bluuebunny/crossref_metadata_2025 huggingface dataset:
Residual Energy-Based Strategies for the Transmission Probability and Duty-Cycle Selection in Wireless Sensor Networks
Authors: Guzmán-Medina Carlos A. , Rivero-Angeles Mario E. , Orea-Flores Izlian Y.
Published: May 2016

WSNs are complex systems that are mainly limited by the battery life of the nodes in order to have an adequate performance. During the operation of the system, it is not uncommon to have a portion of nodes with low energy levels while other nodes have high energy levels. Nodes with very low residual energy must reduce their energy consumption since their operational lifetime is almost over. In this paper, we consider cluster-based WSNs for the event detection where there is a high concentration of high energy nodes and low concentration of low energy nodes. Building on this, we propose extending the battery life of low energy nodes in both the cluster formation and the steady-state phases. For the former, energy efficiency is achieved by means of assigning prioritized access to the shared channel to low energy nodes while delaying the contention access of high energy nodes which can support higher number of collisions before energy depletion. For the latter, we consider the duty-cycle of nodes where the sleep and active modes have dwelling times related to their residual energy levels. The system and the impact of the proposed residual energy-based mechanisms are mathematically evaluated using Markovian models.
Obstacle Aware Connectivity Restoration for Disjoint Wireless Sensor Networks Using a Mix of Stationary and Mobile Nodes
Authors: Ma Guizhen , Yang Yang , Qiu Xuesong , Gao Zhipeng
Published: May 2016

In many applications, wireless sensor networks (WSNs) are deployed in inhospitable environments and therefore the nodes are at increased risk of failure. Large scale damage may partition a network into disjoint segments, which has very negative effect on the application. Mobile nodes have been exploited to act as mobile data collectors (MDCs) among segments to restore the connectivity of WSNs in the previous works. However, almost all of the works assumed that mobile nodes travel via a direct path, which may not be the case in real-world applications. In order to improve the applicability of the recovery strategy, obstacles should be taken into account. In this paper, we present an obstacle aware connectivity restoration strategy (OACRS) to fit these requirements. Our algorithm is designed for the scenarios that the number of available relays is less than the number of relays required to construct stable links and more than the number of segments. At first we construct and optimize the obstacle-avoiding minimum spanning tree of the segments and then determine the relays which keep static and the ones which act as MDCs. Finally we optimize the tour path of MDCs. The effectiveness of the proposed algorithm is validated through simulation experiments.
Synchronization between Different Networks with Time-Varying Delay and Its Application in Bilayer Coupled Public Traffic Network
Authors: Du Wenju , Zhang Jiangang , Li Yinzhen , Qin Shuang
Published: May 2016

In order to study the dynamic characteristics of urban public traffic network, this paper establishes the conventional bus traffic network and the urban rail traffic network based on the spaceRmodeling method. Then regarding these two networks as the subnetwork, the paper presents a new bilayer coupled public traffic network through the transfer relationship between subway and bus, and this model well reflects the connection between the passengers and bus operating vehicles. Based on the synchronization theory of coupling network with time-varying delay and taking “Lorenz system” as the network node, the paper studies the synchronization of bilayer coupled public traffic network. Finally, numerical results are given to show the impact of public traffic dispatching, delayed departure, the number of public bus stops between bus lines, and the number of transfer stations between two traffic modes on the bilayer coupled public traffic network balance through Matlab simulation.
Finite Element Modelling and Mechanical Characterization of Graphyne
Authors: Couto Ricardo , Silvestre Nuno
Published: May 2016

Graphyne is an allotrope of carbon with excellent mechanical, electrical, and optical properties. The scientific community has been increasingly interested in its characterization and computational simulation, using molecular dynamics (MD) simulations and density functional theory (DFT). The present work presents, for the first time (to the authors’ knowledge), a finite element (FE) model to evaluate the elastic properties of graphyne. After presenting a brief literature review on the latest developments of graphyne and its mechanical characterization through computational methods, the FE model of graphyne sheet is presented in detail and the calculation of its elastic properties described. The linear elastic properties (Young’s modulus, Poisson’s ratio, bulk modulus, and shear modulus) obtained from the proposed FE models are in general agreement with those previously obtained by other authors using more complex computational models (MD and DFT). The influence of van der Waals (vdW) interatomic forces on the linear elastic properties of planar graphyne is negligible and can be disregarded if small strain hypothesis is adopted. The FE models also show that graphyne exhibits marginal orthotropic behavior, that is, “quasi-isotropic” behavior, a fact that agrees with the conclusions reported by other researchers.
Markedly Improved Glycemic Control in Poorly Controlled Type 2 Diabetes following Direct Acting Antiviral Treatment of Genotype 1 Hepatitis C
Authors: Pashun Raymond Anthony , Shen Nicole T. , Jesudian Arun
Published: May 2016

Type 2 diabetes mellitus (T2DM) is often associated with hepatitis C virus (HCV) infection. Successful HCV treatment may improve glycemic control and potentially induce remission of T2DM. We report a case of an obese 52-year-old woman with mixed genotype 1a/1b HCV infection with compensated cirrhosis and a 10-year history of poorly controlled T2DM on insulin therapy. Following successful therapy with sofosbuvir, simeprevir, and ribavirin, her insulin requirements decreased and her glycosylated hemoglobin (HgA1c) normalized despite weight gain. This case suggests an association between HCV and T2DM and the potential for significant improvement in glycemic control with eradication of HCV.
Photostability and Photostabilization of Drugs and Drug Products
Authors: Ahmad Iqbal , Ahmed Sofia , Anwar Zubair , Sheraz Muhammad Ali , Sikorski Marek
Published: May 2016

Photostability studies of drugs and drug products are an integral part of the product development process in the pharmaceutical industry. These studies are carried out to ensure quality, efficacy, and safety of the formulated products during manufacture, storage, and use. This review deals with the concept of photostability and related aspects and the literature available in the field. It highlights the role of the photochemistry in the photostability studies, describes the functional groups important for the photoreactivity of drugs, explains photophysical processes, and deals with the kinetics of photochemical reactions. The various modes of photodegradation of drugs with examples of selected compounds are presented. The biological consequences of the effect of light on the drug degradation are described. The photostability testing of drugs and drug products and the requirements under ICH guideline are discussed. Some information on the packaging requirements for the formulated products is provided. The various methods used for the photostabilization of solid and liquid dosage forms are also discussed.
Effect of Reinforcement of Hydrophobic Grade Banana (Musa ornata) Bark Fiber on the Physicomechanical Properties of Isotactic Polypropylene
Authors: Mamunur Rashid Md. , Samad Sabrin A. , Gafur M. A. , Rakibul Qadir Md. , Chowdhury A. M. Sarwaruddin
Published: May 2016

This research studied the physicomechanical as well as morphological properties of alkali treated (NaOH and KMnO4) and untreated banana bark fiber (BBF) reinforced polypropylene composites. A detailed structural and morphological characterization was performed using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and mechanical properties testing (tensile strength, flexural strength, and microhardness). Chemical treatments improved the hydrophobic property of the fiber and it is found to be better for KMnO4treatment. Composites with 0, 5, 10, and 15 wt.% loadings were then compared for water uptake studies and revealed that KMnO4treated fiber composites absorb less water compared to others. KMnO4treatment with 15% fiber loading improved the tensile strength, flexural strength, and microhardness of the composites compared to raw and NaOH treated fiber loadings. TGA analysis also shows onset temperature at 400~500°C that is associated with the decomposition of the banana fibers constituents including lignin, cellulose, and hemicelluloses which suggests better thermomechanical stability. All of the values suggest that 15% KMnO4treated banana bark fiber (BBF)/PP composites were found to be better than those of the raw and NaOH treated ones.
Border Collision Bifurcations in a Generalized Model of Population Dynamics
Authors: Ladino Lilia M. , Mammana Cristiana , Michetti Elisabetta , Valverde Jose C.
Published: May 2016

We analyze the dynamics of a generalized discrete time population model of a two-stage species with recruitment and capture. This generalization, which is inspired by other approaches and real data that one can find in literature, consists in considering no restriction for the value of the two key parameters appearing in the model, that is, the natural death rate and the mortality rate due to fishing activity. In the more general case the feasibility of the system has been preserved by posing opportune formulas for the piecewise map defining the model. The resulting two-dimensional nonlinear map is not smooth, though continuous, as its definition changes as any border is crossed in the phase plane. Hence, techniques from the mathematical theory of piecewise smooth dynamical systems must be applied to show that, due to the existence of borders, abrupt changes in the dynamic behavior of population sizes and multistability emerge. The main novelty of the present contribution with respect to the previous ones is that, while using real data, richer dynamics are produced, such as fluctuations and multistability. Such new evidences are of great interest in biology since new strategies to preserve the survival of the species can be suggested.
Efficacy and Safety of a Dexamethasone Implant in Patients with Diabetic Macular Edema at Tertiary Centers in Korea
Authors: Moon Byung Gil , Lee Joo Yong , Yu Hyeong Gon , Song Ji Hun , Park Young-Hoon , Kim Hyun Woong , Ji Yong-Sok , Chang Woohyok , Lee Joo Eun , Oh Jaeryung , Chung Inyoung
Published: May 2016

Purpose. To evaluate the real-world efficacy and safety of the dexamethasone implant (DEX implant) in patients with diabetic macular edema (DME). Methods. Retrospective, multicenter, and noncomparative study of DME patients who were treated with at least one DEX implant. A total of 186 eyes from 165 patients were included. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), complications, and number of retreatments were collected. Data at baseline and monthly for 6 months were analyzed. Results. The average baseline BCVA and CRT were 0.60 LogMAR and 491.6 μm, respectively. The mean BCVA improved until 3 months and then decreased up to 6 months of follow-up (0.53, 0.49, and 0.55 LogMAR at 1, 3, and 6 months; p=0.001, <0.001, and 0.044, resp.). The change of mean CRT was similar to BCVA (345.0, 357.7, and 412.5 μm at 1, 3, and 6 months, p<0.001, <0.001, and <0.001, resp.). 91 eyes (48.9%) received additional treatment with anti-VEGF or DEX implant. The average treatment-free interval was 4.4 months. In group analyses, the DEX implant was more effective in pseudophakic eyes, DME with subretinal fluid (SRF), or diffuse type. Conclusions. Intravitreal dexamethasone implants are an effective treatment for patients with DME, most notably in pseudophakic eyes, DME with SRF, or diffuse type. A half of these patients require additional treatment within 6 months.
Association of Common Susceptibility Variants of Pancreatic Cancer in Higher-Risk Patients: A PACGENE Study
Authors: Childs Erica J. , Chaffee Kari G. , Gallinger Steven , Syngal Sapna , Schwartz Ann G. , Cote Michele L. , Bondy Melissa L. , Hruban Ralph H. , Chanock Stephen J. , Hoover Robert N. , Fuchs Charles S. , Rider David N. , Amundadottir Laufey T. , Stolzenberg-Solomon Rachael , Wolpin Brian M. , Risch Harvey A. , Goggins Michael G. , Petersen Gloria M. , Klein Alison P.
Published: May 2016

Individuals from pancreatic cancer families are at increased risk, not only of pancreatic cancer, but also of melanoma, breast, ovarian, and colon cancers. While some of the increased risk may be due to mutations in high-penetrance genes (i.e., BRCA2, PALB2, ATM, p16/CDKN2A or DNA mismatch repair genes), common genetic variants may also be involved. In a high-risk population of cases with either a family history of pancreatic cancer or early-onset pancreatic cancer (diagnosis before the age of 50 years), we examined the role of genetic variants previously associated with risk of pancreatic, breast, ovarian, or prostate cancer. We genotyped 985 cases (79 early-onset cases, 906 cases with a family history of pancreatic cancer) and 877 controls for 215,389 SNPs using the iSelect Collaborative Oncological Gene-Environment Study (iCOGS) array with custom content. Logistic regression was performed using a log-linear additive model. We replicated several previously reported pancreatic cancer susceptibility loci, including recently identified variants on 2p13.3 and 7p13 (2p13.3, rs1486134: OR = 1.36; 95% CI, 1.13–1.63; P = 9.29 × 10−4; 7p13, rs17688601: OR = 0.76; 95% CI, 0.63–0.93; P = 6.59 × 10−3). For the replicated loci, the magnitude of association observed in these high-risk patients was similar to that observed in studies of unselected patients. In addition to the established pancreatic cancer loci, we also found suggestive evidence of association (P < 5 × 10−5) to pancreatic cancer for SNPs at HDAC9 (7p21.1) and COL6A2 (21q22.3). Even in high-risk populations, common variants influence pancreatic cancer susceptibility. Cancer Epidemiol Biomarkers Prev; 25(7); 1185–91. ©2016 AACR.
ACRIN 6684: Assessment of Tumor Hypoxia in Newly Diagnosed Glioblastoma Using 18F-FMISO PET and MRI
Authors: Gerstner Elizabeth R. , Zhang Zheng , Fink James R. , Muzi Mark , Hanna Lucy , Greco Erin , Prah Melissa , Schmainda Kathleen M. , Mintz Akiva , Kostakoglu Lale , Eikman Edward A. , Ellingson Benjamin M. , Ratai Eva-Maria , Sorensen A. Gregory , Barboriak Daniel P. , Mankoff David A.
Published: May 2016

Purpose: Structural and functional alterations in tumor vasculature are thought to contribute to tumor hypoxia which is a primary driver of malignancy through its negative impact on the efficacy of radiation, immune surveillance, apoptosis, genomic stability, and accelerated angiogenesis. We performed a prospective, multicenter study to test the hypothesis that abnormal tumor vasculature and hypoxia, as measured with MRI and PET, will negatively impact survival in patients with newly diagnosed glioblastoma.

Experimental Design: Prior to the start of chemoradiation, patients with glioblastoma underwent MRI scans that included dynamic contrast enhanced and dynamic susceptibility contrast perfusion sequences to quantitate tumor cerebral blood volume/flow (CBV/CBF) and vascular permeability (ktrans) as well as 18F-Fluoromisonidazole (18F-FMISO) PET to quantitate tumor hypoxia. ROC analysis and Cox regression models were used to determine the association of imaging variables with progression-free and overall survival.

Results: Fifty patients were enrolled of which 42 had evaluable imaging data. Higher pretreatment 18F-FMISO SUVpeak (P = 0.048), mean ktrans (P = 0.024), and median ktrans (P = 0.045) were significantly associated with shorter overall survival. Higher pretreatment median ktrans (P = 0.021), normalized RCBV (P = 0.0096), and nCBF (P = 0.038) were significantly associated with shorter progression-free survival. SUVpeak [AUC = 0.75; 95% confidence interval (CI), 0.59–0.91], nRCBV (AUC = 0.72; 95% CI, 0.56–0.89), and nCBF (AUC = 0.72; 95% CI, 0.56–0.89) were predictive of survival at 1 year.

Conclusions: Increased tumor perfusion, vascular volume, vascular permeability, and hypoxia are negative prognostic markers in newly diagnosed patients with gioblastoma, and these important physiologic markers can be measured safely and reliably using MRI and 18F-FMISO PET. Clin Cancer Res; 22(20); 5079–86. ©2016 AACR.
Intratumor Heterogeneity Affects Gene Expression Profile Test Prognostic Risk Stratification in Early Breast Cancer
Authors: Gyanchandani Rekha , Lin Yan , Lin Hui-Min , Cooper Kristine , Normolle Daniel P. , Brufsky Adam , Fastuca Michael , Crosson Whitney , Oesterreich Steffi , Davidson Nancy E. , Bhargava Rohit , Dabbs David J. , Lee Adrian V.
Published: May 2016

Purpose: To examine the effect of intratumor heterogeneity (ITH) on detection of genes within gene expression panels (GEPs) and the subsequent ability to predict prognostic risk.

Experimental Design: Multiplexed barcoded RNA analysis was used to measure the expression of 141 genes from five GEPs (Oncotype Dx, MammaPrint, PAM50, EndoPredict, and Breast Cancer Index) in breast cancer tissue sections and tumor-rich cores from 71 estrogen receptor (ER)-positive node-negative tumors, on which clinical Oncotype Dx testing was previously performed. If the tumor had foci of high Ki67 (n = 26), low/negative progesterone receptor (PR; n = 13), or both (n = 5), additional cores were obtained. In total, 181 samples were processed. Oncotype Dx recurrence scores were calculated from NanoString nCounter gene expression data.

Results: Hierarchical clustering using all GEP genes showed that majority (61 of 71) of tumor samples clustered by patient, indicating greater interpatient heterogeneity (IPH) than ITH. We found a strikingly high correlation between Oncotype Dx recurrence scores obtained from whole sections versus tumor-rich cores (r = 0.94). However, high Ki67 and low PR cores had slightly higher but not statistically significant recurrence scores. For 18 of 71 (25%) patients, scores were divergent between sections and cores and crossed the boundaries for low, intermediate, and high risk.

Conclusions: Our study indicates that in patients with highly heterogeneous tumors, GEP recurrence scores from a single core could under- or overestimate prognostic risk. Hence, it may be a useful strategy to assess multiple samples (both representative and atypical cores) to fully account for the ITH-driven variation in risk prediction. Clin Cancer Res; 22(21); 5362–9. ©2016 AACR.
TransCONFIRM: Identification of a Genetic Signature of Response to Fulvestrant in Advanced Hormone Receptor–Positive Breast Cancer
Authors: Jeselsohn Rinath , Barry William T. , Migliaccio Ilenia , Biagioni Chiara , Zhao Jin , De Tribolet-Hardy Jonas , Guarducci Cristina , Bonechi Martina , Laing Naomi , Winer Eric P. , Brown Myles , Leo Angelo Di , Malorni Luca
Published: May 2016

Purpose: Fulvestrant is an estrogen receptor (ER) antagonist and an approved treatment for metastatic estrogen receptor–positive (ER+) breast cancer. With the exception of ER levels, there are no established predictive biomarkers of response to single-agent fulvestrant. We attempted to identify a gene signature of response to fulvestrant in advanced breast cancer.

Experimental Design: Primary tumor samples from 134 patients enrolled in the phase III CONFIRM study of patients with metastatic ER+ breast cancer comparing treatment with either 250 mg or 500 mg fulvestrant were collected for genome-wide transcriptomic analysis. Gene expression profiling was performed using Affymetrix microarrays. An exploratory analysis was performed to identify biologic pathways and new signatures associated with response to fulvestrant.

Results: Pathway analysis demonstrated that increased EGF pathway and FOXA1 transcriptional signaling is associated with decreased response to fulvestrant. Using a multivariate Cox model, we identified a novel set of 37 genes with an expression that is independently associated with progression-free survival (PFS). TFAP2C, a known regulator of ER activity, was ranked second in this gene set, and high expression was associated with a decreased response to fulvestrant. The negative predictive value of TFAP2C expression at the protein level was confirmed by IHC.

Conclusions: We identified biologic pathways and a novel gene signature in primary ER+ breast cancers that predicts for response to treatment in the CONFIRM study. These results suggest potential new therapeutic targets and warrant further validation as predictive biomarkers of fulvestrant treatment in metastatic breast cancer. Clin Cancer Res; 22(23); 5755–64. ©2016 AACR.
Noninvasive Detection of Metastases and Follicle Density in Ovarian Tissue Using Full-Field Optical Coherence Tomography
Authors: Peters Inge T.A. , Stegehuis Paulien L. , Peek Ronald , Boer Florine L. , van Zwet Erik W. , Eggermont Jeroen , Westphal Johan R. , Kuppen Peter J.K. , Trimbos J. Baptist , Hilders Carina G.J.M. , Lelieveldt Boudewijn P.F. , van de Velde Cornelis J.H. , Bosse Tjalling , Dijkstra Jouke , Vahrmeijer Alexander L.
Published: May 2016

Purpose: Autotransplantation of ovarian tissue can be used to restore fertility in patients with cancer following gonadotoxic treatment. Whether this procedure is safe remains unclear, as current tumor detection methods render the ovarian tissue unsuitable for transplantation. Full-field optical coherence tomography (FF-OCT) is an imaging modality that rapidly produces high-resolution histology-like images without the need to fix, freeze, or stain the tissue. In this proof-of-concept study, we investigated whether FF-OCT can be used to detect metastases in ovarian tissue, thereby increasing the safety of ovarian tissue autotransplantation. We also evaluated whether cortical ovarian tissue and follicles remain viable following FF-OCT imaging.

Experimental Design: Formalin-fixed, paraffin-embedded tissue samples were obtained from seven normal ovaries and fourteen ovaries containing metastases and/or micrometastases. These samples were deparaffinized and imaged using FF-OCT. The FF-OCT images were then compared with corresponding hematoxylin and eosin–stained tissue sections. Finally, we examined the effect of FF-OCT imaging on the viability of ovarian tissues and follicles in fresh bovine ovarian tissue using a glucose uptake and neutral red staining, respectively.

Results: FF-OCT illustrated both normal structures and metastases in ovarian tissue within minutes. Primordial follicles were readily identifiable. Finally, tissues and follicles remained viable following FF-OCT imaging for up to 180 and 60 minutes, respectively.

Conclusions: FF-OCT imaging is a promising method for the noninvasive detection of metastases, including micrometastases, in ovarian tissue. Moreover, this method facilitates the selection of cortical ovarian tissue with the highest density of primordial follicles, potentially increasing the likelihood of restoring ovarian function following ovarian tissue autotransplantation. Clin Cancer Res; 22(22); 5506–13. ©2016 AACR.
The Effect of F877L and T878A Mutations on Androgen Receptor Response to Enzalutamide
Authors: Prekovic Stefan , van Royen Martin E. , Voet Arnout R.D. , Geverts Bart , Houtman Rene , Melchers Diana , Zhang Kam Y.J. , Van den Broeck Thomas , Smeets Elien , Spans Lien , Houtsmuller Adriaan B. , Joniau Steven , Claessens Frank , Helsen Christine
Published: May 2016

Treatment-induced mutations in the ligand-binding domain of the androgen receptor (AR) are known to change antagonists into agonists. Recently, the F877L mutation has been described to convert enzalutamide into an agonist. This mutation was seen to co-occur in the endogenous AR allele of LNCaP cells, next to the T878A mutation. Here, we studied the effects of enzalutamide on the F877L and T878A mutants, as well as the double-mutant AR (F877L/T878A). Molecular modeling revealed favorable structural changes in the double-mutant AR that lead to a decrease in steric clashes for enzalutamide. Ligand-binding assays confirmed that the F877L mutation leads to an increase in relative binding affinity for enzalutamide, but only the combination with the T878A mutation resulted in a strong agonistic activity. This correlated with changes in coregulator recruitment and chromatin interactions. Our data show that enzalutamide is only a very weak partial agonist of the AR F877L, and a strong partial agonist of the double-mutant AR. Mol Cancer Ther; 15(7); 1702–12. ©2016 AACR.
Chromatin Regulators as a Guide for Cancer Treatment Choice
Authors: Gurard-Levin Zachary A. , Wilson Laurence O.W. , Pancaldi Vera , Postel-Vinay Sophie , Sousa Fabricio G. , Reyes Cecile , Marangoni Elisabetta , Gentien David , Valencia Alfonso , Pommier Yves , Cottu Paul , Almouzni Geneviève
Published: May 2016

The limited capacity to predict a patient's response to distinct chemotherapeutic agents is a major hurdle in cancer management. The efficiency of a large fraction of current cancer therapeutics (radio- and chemotherapies) is influenced by chromatin structure. Reciprocally, alterations in chromatin organization may affect resistance mechanisms. Here, we explore how the misexpression of chromatin regulators—factors involved in the establishment and maintenance of functional chromatin domains—can inform about the extent of docetaxel response. We exploit Affymetrix and NanoString gene expression data for a set of chromatin regulators generated from breast cancer patient-derived xenograft models and patient samples treated with docetaxel. Random Forest classification reveals specific panels of chromatin regulators, including key components of the SWI/SNF chromatin remodeler, which readily distinguish docetaxel high-responders and poor-responders. Further exploration of SWI/SNF components in the comprehensive NCI-60 dataset reveals that the expression inversely correlates with docetaxel sensitivity. Finally, we show that loss of the SWI/SNF subunit BRG1 (SMARCA4) in a model cell line leads to enhanced docetaxel sensitivity. Altogether, our findings point toward chromatin regulators as biomarkers for drug response as well as therapeutic targets to sensitize patients toward docetaxel and combat drug resistance. Mol Cancer Ther; 15(7); 1768–77. ©2016 AACR.
PIM Kinase Inhibitors Kill Hypoxic Tumor Cells by Reducing Nrf2 Signaling and Increasing Reactive Oxygen Species
Authors: Warfel Noel A. , Sainz Alva G. , Song Jin H. , Kraft Andrew S.
Published: May 2016

Intratumoral hypoxia is a significant obstacle to the successful treatment of solid tumors, and it is highly correlated with metastasis, therapeutic resistance, and disease recurrence in cancer patients. As a result, there is an urgent need to develop effective therapies that target hypoxic cells within the tumor microenvironment. The Proviral Integration site for Moloney murine leukemia virus (PIM) kinases represent a prosurvival pathway that is upregulated in response to hypoxia, in a HIF-1–independent manner. We demonstrate that pharmacologic or genetic inhibition of PIM kinases is significantly more toxic toward cancer cells in hypoxia as compared with normoxia. Xenograft studies confirm that PIM kinase inhibitors impede tumor growth and selectively kill hypoxic tumor cells in vivo. Experiments show that PIM kinases enhance the ability of tumor cells to adapt to hypoxia-induced oxidative stress by increasing the nuclear localization and activity of nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), which functions to increase the expression of antioxidant genes. Small molecule PIM kinase inhibitors prevent Nrf2 from accumulating in the nucleus, reducing the transcription of cytoprotective genes and leading to the build-up of intracellular reactive oxygen species (ROS) to toxic levels in hypoxic tumor cells. This toxic effect of PIM inhibitors can be successfully blocked by ROS scavengers, including N-acetyl cystine and superoxide dismutase. Thus, inhibition of PIM kinases has the potential to oppose hypoxia-mediated therapeutic resistance and induce cell death in the hypoxic tumor microenvironment. Mol Cancer Ther; 15(7); 1637–47. ©2016 AACR.
Cognitive and Functional Decline among Individuals 50 Years of Age or Older in Cambé, Paraná, Brazil: A Population-Based Study
Authors: Cabrera Marcos Aparecido Sarria , Bortoletto Maira Aira Sayuri Sakay , de Souza Regina Kazue Tanno , Prina Douglas Manuel Carrapeiro , Vieira Maria Cristina Umpierrez , Silva Ana Maria Rigo
Published: May 2016

Aims: To identify the frequency of cognitive and functional decline (CFD) among adults 50 years of age and older by a population-based study. Methods: Cognitive function was analyzed by the Mini-Mental State Examination, and the functional conditions were based on instrumental activities of daily living (IADL). Cases of CFD included individuals with cognitive decline and 2 or more compromised IADL. Results: A total of 693 individuals were studied. The frequency of CFD was 16.3%. A low socioeconomic profile was associated with greater CFD independent of gender, age, education, and presence of depression (OR = 2.46; 95% CI: 1.53-3.97). Conclusions: These data show a high frequency of CFD among adults 50 years and older. Individuals with less education and a lower socioeconomic level exhibited poorer cognitive and functional conditions.
Lack of Sphingosine Causes Susceptibility to Pulmonary Staphylococcus Aureus Infections in Cystic Fibrosis
Authors: Tavakoli Tabazavareh Shaghayegh , Seitz Aaron , Jernigan Peter , Sehl Carolin , Keitsch Simone , Lang Stephan , Kahl Barbara C. , Edwards Michael , Grassmé Heike , Gulbins Erich , Becker Katrin Anne
Published: May 2016

Background: Pulmonary Staphylococcus aureus (S. aureus) infections occur early in a high percentage of cystic fibrosis (CF) patients and it is believed that these infections facilitate further colonization of CF lungs with Pseudomonas aeruginosa (P. aeruginosa). Previous studies demonstrated a marked reduction of sphingosine in tracheal and bronchial epithelial cells in CF compared to wild type mice, while ceramide is massively increased in CF mice. Methods: We investigated the effect of C18-sphingosine and C16-ceramide on S. aureus in vitro. Based on our results we performed pulmonary infections with S. aureus and tested the influence of sphingosine inhalation. Results: In vitro incubation of S. aureus with C18-sphingosine rapidly killed S. aureus, while C16-ceramide did not affect bacterial survival, but abrogated the effect of C18-sphingosine when applied together. The in vivo infection experiments revealed a high susceptibility of CF mice to pulmonary infection with S. aureus. Inhalation of C18-sphingosine rescued CF mice from pulmonary infections with different clinical S. aureus isolates, including a methicillin-resistant S. aureus (MRSA) strain. Conclusions: Our data indicate that the imbalance between ceramide and sphingosine in the CF respiratory tract prevents killing of S. aureus and causes the high susceptibility of CF mice to pulmonary S. aureus infections.
Nmnat 1: a Security Guard of Retinal Ganglion Cells (RGCs) in Response to High Glucose Stress
Authors: Zhou Rong-Mei , Shen Yi , Yao Jin , Yang Hong , Shan Kun , Li Xiu-Miao , Jiang Qin , Yan Biao
Published: May 2016

Background/Aims: Retinal neurodegeneration is an early event in the pathological process of diabetic retinopathy (DR). Retinal ganglion cell (RGC) injury is an important pathological feature during neurodegenerative process. Protecting RGCs from high glucose-induced injury is a promising strategy for delaying or hindering diabetes mellitus-related retinal neuropathy. This study aims to investigate the role of Nmnat1, an enzyme which catalyzes a key step in the biosynthesis of nicotinamide adenine dinucleotide (NAD), in high glucose-induced RGC injury. Methods: Western blot and immunofluorescence analysis was conducted to detect Nmnat1 expression pattern in the retina and RGC-5 cell. MTT assay, Hoechst staining, trypan blue staining, and calcein-AM/ propidium iodide (PI) staining was conducted to determine the effect of Nmnat1 knockdown on RGC-5 cell function. Microarray and bioinformatics analysis was conducted to identify potential signaling pathways affected by Nmnat1 knockdown. Pharmacological intervention, molecular intervention, and in vitro experiments were conducted to reveal molecular mechanism of Nmnat1-mediated protective effect on RGC-5 cell function. Results: Nmnat1 is constitutively expressed in retina and RGC-5 cells. Nmnat1 knockdown aggravates RGC injury, and accelerates the development of RGC-5 cell apoptosis upon high glucose stress. MAPK signaling is the primary signaling pathway affected by Nmnat1 knockdown. Under high glucose stress, Nmnat1 knockdown leads to p38-MAPK signaling inactivation. p38-MAPK pathway inhibitor strongly blocks Nmnat1-mediated protective effect on RGC-5 cell function. Conclusion: Nmnat1 protects RGC against high glucose-induced injury via p38-MAPK signaling pathway. Nmnat1 may serve as a neuroprotective target for diabetes mellitus-related retinal neuropathy.
Proposing a Simpler Classification of Telogen Effluvium
Authors: Rebora Alfredo
Published: May 2016

Telogen effluvium (TE) is a pathogenically heterogeneous condition which so far has been classified into acute and chronic forms - or, according to Headington, into 5 different pathogenetic forms. Regrettably, Headington's classification is difficult to apply in the office, and most papers dealing with TE ignore it. The present review intends to propose a novel classification of TE and to introduce, tentatively, a new variety of TE. Three pathogenetic types of TE can be identified, whose common clinical element is the profuse shedding of hairs: (1) premature teloptosis, (2) collective teloptosis, and (3) premature entry into the telogen phase. In particular conditions, they may also be associated, as occurs in seasonal shedding and postpartum TE.
Spontaneous Left Renal Subcapsular Hematoma and Right Hip Hematoma in a Hemodialysis Patient: A Case Report and Review of the Literature
Authors: Ye Muyao , Liu Yinghong , Zhou Letian , Wang Chang , Fu Xiao , Peng Youming , Liu Hong
Published: May 2016

For maintenance hemodialysis (MHD) patients, the blood is in low hypercoagulable state due to the use of heparin or low molecular weight heparin during dialysis. It is not rare to see hematoma in the puncture site. In recent years, several cases have been reported of spontaneous kidney rupture, but no hip hematoma, let alone both occurred in succession. There was one MHD patient with spontaneous kidney bleeding and hip hematoma in our hospital in 2014, and we provided effective treatment and follow-up.
Rosacea Management
Authors: Abokwidir Manal , Feldman Steven R.
Published: May 2016

Background: Rosacea is a chronic inflammatory skin condition associated with four distinct subtypes: erythematotelangiectatic, papulopustular, phymatous, and ocular. Purpose: To review the different kinds of management for all subtypes. Methods: We divided rosacea management into three main categories: patient education, skin care, and pharmacological/procedural interventions. Results: Flushing is better prevented rather than treated, by avoiding specific triggers, decreasing transepidermal water loss by moisturizers, and blocking ultraviolet light. Nonselective β-blockers and α2-adrenergic agonists decrease erythema and flushing. The topical α-adrenergic receptor agonist brimonidine tartrate 0.5% reduces persistent facial erythema. Intradermal botulinum toxin injection is almost safe and effective for the erythema and flushing. Flashlamp-pumped dye, potassium-titanyl-phosphate and pulsed-dye laser, and intense pulsed light are used for telangiectasias. Metronidazole 1% and azelaic acid 15% cream reduce the severity of erythema. Both systemic and topical remedies treat papulopustules. Systemic remedies include metronidazole, doxycycline, minocycline, clarithromycin and isotretinoin, while topical remedies are based on metronidazole 0.75%, azelaic acid 15 or 20%, sodium sulfacetamide, ivermectin 1%, permethrin 5%, and retinoid. Ocular involvement can be treated with oral or topical antibacterial. Rhinophyma can be corrected by dermatosurgical procedures, decortication, and various types of lasers. Conclusion: There are many options for rosacea management. Patients may have multiple subtypes, and each phase has its own treatment.
Hypercalcemia due to Milk-Alkali Syndrome and Fracture-Induced Immobilization in an Adolescent Boy with Hypoparathyroidism
Authors: Henry Rohan K. , Gafni Rachel I.
Published: May 2016

Background: Hypercalcemia of immobilization, while rare, may occur in adolescent boys after fracture. Although not fully understood, the mechanism appears to be related to bone turnover uncoupling, in part mediated by upregulation of RANKL. Animal studies suggest that parathyroidectomy suppresses RANKL-stimulated osteoclastogenesis in immobilized bone. Thus, immobilization-induced hypercalcemia should be uncommon in patients with hypoparathyroidism. Methods/Results: We present a 15-year-old boy with well-controlled hypoparathyroidism who developed hypercalcemia and milk-alkali syndrome 5 weeks after sustaining a severe tibia/fibula fracture requiring bedrest. Milk-alkali syndrome (hypercalcemia, alkalosis, and renal insufficiency) results from chronic excessive ingestion of calcium and absorbable alkali. Prior to fracture, our patient had not experienced hypercalcemia despite high doses of supplements, necessary during puberty. Supplements were discontinued and his biochemistries normalized with saline diuresis and a dose of pamidronate. Alkaline phosphatase, which was low at presentation, returned to normal 5 weeks later with remobilization. Conclusions: Fracture and immobilization caused acute suppression of bone formation with persistent bone resorption in this rapidly growing adolescent; continuation of carbonate-containing calcium supplements resulted in the milk-alkali syndrome. Therefore, close monitoring of serum calcium with adjustments in supplementation are indicated in immobilized patients with hypoparathyroidism.
Debt Instruments in Islamic Finance: A Critique
Authors: Ebrahim Muhammed Shahid , Sheikh Mustapha
Published: May 2016

This article assesses the employment of traditional Islamic debt instruments by contemporary Islamic banks from an economic efficiency perspective. We highlight the fact that the performance of the bulk of the instruments pales in front of the modern facility of participating preferred ijāra. Thus, the shortcomings of the traditional instruments illustrate that the future does not augur well for either the Islamic banking industry or the emerging Muslim economies. For the Muslim world to move beyond its current malaise, it is necessary to scientifically restructure its financial intermediation system in such a way as to meet the challenges of the modern age also conforming to the spirit of the Sharīʿa.
The Legal Implications of ‘Fatwā Shopping’ in the Islamic Finance Industry: Problems, Perceptions and Prospects
Authors: Oseni Umar A. , Ahmad Abu Umar Faruq , Hassan M. Kabir
Published: May 2016

This article examines the occurrence and legal implications of ‘fatwā shopping’ in the Islamic finance industry and the need to put the proper legal mechanisms in place to regulate the phenomenon. It provides a case study of the existing legal restrictions in some jurisdictions with a centralised Sharīʿah Supervisory Board at the national level such as in Malaysia. As a preliminary review of the implications of ‘fatwā shopping’ in the industry, this study examines the consequential problems, current perceptions and prospects of such practice. The study finds that instances of ‘fatwā shopping’ are common in cross-border Islamic finance transactions such as cross-border ṣukūk transactions where there is less regulation.
Children and Christian Missions: Historical Aspects and Missiological Challenges
Authors: Grundmann Christoffer
Published: May 2016

Introducing the topic with a personal story highlighting the complex issues faced when dealing with children and Christian missions, the first section defines who counts as a child reads better and screens the scriptural references to Jesus and children. Sections two and three list what happened in the history of Christianity with regard to minors from earliest times to the present. Section four documents the actual impact Christian missions had on children and their lot, while the fifth looks at structures, strategies, and concepts at work in respective programs. The last part followed by a summarizing conclusion, addresses questions arising for a missiology for all of God’s people when the focus is on children.
Additional species and records of the “horn-backed” Pilophorus plant bugs in Southeast Asia (Heteroptera: Miridae: Phylinae)
Authors: Nakatani Y. , Komatsu T. , Shimizu-kaya U. , Itioka T. , Itino T. , Hashim R. , Ueda S. , Asfiya W. , Herwina H. , Hartini S.
Published: May 2016

Three new species of the “horn-backed” phyline plant bug genus Pilophorus Hahn, namely, P. erinaceulus, P. maruyamai and P. parvolus, are described from Borneo, Malaysia and Sumatra, Indonesia. The following species are newly recorded within Southeast Asia: P. lambirensis from the Malay Peninsula; P. laticollaris from Sumatra; P. longirostris and P. multivillus from Borneo. A supplementary key to the key by Nakatani et al. (2013) is provided.

Y. Nakatani*, Natural Resources Inventory Center, National Institute for Agro-Environmental Sciences, Kannondai, 3-1-3, Tsukuba, Ibaraki, 305-8604, Japan. nakatany@affrc.go.jp

T. Komatsu, Institute of Tropical Agriculture, Kyushu University, Hakozaki 6-10-1, Higashi-ku, Fukuoka 812-8581, Japan. corocoro1232000@yahoo.co.jp

U. Shimizu-kaya, Center for Ecological Research, Kyoto University, Hirano, Otsu, Shiga 520-2113, Japan. shimizu.kaya.55c@st.kyoto-u.ac.jp

T. Itioka, Graduate School of Human and Environmental Studies, Kyoto University, Yoshida-nihonmatsu-cho, Sakyo-ku, Kyoto 606-8501, Japan. ichioka.takao.5m@kyoto-u.ac.jp

T. Itino, S. Ueda, Department of Biology, Faculty of Science, Shinshu University 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan. ueda32@shinshu-u.ac.jp

R. Hashim, Institute of Biological Science, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia. rh4758@gmail.com

W. Asfiya, S. Hartini, Division of Zoology, Research Center for Biology, Indonesian Institute of Sciences, Jl. Raya Jakarta-Bogor Km. 46, Cibinong, Bogor, 16911, Indonesia. wara.asfiya@lipi.go.id

H. Herwina, Laboratorium Riset Taksonomi Hewan, Jurusan Biologi, Fakultas Matematika dan Ilmu Pengetahuan Alam, Universitas Andalas, Kampus UNAND Limau Manis, Padang, 25163, Indonesia. hennyf91@gmail.com
Hydrometeor Mixing Ratio Retrievals for Storm-Scale Radar Data Assimilation: Utility of Current Relations and Potential Benefits of Polarimetry
Authors: Carlin Jacob T. , Ryzhkov Alexander V. , Snyder Jeffrey C. , Khain Alexander
Published: May 2016

The assimilation of radar data into storm-scale numerical weather prediction models has been shown to be beneficial for successfully modeling convective storms. Because of the difficulty of directly assimilating reflectivity (Z), hydrometeor mixing ratios, and sometimes rainfall rate, are often retrieved from Z observations using retrieval relations, and are assimilated as state variables. The most limiting (although widely employed) cases of these relations are derived, and their assumptions and limitations are discussed.

To investigate the utility of these retrieval relations for liquid water content (LWC) and ice water content (IWC) in rain and hail as well as the potential for improvement using polarimetric variables, two models with spectral bin microphysics coupled with a polarimetric radar operator are used: a one-dimensional melting hail model and the two-dimensional Hebrew University Cloud Model. The relationship between LWC and Z in pure rain varies spatially and temporally, with biases clearly seen using the normalized number concentration. Retrievals using Z perform the poorest while specific attenuation and specific differential phase shift (KDP) perform much better. Within rain–hail mixtures, separate estimation of LWC and IWC is necessary. Prohibitively large errors in the retrieved LWC may result when using Z. The quantity KDP can be used to effectively retrieve the LWC and to isolate the contribution of IWC to Z. It is found that the relationship between Z and IWC is a function of radar wavelength, maximum hail diameter, and principally the height below the melting layer, which must be accounted for in order to achieve accurate retrievals.
Boss Competence and Worker Well-Being
Authors: Artz Benjamin M. , Goodall Amanda H. , Oswald Andrew J.
Published: May 2016

Nearly all workers have a supervisor or “boss.” Yet little is known about how bosses influence the quality of employees’ lives. This study offers new evidence. First, the authors find that a boss’s technical competence is the single strongest predictor of a worker’s job satisfaction. Second, they demonstrate using longitudinal data, after controlling for fixed-effects, that even if a worker stays in the same job and workplace, a rise in the competence of a supervisor is associated with an improvement in the worker’s well-being. Third, the authors report a variety of robustness checks, including tentative instrumental variable results. These findings, which draw on U.S. and British data, contribute to an emerging literature on the role of “expert leaders” in organizations.
Validation of the Mandarin Version of the Vocabulary Size Test
Authors: Zhao Ping , Ji Xiaoli
Published: May 2016

This article provides preliminary validity evidence for the shorter Mandarin version of the Vocabulary Size Test (VST) under the content aspect, technical quality, substantive and generalizability aspect of Messick’s (1995) construct validity framework. The shorter version with 177 Chinese university students in three proficiency levels indicates that the test enjoys a high level of validity both from the perspective of classical test theory and item response theory. A one-way ANOVA and detailed statistics of Rasch analyses demonstrate that the test could effectively distinguish learners from different proficiency levels. The first eight levels of the VST generally display an ascending difficulty continuum except that some loan words in the seventh and the eighth level prove to be problematic in assessing Chinese learners’ vocabulary size accurately. The generalizability aspect of construct validity is demonstrated in that there is no item bias for learners of the same proficiency group in terms of gender. Compared with the results of other studies either on monolingual or bilingual version, this research attempts to justify the appropriateness of the Mandarin version and calls for cautious applications of the test instrument on Chinese learners.
Reverse ballistics penetration of Kevlar® fabric with different indenters at different loading rates
Authors: Guo Zherui , Zheng James , Chen Weinong
Published: May 2016

In this study, the mechanical load on a bullet-shaped indenter when impacted by a single-ply Kevlar fabric was experimentally investigated using a reverse ballistics method at both quasi-static and dynamic rates. Different indenter geometries, namely the 9-mm Luger, .223 Remington, and .308 Winchester bullet geometries, were used. The penetration load of the stationary indenter was measured using a force transducer located behind the indenter, and the penetration load was then plotted against the impact velocity of the fabric sample. Different mechanisms of penetration were observed at different impact velocities. Penetration mechanisms were also found to be highly dependent on projectile nose geometry. A modified method to obtain an approximate ballistic limit based on the impact loads was used to compare the efficacy of different geometry types.