bluuebunny/crossref_metadata_2025 huggingface dataset:
Initiation of Triangle Zones by Delamination, Shear, and Compaction at the Front of Fold-and-Thrust Belts
Authors: Liu Chang , Shi Yaolin
Published: March 2016

The interest of this paper is to investigate the initiation of triangle zones at the front of fold-and-thrust belts by analyzing the virtual velocity fields in triangle wedges. It allows achieving five collapse mechanisms by delamination, shear, and compaction of competing for the formation of triangle zones as follows. The first mechanism is the classical Coulomb shear thrust. The second is delamination at the frontal part of the décollement with straight back thrust, while the third is delamination with curvy back thrust. The fourth is the combination of ramp with Coulomb shear and shear-enhanced compact fault, while the fifth is the combination of the exchanging motion on the ramp and thrust. The dominating mechanism in the formation of triangle zones relies on the competition of the least upper bound of each mechanism when subjected to tectonic force. The controlling factors of the competition are discovered as follows: (1) the frictional characters and cohesion of horizontal décollements and thrust, (2) the slope of the topography of accretion wedge, and (3) the thickness and rock density of the front toe of accretion wedge.
Protection Efficacy of the Extract of Ginkgo biloba against the Learning and Memory Damage of Rats under Repeated High Sustained +Gz Exposure
Authors: Chen Liang-En , Wu Feng , Zhao Andong , Ge Hua , Zhan Hao
Published: March 2016

Repeated high sustained positive Gz (+Gz) exposures are known for the harmful pathophysiological impact on the brain of rats, which is reflected as the interruption of normal performance of learning and memory. Interestingly, extract of Ginkgo biloba (EGb) has been reported to have neuroprotective effects and cognition‐enhancing effects. In this study, we are interested in evaluating the protective effects of EGb toward the learning and memory abilities. Morris Water Maze Test (MWM) was used to evaluate the cognitive function, and the physiological status of the key components in central cholinergic system was also investigated. Our animal behavioral tests indicated that EGb can release the learning and memory impairment caused by repeated high sustained +Gz. Administration of EGb to rats can diminish some of the harmful physiological effects caused by repeated +Gz exposures. Moreover, EGb administration can increase the biological activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px) but reduce the production of malondialdehyde (MDA). Taken together, our study showed that EGb can ameliorate the impairment of learning and memory abilities of rats induced by repeated high sustained +Gz exposure; the underlying mechanisms appeared to be related to the signal regulation on the cholinergic system and antioxidant enzymes system.
Effects of Yishen Pinggan Recipe on Renal Protection and NF‐κB Signaling Pathway in Spontaneously Hypertensive Rats
Authors: Luo Guodong , Zhu Xiying , Gao Zhongxiang , Ge Huaxun , Yu Yang , Guo Yuanyuan , Zheng Jian-Pu , Liu Longmin
Published: March 2016

Inflammation is an important etiological factor of hypertensive renal damage. The effects of Yishen Pinggan Recipe (YPR) on urine microalbumin, histology, and NF‐κB/P65, IκB‐α, IL‐1β, IL‐6, and TNF‐α in renal tissues were evaluated in SHR to explore the mechanism of its renal protection in hypertensive renal damage. The SBP of 12‐week‐old SHR was 192.41 ± 3.93 mmHg and DBP was 142.38 ± 5.79 mmHg. Without treatment, the 24‐week‐old SHRs’ SBP was 196.96 ± 3.77 mmHg and DBP was 146.08 ± 4.82 mmHg. After the 12‐week‐old SHR were administered YPR for 12 weeks, the rats’ SBP was 161.45 ± 7.57 mmHg and DBP was 117.21 ± 5.17 mmHg; YPR could lower blood pressure in SHR. And renal function damage was observed in 24‐week‐old SHR without treatment, manifested as urine protein and morphological changes which could be inhibited by YPR. In addition, YPR could reduce the expression of inflammatory cytokines (IL‐1β, IL‐6, and TNF‐α) in kidneys. It could also inhibit the nuclear translocation of NF‐κB p65 and degradation of IκB‐α in renal cells, indicating that the NF‐κB signaling pathway was inhibited by YPR. Finally, the study suggests that YPR could significantly improve the renal function in SHR. The mechanism could be attributed to its inhibition of renal NF‐κB signaling pathway and inflammation.
Variable Selection and Parameter Estimation with the Atan Regularization Method
Authors: Wang Yanxin , Zhu Li
Published: March 2016

Variable selection is fundamental to high-dimensional statistical modeling. Many variable selection techniques may be implemented by penalized least squares using various penalty functions. In this paper, an arctangent type penalty which very closely resemblesl0penalty is proposed; we call it Atan penalty. The Atan-penalized least squares procedure is shown to consistently select the correct model and is asymptotically normal, provided the number of variables grows slower than the number of observations. The Atan procedure is efficiently implemented using an iteratively reweighted Lasso algorithm. Simulation results and data example show that the Atan procedure with BIC-type criterion performs very well in a variety of settings.
Diagnosis and Prognostic Significance of c-Met in Cervical Cancer: A Meta-Analysis
Authors: Peng Jifeng , Qi Shengnan , Wang Ping , Li Wanyu , Liu Chunxia , Li Feng
Published: March 2016

Objective. A meta-analysis was conducted to analyze c-Met expression in cervical cancer.Methods. Articles related to our study were retrieved from PubMed, Elsevier, and China National Knowledge Infrastructure. State 12.0 was used for literature review, data extraction, and meta-analysis. The random-effects model and fixed-effects model were utilized to pool the relative ratio based on the heterogeneity test in the meta-analysis.Results.Nine studies that include data of 685 cervical carcinoma tissues were analyzed. However, three studies did not thoroughly discuss c-Met expression in nonneoplastic cervical tissue; thus, only six studies involving 364 patients and 228 nonneoplastic cervical tissues were included in the review. c-Met expression was higher in cervical cancer (60.99%) than in nonneoplastic cervical tissue (19.74%). Cervical carcinoma, cervical intraepithelial neoplasm, and normal cervical tissue were also examined. Results showed that increasing malignancy resulted in elevated c-Met expression. The relationship between c-Met expression and clinicopathologic features was also evaluated. c-Met expression correlated with disease-free survival, lymph node involvement, and lymphovascular space invasion. No statistical difference was observed between c-Met expression and other clinicopathological factors.Conclusions.c-Met is a potential diagnostic and prognostic indicator of cervical cancer.
Development of Monoclonal Antibodies against HIV-1 p24 Protein and Its Application in Colloidal Gold Immunochromatographic Assay for HIV-1 Detection
Authors: Ma Yi , Ni Chao , Dzakah Emmanuel E. , Wang Haiying , Kang Keren , Tang Shixing , Wang Jihua , Wang Jufang
Published: March 2016

Human immunodeficiency virus type 1 (HIV-1) p24 protein is the most abundant viral protein of HIV-1. This protein is secreted in blood serum at high levels during the early stages of HIV-1 infection, making it a biomarker for early diagnosis. In this study, a colloidal gold immunochromatographic assay (GICA) was established for detecting p24 protein using mouse monoclonal antibodies (mAbs). The HIV-1 p24 protein was expressed inE. colistrain BL21 and the purified protein was used to immunize mice. Stable hybridoma cell lines secreting anti-p24 monoclonal antibodies were obtained after ELISA screening and subcloning by limiting dilution. 34 different capture and labeling mAb pairs were selected by a novel antibody-capture indirect sandwich ELISA and then applied in GICA to detect p24 protein. The GICA method has a limit of detection (LOD) of 25 pg/mL and could detect p24 protein in all 10 positive samples obtained from the National Reference of HIV-1 p24 antigen. Out of 153 negative samples tested, 3 false positives results were obtained. The overall specificity of this test was 98.03%. The good sensitivity and specificity of this method make it a suitable alternative to provide a more convenient and efficient tool for early diagnosis of HIV infection.
Different Occlusal Schemes in a Persistent Protruding Complete Denture Wearer
Authors: Iegami Carolina Mayumi , Lopes Danilo de Melo , Nakamae Atlas Edson Moleros , Uehara Priscila Nakasone , Tamaki Regina
Published: March 2016

Different types of artificial teeth and occlusal designs can be used in complete dentures. Bilateral balanced occlusion, lingualized occlusion, canine guidance, and monoplane are the main occlusal designs; however there is no agreement on which tooth arrangement is ideal for achieving success in complete dentures. This report presents an alternative for persistent involuntary protruding complete denture wearers through the use of artificial teeth with higher cusps. Due to an old and worn pair of complete dentures, the patient had the habit of protruding. New dentures were made with Biotone artificial teeth and in the trial session, the patient would still protrude. A new set was made with Premium artificial teeth, which present higher cusps. With these dentures, the involuntary protrusion did not occur. From the delivery to the follow-up sessions, the patient stopped protruding.
Recent Advances in Unconventional Lithography for Challenging 3D Hierarchical Structures and Their Applications
Authors: Kim Jong Uk , Lee Sori , Kim Tae-il
Published: March 2016

In nanoscience and nanotechnology, nanofabrication is critical. Among the required processes for nanofabrication, lithography is one of core issues. Although conventional photolithography with recent remarkable improvement has contributed to the industry during the past few decades, fabrication of 3-dimensional (3D) nanostructure is still challenging. In this review, we summarize recent advances for the construction of 3D nanostructures by unconventional lithography and the combination of twotop-downapproaches ortop-downandbottom-upapproaches. We believe that the 3D hierarchical nanostructures described here will have a broad range of applications having adaptable levels of functional integration of precisely controlled nanoarchitectures that are required by not only academia, but also industry.
Predictors of Postoperative Seizure Recurrence: A Longitudinal Study of Temporal and Extratemporal Resections
Authors: Chen Hai , Modur Pradeep N. , Barot Niravkumar , Van Ness Paul C. , Agostini Mark A. , Ding Kan , Gupta Puneet , Hays Ryan , Mickey Bruce
Published: March 2016

Objective. We investigated the longitudinal outcome of resective epilepsy surgery to identify the predictors of seizure recurrence. Materials and Methods. We retrospectively analyzed patients who underwent resections for intractable epilepsy over a period of 7 years. Multiple variables were investigated as potential predictors of seizure recurrence. The time to first postoperative seizure was evaluated using survival analysis and univariate analysis at annual intervals. Results. Among 70 patients, 54 (77%) had temporal and 16 (23%) had extratemporal resections. At last follow-up (mean 48 months; range 24–87 months), the outcome was Engel class I in 84% (n=59) of patients. Seizure recurrence followed two patterns: recurrence was “early” (within 2 years) in 82% of patients, of whom 83% continued to have seizures despite optimum medical therapy; recurrence was “late” (after 2 years) in 18%, of whom 25% continued to have seizures subsequently. Among the variables of interest, only resection site and ictal EEG remained as independent predictors of seizure recurrence over the long term (p<0.05). Extratemporal resection and discordance between ictal EEG and resection area were associated with 4.2-fold and 5.6-fold higher risk of seizure recurrence, respectively. Conclusions. Extratemporal epilepsy and uncertainty in ictal EEG localization are independent predictors of unfavorable outcome. Seizure recurrence within two years of surgery indicates poor long-term outcome.
Impact of Opioid and Nonopioid Drugs on Postsurgical Pain Management in the Rat
Authors: Wilson Natalie M. , Ripsch Matthew S. , White Fletcher A.
Published: March 2016

Aim. Nonsteroidal anti-inflammatory drugs or opioids are commonly used to control surgical pain following veterinary and clinical procedures. This study evaluated the efficacy of postoperative ketorolac or buprenorphine following abdominal surgery. Main Methods. Mean arterial pressure (MAP), heart rate, animal activity, corticosterone levels, and a nociceptive sensitivity assay were used to evaluate 18 adult male Sprague-Dawley rats which underwent aortic artery occlusion for implantation of a radiotelemetry device. The animals were treated postoperatively with intraperitoneal injections of vehicle, ketorolac (10 mg/kg), or buprenorphine (0.06 mg/kg) every 8 hours for 3 days. Key Findings. There were no consistent significant changes in any of the telemetry parameters after treatment with ketorolac compared with no saline treatment with the exception of increased MAP in the buprenorphine group during the first 48 hours when compared with other treatment groups. There was a sustained increase in fecal corticosterone levels from baseline on days 2–7 with buprenorphine compared with vehicle- or ketorolac-treated animals. All treatment conditions displayed reduced paw withdrawal thresholds (PWTs) from day 1 to day 21 following surgery. Compared with the vehicle treatment group, buprenorphine-treated animals exhibited significantly lower PWT levels from day 4 to 14 days. Significance. Given the prolonged increase in fecal corticosterone levels and pronounced changes in tactile hyperalgesia behavior in rodents subjected to buprenorphine treatment, these data suggest that ketorolac may be superior to buprenorphine for the treatment of postprocedure pain behavior in rodents.
Quantitative Evaluation and Selection of Reference Genes for Quantitative RT-PCR in Mouse Acute Pancreatitis
Authors: Yan Zhaoping , Gao Jinhang , Lv Xiuhe , Yang Wenjuan , Wen Shilei , Tong Huan , Tang Chengwei
Published: March 2016

The analysis of differences in gene expression is dependent on normalization using reference genes. However, the expression of many of these reference genes, as evaluated by quantitative RT-PCR, is upregulated in acute pancreatitis, so they cannot be used as the standard for gene expression in this condition. For this reason, we sought to identify a stable reference gene, or a suitable combination, for expression analysis in acute pancreatitis. The expression stability of 10 reference genes (ACTB, GAPDH, 18sRNA, TUBB, B2M, HPRT1, UBC, YWHAZ, EF-1α, and RPL-13A) was analyzed using geNorm, NormFinder, and BestKeeper software and evaluated according to variations in the raw Ct values. These reference genes were evaluated using a comprehensive method, which ranked the expression stability of these genes as follows (from most stable to least stable): RPL-13A, YWHAZ > HPRT1 > GAPDH > UBC > EF-1α> 18sRNA > B2M > TUBB > ACTB. RPL-13A was the most suitable reference gene, and the combination of RPL-13A and YWHAZ was the most stable group of reference genes in our experiments. The expression levels of ACTB, TUBB, and B2M were found to be significantly upregulated during acute pancreatitis, whereas the expression level of 18sRNA was downregulated. Thus, we recommend the use of RPL-13A or a combination of RPL-13A and YWHAZ for normalization in qRT-PCR analyses of gene expression in mouse models of acute pancreatitis.
Significant Enhancement of Mechanical and Thermal Properties of Thermoplastic Polyester Elastomer by Polymer Blending and Nanoinclusion
Authors: Hussain Manwar , Ko Young Hui , Choa Yong Ho
Published: March 2016

Thermoplastic elastomer composites and nanocomposites were fabricated via melt processing technique by blending thermoplastic elastomer (TPEE) with poly(butylene terephthalate) (PBT) thermoplastic and also by adding small amount of organo modified nanoclay and/or polytetrafluoroethylene (PTFE). We study the effect of polymer blending on the mechanical and thermal properties of TPEE blends with and without nanoparticle additions. Significant improvement was observed by blending only TPEE and virgin PBT polymers. With a small amount (0.5 wt.%) of nanoclay or PTFE particles added to the TPEE composite, there was further improvement in both the mechanical and thermal properties. To study mechanical properties, flexural strength (FS), flexural modulus (FM), tensile strength (TS), and tensile elongation (TE) were all investigated. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) were used to analyze the thermal properties, including the heat distortion temperature (HDT), of the composites. Scanning electron microscopy (SEM) was used to observe the polymer fracture surface morphology. The dispersion of the clay and PTFE nanoparticles was confirmed by transmission electron microscopy (TEM) analysis. This material is proposed for use as a baffle plate in the automotive industry, where both high HDT and high modulus are essential.
Developmental and Evolutionary Lexicon Acquisition in Cognitive Agents/Robots with Grounding Principle: A Short Review
Authors: Rasheed Nadia , Amin Shamsudin H. M.
Published: March 2016

Grounded language acquisition is an important issue, particularly to facilitate human-robot interactions in an intelligent and effective way. The evolutionary and developmental language acquisition are two innovative and important methodologies for the grounding of language in cognitive agents or robots, the aim of which is to address current limitations in robot design. This paper concentrates on these two main modelling methods with the grounding principle for the acquisition of linguistic ability in cognitive agents or robots. This review not only presents a survey of the methodologies and relevant computational cognitive agents or robotic models, but also highlights the advantages and progress of these approaches for the language grounding issue.
An Atomistic-Based Continuum Modeling for Evaluation of Effective Elastic Properties of Single-Walled Carbon Nanotubes
Authors: Al-Kharusi M. S. M. , Alzebdeh K. , Pervez T.
Published: March 2016

The mechanical behavior of SWCNTs is characterized using an atomistic-based continuum method. At nanoscale, interatomic energy among carbon atoms and the corresponding force constants are defined. Subsequently, we used an atomistic finite element analysis to calculate the energy stored in the SWCNT model, which forms a basis for calculating effective elastic moduli. In the finite element model, the force interaction among carbon atoms in a SWCNT is modeled using load-carrying structural beams. At macroscale, the SWCNT is taken as cylindrical continuum solid with transversely isotropic mechanical properties. Equivalence of energies of both models establishes a framework to calculate effective elastic moduli of armchair and zigzag nanotubes. This is achieved by solving five boundary value problems under distinct essential-controlled boundary conditions, which generates a prescribed uniform strain field in both models. Elastic constants are extracted from the calculated elastic moduli. While results of Young’s modulus obtained in this study generally concur with the published theoretical and numerical predictions, values of Poisson’s ratio are on the high side.
Contrast Induced Nephropathy with Intravenous Iodinated Contrast Media in Routine Diagnostic Imaging: An Initial Experience in a Tertiary Care Hospital
Authors: Bhatt Shuchi , Rajpal Nipun , Rathi Vineeta , Avasthi Rajneesh
Published: March 2016

Background. Contrast induced nephropathy (CIN) is common cause of hospital acquired renal failure, defined as iatrogenic deterioration of renal function following intravascular contrast administration in the absence of another nephrotoxic event.Objectives. Objectives were to calculate incidence of CIN with routine IV contrast usage and to identify its risk factors.Materials and Methods. Study was conducted on 250 patients (having eGFR ≥ 45 mL/min/1.73 m2) receiving intravenous contrast. Various clinical risk factors and details of contrast media were recorded. Patients showing 25% increase in postprocedural serum creatinine value or an absolute increase of 0.5 mg/dL (44.2 mmol/L) were diagnosed as having CIN.Results and Conclusions. Postprocedural serum creatinine showed significant increase from baseline levels. 25 patients (10%) developed CIN. CIN was transient in 21 (84%) patients developing CIN. One patient (4%) developed renal failure and another died due to unknown cause. Dehydration, preexisting renal disease, cardiac failure, previous contrast administration, and volume of contrast had significant correlation with development of CIN (p<0.05); whereas demographic variables, baseline serum creatinine/eGFR, previous renal surgery, diabetes mellitus, hypertension, nephrotoxic drug intake, abnormal routine hematology, and contrast characteristics had no correlation with CIN. CIN is a matter of concern even in routine imaging requiring intravenous contrast media, in our set-up.
Identification of Candidate Tolerogenic CD8+T Cell Epitopes for Therapy of Type 1 Diabetes in the NOD Mouse Model
Authors: Yu Cailin , Burns Jeremy C. , Robinson William H. , Utz Paul J. , Ho Peggy P. , Steinman Lawrence , Frey Alan B.
Published: March 2016

Type 1 diabetes is an autoimmune disease in which insulin-producing pancreatic isletβcells are the target of self-reactive B and T cells. T cells reactive with epitopes derived from insulin and/or IGRP are critical for the initiation and maintenance of disease, but T cells reactive with other islet antigens likely have an essential role in disease progression. We sought to identify candidate CD8+T cell epitopes that are pathogenic in type 1 diabetes. Proteins that elicit autoantibodies in human type 1 diabetes were analyzed by predictive algorithms for candidate epitopes. Using several different tolerizing regimes using synthetic peptides, two new predicted tolerogenic CD8+T cell epitopes were identified in the murine homolog of the major human islet autoantigen zinc transporter ZnT8 (aa 158–166 and 282–290) and one in a non-βcell protein, dopamineβ-hydroxylase (aa 233–241). Tolerizing vaccination of NOD mice with a cDNA plasmid expressing full-length proinsulin prevented diabetes, whereas plasmids encoding ZnT8 and DβH did not. However, tolerizing vaccination of NOD mice with the proinsulin plasmid in combination with plasmids expressing ZnT8 and DβH decreased insulitis and enhanced prevention of disease compared to vaccination with the plasmid encoding proinsulin alone.
Purification and Characterization of a New Thermostable, Haloalkaline, Solvent Stable, and Detergent Compatible Serine Protease fromGeobacillus toebiiStrain LBT 77
Authors: Thebti Wajdi , Riahi Yosra , Belhadj Omrane
Published: March 2016

A new thermostable, haloalkaline, solvent stable SDS-induced serine protease was purified and characterized from a thermophilicGeobacillus toebiiLBT 77 newly isolated from a Tunisian hot spring. This study reveals the potential of the protease fromGeobacillus toebiiLBT 77 as an additive to detergent with spectacular proprieties described for the first time. The protease was purified to homogeneity by ammonium sulfate precipitation followed by Sephadex G-75 and DEAE-Cellulose chromatography. It was a monomeric enzyme with molecular weight of 30 kDa. The optimum pH, temperature, and NaCl for maximum protease activity were 13.0, 95°C, and 30%, respectively. Activity was stimulated by Ca2+, Mg2+, DTNB,β-mercaptoethanol, and SDS. The protease was extremely stable even at pH 13.25, 90°C, and 30% NaCl and in the presence of hydrophilic, hydrophobic solvents at high concentrations. The high compatibility with ionic, nonionic, and commercial detergents confirms the utility as an additive to cleaning products. Kinetic and thermodynamic characterization of protease revealedKm=1 mg mL−1,  Vmax=217.5 U mL−1,Kcat/Km=99 mg mL−1 S−1,Ea=51.5 kJ mol−1, andΔG⁎=56.5 kJ mol−1.
Current Advance and Future Prospects of Tissue Engineering Approach to Dentin/Pulp Regenerative Therapy
Authors: Gong Ting , Heng Boon Chin , Lo Edward Chin Man , Zhang Chengfei
Published: March 2016

Recent advances in biomaterial science and tissue engineering technology have greatly spurred the development of regenerative endodontics. This has led to a paradigm shift in endodontic treatment from simply filling the root canal systems with biologically inert materials to restoring the infected dental pulp with functional replacement tissues. Currently, cell transplantation has gained increasing attention as a scientifically valid method for dentin‐pulp complex regeneration. This multidisciplinary approach which involves the interplay of three key elements of tissue engineering—stem cells, scaffolds, and signaling molecules—has produced an impressive number of favorable outcomes in preclinical animal studies. Nevertheless, many practical hurdles need to be overcome prior to its application in clinical settings. Apart from the potential health risks of immunological rejection and pathogenic transmission, the lack of a well‐established banking system for the isolation and storage of dental‐derived stem cells is the most pressing issue that awaits resolution and the properties of supportive scaffold materials vary across different studies and remain inconsistent. This review critically examines the classic triad of tissue engineering utilized in current regenerative endodontics and summarizes the possible techniques developed for dentin/pulp regeneration.
Strategic Inventory Positioning in BOM with Multiple Parents Using ASR Lead Time
Authors: Jiang Jingjing , Rim Suk-Chul
Published: March 2016

In order to meet the lead time that the customers require, work-in-process inventory (WIPI) is necessary at almost every station in most make-to-order manufacturing. Depending on the station network configuration and lead time at each station, some of the WIPI do not contribute to reducing the manufacturing lead time of the final product at all. Therefore, it is important to identify the optimal set of stations to hold WIPI such that the total inventory holding cost is minimized, while the required due date for the final product is met. The authors have presented a model to determine the optimal position and quantity of WIPI for a given simple bill of material (S-BOM), in which any part in the BOM has only one immediate parent node. In this paper, we extend the previous study to the general BOM (G-BOM) in which parts in the BOM can have more than one immediate parent and present a new solution procedure using genetic algorithm.
Skeletal Muscle‐Derived Stem/Progenitor Cells: A Potential Strategy for the Treatment of Acute Kidney Injury
Authors: Pavyde Egle , Maciulaitis Romaldas , Mauricas Mykolas , Sudzius Gintaras , Ivanauskaite Didziokiene Ernesta , Laurinavicius Arvydas , Sutkeviciene Neringa , Stankevicius Edgaras , Maciulaitis Justinas , Usas Arvydas
Published: March 2016

Skeletal muscle‐derived stem/progenitor cells (MDSPCs) have been thoroughly investigated and already used in preclinical studies. However, therapeutic potential of MDSPCs isolated using preplate isolation technique for acute kidney injury (AKI) has not been evaluated. We aimed to characterize rat MDSPCs, compare them with bone marrow mesenchymal stem cells (BM‐MSCs), and evaluate the feasibility of MDSPCs therapy for gentamicin‐induced AKI in rats. We have isolated and characterized rat MDSPCs and BM‐MSCs. Characteristics of rat BM‐MSCs and MDSPCs were assessed by population doubling time, flow cytometry, immunofluorescence staining, RT‐PCR, and multipotent differentiation capacity. Gentamicin‐induced AKI model in rat was used to examine MDSPCs therapeutic effect. Physiological and histological kidney parameters were determined. MDSPCs exhibited similar immunophenotype, stem cell gene expression, and multilineage differentiation capacities as BM‐MSCs, but they demonstrated higher proliferation rate. Single intravenous MDSPCs injection accelerated functional and morphological kidney recovery, as reflected by significantly lower serum creatinine levels, renal injury score, higher urinary creatinine, and GFR levels. PKH‐26‐labeled MDSPCs were identified within renal cortex 1 and 2 weeks after cell administration, indicating MDSPCs capacity to migrate and populate renal tissue. In conclusion, MDSPCs are capable of mediating functional and histological kidney recovery and can be considered as potential strategy for AKI treatment.
Geometric Process-Based Maintenance and Optimization Strategy for the Energy Storage Batteries
Authors: Li Yan , Han Peng , Wang Jinkuan , Song Xin
Published: March 2016

Renewable energy is critical for improving energy structure and reducing environment pollution. But its strong fluctuation and randomness have a serious effect on the stability of the microgrid without the coordination of the energy storage batteries. The main factors that influence the development of the energy storage system are the lack of valid operation and maintenance management as well as the cost control. By analyzing the typical characteristics of the energy storage batteries in their life cycle, the geometric process-based model including the deteriorating system and the improving system is firstly built for describing the operation process, the preventive maintenance process, and the corrective maintenance process. In addition, this paper proposes an optimized management strategy, which aims to minimize the long-run average cost of the energy storage batteries by defining the time interval of the detection and preventive maintenance process as well as the optimal corrective maintenance times, subjected to the state of health and the reliability conditions. The simulation is taken under the built model by applying the proposed energy storage batteries’ optimized management strategy, which verifies the effectiveness and applicability of the management strategy, denoting its obvious practicality on the current application.
Enhanced Histone Deacetylase Activity in Malignant Melanoma Provokes RAD51 and FANCD2-Triggered Drug Resistance
Authors: Krumm Andrea , Barckhausen Christina , Kücük Pelin , Tomaszowski Karl-Heinz , Loquai Carmen , Fahrer Jörg , Krämer Oliver Holger , Kaina Bernd , Roos Wynand Paul
Published: March 2016

DNA-damaging anticancer drugs remain a part of metastatic melanoma therapy. Epigenetic reprogramming caused by increased histone deacetylase (HDAC) activity arising during tumor formation may contribute to resistance of melanomas to the alkylating drugs temozolomide, dacarbazine, and fotemustine. Here, we report on the impact of class I HDACs on the response of malignant melanoma cells treated with alkylating agents. The data show that malignant melanomas in situ contain a high level of HDAC1/2 and malignant melanoma cells overexpress HDAC1/2/3 compared with noncancer cells. Furthermore, pharmacologic inhibition of class I HDACs sensitizes malignant melanoma cells to apoptosis following exposure to alkylating agents, while not affecting primary melanocytes. Inhibition of HDAC1/2/3 caused sensitization of melanoma cells to temozolomide in vitro and in melanoma xenografts in vivo. HDAC1/2/3 inhibition resulted in suppression of DNA double-strand break (DSB) repair by homologous recombination because of downregulation of RAD51 and FANCD2. This sensitized cells to the cytotoxic DNA lesion O6-methylguanine and caused a synthetic lethal interaction with the PARP-1 inhibitor olaparib. Furthermore, knockdown experiments identified HDAC2 as being responsible for the regulation of RAD51. The influence of class I HDACs on DSB repair by homologous recombination and the possible clinical implication on malignant melanoma therapy with temozolomide and other alkylating drugs suggests a combination approach where class I HDAC inhibitors such as valproic acid or MS-275 (entinostat) appear to counteract HDAC- and RAD51/FANCD2-mediated melanoma cell resistance. Cancer Res; 76(10); 3067–77. ©2016 AACR.
CK2α' Drives Lung Cancer Metastasis by Targeting BRMS1 Nuclear Export and Degradation
Authors: Liu Yuan , Amin Elianna B. , Mayo Marty W. , Chudgar Neel P. , Bucciarelli Peter R. , Kadota Kyuichi , Adusumilli Prasad S. , Jones David R.
Published: March 2016

Breast cancer metastasis suppressor 1 (BRMS1) is decreased in non–small cell lung cancer (NSCLC) and other solid tumors, and its loss correlates with increased metastases. We show that BRMS1 is posttranslationally regulated by TNF-induced casein kinase 2 catalytic subunit (CK2α') phosphorylation of nuclear BRMS1 on serine 30 (S30), resulting in 14-3-3ϵ–mediated nuclear exportation, increased BRMS1 cytosolic expression, and ubiquitin-proteasome–induced BRMS1 degradation. Using our in vivo orthotopic mouse model of lung cancer metastases, we found that mutation of S30 in BRMS1 or the use of the CK2-specific small-molecule inhibitor CX4945 abrogates CK2α'-induced cell migration and invasion and decreases NSCLC metastasis by 60-fold. Analysis of 160 human NSCLC specimens confirmed that tumor CK2α' and cytoplasmic BRMS1 expression levels are associated with increased tumor recurrence, metastatic foci, and reduced disease-free survival. Collectively, we identify a therapeutically exploitable posttranslational mechanism by which CK2α-mediated degradation of BRMS1 promotes metastases in lung cancer. Cancer Res; 76(9); 2675–86. ©2016 AACR.
Effectiveness of Prophylactic Surgeries inBRCA1orBRCA2Mutation Carriers: A Meta-analysis and Systematic Review
Authors: Li Xiao , You Ran , Wang Xinwei , Liu Congxin , Xu Zicheng , Zhou Jin , Yu Bin , Xu Ting , Cai Hongzhou , Zou Qing
Published: March 2016

Purpose: To systematically investigate the effectiveness of prophylactic surgeries (PS) implemented in women carrying BRCA1/2 mutations.

Experimental Design: The PubMed database was searched till August 2014 and 15 studies met the inclusion criteria. Fixed- or random-effects models were conducted according to study heterogeneity. We calculated the pooled relative risks (RR) for cancer risk or mortality along with 95% confidence intervals (CI).

Results: Prophylactic bilateral salpingo-oophorectomy (PBSO) and bilateral prophylactic mastectomy (BPM) were both associated with a decreased breast cancer risk in BRCA1/2 mutation carriers (RR, 0.552; 95% CI, 0.448–0.682; RR, 0.114; 95% CI, 0.041–0.317, respectively). Similar findings were observed in BRCA1 and BRCA2 mutation carriers separately. Moreover, contralateral prophylactic mastectomy (CPM) significantly decreased contralateral breast cancer incidence in BRCA1/2 mutation carriers (RR, 0.072; 95% CI, 0.035–0.148). Of note, PBSO was associated with significantly lower all-cause mortality in BRCA1/2 mutation carriers without breast cancer (HR, 0.349; 95% CI, 0.190–0.639) and those with breast cancer (HR, 0.432; 95% CI, 0.318–0.588). In addition, all-cause mortality was significantly lower for patients with CPM than those without (HR, 0.512; 95% CI, 0.368–0.714). However, BPM was not significantly associated with reduced all-cause mortality. Data were insufficient to obtain separate estimates of survival benefit with PS in BRCA1 or BRCA2 mutation carriers.

Conclusions: BRCA1/2 mutation carriers who have been treated with PS have a substantially reduced breast cancer incidence and mortality. Clin Cancer Res; 22(15); 3971–81. ©2016 AACR.
Chemotherapy-Induced Inflammatory Gene Signature and Protumorigenic Phenotype in Pancreatic CAFs via Stress-Associated MAPK
Authors: Toste Paul A. , Nguyen Andrew H. , Kadera Brian E. , Duong Mindy , Wu Nanping , Gawlas Irmina , Tran Linh M. , Bikhchandani Mihir , Li Luyi , Patel Sanjeet G. , Dawson David W. , Donahue Timothy R.
Published: March 2016

Pancreatic ductal adenocarcinoma (PDAC) has a characteristically dense stroma comprised predominantly of cancer-associated fibroblasts (CAF). CAFs promote tumor growth, metastasis, and treatment resistance. This study aimed to investigate the molecular changes and functional consequences associated with chemotherapy treatment of PDAC CAFs. Chemoresistant immortalized CAFs (R-CAF) were generated by continuous incubation in gemcitabine. Gene expression differences between treatment-naïve CAFs (N-CAF) and R-CAFs were compared by array analysis. Functionally, tumor cells (TC) were exposed to N-CAF– or R-CAF–conditioned media and assayed for migration, invasion, and viability in vitro. Furthermore, a coinjection (TC and CAF) model was used to compare tumor growth in vivo. R-CAFs increased TC viability, migration, and invasion compared with N-CAFs. In vivo, TCs coinjected with R-CAFs grew larger than those accompanied by N-CAFs. Genomic analysis demonstrated that R-CAFs had increased expression of various inflammatory mediators, similar to the previously described senescence-associated secretory phenotype (SASP). In addition, SASP mediators were found to be upregulated in response to short duration treatment with gemcitabine in both immortalized and primary CAFs. Inhibition of stress-associated MAPK signaling (P38 MAPK or JNK) attenuated SASP induction as well as the tumor-supportive functions of chemotherapy-treated CAFs in vitro and in vivo. These results identify a negative consequence of chemotherapy on the PDAC microenvironment that could be targeted to improve the efficacy of current therapeutic regimens.

Implications: Chemotherapy treatment of pancreatic cancer–associated fibroblasts results in a proinflammatory response driven by stress-associated MAPK signaling that enhances tumor cell growth and invasiveness. Mol Cancer Res; 14(5); 437–47. ©2016 AACR.
Clinicopathological Features and Prognosis of Sinonasal Mucosal Malignant Melanoma: A Retrospective Study of 83 Cases in a Chinese Population
Authors: Zhu Wenjia , Zou Bingqing , Wang Shuyi
Published: March 2016

Aims: Sinonasal mucosal malignant melanoma (SNMMM) is a rare disease. The aim of the present study was to describe its clinicopathological features and prognosis in a Chinese population. Methods: Data on 83 SNMMM patients were collected and analyzed. A survival analysis was performed using the Kaplan-Meier method and a log-rank test. Results: The most common presenting symptoms of SNMMM were nasal obstruction, epistaxis, and bloody rhinorrhea. Histopathologically, 38 cases (45.78%) were amelanotic. Five cell types (epithelioid, undifferentiated, plasmacytoid, spindle, and clear) were identified. Positive staining for human melanoma black-45 and Melan-A was diagnostic of SNMMM. Advanced age, multiple tumor sites, and amelanotic-type SNMMM indicated a worse outcome (p = 0.008, p = 0.009, and p = 0.013, respectively). Neither adjuvant therapy nor the tumor stage was associated with overall survival. Conclusions: SNMMM is an uncommon disease with atypical symptoms. Its histopathological appearance is variable, especially in the amelanotic type. Thus, immunohistochemistry is important in the diagnosis, and it should be performed according to the histology.
Utilização de multimétodos de caracterização e análise da paisagem e dos espaços livres intraurbanos de Santa Maria - RS
Authors: Pippi Luis Guilherme Aita , Gabriel Letícia De Castro , Cocco Renata Michelon , Coutinho Letícia de Fátima Durlo , Schwingel Henrique , Giovelli Marcos Guterres
Published: March 2016

O presente artigo visa apresentar os multimétodos de caracterização e análise dos espaços livres intraurbanos (ELIUs) públicos de Santa Maria (RS) de maneira a contextualizar e divulgar as metodologias organizadas e em fase inicial de aplicação pelo grupo Quapá-SEL II – Núcleo Santa Maria. Parte-se da categorização, espacialização e caracterização dos ELIUs públicos para o entendimento da dinâmica da vida pública. Na sequência o artigo busca explanar sobre a etapa operacional da pesquisa, ilustrando o procedimento de análise com caracterização dos arranjos formais e funcionais, das apropriações, dos comportamentos e das interações dos usuários dos Espaços Livres Intraurbanos de Lazer e Recreação (ELIULRs) e Espaços Livres Intraurbanos de Circulação (ELIUCs) – todos ilustrados com tabelas, imagens e mapas –, além da apresentação dos quatro métodos utilizados: três quantitativos, com e sem interação dos usuários, e um qualitativo com interação dos usuários, que seguem o mesmo protocolo – o estudo minucioso atento às variáveis temporais, sociais e físico-ambientais. Tendo em vista a compreensão da dinâmica social e caracterização dos elementos naturais e construídos dos ELIUs públicos, ao serem ancorados numa sistemática, é lançada uma base para o aprofundamento do conteúdo obtido como forma de reverter condições precárias de planejamentos urbano e paisagístico dos atuais espaços livres intraurbanos do município. As metodologias podem ser replicadas em outras categorias de ELIUs públicos e em outras cidades. Almeja-se promover diretrizes de projetos urbano-paisagísticos qualificados em termos de recreação, lazer, circulação e promoção de coletividade e cidadania, atendendo necessidades reais da comunidade santa-mariense e potencializando as condições do meio físico-ambiental.
Genetic Risk Scores Predict Recurrence of Acute Coronary Syndrome
Authors: Vaara Satu , Tikkanen Emmi , Parkkonen Olavi , Lokki Marja-Liisa , Ripatti Samuli , Perola Markus , Nieminen Markku S. , Sinisalo Juha
Published: March 2016

Background—

Several clinical risk estimation tools have established their role in the prediction of recurrence of acute coronary syndrome (ACS), but the value of genetic risk scores (GRSs) remains unclear. We examined how well 2 different GRSs estimate recurrent ACS and whether clinical factors are associated with GRSs.

Methods and Results—

A cohort of 2090 consecutive patients with ACS who underwent coronary angiography between July 2006 and March 2008 in a single tertiary center was genotyped and prospectively followed up for a median of 5.5 years. We formed 2 partially overlapping GRSs: GRS47 of 47 single-nucleotide polymorphisms with previously reported significant association with coronary artery disease and GRS153 of 153 single-nucleotide polymorphisms with significant or suggestive association with coronary artery disease. GRS47 showed association with recurrent ACS independent of clinical factors (
P
=0.037; hazard ratio, 1.17; 95% confidence interval, 1.01–1.36). GRS153 had no association with either recurrent ACS or composite of recurrent ACS or death. Also, GRS47 was associated inversely with smoking and ST-segment–elevation myocardial infarction (
P
=0.004; odds ratio, 0.22; 95% confidence interval, 0.08–0.62 and
P
=0.041; odds ratio, 0.36; 95% confidence interval, 0.13–0.96, respectively).

Conclusions—

GRSs combined of 47 known coronary artery disease risk single-nucleotide polymorphisms were associated with recurrent ACS after multivariable adjustments in a heterogenic ACS population for the first time. Smoking and ST-segment–elevation myocardial infarction had an inverse association with the GRSs. The significance of smoking in relation to genetic coronary artery disease predisposition may merit further evaluation in patients with ACS.
Retinal Microvascular Calibers Are Associated With Enlarged Perivascular Spaces in the Brain
Authors: Mutlu Unal , Adams Hieab H.H. , Hofman Albert , Lugt Aad van der , Klaver Caroline C.W. , Vernooij Meike W. , Ikram M. Kamran , Ikram M. Arfan
Published: March 2016

Background and Purpose—

Perivascular enlargement in the brain is a putative imaging marker for microvascular brain damage, but this link has not yet been confirmed using direct in vivo visualization of small vessels. We investigated the relation between microvascular calibers on retinal imaging and enlarged perivascular spaces (ePVSs) on brain magnetic resonance imaging.

Methods—

We included 704 participants from the Rotterdam study. Retinal arteriolar and venular calibers were measured semiautomatically on fundus photographs. ePVSs were counted in the centrum semiovale, basal ganglia, hippocampus, and mesencephalon, using a standardized rating method. We determined the association between retinal microvascular calibers and ePVSs with negative binomial regression models, adjusting for age, sex, the other vascular caliber, structural brain magnetic resonance imaging markers, and cardiovascular risk factors.

Results—

Both narrower arteriolar and wider venular calibers were associated with more ePVSs in the centrum semiovale and hippocampal region. Rate ratios (95% confidence interval) for arterioles in the centrum semiovale and hippocampus were 1.07 (1.01–1.14) and 1.13 (1.04–1.22), respectively, and for venules 1.08 (1.01–1.16) and 1.09 (1.00–1.18), respectively. These associations were independent from other brain magnetic resonance imaging markers and cardiovascular risk factors.

Conclusions—

Retinal microvascular calibers are related to ePVSs, confirming the putative link between microvascular damage and ePVSs.
Does Diffusion Lesion Volume Above 70 mL Preclude Favorable Outcome Despite Post-Thrombolysis Recanalization?
Authors: Tisserand Marie , Turc Guillaume , Charron Sylvain , Legrand Laurence , Edjlali Myriam , Seners Pierre , Roca Pauline , Lion Stéphanie , Naggara Olivier , Mas Jean-Louis , Méder Jean-François , Baron Jean-Claude , Oppenheim Catherine
Published: March 2016

Background and Purpose—

Whether to withhold recanalization treatment when the diffusion-weighted imaging (DWI) lesion exceeds a given volume is unsettled. Our aim was to assess the impact of recanalization on outcome in patients with baseline DWI lesion ≥70 mL (DWI≥70 mL) treated ≤4.5 hours from onset. We hypothesized that recanalization is beneficial in a sizeable fraction of these patients and that this is associated with a larger DWI lesion reversal.

Methods—

We analyzed 267 consecutive patients treated with intravenous recombinant tissue-type plasminogen activator for middle cerebral artery territory stroke in whom an occlusion was present on magnetic resonance angiography and 24-hour recanalization and 90-day clinical outcome could be assessed. After stratification relative to the 70-mL DWI lesion cut point, we calculated the odds ratio for recanalization of the primary arterial occlusive lesion (AOL score ≥2) to predict favorable outcome (modified Rankin scale score ≤2). DWI lesion reversal was compared between recanalizers with DWI≥70 mL with favorable and unfavorable outcomes.

Results—

Median (interquartile range) DWI lesion volume was 22 mL (10–60), and median onset time to imaging was 116 minutes (86–151). Twelve (22%) of the 54 patients with DWI≥70 mL experienced favorable outcome, of which 9 had recanalized. In patients with DWI≥70 mL, recanalization was significantly associated with favorable outcome after adjustment for age and National Institutes of Health Stroke Scale (odds ratio =4.72 [1.09–20.32];
P
=0.0375). Among recanalizers with DWI≥70 mL, absolute and relative DWI reversal volumes were larger in those with favorable as compared with unfavorable outcome (18.8 mL [12.2–47.6] versus 8.5 mL [4.3–31.1];
P
=0.17; and 19.6% [10.9–62.8] versus 8.7% [3.9–16.5], respectively;
P
=0.049).

Conclusions—

Patients with DWI lesion volume ≥70 mL can benefit from recanalization after intravenous recombinant tissue-type plasminogen activator. This may partly reflect a larger amount of DWI lesion reversal.
THE HONG KONG CANTONESE SPEECH COMMUNITY
Authors: Bauer Robert S.
Published: March 2016

Paroe qu'il est parlé par plus de 90 % de la population de Hong Kong qui compte 5 millions 300 000 personnes, le cantonais est le dialecte chinois le plus important après le mandarin. Nul doute que cette situation changera lorsque le statut politique de Hong Kong sera modifié en 1997.

Cet article retrace l'évolution historique et linguistique de Hong Kong et analyse les facteurs de développement du cantonais dans l'île avant de caractériser dans le détail la situation socio-linguistique de Hong Kong par un examen attentif des données statistiques dont on dispose sur la population de Hong Kong.