Pursuit Game with Phase Constraints
Authors: Raxmanov Asqar , Ibragimov Gafurjan
Published: October 2014

We consider a linear pursuit game of one pursuer and one evader whose motions are described by different-type linear discrete systems. Position of the evader satisfies phase constraints:y∈G, whereGis a subset ofRn. We considered two cases: (1) controls of the players satisfy geometric constraints, and (2) controls of the players satisfy total constraints. Terminal setMis a subset ofRnand it is assumed to have a nonempty interior. Game is said to be completed ifyk-x(k)∈Mat some stepk; thus, the evader has not the right to leave setG. To construct the control of the pursuer, at each stepi, we use the value of the control parameter of the evader at the stepi. We obtain sufficient conditions of completion of pursuit from certain initial positions of the players in finite time interval and construct a control for the pursuer in explicit form.
Syntheses of Isoxazoline-Carbocyclic Nucleosides and Their Antiviral Evaluation: A Standard Protocol
Authors: Quadrelli Paolo , Vazquez Martinez Naiara , Scrocchi Roberto , Corsaro Antonino , Pistarà Venerando
Published: October 2014

The current synthesis of racemic purine and pyrimidine isoxazoline-carbocyclic nucleosides is reported, detailing the key-steps for standard and reliable preparations. Improved yields were obtained by the proper tuning of the single synthetic steps, opening the way for the preparation of a variety of novel compounds. Some of the obtained compounds were also evaluated against a wide variety of DNA and RNA viruses including HIV. No specific antiviral activity was observed in the cases at hand. Novel compounds were prepared for future biological tests.
Spatial‐Temporal ARX Modeling and Optimization for Polymer Flooding
Authors: Ge Yulei , Li Shurong , Lu Songlin , Chang Peng , Lei Yang
Published: October 2014

A new polymer flooding model based on spatial‐temporal decomposition and autoregressive model with external input (ARX) (STDARX model) is proposed. Karhunen‐Loeve (K‐L) decomposition is used to model the two‐dimensional state parameters of reservoir (such as water saturation, pressure, and grid concentration). The polymer injection concentration and time coefficient got from the decomposition are taken as the input and output information. After being identified by least square method, the time iterative ARX models of all state variables are obtained, we build the ARX model among pressure, water saturation, grid concentration, and moisture content of production well, and identify it with recursive least‐squares (RLS) method. After combining the above two models, we get the STDARX model of polymer flooding. The accuracy is proved by model with four injection wells and nine production wells through data which is obtained from mechanism model. In order to enhance the polymer flooding oil recovery when oil price is changing, iterative dynamic programming (IDP) is applied to optimize the STDARX model, to get the optimal injection of production scheme.
An Alternative to Current Therapies of Functional Dyspepsia: Self‐Administrated Transcutaneous Electroacupuncture Improves Dyspeptic Symptoms
Authors: Ji Ting , Li Xueliang , Lin Lin , Jiang Liuqin , Wang Meifeng , Zhou Xiaopin , Zhang Ranran , Chen Jiande DZ
Published: October 2014

Functional dyspepsia is of high prevalence with little treatment options. The aim of this study was to develop a new treatment method using self‐management transcutaneous electroacupuncture (TEA) for functional dyspepsia (FD). Twenty‐eight patients with FD were enrolled and underwent a crossover clinical trial with 2‐week TEA at ST36 and PC6 and 2‐week sham‐TEA at nonacupuncture sham‐points. Questionnaires were used to assess symptoms of dyspepsia and quality of life. Physiological testing included gastric emptying and electrogastrography. It was found that (1) TEA but not sham‐TEA significantly improved dyspeptic symptoms and 4 domains in quality of life; improvement was also noted in self‐rated anxiety and depression scores; (2) gastric emptying was significantly and substantially increased with 2‐week TEA but not sham‐TEA; and (3) gastric accommodation was also improved with TEA but not sham‐TEA, reflected as increased ingested nutrient volumes at the levels of satiety and maximum tolerance. These findings suggest a therapeutic potential of self‐administrated TEA method for functional dyspepsia, possibly attributed to improvement in gastric motility.
Multiresponse Optimization of Process Parameters in Turning of GFRP Using TOPSIS Method
Authors: Parida Arun Kumar , Routara Bharat Chandra
Published: October 2014

Taguchi’s design of experiment is utilized to optimize the process parameters in turning operation with dry environment. Three parameters, cutting speed (v), feed (f), and depth of cut (d), with three different levels are taken for the responses like material removal rate (MRR) and surface roughness (Ra). The machining is conducted with Taguchi L9 orthogonal array, and based on the S/N analysis, the optimal process parameters for surface roughness and MRR are calculated separately. Considering the larger-the-better approach, optimal process parameters for material removal rate are cutting speed at level 3, feed at level 2, and depth of cut at level 3, that is, v3-f2-d3. Similarly for surface roughness, considering smaller-the-better approach, the optimal process parameters are cutting speed at level 1, feed at level 1, and depth of cut at level 3, that is, v1-f1-d3. Results of the main effects plot indicate that depth of cut is the most influencing parameter for MRR but cutting speed is the most influencing parameter for surface roughness and feed is found to be the least influencing parameter for both the responses. The confirmation test is conducted for both MRR and surface roughness separately. Finally, an attempt has been made to optimize the multiresponses using technique for order preference by similarity to ideal solution (TOPSIS) with Taguchi approach.
The Novel IKK2 Inhibitor LY2409881 Potently Synergizes with Histone Deacetylase Inhibitors in Preclinical Models of Lymphoma through the Downregulation of NF-κB
Authors: Deng Changchun , Lipstein Mark , Rodriguez Richard , Serrano Xavier O. Jirau , McIntosh Christine , Tsai Wei-Yann , Wasmuth Andrew S. , Jaken Susan , O'Connor Owen A.
Published: October 2014

Purpose: To evaluate the pharmacologic activity of a novel inhibitor of IκB kinase β (IKK2), LY2409881, in preclinical models of B- and T-cell lymphoma, as a single agent and in combination with histone deacetylase (HDAC) inhibitors.

Experimental Design: The in vitro activity of LY2409881 was determined using an ATP-based growth inhibition assay and flow cytometric assay of apoptosis in lymphoma cell lines. The in vivo activity of LY2409881 was determined using SCID-beige xenograft mouse model. The mechanism of action was determined using immunoblotting, immuofluorescence, and electrophoretic mobility shift assay. Synergy of LY2409881 with other drugs active in lymphoma was determined by calculating relative risk ratio (RRR) and combination index (CI).

Results: LY2409881 inhibited constitutively activated NF-κB, and caused concentration- and time-dependent growth inhibition and apoptosis in lymphoma cells. In models of diffuse large B-cell lymphoma (DLBCL), the cytotoxicity of LY2409881 correlated with the overall activation status of NF-κB, but not simply in a pattern predicted by the cell-of-origin classification of these cell lines. LY2409881 was safe to mice at three dose levels, 50, 100, and 200 mg/kg, all of which caused significant inhibition of tumor growth. LY2409881 suppressed the activity of the NF-κB subunit p65 in lymphoma cells treated by the HDAC inhibitor romidepsin, underlying a potential mechanism of the marked synergy observed of these two drugs.

Conclusion: Collectively, these data strongly suggest that targeting the NF-κB pathway in combination with romidepsin could represent a novel and potent regimen for the treatment of B- and T-cell lymphoma. Clin Cancer Res; 21(1); 134–45. ©2014 AACR.
A Phase I Study of Veliparib (ABT-888) in Combination with Low-Dose Fractionated Whole Abdominal Radiation Therapy in Patients with Advanced Solid Malignancies and Peritoneal Carcinomatosis
Authors: Reiss Kim A. , Herman Joseph M. , Zahurak Marianna , Brade Anthony , Dawson Laura A. , Scardina Angela , Joffe Caitlin , Petito Emily , Hacker-Prietz Amy , Kinders Robert J. , Wang Lihua , Chen Alice , Temkin Sarah , Horiba Naomi , Siu Lillian L. , Azad Nilofer S.
Published: October 2014

Purpose: The combination of low-dose radiotherapy with PARP inhibition has been shown to enhance antitumor efficacy through potentiating DNA damage. We combined low-dose fractionated whole abdominal radiation (LDFWAR) with escalating doses of veliparib (ABT-888), a small-molecule PARP inhibitor, in patients with peritoneal carcinomatosis from advanced solid tumor malignancies.

Experimental Design: Patients were treated with veliparib (80–320 mg daily) for a total of 3 cycles. LDFWAR consisted of 21.6 Gy in 36 fractions, 0.6 Gy twice daily on days 1 and 5 for weeks 1–3 of each cycle. Circulating tumor cells (CTC) were collected and evaluated for γ-H2AX. Quality of life (QoL) was assessed using the EORTC-QLQ-C30 questionnaire.

Results: Twenty-two patients were treated. Treatment-related grade 3 and 4 toxicities included lymphopenia (68%), anemia (9%), thrombocytopenia (14%), neutropenia (4%), leukopenia (9%), ascites (4%), vomiting (4%), and dyspnea (4%). No objective responses were observed. Disease stabilization (≥24 weeks) was observed in 7 patients (33%). Median progression-free survival (mPFS) was 4.47 months and median overall survival (mOS) was 13.04 months. In the subset of 8 ovarian and fallopian cancers, mPFS was 6.77 months and mOS was 17.54 months compared with mPFS 2.71 months and mOS 13.01 months in others. Patients with ovarian and fallopian cancers had better QoL over time than those with other cancers. An increased percentage of γ-H2AX–positive CTCs was observed in a subset of patients (3/6 with >2 CTCs at baseline).

Conclusions: Combined veliparib and LDFWAR is a well-tolerated regimen that resulted in prolonged disease stability for some patients with advanced solid tumors and carcinomatosis, particularly in the ovarian and fallopian cancer subpopulation. Clin Cancer Res; 21(1); 68–76. ©2014 AACR.
Accuracy of Real-Time Tissue Elastography for the Evaluation of Hepatic Fibrosis in Patients with Chronic Hepatitis B: A Prospective Multicenter Study
Authors: Wu Tao , Ren Jie , Cong Shu-zhen , Meng Fan-kun , Yang Hong , Luo Yan , Lin Hong-jun , Sun Yan , Wang Xiu-yan , Pei Shu-Fang , Zheng Ying , He Yun , Chen Yang , Hu Yu , Yang Na , Li Ping , Kudo Masatoshi , Zheng Rong-qin
Published: October 2014

Background: The prognosis and management of hepatic fibrosis are closely related to the stage of the disease. The limitations of liver biopsy, which is the gold standard for treatment, include its invasiveness and sampling error. Ultrasound elasticity might be the most promising imaging technology for the noninvasive and accurate assessment of hepatic fibrosis. Real-time tissue elastography (RTE) measures the relative stiffness of the tissue in the region of interest caused by the heartbeat. Many studies have verified that RTE is useful for the diagnosis of hepatic fibrosis in patients with chronic hepatitis C (CHC). Purpose: To determine the formula of the liver fibrosis index for chronic hepatitis B (BLFI) and to validate the diagnostic accuracy of the BLFI for hepatic ﬁbrosis compared with the liver fibrosis index (LFI). Materials and Methods: RTE was performed in 747 prospectively enrolled patients with chronic hepatitis B (CHB) or cirrhosis from 8 centers in China; 375 patients were analyzed as the training set, and 372 patients were evaluated as the validation set. The fibrosis stage was diagnosed from pathological specimens obtained by ultrasound-guided liver biopsy. Nine image features were measured from strain images, and the new formula for the BLFI was obtained by combining the nine imaging features of the RTE images using multiple regression analysis of the training set. The BLFI and LFI were compared with the pathological fibrosis stage at diagnosis, and the diagnostic performances of the indexes were compared. Results: The Spearman correlation coefficient between the BLFI and hepatic fibrosis stages was significantly positive (r = 0.711, p < 0.001), and significant differences were present between all disease stages. The areas under the receiver-operating characteristic (AUROC) curves of the BLFI and LFI for predicting signiﬁcant fibrosis (S0-S1 vs. S2-S4) were 0.858 and 0.858, respectively. For cirrhosis (S0-S3 vs. S4), the AUROC curves of the BLFI and LFI were 0.868 and 0.862, respectively. Conclusion: The results of this large, multicenter study confirmed that RTE is valuable for the diagnosis of hepatic fibrosis in patients with CHB. However, the diagnostic efficiencies of the new BLFI and the original LFI, which were based on CHC, for the assessment of CHB hepatic fibrosis were similar; thus, the LFI has the potential to be used to directly evaluate the extent of hepatic fibrosis in patients with CHB.
Bone-Targeted Therapy in Metastatic Breast Cancer - All Well-Established Knowledge?
Authors: Gampenrieder Simon P. , Rinnerthaler Gabriel , Greil Richard
Published: October 2014

Bone-targeted therapies like bisphosphonates (zoledronic acid or pamidronate) or denosumab are recommended in all patients with metastatic breast cancer and bone metastases, whether they are symptomatic or not. The choice between these 2 different agents, however, remains open. In this review, we critically discuss the emerging evidence for direct anti-tumor activity of bone-targeting agents, the utility of bone turnover markers for treatment decision and efficacy prediction, as well as the safety and financial aspects of bisphosphonates and denosumab. Furthermore, we provide a possible therapeutic algorithm, and present new pharmacologic agents which are being investigated for the treatment of meta-static bone disease.
Early Structural Valve Deterioration of Mitroflow Aortic Bioprosthesis
Authors: Sénage Thomas , Le Tourneau Thierry , Foucher Yohann , Pattier Sabine , Cueff Caroline , Michel Magali , Serfaty Jean-Michel , Mugniot Antoine , Périgaud Christian , Carton Hubert François , Al Habash Ousama , Baron Olivier , Roussel Jean Christian
Published: October 2014

Background—

Structural valve deterioration (SVD) is a major flaw of bioprostheses. Early SVD has been suspected in the last models of Mitroflow bioprosthesis. We sought to assess the incidence, mode, and impact of SVD on outcome in a large series of Mitroflow aortic valve replacement.

Methods and Results—

Six hundred seventeen consecutive patients (aged 76.1±6.3 years) underwent aortic valve replacement with a Mitroflow prosthesis (models 12A/LX) between 2002 and 2007. By echocardiography, 39 patients developed early SVD (1.66% per patient-year), with stenosis as the main mode (n=36). Mean delay to SVD was only 3.8±1.4 years, and 5-year SVD-free survival was 91.6% (95% confidence interval [CI], 88.7–94.7) for the whole cohort and 79.8% (95% CI, 71.2–89.4) and 94.0% (95% CI, 90.3–97.8) for 19- and 21-mm sizes, respectively. Among the 39 patients with SVD, 13 patients (33%) had an accelerated SVD once the mean gradient exceeded 30 mm Hg. Valve-related death was 46.2% in this SVD subgroup. Five-year overall survival was 69.6% (95% CI, 65.7–73.9). In multivariable analysis, SVD was the strongest correlate of overall mortality (hazard ratio=7.7; 95% CI, 4.4–13.6).

Conclusions—

Early SVD is frequent in Mitroflow bioprosthesis (models 12A/LX), especially for small sizes (19 and 21 mm), and reduces overall survival. An unpredictable accelerated pattern of SVD constitutes a life-threatening condition. In view of the large number of Mitroflow valves implanted worldwide, one can expect an epidemic of SVD and valve-related deaths, which represents a major public health issue, especially in the elderly. Hence, a close follow-up with yearly echocardiography after Mitroflow implantation is advisable. An urgent reoperation should be discussed in patients with severe SVD even though they are still asymptomatic.
Quality of Life and Functional Outcomes 12 Months After Out-of-Hospital Cardiac Arrest
Authors: Smith Karen , Andrew Emily , Lijovic Marijana , Nehme Ziad , Bernard Stephen
Published: October 2014

Background—

Out-of-hospital cardiac arrest (OHCA) is a significant global health problem. There has been considerable investment in improving the emergency medical response to OHCA, with associated improvements in survival. However, concern remains that survivors have a poor quality of life. This study describes the quality of life of OHCA survivors at 1-year postarrest in Victoria, Australia.

Methods and Results—

Adult OHCA patients who arrested between 2010 and 2012 were identified from the Victorian Ambulance Cardiac Arrest Registry. Paramedics attended 15 113 OHCA patients of which 46.3% received an attempted resuscitation. Nine hundred and twenty-seven (13.2%) survived to hospital discharge of which 76 (8.2%) died within 12 months. Interviews were conducted with 697 (80.7%) patients or proxies, who were followed-up via telephone interview, including the Glasgow Outcome Scale–Extended, the 12-item short form health survey, and the EuroQol. The majority (55.6%) of respondents had a good recovery via the Glasgow Outcome Scale–Extended≥7 (41.1% if patients who died postdischarge were included and nonrespondents were assumed to have poor recovery). The mean EuroQol index score for respondents was 0.82 (standard deviation, 0.19), which compared favorably with an adjusted population norm of 0.81 (standard deviation, 0.34). The mean 12-item short form Mental Component Summary score for patients was 53.0 (standard deviation, 10.2), whereas the mean Physical Component Summary score was 46.1 (standard deviation, 11.2).

Conclusions—

This is the largest published study assessing the quality of life of OHCA survivors. It provides good evidence that many survivors have an acceptable quality of life 12 months postarrest, particularly in comparison with population norms.
The Fall of New Netherland and Seventeenth-Century Anglo-American Imperial Formation, 1654–1676
Authors: Roper L. H.
Published: October 2014

The English takeover of the Dutch colony of New Netherland in 1664 illustrates the enduring centrality of colonial agendas in the political culture of the seventeenth-century English Empire but also provided an occasion by which the metropolitan government and its perspective ironically assumed greater weight in colonial-imperial relations.
Global Sea Ice Coverage from Satellite Data: Annual Cycle and 35-Yr Trends
Authors: Parkinson Claire L.
Published: October 2014

Well-established satellite-derived Arctic and Antarctic sea ice extents are combined to create the global picture of sea ice extents and their changes over the 35-yr period 1979–2013. Results yield a global annual sea ice cycle more in line with the high-amplitude Antarctic annual cycle than the lower-amplitude Arctic annual cycle but trends more in line with the high-magnitude negative Arctic trends than the lower-magnitude positive Antarctic trends. Globally, monthly sea ice extent reaches a minimum in February and a maximum generally in October or November. All 12 months show negative trends over the 35-yr period, with the largest magnitude monthly trend being the September trend, at −68 200 ± 10 500 km2 yr−1 (−2.62% ± 0.40% decade−1), and the yearly average trend being −35 000 ± 5900 km2 yr−1 (−1.47% ± 0.25% decade−1).
Correction of Depth Bias in Upper-Ocean Temperature and Salinity Profiling Measurements from Airborne Expendable Probes
Authors: Alappattu Denny P. , Wang Qing
Published: October 2014

During the Dynamics of Madden–Julian Oscillation (DYNAMO) Experiment in 2011, airborne expendable conductivity–temperature–depth (AXCTD) probes and airborne expendable bathythermographs (AXBTs) were deployed using NOAA’s WP-3D Orion aircraft over the southern tropical Indian Ocean. From initial analysis of the AXCTD data, about 95% of profiles exhibit double mixed layer structures. The presence of a mixed layer from some of these profiles were erroneous and were introduced because of the AXCTD processing software not being able to correctly identify the starting point of the probe descent. This work reveals the impact of these errors in data processing and presents an objective method to remove such erroneous data from the profiles using spectrograms from raw audio files. Reconstructed AXCTD/AXBT profiles are compared with collocated shipborne conductivity–temperature–depth (CTD) and expendable bathythermograph (XBT) profiles and are found to be in good agreement.
Influence of freeze-drying on the recovery of the tumour invasion markers uPA and PAI-1 from prostate cancer resections
Authors: Serafin AM , Akudugu JM , Bohm L
Published: October 2014

Background

Urokinase plasminogen activator (uPA) and its inhibitor (PAI-1) have been shown to be of merit as biomarkers for a variety of cancers. Prostate tissue resections from patients with prostate cancer (PCa) and benign prostatic hyperplasia were analysed to determine the influence of freeze-drying on the recovery of uPA and PAI-1 and their predictive performance.

Methods

Prostate tissue was frozen in liquid nitrogen and homogenised into a fine powder in a precooled stainless steel punch homogeniser. One aliquot of the powder was extracted directly, and a second aliquot was freeze-dried overnight and then extracted. The extracts were analysed by FEMTELLE assay to determine the concentrations of uPA and PAI-1. uPA/PAI-1 ratios were calculated for each sample, and the mean ratios for the frozen and the lyophilised tissue were compared.

Results

The concentrations of uPA measured for the frozen and lyophilised samples are strongly correlated ( R = 0.90 ± 0.05). The same applies to the PAI-1 measured ( R = 0.89 ± 0.03). The uPA/PAI-1 ratios for the lyophilised and frozen samples were strongly correlated. The uPA/PAI-1 ratios for frozen and lyophilised samples were found to be essentially the same with values of 0.0344 ± 0.0066 and 0.0340 ± 0.0068, respectively ( P = 0.9633).

Conclusion

The recovery of uPA and PAI-1 from a deep frozen prostate tissue homogenate followed by freeze-drying proceeds with a loss of 10 and 11%, respectively, with no influence on the uPA/PAI-1 ratio. Lyophilisation is a safe procedure for the preservation of frozen prostate tissue samples as it permits recovery of the markers without compromising their use for diagnostic purposes.
From the West to the East
Authors: Liu Bangcheng , Hu Wei , Cheng Yen-Chuan
Published: October 2014

This study examined the generalizability of servant leadership constructs observed in Western society to China. Using a sample of 659 Chinese public employees, we observed the servant leadership in China, but the generalizability of the construct is limited, in that some of the dimensions of the construct were violated. This study also tested the relationships between supervisors’ servant leadership and the public service motivation (PSM) of their immediate subordinates. This empirical study concluded that servant leadership is positively associated with public service motivation. The authors discussed the implications of the results for the administrative practices in Chinese public sector and raised issues for future research.
What’s wrong with Africanization!
Authors: Dick Archie L
Published: October 2014

The birth of the African Library and Information Association and Institutions provides an opportunity to re-visit the idea of Africanization. Five things that are wrong with Africanization are identified and discussed.
Second-Generation Prisoners and the Transmission of Domestic Violence
Authors: Will Joanna L. , Loper Ann B. , Jackson Shelly L.
Published: October 2014

Adult inmates who experienced the incarceration of a parent, known as “second-generation prisoners,” experience unique challenges and are at heightened risk for experiencing other adversities throughout the life span. Our study investigated one specific, and previously unexplored, type of adversity—domestic violence—within a sample of 293 incarcerated adults. We examined the relation between generation status (first- or second-generation prisoners), childhood exposure to domestic violence, and participation in adult relationship violence prior to incarceration. Results indicate that prisoners who had been exposed to domestic violence in childhood were more likely to engage in intimate partner violence resulting in inflicted and received injury. Relative to first-generation prisoners, second-generation prisoners reported more childhood domestic violence exposure and were more likely to have been injured by a relationship partner. However, this relation between second-generation status and injury victimization was mediated by domestic violence exposure. These results support an intergenerational pattern of domestic violence and suggest that second-generation prisoners are a unique population worthy of future investigation and mental health intervention.
Persecutory delusions and first-person authority
Authors: Kumazaki Tsutomu
Published: October 2014

Although clinical diagnosis of delusions is usually not difficult, defining delusions is more complicated. This study analyzes the concept of delusions, in particular persecutory delusions. Patients with persecutory delusions are convinced of others’ malicious intentions and are impervious to counterevidence. Conventionally, expression of intention is accepted at face value unless contradictory evidence is available. First-person authority regarding intention is respected in human society. Contemporary philosophy tends to limit the scope of first-person authority, but it cannot be eliminated. Persecutory delusions contravene first-person authority as one of the fundamental principles of daily life, even in the absence of malicious intention on the part of the patients. Two ways of denying others’ first-person authority are investigated. This study adds new insight to Manfred Spitzer’s formal definition of delusions.
Dependence of States on Central Transfers: State-wise Analysis
Authors: Rao C. Bhujanga , Srivastava D.K.
Published: October 2014

This article examines the dependence of states on central fiscal transfers. The pattern of dependence of states on central transfers is studied with respect to five groups of states, namely, high-, middle- and low-income general-category states and two groups of special-category states categorized into high- and low-income states. We make a distinction between transfers that are in the form of an entitlement like states’ share in central taxes or statutory grants vis-à-vis transfers that are discretionary and depend on centre’s decisions. In terms of groups of states, the extent of dependence is relatively quite high for the special-category states and the low-income states. The extent of dependence was lowest during the period covered under the Tenth Finance Commission period. It has since increased, for all states considered together, by about 3.5 percentage points, from 37.4 per cent to 40.9 per cent of states’ revenue receipts. This increase comes both from entitlement transfers and discretionary transfers to the extent of 2.1 and 1.3 percentage points, respectively.
Impact of Corporate Culture on the Relationship between Efficient Technology Transfer and Business Performance
Authors: Nguyen Nguyen Thi Duc , Aoyama Atsushi
Published: October 2014

This study focuses on the impact of corporate culture on the relationship between efficient technology transfer and a firm’s business performance, emphasizing a firm’s productivity and innovation capacity.

 Exploratory factor analysis (EFA), confirmatory factor analysis (CFA) and structural equation modelling (SEM) multi-group analysis are used to analyze structured survey data from 223 Japanese manufacturing subsidiaries in Vietnam. The results indicate that efficient technology transfer has a 40 per cent positive effect on a firm’s productivity and a 29 per cent positive effect on its innovation capacity. Corporate culture produces significant differences in the effects of efficient technology transfer on business performance. The higher value the company places on learning, encourages staff to participate in decision making and accepts risk, the higher the success of a firm’s business performance with the efficiently transferred technology.