bluuebunny/crossref_metadata_2025 huggingface dataset:
Normal Metabolic Levels in Prefrontal Cortex in Euthymic Bipolar I Patients with and without Suicide Attempts
Authors: Rocha Marlos Vasconcelos , Nery-Fernandes Fabiana , Guimarães José Luiz , Quarantini Lucas de Castro , de Oliveira Irismar Reis , Ladeia-Rocha Giovanna G. , Jackowski Andrea Parolin , de Araujo Neto César , Miranda-Scippa Ângela
Published: May 2015

Introduction/Objective. Evidence suggests that the prefrontal cortex has been implicated in the pathophysiology of bipolar disorder (BD), but few neurochemical studies have evaluated this region in bipolar patients and there is no information from BD suicide attempters using Proton Magnetic Resonance Spectroscopy (H+MRS). The objective was to evaluate the metabolic function of the medial orbital frontal cortex in euthymic BD type I suicide and nonsuicide attempters compared to healthy subjects by H+MRS.Methods. 40 euthymic bipolar I outpatients, 19 without and 21 with history of suicide attempt, and 22 healthy subjects were interviewed using the Structured Clinical Interview with the DSM-IV axis I, the Hamilton Depression Rating Scale, the Young Mania Rating Scale, and the Barratt Impulsiveness Scale-11 and underwent H+MRS.Results. We did not find any metabolic abnormality in medial orbital frontal regions of suicide and nonsuicide BD patients and BD patients as a group compared to healthy subjects.Conclusions. The combined chronic use of psychotropic drugs with neuroprotective or neurotrophic effects leading to a euthymic state for longer periods of time may improve neurometabolic function, at least measured by H+MRS, even in suicide attempters. Besides, these results may implicate mood dependent alterations in brain metabolic activity. However, more studies with larger sample sizes of this heterogeneous disorder are warranted to clarify these data.
Metformin Ameliorates Podocyte Damage by Restoring Renal Tissue Podocalyxin Expression in Type 2 Diabetic Rats
Authors: Zhai Limin , Gu Junfei , Yang Di , Wang Wei , Ye Shandong
Published: May 2015

Podocalyxin (PCX) is a signature molecule of the glomerular podocyte and of maintaining integrity of filtration function of glomerulus. The aim of this study was to observe the effect of different doses of metformin on renal tissue PCX expression in type 2 diabetic rats and clarify its protection on glomerular podocytes. Type 2 diabetic Sprague-Dawley (SD) rats in which diabetes was induced by high-fat diet/streptozotocin (HFD-STZ) were treated with different doses of metformin (150, 300, and 500 mg/kg per day, resp.) for 8 weeks. Various biochemical parameters, kidney histopathology, and renal tissue PCX expression levels were examined. In type 2 diabetic rats, severe hyperglycemia and hyperlipidemia were developed. Urinary albumin and PCX were markedly increased. Diabetes induced significant alterations in renal glomerular structure. In addition, protein and mRNA expression of renal tissue PCX were highly decreased. However, treatment of rats with different doses of metformin restored all these changes to a varying degree. These results suggested that metformin can ameliorate glomerular podocyte damage in type 2 diabetic rats, which may be partly associated with its role in restoring PCX expression and inhibiting urinary excretion of PCX with dose dependence.
Constrained Cross Entropy Localization Technique for Wireless Sensor Networks
Authors: Azim Mohammad Abdul , Aung Zeyar , Xiao Weidong , Khadkikar Vinod
Published: May 2015

Challenges in wireless sensor networks (WSNs) localization are diverse. Addressing the challenges in cross entropy (CE) localization utilizing cross entropy optimization technique in turn minimizes the localization error with a reasonable processing cost and provides a balance between the algorithmic runtime and error. The drawback of such minimization commonly known as flip phenomenon introduces errors in the derived locations. Beyond CE, the whole class of localization techniques utilizing the same cost function suffers from the same phenomenon. This paper introduces constrained cross entropy (CCE), which enhances the localization accuracy by penalizing the identified sensor nodes affected by the aforementioned flip phenomenon in the neighborhood through neighbor sets. Simulation results comparing CCE with both simulated annealing- (SA-) based and original CE localization techniques demonstrate CCE's superiority in a consistent and reliable manner under various circumstances thereby justifing the proposed localization technique.
Probabilistic Model Checking: One Step Forward in Wireless Sensor Networks Simulation
Authors: Mateo José A. , Macià Hermenegilda , Ruiz M. Carmen , Calleja Javier , Royo Fernando
Published: May 2015

A novel collision resolution algorithm for wireless sensor networks is formally analysed via probabilistic model checking. The algorithm called 2CS-WSN is specifically designed to be used during the contention phase of IEEE 802.15.4. Discrete time Markov chains (DTMCs) have been proposed as modelling formalism and the well-known probabilistic symbolic model checker PRISM is used to check some correctness properties and different operating modes and, furthermore, to collect some performance measures. Thus, all the benefits of formal verification and simulation are gathered. These correctness properties as well as practical and relevant scenarios for the real world have agreed with the algorithm designers.
A Distributed Q Learning Spectrum Decision Scheme for Cognitive Radio Sensor Network
Authors: He Jian , Peng Jun , Jiang Fu , Qin Gaorong , Liu Weirong
Published: May 2015

Cognitive spectrum management can improve the utilization efficiency of spectrum while increasing the energy consumption of sensor network nodes. Hence, how to balance the energy consumption and spectrum efficiency has become a critical challenge in the resource-constrained cognitive radio sensor networks. In this paper, by analyzing the channel characteristics and the energy efficiency of networks, a joint channel selection and power control spectrum decision algorithm based on distributed Q learning is proposed. To evaluate the performance of the proposed framework, an optimal Q value subject to communication efficiency index is formulated. Then, the learning strategy selection scheme is designed to solve the optimization problem by establishing a learning model. In this learning model, each node can get the strategy of other nodes to select the optimal strategy by introducing distributed strategy estimation. The simulation results show that the proposed algorithm has better performance than the existing methods.
Correlation between Peripheral Levels of Brain-Derived Neurotrophic Factor and Hippocampal Volume in Children and Adolescents with Bipolar Disorder
Authors: Lauxen Peruzzolo Tatiana , Anes Mauricio , Kohmann Andre de Moura , Souza Ana Claudia Mércio Loredo , Rodrigues Ramiro Borges , Brun Juliana Basso , Peters Roberta , de Aguiar Bianca Wollenhaupt , Kapczinski Flavio , Tramontina Silzá , Rohde Luis Augusto Paim , Zeni Cristian Patrick
Published: May 2015

Pediatric bipolar disorder (PBD) is a serious mental disorder that affects the development and emotional growth of affected patients. The brain derived neurotrophic factor (BDNF) is recognized as one of the possible markers of the framework and its evolution. Abnormalities in BDNF signaling in the hippocampus could explain the cognitive decline seen in patients with TB. Our aim with this study was to evaluate possible changes in hippocampal volume in children and adolescents with BD and associate them to serum BDNF. Subjects included 30 patients aged seven to seventeen years from the ProCAB (Program for Children and Adolescents with Bipolar Disorder). We observed mean right and left hippocampal volumes of 41910.55 and 41747.96 mm3, respectively. No statistically significant correlations between peripheral BDNF levels and hippocampal volumes were found. We believe that the lack of correlation observed in this study is due to the short time of evolution of BD in children and adolescents. Besides studies with larger sample sizes to confirm the present findings and longitudinal assessments, addressing brain development versus a control group and including drug-naive patients in different mood states may help clarify the role of BDNF in the brain changes consequent upon BD.
Selective Herbicides for Cultivation ofEucalyptus urograndisClones
Authors: Minogue Patrick J. , Osiecka Anna
Published: May 2015

Competition control is essential for successful eucalyptus plantation establishment, yet few selective herbicides have been identified. Five herbicides, flumioxazin, imazamox, imazapic, oxyfluorfen, and sulfometuron methyl, were evaluated for selective weed control in the establishment of genetically modified frost tolerantEucalyptus urograndisclones. Herbicides were applied at two or three rates, either before or after weed emergence, and compared to a nontreated control and to near-complete weed control obtained with glyphosate directed sprays. Applications prior to weed emergence were most effective for weed control and, with the exception of imazapic, all resulted in enhanced eucalyptus growth relative to the nontreated control. Among postemergent treatments, only imazamox enhanced stem volume. Among selective herbicide treatments, preemergent 2240 g ha−1oxyfluorfen produced the best growth response, resulting in stem volume index that was 860% greater than the nontreated control, although only 15% of the volume index obtained with near-complete weed control. Imazapic was the most phytotoxic of all herbicides, resulting in 40% mortality when applied preemergent. Survival was 100% for all other herbicide treatments. This research found the previously nontested herbicides imazamox and imazapic to be effective for selective weed control and refined application rate and timing of five herbicides for use in clonal plantations.
Endoscopic Ex Vivo Evaluation of Bile Concentrations by Narrow Band Imaging: A Pilot Study
Authors: Maselli Roberta , Inoue Haruhiro , Ikeda Haruo , Onimaru Manabu , Yoshida Akira , Santi Esperanza Grace , Sato Hiroki , Eleftheriadis Nikolas , Kudo Shin-ei
Published: May 2015

Background. Bile juice plays a major role in duodenogastroesophageal reflux (DGERD). Several devices to directly measure the bile concentration have been proposed. We aimed to ex-vivo evaluate the bile concentration by narrow band imaging (NBI).Method. From six surgical cholecystectomies, the content of the gallbladders was aspirated and the total biliary acid (TBA) concentration was evaluated. 2 mL was employed for serial twofold dilutions. Each dilution was scoped. Images on white light (WL) and NBI were captured and grouped accordingly to NBI-appearance and TBA-concentration.Results. Nondiluted bile had a TBA-concentration of 61965 ± 32989 μmol/L. Final dilution (1 : 4096) had 1.16 μmol/L. NBI and correspondent WL images were grouped into seven groups, and an NBI/Bile scale was created.Conclusion. The scale showed that not only NBI scale but also white light scale could be useful to predict the bile concentration. This initial study shows that NBI has a potential role in the detection of DGERD and further investigation is warranted to distinguish the presence and the concentration of bile, especially at very low TBA concentrations.
Kaurenoic Acid Possesses Leishmanicidal Activity by Triggering a NLRP12/IL‐1β/cNOS/NO Pathway
Authors: Miranda Milena Menegazzo , Panis Carolina , da Silva Suelen Santos , Macri Juliana Aparecida , Kawakami Natalia Yoshie , Hayashida Thiago Hideki , Madeira Tiago Bervelieri , Acquaro Vinicius Ricardo , Nixdorf Suzana Lucy , Pizzatti Luciana , Ambrósio Sérgio Ricardo , Cecchini Rubens , Arakawa Nilton Syogo , Verri Waldiceu Aparecido , Conchon Costa Ivete , Pavanelli Wander Rogério
Published: May 2015

Leishmania amazonensis (L. amazonensis) infection can cause severe local and diffuse injuries in humans, a condition clinically known as American cutaneous leishmaniasis (ACL). Currently, the therapeutic approach for ACL is based on Glucantime, which shows high toxicity and poor effectiveness. Therefore, ACL remains a neglected disease with limited options for treatment. Herein, the in vitro antiprotozoal effect and mechanisms of the diterpene kaurenoic acid [ent‐kaur‐16‐en‐19‐oic acid] (KA) against L. amazonensis were investigated. KA exhibited a direct antileishmanial effect on L. amazonensis promastigotes. Importantly, KA also reduced the intracellular number of amastigote forms and percentage of infected peritoneal macrophages of BALB/c mice. Mechanistically, KA treatment reestablished the production of nitric oxide (NO) in a constitutive NO synthase‐ (cNOS‐) dependent manner, subverting the NO‐depleting escape mechanism of L. amazonensis. Furthermore, KA induced increased production of IL‐1β and expression of the inflammasome‐activating component NLRP12. These findings demonstrate the leishmanicidal capability of KA against L. amazonensis in macrophage culture by triggering a NLRP12/IL‐1β/cNOS/NO mechanism.
The Potential Role of the NLRP3 Inflammasome as a Link between Mitochondrial Complex I Dysfunction and Inflammation in Bipolar Disorder
Authors: Kim Helena Kyunghee , Chen Wenjun , Andreazza Ana Cristina
Published: May 2015

Mitochondrial dysfunction and activation of the inflammatory system are two of the most consistently reported findings in bipolar disorder (BD). More specifically, altered levels of inflammatory cytokines and decreased levels of mitochondrial complex I subunits have been found in the brain and periphery of patients with BD, which could lead to increased production of mitochondrial reactive oxygen species (ROS). Recent studies have shown that mitochondrial production of ROS and inflammation may be closely linked through a redox sensor known as nod-like receptor pyrin domain-containing 3 (NLRP3). Upon sensing mitochondrial release of ROS, NLRP3 assembles the NLRP3 inflammasome, which releases caspase 1 to begin the inflammatory cascade. In this review, we discuss the potential role of the NLRP3 inflammasome as a link between complex I dysfunction and inflammation in BD and its therapeutic implications.
Robust TDOA Localization Algorithm for Asynchronous Wireless Sensor Networks
Authors: Xiong Hui , Chen Zhiyuan , An Wei , Yang Beiya
Published: May 2015

This paper presents a tag localization algorithm based on the time-difference-of-arrival (TDOA) of mobile tag signal for asynchronous wireless sensor network (WSN) with N anchors (nodes with known locations) and a large number of mobile tags. To obtain time synchronization, all anchors broadcast signals periodically; relative clock offsets and skews of anchor pairs are estimated by the least-square (LS) method using the times-of-arrival (TOAs) of broadcast signals at anchors. When a tag transmits signal, the TOA of tag signal at each anchor is stamped and errors in original TDOAs of tag signal due to relative clock offsets and skews of anchor pairs are eliminated. Based on Gaussian noise model, maximum likelihood estimation (MLE) for the tag position is obtained. Performance issues are addressed by evaluating the Cramér-Rao lower bound of synchronization and localization algorithms. Since the tag can be located via a single transmission, least power consumption of tag is required, and large number of tags can be served in WSN. The proposed algorithm is simple and effective, with performance close to that of synchronous TDOA algorithm.
Retrieval of a Dislodged Catheter Using Combined Fluoroscopy and Intracardiac Echocardiography
Authors: Mitsopoulos Gus , Hanna Robert F. , Brejt Sidney Z. , Goldstein Greg E. , Sheynzon Vladimir , Weintraub Joshua L. , Gray William A.
Published: May 2015

This report details a method of percutaneous, transluminal retrieval of an intracardiac foreign body using fluoroscopy in combination with intracardiac echocardiography. During retrieval, intracardiac echocardiography (ICE) provided real-time anatomic localization of a constantly moving, almost radiolucent micropuncture coaxial dilator fragment with respect to the tricuspid and pulmonary valves. This method may serve as a crucial aid in retrieval of intracardiac foreign bodies that are difficult to see with fluoroscopy and which may be adjacent to cardiac valves.
The Different Characteristics of Cirrus Optical Coherence Tomography between Superior Segmental Optic Hypoplasia and Normal Tension Glaucoma with Superior Retinal Nerve Fiber Defect
Authors: Han Jong Chul , Choi Da Ye , Kee Changwon
Published: May 2015

Purpose. To evaluate the different characteristics in superior segmental optic hypoplasia (SSOH) and normal tension glaucoma (NTG) with superior retinal nerve fiber layer (RNFL) defect (NTG-SRD) compared to normal control using cirrus optical coherence tomography (OCT).Methods. SSOH eyes and NTG-SRD eyes were reviewed. The peripapillary RNFL (pRNFL) and ganglion cell inner plexiform layer (GCIPL) of the two groups were compared to age-matched normal controls using cirrus OCT.Results. Included in this study were 31 SSOH eyes, 33 NTG patients, and 49 healthy normal controls. Compared to normal controls, pRNFL thickness in SSOH eyes was thinner except in the inferotemporal to the temporal segment. NTG-SRD eyes had thinner pRNFL except in the nasal to inferonasal segment. Meanwhile, GCIPL thickness in SSOH eyes was thinner in the global and sectoral segment, but not in the superonasal and inferonasal sectors compared to normal controls. NTG-SRD eyes showed thinner GCIPL in all sectors compared to normal controls. In case of comparison between SSOH and NTG-SRD, superonasal sector was thinner in NTG-SRD than in SSOH (P=0.03).Conclusions. The different distributions of nerve fiber layer were shown in pRNFL and GCIPL between SSOH eyes and NTG-SRD eyes.
Simulation of Bimetallic Bush Hot Rolling Bonding Process
Authors: Tian Yaqin , Huang Qingxue
Published: May 2015

Three-dimensional model of bimetallic bush was established including the drive roller and the core roller. The model adopted the appropriate interface assumptions. Based on the bonding properties of bimetallic bush the hot rolling process was analyzed. The optimum reduction ratio of 28% is obtained by using the finite element simulation software MARC on the assumption of the bonding conditions. The stress-strain distribution of three dimensions was research assumptions to interface deformation of rolling. At the same time, based on the numerical simulation, the minimum reduction ratio 20% is obtained by using a double metal composite bush rolling new technology from the experiment research. The simulation error is not more than 8%.
Evaluation of Transduction Properties of an Adenovirus Vector in Neonatal Mice
Authors: Iizuka Shunsuke , Sakurai Fuminori , Shimizu Kahori , Ohashi Kazuo , Nakamura Shin-ichiro , Tachibana Masashi , Mizuguchi Hiroyuki
Published: May 2015

In gene therapy for congenital disorders, treatments during neonate and infant stages are promising. Replication-incompetent adenovirus (Ad) vectors have been used in gene therapy studies of genetic disorders; however, the transduction properties of Ad vectors in neonates and infants have not been fully examined. Accordingly, this study examined the properties of Ad vector-mediated transduction in neonatal mice. A first-generation Ad vector containing a cytomegalovirus (CMV) promoter-driven luciferase expression cassette was administered to neonatal mice on the second day of lifeviaretro-orbital sinus. The highest Ad vector genome copy numbers and transgene expression were found in the neonatal liver. The neonatal heart exhibited the second highest levels of transgene expression among the organs examined. There was an approximately 1500-fold difference in the transgene expression levels between the adult liver and heart, while the neonatal liver exhibited only an approximately 30-fold higher level of transgene expression than the neonatal heart. A liver-specific promoter for firefly luciferase expression conferred a more than 100-fold higher luciferase expression in the liver relative to the other organs. No apparent hepatotoxicity was observed in neonatal mice following Ad vector administration. These findings should provide valuable information for gene therapy using Ad vectors in neonates and infants.
Ovarian Seromucinous Borderline Tumor and Clear Cell Carcinoma: An Unusual Combination
Authors: Nakamura Eriko , Sato Yuichiro , Moriguchi Sayaka , Yamashita Atsushi , Higo Takashi , Asada Yujiro
Published: May 2015

Ovarian seromucinous borderline tumors (SMBTs) are rare. They architecturally resemble serous borderline tumors but are much more frequently associated with endometriosis. The coexistence of other tumors with seromucinous tumors is also extremely rare. Here, we report an unusual combination of bilateral ovarian SMBT and clear cell carcinoma associated with polypoid endometriosis of the colon, in a 62-year-old woman. There was no transitional lesion between the two tumors. Immunohistochemistry showed different staining patterns in tumor components. Seromucinous tumor cells were positive for estrogen receptor (ER) and progesterone receptor (PgR) but negative for Napsin A, p504S, and HNF1B. Clear cell tumor cells were positive for Napsin A and p504S and focally positive for HNF1B but negative for ER and PgR. Loss of ARID1A expression was not observed in SMBTs, clear cell tumors, or endometriosis. These findings suggest that these tumors arose from separate endometriosis foci and collided within the same ovary. To the best of our knowledge, this is the first case of this unusual combination of ovarian seromucinous tumor and clear cell carcinoma to be reported in the English literature.
An Approximation Method for Solving Volterra Integrodifferential Equations with a Weighted Integral Condition
Authors: Guezane-Lakoud A. , Bendjazia N. , Khaldi R.
Published: May 2015

We apply the reproducing kernel Hilbert space (RKHS) method for getting analytical and approximate solutions for second-order hyperbolic integrodifferential equations with a weighted integral condition. The analytical solution is represented in the form of series; thus, then-terms approximate solutions are obtained. The results of the numerical examples are compared with the exact solutions to illustrate the accuracy and the effectivity of this method.
Standard and Nonstandard Neutrino-Nucleus Reactions Cross Sections and Event Rates to Neutrino Detection Experiments
Authors: Papoulias D. K. , Kosmas T. S.
Published: May 2015

In this work, we exploreν-nucleus processes from a nuclear theory point of view and obtain results with high confidence level based on accurate nuclear structure cross sections calculations. Besides cross sections, the present study includes simulated signals expected to be recorded by nuclear detectors and differential event rates as well as total number of events predicted to be measured. Our original cross sections calculations are focused on measurable rates for the standard model process, but we also perform calculations for various channels of the nonstandard neutrino-nucleus reactions and come out with promising results within the current upper limits of the corresponding exotic parameters. We concentrate on the possibility of detecting (i) supernova neutrinos by using massive detectors like those of the GERDA and SuperCDMS dark matter experiments and (ii) laboratory neutrinos produced near the spallation neutron source facilities (at Oak Ridge National Lab) by the COHERENT experiment. Our nuclear calculations take advantage of the relevant experimental sensitivity and employ the severe bounds extracted for the exotic parameters entering the Lagrangians of various particle physics models and specifically those resulting from the charged lepton flavour violatingμ-→e-experiments (Mu2e and COMET experiments).
Epidemiologic Study ofBlastocystisInfection in an Urban Community in the Philippines
Authors: Belleza Maria Luz B. , Cadacio Jessa Louise C. , Borja Maridel P. , Solon Juan Antonio A. , Padilla Mildred A. , Tongol-Rivera Pilarita N. , Rivera Windell L.
Published: May 2015

Blastocystishas been considered as the most common intestinal parasite in humans and has an augmented impact on public health. However, the prevalence of this parasite in the Philippines has not been determined. To contribute to a better understanding of the epidemiology of this infection, a cross-sectional study aimed at providing the first documented data on the prevalence and correlates, sociodemographic factors, hygiene practices, source of water supply, and dog ownership, associated withBlastocystisinfection was carried out in randomly selected communities at Pateros, Metro Manila. Fecal samples from respondents were collected and cultured in diphasic agar medium for 3–7 days and examined using light microscopy. Of the 1,271 respondents, 12.98% (95% CI: 11.13–14.83) were detected positive forBlastocystis. Among the correlates ofBlastocystisinfection, dog ownership was found significantly associated as confirmed by multivariate analysis. Therefore, this factor should be considered in information to create awareness aboutBlastocystisand to prevent and controlBlastocystisinfection in particular and diarrheal diseases in general. Further studies using molecular approaches to distinguish subtype and to determine genetic characteristics of isolates from humans and dogs are recommended to analyze their relationship and provide more conclusive evidence of cross-transmission.
Serum Uric Acid, Alanine Aminotransferase, Hemoglobin and Red Blood Cell Count Levels in Pseudoexfoliation Syndrome
Authors: Simavlı Hüseyin , Bucak Yasin Yücel , Tosun Mehmet , Erdurmuş Mesut
Published: May 2015

Purpose. The pathogenesis of pseudoexfoliation (PEX), the most common cause of secondary glaucoma, has not been clearly identified, but there is increasing evidence that points out the role of oxidative stress. The aim of this study is to evaluate some of the most commonly used blood parameters, hemoglobin (Hb), red blood cell count (RBC), alanine aminotransferase (ALT), and uric acid (UA) levels, in subjects with PEX.Materials and Methods. This study is performed in a state hospital between November 2011 and December 2012. Retrospective chart review of subjects who underwent cataract surgery was performed. Thirty-one healthy subjects with PEX and 34 healthy subjects without PEX were evaluated. Hb, RBC, ALT, and UA levels were recorded. Student’st-test was used to compare the two groups.Results. The mean age was73.6±14.1years in PEX group and70.1±12.7in control groupp=0.293. Hb, RBC, ALT, and UA levels did not show a statistically significant difference among PEX and control groups (p>0.05for all).Conclusion. Serum levels of Hb, RBC, ALT, and UA levels were similar in subjects with and without PEX. Further studies are needed to clarify the precise role of Hb, RBC, ALT, and UA in the pathogenesis of PEX.
Synthesis and Antibacterial Activity of New Spiro[thiadiazoline-(pyrazolo[3,4-d]pyrimidine)] Derivatives
Authors: El Fal Mohammed , Ramli Youssef , Zerzouf Abdelfettah , Talbaoui Ahmed , Bakri Youssef , Essassi El Mokhtar
Published: May 2015

New heterocyclic compounds spiroderivatives of allopurinol of biological interest were prepared from allopurinol via thionation and 1,3-dipolar cycloaddition and were produced in high to excellent yields. These compounds were characterized on the basis of spectral and spectroscopic data (1H NMR,13C, IR, and MS). The antibacterial activity of the synthesized products was studied using bacterial strains:Staphylococcus aureus,Enterococcus faecalis,Escherichia coli, andPseudomonas aeruginosa. Compounds having an ethyl group showed the best activity with MIC value of 31.25 µg/mL againstStaphylococcus aureusandStreptococcus fasciens.
KRAS Genomic Status Predicts the Sensitivity of Ovarian Cancer Cells to Decitabine
Authors: Stewart Michelle L. , Tamayo Pablo , Wilson Andrew J. , Wang Stephanie , Chang Yun Min , Kim Jong W. , Khabele Dineo , Shamji Alykhan F. , Schreiber Stuart L.
Published: May 2015

Decitabine, a cancer therapeutic that inhibits DNA methylation, produces variable antitumor response rates in patients with solid tumors that might be leveraged clinically with identification of a predictive biomarker. In this study, we profiled the response of human ovarian, melanoma, and breast cancer cells treated with decitabine, finding that RAS/MEK/ERK pathway activation and DNMT1 expression correlated with cytotoxic activity. Further, we showed that KRAS genomic status predicted decitabine sensitivity in low-grade and high-grade serous ovarian cancer cells. Pretreatment with decitabine decreased the cytotoxic activity of MEK inhibitors in KRAS-mutant ovarian cancer cells, with reciprocal downregulation of DNMT1 and MEK/ERK phosphorylation. In parallel with these responses, decitabine also upregulated the proapoptotic BCL-2 family member BNIP3, which is known to be regulated by MEK and ERK, and heightened the activity of proapoptotic small-molecule navitoclax, a BCL-2 family inhibitor. In a xenograft model of KRAS-mutant ovarian cancer, combining decitabine and navitoclax heightened antitumor activity beyond administration of either compound alone. Our results define the RAS/MEK/DNMT1 pathway as a determinant of sensitivity to DNA methyltransferase inhibition, specifically implicating KRAS status as a biomarker of drug response in ovarian cancer. Cancer Res; 75(14); 2897–906. ©2015 AACR.
Molecular Pathways: Targeting Tumor-Infiltrating Myeloid-Derived Suppressor Cells for Cancer Therapy
Authors: Di Mitri Diletta , Toso Alberto , Alimonti Andrea
Published: May 2015

Tumor-infiltrating myeloid-derived suppressor cells (MDSC) are a heterogeneous and immunosuppressive cell subset that blocks the proliferation and the activity of both T and natural killer (NK) cells and promotes tumor vasculogenesis and progression. Recent evidences demonstrate that the recruitment of MDSCs in tumors also blocks senescence induced by chemotherapy promoting chemoresistance. Hence, the need of novel therapeutic approaches that can efficiently target MDSC recruitment and function in cancer. Among them, novel combinatorial treatments of chemotherapy and immunotherapy or treatments that induce depletion of MDSCs in peripheral sites should be taken in consideration. Clin Cancer Res; 21(14); 3108–12. ©2015 AACR.
Effect of Sulforaphane in Men with Biochemical Recurrence after Radical Prostatectomy
Authors: Cipolla Bernard G. , Mandron Eric , Lefort Jean Marc , Coadou Yves , Della Negra Emmanuel , Corbel Luc , Le Scodan Ronan , Azzouzi Abdel Rahmene , Mottet Nicolas
Published: May 2015

Increases in serum levels of prostate-specific antigen (PSA) occur commonly in prostate cancer after radical prostatectomy and are designated “biochemical recurrence.” Because the phytochemical sulforaphane has been studied extensively as an anticancer agent, we performed a double-blinded, randomized, placebo-controlled multicenter trial with sulforaphane in 78 patients (mean age, 69 ± 6 years) with increasing PSA levels after radical prostatectomy. Treatment comprised daily oral administration of 60 mg of a stabilized free sulforaphane for 6 months (M0–M6) followed by 2 months without treatment (M6–M8). The study was designed to detect a 0.012 log (ng/mL)/month decrease in the log PSA slope in the sulforaphane group from M0 to M6. The primary endpoint was not reached. For secondary endpoints, median log PSA slopes were consistently lower in sulforaphane-treated men. Mean changes in PSA levels between M6 and M0 were significantly lower in the sulforaphane group (+0.099 ± 0.341 ng/mL) than in placebo (+0.620 ± 1.417 ng/mL; P = 0.0433). PSA doubling time was 86% longer in the sulforaphane than in the placebo group (28.9 and 15.5 months, respectively). PSA increases >20% at M6 were significantly greater in the placebo group (71.8%) than in the sulforaphane group (44.4%); P = 0.0163. Compliance and tolerance were very good. Sulforaphane effects were prominent after 3 months of intervention (M3–M6). After treatment, PSA slopes from M6 to M8 remained the same in the 2 arms. Daily administration of free sulforaphane shows promise in managing biochemical recurrences in prostate cancer after radical prostatectomy. Cancer Prev Res; 8(8); 712–9. ©2015 AACR.
Interleukin-6/STAT3 Pathway Signaling Drives an Inflammatory Phenotype in Group A Ependymoma
Authors: Griesinger Andrea M. , Josephson Rebecca J. , Donson Andrew M. , Mulcahy Levy Jean M. , Amani Vladimir , Birks Diane K. , Hoffman Lindsey M. , Furtek Steffanie L. , Reigan Phillip , Handler Michael H. , Vibhakar Rajeev , Foreman Nicholas K.
Published: May 2015

Ependymoma (EPN) in childhood is a brain tumor with substantial mortality. Inflammatory response has been identified as a molecular signature of high-risk Group A EPN. To better understand the biology of this phenotype and aid therapeutic development, transcriptomic data from Group A and B EPN patient tumor samples, and additional malignant and normal brain data, were analyzed to identify the mechanism underlying EPN Group A inflammation. Enrichment of IL6 and STAT3 pathway genes were found to distinguish Group A EPN from Group B EPN and other brain tumors, implicating an IL6 activation of STAT3 mechanism. EPN tumor cell growth was shown to be dependent on STAT3 activity, as demonstrated using shRNA knockdown and pharmacologic inhibition of STAT3 that blocked proliferation and induced apoptosis. The inflammatory factors secreted by EPN tumor cells were shown to reprogram myeloid cells, and this paracrine effect was characterized by a significant increase in pSTAT3 and IL8 secretion. Myeloid polarization was shown to be dependent on tumor secretion of IL6, and these effects could be reversed using IL6-neutralizing antibody or IL6 receptor–targeted therapeutic antibody tocilizumab. Polarized myeloid cell production of IL8 drove unpolarized myeloid cells to upregulate CD163 and to produce a number of proinflammatory cytokines. Collectively, these findings indicate that constitutive IL6/STAT3 pathway activation is important in driving tumor growth and inflammatory cross-talk with myeloid cells within the Group A EPN microenvironment. Effective design of Group A–targeted therapy for children with EPN may require reversal of this potentially immunosuppressive and protumor pathway. Cancer Immunol Res; 3(10); 1165–74. ©2015 AACR.
The BS/BSOB Ratio in Aneuploidy Fetuses at 11-13 Weeks Gestation
Authors: Hsiao Ching Hua , Cheng Po Jen , Shaw S.W. Steven , Tseng Yin Jiun , Chen Ran Chou , Chu Woei-Chyn
Published: May 2015

Objective: The posterior fossa of normal fetuses was evaluated and compared with those having chromosomal abnormalities at 11-13+6 weeks' gestation in Chinese population. Methods: In 518 normal fetuses referred to first trimester screening, fetal brain stem (BS) and brain stem to occipital bone distance (BSOB) were measured prospectively. The BS and BSOB were also measured on stored images in fetuses with confirmed trisomy 21 (n = 38), Trisomy 18 (n = 26), Trisomy 13 (n = 8), and monosomy X (n = 8). Results: The BS diameter and BSOB distance correlated linearly with fetal crown-rump length (CRL) by regression analysis. The BS to BSOB ratio was below the 5th percentile in 2 (5.26%), 11 (44%), 4 (50%) and 4 (50%) fetuses with trisomy 21, trisomy 18, trisomy 13 and monosomy X, respectively. Thus, both BS and BS/BSOB ratio were significantly lower in trisomy 18, trisomy 13 and monosomy X fetuses when compared to the reference range but not in fetuses with Trisomy 21. Conclusion: In ultrasound scans performed at the 11-13+6 gestation weeks, fetuses with trisomy 18, 13, and monosomy X had lower BS/BSOB ratios. But trisomy 21 fetuses did not show significant differences in posterior fossa compared to the normal population.
Cadmium Induced Apoptosis in MG63 Cells by Increasing ROS, Activation of p38 MAPK and Inhibition of ERK 1/2 Pathways
Authors: Hu Kong-He , Li Wen-Xue , Sun Min-Ying , Zhang She-Bing , Fan Cai-Xia , Wu Qiang , Zhu Wei , Xu Xin
Published: May 2015

Background/Aims: Cadmium (Cd) induces apoptosis in different kinds of cells, including osteoblasts, both in vivo and in vitro. However, little is known about the mechanisms by which Cd induces apoptosis. Methods: In the present study, we used the human osteosarcoma cell line MG63, which has characteristics similar to human osteoblasts, as an in vitro model to determine the cellular mechanisms by which Cd induces apoptosis. Results: We found that short-term exposure to CdCl2 induced apoptosis in MG63 cells. Furthermore, the incubation of cells with CdCl2 significantly increased the level of phosphorylated p38MAPK and significantly decreased the phosphorylation of ERK1/2 in a concentration-dependent manner. Additionally, the inhibition of the phosphorylation of p38 MAPK by SB202190 protected MG63 cells from Cd-induced apoptosis. The incubation of MG63 cells with the ERK1/2 inhibitor PD98059 significantly increased apoptosis in MG63 cells. CdCl2 also significantly increased the intracellular levels of ROS. N-acetylcysteine (NAC) significantly reduced ROS levels and reversed the effects of CdCl2 on MAPK signaling. Conclusion: Our results suggested that Cd induced apoptosis in MG63 cells by increasing ROS, activation of p38 MAPK and inhibition of ERK1/2 pathways.
HuangQi Decoction Improves Renal Tubulointerstitial Fibrosis in Mice by Inhibiting the Up-Regulation of Wnt/β-Catenin Signaling Pathway
Authors: Jiang Ming-Qian , Wang Li , Cao Ai-li , Zhao Jie , Chen Xia , Wang Yun-man , Wang Hao , Peng Wen
Published: May 2015

Object: To explore the effects of HuangQi decoction on tubulointerstitial fibrosis in mice and the Wnt/β-catenin signaling pathway. Methods: Unilateral ureteral obstruction (UUO) model was used. A total of 120 C57/BL mice were randomly divided into 6 groups, sham group, sham+HuangQi decoction group (1.08 g/kg), UUO group, UUO+HuangQi decoction group (0.12, 0.36, 1.08 g/kg). Immunohistochemical analysis, RT-PCR and Western blot were employed to examine the proteins and genes related to the Wnt/β-catenin signaling pathway. Results: In UUO mice models, expression levels of Wnt3,4, Frizzled4, LRP5,6, β-catenin, LEF-1, TCF-1, Snail, MMP2,7 genes were positively correlated with the degree of renal tubulointerstitial fibrosis, while expression levels of GSK-3β, Axin, APC, CK1 were negatively correlated. HuangQi decoction could down-regulate expression levels of Wnt3,4, Frizzled4, LRP5,6, β-catenin, LEF-1, TCF-1, Snail, Twist, MMP2,7 and up-regulate expression levels of GSK-3β, Axin, APC, CK1 and E-cadherin. Conclusion: HuangQi decoction could effectively inhibit the up-regulation of Wnt/β-catenin signaling pathway induced by UUO, implying a possible role in improving renal interstitial fibrosis.
Perivascular Adipose Adiponectin Correlates With Symptom Status of Patients Undergoing Carotid Endarterectomy
Authors: Sharma Gaurav , Tao Ming , Ding Kui , Yu David , King William , Deyneko Galina , Wang Xiaosong , Longchamp Alban , Schoen Frederick J. , Ozaki C. Keith , Semel Marcus E.
Published: May 2015

Background and Purpose—

Recent symptoms stand as a major determinant of stroke risk in patients with carotid stenosis, likely reflective of atherosclerotic plaque destabilization. In view of emerging links between vascular and adipose biology, we hypothesized that human perivascular adipose characteristics associate with carotid disease symptom status.

Methods—

Clinical history, carotid plaques, blood, and subcutaneous and perivascular adipose tissues were prospectively collected from patients undergoing carotid endarterectomy. Nine adipose-associated biological mediators were assayed and compared in patients with symptomatic (n=15) versus asymptomatic (n=19) disease. Bonferroni correction was performed for multiple testing (
α
/9=0.006).

Results—

Symptomatic patients had 1.9-fold higher perivascular adiponectin levels (
P
=0.005). Other circulating, subcutaneous, and perivascular biomarkers, as well as microscopic plaque characteristics, did not differ between symptomatic and asymptomatic patients.

Conclusions—

Symptomatic and asymptomatic carotid endarterectomy patients display a tissue-specific difference in perivascular adipose adiponectin. This difference, which was not seen in plasma or subcutaneous compartments, supports a potential local paracrine relationship with vascular disease processes that may be related to stroke mechanisms.
White Matter Damage Relates to Oxygen Saturation in Children With Sickle Cell Anemia Without Silent Cerebral Infarcts
Authors: Kawadler Jamie M. , Kirkham Fenella J. , Clayden Jonathan D. , Hollocks Matthew J. , Seymour Emma L. , Edey Rosanna , Telfer Paul , Robins Andrew , Wilkey Olu , Barker Simon , Cox Tim C.S. , Clark Chris A.
Published: May 2015

Background and Purpose—

Sickle cell anemia is associated with compromised oxygen-carrying capability of hemoglobin and a high incidence of overt and silent stroke. However, in children with no evidence of cerebral infarction, there are changes in brain morphometry relative to healthy controls, which may be related to chronic anemia and oxygen desaturation.

Methods—

A whole-brain tract-based spatial statistics analysis was carried out in 25 children with sickle cell anemia with no evidence of abnormality on T2-weighted magnetic resonance imaging (13 male, age range: 8–18 years) and 14 age- and race-matched controls (7 male, age range: 10–19 years) to determine the extent of white matter injury. The hypotheses that white matter damage is related to daytime peripheral oxygen saturation and steady-state hemoglobin were tested.

Results—

Fractional anisotropy was found to be significantly lower in patients in the subcortical white matter (corticospinal tract and cerebellum), whereas mean diffusivity and radial diffusivity were higher in patients in widespread areas. There was a significant negative relationship between radial diffusivity and oxygen saturation (
P
<0.05) in the anterior corpus callosum and a trend-level negative relationship between radial diffusivity and hemoglobin (
P
<0.1) in the midbody of the corpus callosum.

Conclusions—

These data show widespread white matter abnormalities in a sample of asymptomatic children with sickle cell anemia, and provides for the first time direct evidence of a relationship between brain microstructure and markers of disease severity (eg, peripheral oxygen saturation and steady-state hemoglobin). This study suggests that diffusion tensor imaging metrics may serve as a biomarker for future trials of reducing hypoxic exposure.
Stroke Induces Nuclear Shuttling of Histone Deacetylase 4
Authors: Kassis Haifa , Shehadah Amjad , Chopp Michael , Roberts Cynthia , Zhang Zheng Gang
Published: May 2015

Background and Purpose—

Histone deacetylases (HDACs) 4 and 5 are abundantly expressed in the brain and have been implicated in the regulation of neurodegeneration. Under physiological conditions, HDACs 4 and 5 are expressed in the cytoplasm of brain cells where they cannot directly access chromatin. In response to external stimuli, they can shuttle to the nucleus and regulate gene expression. However, the effect of stroke on nuclear shuttling of HDACs 4 and 5 remains unknown.

Methods—

Using a rat model of middle cerebral artery occlusion, we examined the subcellular localization of HDACs 4 and 5 in the peri-infarct cortex during brain repair after stroke.

Results—

Stroke significantly increased nuclear HDAC4 immunoreactivity in neurons, but not in astrocytes or in oligodendrocytes, of the peri-infarct cortex at 2, 7, and 14 days after middle cerebral artery occlusion. Neurons with nuclear HDAC4 immunoreactivity distributed across all layers of the peri-infarct cortex and were Ctip2+ excitatory and parvalbumin+ inhibitory neurons. These neurons were not TUNEL or BrdU positive. Furthermore, nuclear HDAC4 immunoreactivity was positively and significantly correlated with increased dendritic, axonal, and myelin densities as determined by microtubule-associated protein 2, phosphorylated neurofilament heavy chain, and myelin basic protein, respectively. Unlike HDAC4, stroke did not alter nuclear localization of HDAC5.

Conclusions—

Our data show that stroke induces nuclear shuttling of HDAC4 in neurons in the peri-infarct cortex, and that increased nuclear HDAC4 is strongly associated with neuronal remodeling but not with neuronal cell death, suggesting a role for nuclear HDAC4 in promoting neuronal recovery after ischemic injury.
Textual Criticism and Nationalist Sentiments
Authors: Muraoka Takamitsu
Published: May 2015

The phrase מבית עבדים was left out in the preamble of the Decalogue according to Papyrus Nash because of a sense of dignity of the local community, for which the Decalogue was its magna carta.
A Kingdom of Priests and its Earthen Altars in Exodus 19-24
Authors: Chavel Simeon
Published: May 2015

This study analyzes the altar law in Exodus 20, the statement that frames it in Exodus 19, and its application in Exodus 24 as a single narrative that denies the professional configuration of sacrifice as essential to religion and divine blessing. It puts the gift-blessing exchange into the hands of every family, and reverses the basic trope of hosting-visiting and the social poetics that govern hierarchical religion: rather than host at his palace through mediating attendants, Yahweh visits wherever he is invited. The study argues that the narrative attacks an Israelian and Judean ideology in which royal success defines territorial extent, shapes the polity, enshrines divine power in temples, and controls divine blessing. It reconfigures the elements such that territory and nationhood are defined by the divine king, who roams freely throughout the land to bless each of his subjects, so long as they invite him to receive a gift.
School Success and FailureChanges Seen in Children of Chinese Descent in Paris学校适应与不适应：巴黎华裔子女的变化
Authors: Yamamoto Sumiko
Published: May 2015

This research examines the difficulties faced by children of recent migrants from mainland China to France in Paris schools, and explains the underlying factors. It is based on fieldwork in Paris schools from 2005 to 2013. Other long-established Chinese communities in France consist mainly of Indo-Chinese refugees of Chinese descent. Their children were born in France and have adjusted to French schools; in contrast, some children of new Chinese immigrants (mainly from Wenzhou) do not attend school regularly and often drop out. My findings show that formation of the folk theory of success that values school education — which explains school success among Indo-Chinese refugee children — is hampered by institutional constraints resulting from parents’ status as illegal immigrants, and unstable parent-child relationships due to the family’s immigration arrangements. This paper reveals the limitations of conventional explanations for Chinese immigrants’ school success and failure based on cultural values.
Structural Challenges Facing International Organizations
Authors: Mathias Stephen
Published: May 2015

This article reflects upon the lessons which might be learned from the League of Nations. It highlights a number of the key differences between the League of Nations and the United Nations, with consideration given to the characteristics which shaped both institutions, and the impact which those aspects have had on their ability to fulfil their respective mandates. The article addresses issues including the composition of the institutions’ memberships, the role of sanctions, the roles of the respective Secretariats, and concludes with reflections on broader lessons which might be learned, drawing on the purposes and principles of the respective institutions. The importance of Article 2(4) of the Charter of the United Nations is emphasised, with recognition given to its central role in securing a peaceful society in which the Organization’s goal of bringing about social progress and better standards of life might be secured.