bluuebunny/crossref_metadata_2025 huggingface dataset:
Transforming physics educator identities: TAs help TAs become teaching professionals
Authors: Gretton Anneke L. , Bridges Terry , Fraser James M.
Published: April 2017

Research-based instructional strategies have been shown to dramatically improve student learning, but widespread adoption of these pedagogies remains limited. Post-secondary teaching assistants (TAs), with their current positions in course delivery and future roles as academic leaders, are an essential target group for teacher training. However, the literature suggests that successful TA professional development must address not only pedagogical practices but also the cultivation of physics educator identity. The primary goal of this study is to build a framework for TA professional development that strengthens the TA's identity as a physics educator. We base this framework on Etienne Wenger's model for communities of practice and Côté and Levine's personality and social structure identity perspective. We explore this framework in the context of a 12-week, low-cost, TA-led and TA-centered professional development intervention. Our qualitative and quantitative data suggest that this efficient community-based intervention strengthened TAs' identification as physics educators.
The Hindenburg Disaster: Combining Physics and History in the Laboratory
Authors: DiLisi Gregory A.
Published: April 2017

This May marks the 80th anniversary of the Hindenburg disaster. On May 6, 1937, the German passenger zeppelin Hindenburg, hovering 300 feet in the air and held aloft by seven million cubic feet of hydrogen gas, burst into flames while preparing to dock at the Naval Air Station in Lakehurst, NJ (Fig. 1). Amazingly, the ensuing fire consumed the massive airship in only 35 seconds! In the aftermath, 35 of 97 people onboard died (13 passengers and 22 crewmen) plus one member of the ground crew. Herbert Morrison, the broadcaster from Chicago’s WLS radio station, was on assignment that day covering the arrival of the majestic airship. Morrison’s eyewitness account of the disaster is legendary audio history. In fact, Morrison’s phrase, “Oh, the humanity!” has become a cultural idiom.
Too Early for Physics? Effect of Class Meeting Time on Student Evaluations of Teaching in Introductory Physics
Authors: Tobin R. G.
Published: April 2017

This paper reports observations that show a significant effect of class meeting time on student evaluations of teaching for an introductory college physics class. Students in a lecture section with an early-morning meeting time gave the class and instructors consistently lower ratings than those in an otherwise nearly identical section that met an hour later, even for aspects of the course that were seemingly identical across the two sections.
Making good physics videos
Authors: Lincoln James
Published: April 2017

Online videos are an increasingly important way technology is contributing to the improvement of physics teaching. Students and teachers have begun to rely on online videos to provide them with content knowledge and instructional strategies. Online audiences are expecting greater production value, and departments are sometimes requesting educators to post video pre-labs or to flip our classrooms. In this article, I share my advice on creating engaging physics videos.
The FOXM1 inhibitor RCM-1 suppresses goblet cell metaplasia and prevents IL-13 and STAT6 signaling in allergen-exposed mice
Authors: Sun Lifeng , Ren Xiaomeng , Wang I-Ching , Pradhan Arun , Zhang Yufang , Flood Hannah M. , Han Bo , Whitsett Jeffrey A. , Kalin Tanya V. , Kalinichenko Vladimir V.
Published: April 2017

An inhibitor of the transcription factor FOXM1 prevents asthma-associated signaling in mice exposed to a common airborne allergen.
Control of potassium homeostasis is an essential function of the second messenger cyclic di-AMP in
Bacillus subtilis
Authors: Gundlach Jan , Herzberg Christina , Kaever Volkhard , Gunka Katrin , Hoffmann Tamara , Weiß Martin , Gibhardt Johannes , Thürmer Andrea , Hertel Dietrich , Daniel Rolf , Bremer Erhard , Commichau Fabian M. , Stülke Jörg
Published: April 2017

The second messenger cyclic di-AMP enables bacteria to adapt to changes in environmental potassium concentrations.
Microbes stimulate hair follicles
Authors: VanHook Annalisa M.
Published: April 2017

Commensal microbes induce hair follicles to release a chemokine that recruits regulatory T cells into neonatal skin.
Comparative Pharmacodynamics of Telavancin and Vancomycin in the Neutropenic Murine Thigh and Lung Infection Models against Staphylococcus aureus
Authors: Lepak Alexander J. , Zhao Miao , Andes David R.
Published: April 2017

The pharmacodynamics of telavancin and vancomycin were compared using neutropenic murine thigh and lung infection models. Four
Staphylococcus aureus
strains were included. The telavancin MIC ranged from 0.06 to 0.25 mg/liter, and the vancomycin MIC ranged from 1 to 4 mg/liter. The plasma pharmacokinetics of escalating doses (1.25, 5, 20, and 80 mg/kg of body weight) of telavancin and vancomycin were linear over the dose range. Epithelial lining fluid (ELF) pharmacokinetics for each drug revealed that penetration into the ELF mirrored the percentage of the free fraction (the fraction not protein bound) in plasma for each drug. Telavancin (0.3125 to 80 mg/kg/6 h) and vancomycin (0.3125 to 1,280 mg/kg/6 h) were administered by the subcutaneous route in treatment studies. Dose-dependent bactericidal activity against all four strains was observed in both models. A sigmoid maximum-effect model was used to determine the area under the concentration-time curve (AUC)/MIC exposure associated with net stasis and 1-log
10
kill relative to the burden at the start of therapy. The 24-h plasma free drug AUC (
f
AUC)/MIC values associated with stasis and 1-log kill were remarkably congruent. Net stasis for telavancin was noted at
f
AUC/MIC values of 83 and 40.4 in the thigh and lung, respectively, and 1-log kill was noted at
f
AUC/MIC values of 215 and 76.4, respectively. For vancomycin, the
f
AUC/MIC values for stasis were 77.9 and 45.3, respectively, and those for 1-log kill were 282 and 113, respectively. The 24-h ELF total drug AUC/MIC targets in the lung model were very similar to the 24-h plasma free drug AUC/MIC targets for each drug. Integration of human pharmacokinetic data for telavancin, the results of the MIC distribution studies, and the pharmacodynamic targets identified in this study suggests that the current dosing regimen of telavancin is optimized to obtain drug exposures sufficient to treat
S. aureus
infections.
Antiviral Activity and Resistance Analysis of NS3/4A Protease Inhibitor Grazoprevir and NS5A Inhibitor Elbasvir in Hepatitis C Virus GT4 Replicons
Authors: Asante-Appiah Ernest , Curry Stephanie , McMonagle Patricia , Ingravallo Paul , Chase Robert , Nickle David , Qiu Ping , Howe Anita , Lahser Frederick C.
Published: April 2017

Although genotype 4 (GT4)-infected patients represent a minor overall percentage of the global hepatitis C virus (HCV)-infected population, the high prevalence of the genotype in specific geographic regions coupled with substantial sequence diversity makes it an important genotype to study for antiviral drug discovery and development. We evaluated two direct-acting antiviral agents—grazoprevir, an HCV NS3/4A protease inhibitor, and elbasvir, an HCV NS5A inhibitor—in GT4 replicons prior to clinical studies in this genotype. Following a bioinformatics analysis of available GT4 sequences, a set of replicons bearing representative GT4 clinical isolates was generated. For grazoprevir, the 50% effective concentration (EC
50
) against the replicon bearing the reference GT4a (ED43) NS3 protease and NS4A was 0.7 nM. The median EC
50
for grazoprevir against chimeric replicons encoding NS3/4A sequences from GT4 clinical isolates was 0.2 nM (range, 0.11 to 0.33 nM;
n
= 5). The difficulty in establishing replicons bearing NS3/4A resistance-associated substitutions was substantially overcome with the identification of a G162R adaptive substitution in NS3. Single NS3 substitutions D168A/V identified from
de novo
resistance selection studies reduced grazoprevir antiviral activity by 137- and 47-fold, respectively, in the background of the G162R replicon. For elbasvir, the EC
50
against the replicon bearing the reference full-length GT4a (ED43) NS5A gene was 0.0002 nM. The median EC
50
for elbasvir against chimeric replicons bearing clinical isolates from GT4 was 0.0007 nM (range, 0.0002 to 34 nM;
n
= 14).
De novo
resistance selection studies in GT4 demonstrated a high propensity to suppress the emergence of amino acid substitutions that confer high-potency reductions to elbasvir. Phenotypic characterization of the NS5A amino acid substitutions identified (L30F, L30S, M31V, and Y93H) indicated that they conferred 15-, 4-, 2.5-, and 7.5-fold potency losses, respectively, to elbasvir. The activity profiles of grazoprevir and elbasvir supported the testing of the direct-acting antivirals in clinical studies.
Pharmacokinetics and Preliminary Safety of Pod-Intravaginal Rings Delivering the Monoclonal Antibody VRC01-N for HIV Prophylaxis in a Macaque Model
Authors: Zhao Chunxia , Gunawardana Manjula , Villinger Francois , Baum Marc M. , Remedios-Chan Mariana , Moench Thomas R. , Zeitlin Larry , Whaley Kevin J. , Bohorov Ognian , Smith Thomas J. , Anderson Deborah J. , Moss John A.
Published: April 2017

The broadly neutralizing antibody (bNAb) VRC01, capable of neutralizing 91% of known human immunodeficiency virus type 1 (HIV-1) isolates
in vitro
, is a promising candidate microbicide for preventing sexual HIV infection when administered topically to the vagina; however, accessibility to antibody-based prophylactic treatment by target populations in sub-Saharan Africa and other underdeveloped regions may be limited by the high cost of conventionally produced antibodies and the limited capacity to manufacture such antibodies. Intravaginal rings of the pod design (pod-IVRs) delivering
Nicotiana
-manufactured VRC01 (VRC01-N) over a range of release rates have been developed. The pharmacokinetics and preliminary safety of VRC01-N pod-IVRs were evaluated in a rhesus macaque model. The devices sustained VRC01-N release for up to 21 days at controlled rates, with mean steady-state VRC01-N levels in vaginal fluids in the range of 10
2
to 10
3
μg g
−1
being correlated with
in vitro
release rates. No adverse safety indications were observed. These findings indicate that pod-IVRs are promising devices for the delivery of the candidate topical microbicide VRC01-N against HIV-1 infection and merit further preclinical evaluation.
Isolated implant metastasis in chest wall due to seeding of transpleurally placed PTBD catheter tract in a case of hilar cholangiocarcinoma
Authors: Talukder Shibojit , Behera Arunanshu , Tandup Cherring , Mitra Suvradeep
Published: April 2017

Percutaneous transhepatic biliary drainage (PTBD) catheter site metastasis in cases of cholangiocarcinoma is reported sporadically. But it is unusual to see left-sided tumour metastasising to the right PTBD catheter site. Metastasis, in general, has a poor prognosis, but recurrence along the catheter tract in the absence of other systemic diseases can be a different scenario altogether. To date, there is no consensus on the management of this form of metastasis. But carefully selected patients can benefit from aggressive surgical resection. We report a case of a young patient with isolated chest wall metastasis 1 year after resection of left-sided hilar cholangiocarcinoma. The metastasis was resected and, on pathological analysis, was confirmed to be due to implantation of malignant cells along the tract of the PTBD catheter placed via a transpleural route.
Relationship between oxygen concentration and temperature in an exothermic warming device
Authors: Brooks Ben , Deakin Charles D
Published: April 2017

Introduction

Actively warming hypothermic patients or preventing hypothermia is critical in optimising outcomes in patients with traumatic injuries. Our aim was to investigate the effect of ambient oxygen concentration on the rate and change in temperature of the TechTrade Ready-Heat II exothermic (oxygen-activated) warming blanket, to evaluate safety and ascertain the risk of thermal injury.

Methods

A mannequin covered with an exothermic blanket was placed in a sealed oxygen tent. An ambulance blanket was placed between the TechTrade Ready-Heat II exothermic blanket and the mannequin. Two temperature probes were placed directly on the surface of the mannequin; one on the torso away from the heating packs and the other directly beneath the exothermic heating pack. The mannequin was exposed to increasing oxygen concentrations at 10% increments, starting at 21%. The experiment was conducted nine times, each time using a new blanket. Maximum temperature of the mannequin ‘skin’ and rate of rise were recorded from both temperature sensors.

Results

In room air (21% oxygen), the mannequin surface reached 52°C after 60 min, matching manufacturer specifications. At 30% oxygen concentration, the temperature directly beneath the exothermic heating pack exceeded the 65°C threshold at which rapid thermal burns occur, reaching 72.5°C, with minimal change in overall torso temperature.

Conclusion

The supplemental use of oxygen in patients with traumatic injuries that increases ambient oxygen levels in the presence of exothermic warming devices may represent a significant risk to the patient. We suggest that prehospital care providers remain highly vigilant of heat when using high-flow oxygen and the subsequent fire risk, while manufacturers of exothermic blankets should consider ways to improve safety.
Pilot Studies
Authors: Truong Khai
Published: April 2017

Evaluating an interactive system with users can be costly and timeconsuming. As a result, it can be extremely frustrating for evaluators whenever they are not able to use any of the data collected from the user evaluation of a system because of problems with how the study was designed or executed. In such instances, evaluators must learn from their mistakes and rerun the study a second time. However, the time, effort, and resources that went into completing the study the first time is still wasted. This problem can be minimized by first conducting a pilot study -- a small-scale version of the actual study -- prior to the final study, to identify, remove, and avoid any potential problems.
uLink
Authors: Azim Tanzirul , Riva Oriana , Nath Suman
Published: April 2017

Web deep links are instrumental to many fundamental user experiences, such as navigating from one web page to another, bookmarking a page, or sharing it with others. Such experiences are not possible with individual pages inside mobile apps, since historically mobile apps did not have links equivalent to web deep links. Mobile deep links, introduced in recent years, still lack many important properties of web deep links. Unlike web links, mobile deep links need significant developer effort to be exposed, cover a small number of predefined pages, and are defined statically to navigate to a page for a given link, but not to dynamically generate a link for a given page. We have built uLink, a novel deep linking mechanism that addresses these problems. uLink is implemented as an application library, which transparently tracks data- and UI-event-dependencies of app pages, and encodes the information in links to the pages; when a link is invoked, the information is utilized to recreate the target page quickly and accurately. uLink also employs techniques, based on static and dynamic analysis of the app, that can provide feedback to users about whether a link may break in the future due to, e.g., modifications of external resources such as a file the link depends on. We have implemented uLink on Android, and tested with 30+ apps. Compared to existing mobile deep links, uLink requires minimal developer effort, achieves significantly higher coverage, and can provide accurate user feedback on a broken link.
Sharing Data to Build a Medical Information Commons: From Bermuda to the Global Alliance
Authors: Cook-Deegan Robert , Ankeny Rachel A. , Maxson Jones Kathryn
Published: April 2017

The Human Genome Project modeled its open science ethos on nematode biology, most famously through daily release of DNA sequence data based on the 1996 Bermuda Principles. That open science philosophy persists, but daily, unfettered release of data has had to adapt to constraints occasioned by the use of data from individual people, broader use of data not only by scientists but also by clinicians and individuals, the global reach of genomic applications and diverse national privacy and research ethics laws, and the rising prominence of a diverse commercial genomics sector. The Global Alliance for Genomics and Health was established to enable the data sharing that is essential for making meaning of genomic variation. Data-sharing policies and practices will continue to evolve as researchers, health professionals, and individuals strive to construct a global medical and scientific information commons.
Vibration Characteristics for Moving Printing Membrane with Variable Density along the Lateral Direction
Authors: Shao Mingyue , Wu Jimei , Wang Yan , Wu Qiumin , Chen Yuan
Published: April 2017

The vibration model of moving membrane with variable density distribution is established, and the density distribution of the moving membrane varies along the lateral direction. The transverse vibration differential equations of moving membrane are established based on D’Alembert’s principle and discretized by using the differential quadrature method (DQM). The relationships of the first three dimensionless complex frequencies between dimensionless speed, density coefficient, and tension ratio of the membrane are analyzed by numerical calculation. The effects of the density coefficient and the tension ratio on transverse vibration characteristics of the membrane are investigated. The relationship between density coefficient and critical speed is obtained. The numerical results show that the density coefficient and the tension ratio have important influence on the stability of moving membrane. So the study provides a theoretical basis for improving the working stability of the membrane in the high-speed printing process.
Study of Lactic Acid Thermal Behavior Using Thermoanalytical Techniques
Authors: Komesu Andrea , Martins Martinez Patricia Fazzio , Lunelli Betânia Hoss , Oliveira Johnatt , Wolf Maciel Maria Regina , Maciel Filho Rubens
Published: April 2017

Actually, there is a growing interest in the biotechnological production of lactic acid by fermentation aiming to substitute fossil fuel routes. The development of an efficient method for its separation and purification from fermentation broth is very important to assure the economic viability of production. Due to its high reactivity and tendency to decompose at high temperatures, the study of lactic acid thermal behavior is essential for its separation processes and potential application. In the present study, differential scanning calorimetry (DSC) analyses showed endothermic peaks related to the process of evaporation. Data of thermogravimetry (TG/DTG) were correlated to Arrhenius and Kissinger equations to provide the evaporation kinetic parameters and used to determine the vaporization enthalpy. Activation energies were 51.08 and 48.37 kJ·mol−1 and frequency values were 859.97 and 968.81 s−1 obtained by Arrhenius and Kissinger equations, respectively. Thermogravimetry, coupled with mass spectroscopy (TG-MS), provided useful information about decomposition products when lactic acid was heated at 573 K for approximately 30 min.
miR-135b Plays a Neuroprotective Role by Targeting GSK3β in MPP+-Intoxicated SH-SY5Y Cells
Authors: Zhang Jianlei , Liu Wei , Wang Yabo , Zhao Shengnan , Chang Na
Published: April 2017

miR-135a-5p was reported to play a crucial role in the protective effects of hydrogen sulfide against Parkinson’s disease (PD) by targeting rho-associated protein kinase 2 (ROCK2). However, the role of another member of miR-135 family (miR-135b) and the underlying mechanism in PD are still unclear. qRT-PCR and western blot showed that miR-135 was downregulated and glycogen synthase kinase 3β(GSK3β) was upregulated at mRNA and protein levels in MPP+-intoxicated SH-SY5Y cells in a dose- and time-dependent manner. MTT, TUNEL, and ELISA assays revealed that miR-135b overexpression significantly promoted cell proliferation and inhibited apoptosis and production of TNF-αand IL-1βin SH-SY5Y cells in the presence of MPP+. Luciferase reporter assay demonstrated that GSK3βwas a direct target of miR-135b. Moreover, sodium nitroprusside (SNP), a GSK3βactivator, dramatically reversed the effects of miR-135b upregulation on cell proliferation, apoptosis, and inflammatory cytokine production in MPP+-intoxicated SH-SY5Y cells. Taken together, miR-135b exerts a protective role via promotion of proliferation and suppression of apoptosis and neuroinflammation by targeting GSK3βin MPP+-intoxicated SH-SY5Y cells, providing a potential therapeutic target for the treatment of PD.
Molecular Cloning and Expression Analysis of Cu/Zn SOD Gene from Gynura bicolor DC.
Authors: Xu Xin , Yu Zhi-fang , Kong Jing , Yi Mei-jun , Huan Chen , Jiang Li
Published: April 2017

Superoxide dismutase is an important antioxidant enzyme extensively existing in eukaryote, which scavenges reactive oxygen species (ROS) and plays an essential role in stress tolerance of higher plants. A full-length cDNA encoding Cu/Zn SOD was cloned from leaves of Gynura bicolor DC. by rapid amplification of cDNA ends (RACE). The full-length cDNA of Cu/Zn SOD is 924 bp and has a 681 bp open reading frame encoding 227 amino acids. Bioinformatics analysis revealed that belonged to the plant SOD super family. Cu/Zn SODs of the Helianthus annuus, Mikania micrantha, and Solidago canadensis var. scabra all have 86% similarity to the G. bicolor Cu/Zn SOD. Analysis of the expression of Cu/Zn SOD under different treatments revealed that Cu/Zn SOD was a stress-responsive gene, especially to 1-MCP. It indicates that the Cu/Zn SOD gene would be an important gene in the resistance to stresses and will be helpful in providing evidence for future research on underlying molecular mechanism and choosing proper postharvest treatments for G. bicolor.
Amino Acid Signatures to Evaluate the Beneficial Effects of Weight Loss
Authors: Geidenstam Nina , Magnusson Martin , Danielsson Anders P. H. , Gerszten Robert E. , Wang Thomas J. , Reinius Lovisa E. , Mulder Hindrik , Melander Olle , Ridderstråle Martin
Published: April 2017

Aims. We investigated the relationship between circulating amino acid levels and obesity; to what extent weight loss followed by weight maintenance can correct amino acid abnormalities; and whether amino acids are related to weight loss.Methods. Amino acids associated with waist circumference (WC) and BMI were studied in 804 participants from the Malmö Diet and Cancer Cardiovascular Cohort (MDC-CC). Changes in amino acid levels were analyzed after weight loss and weight maintenance in 12 obese subjects and evaluated in a replication cohort (n=83).Results. Out of the eight identified BMI-associated amino acids from the MDC-CC, alanine, isoleucine, tyrosine, phenylalanine, and glutamate decreased after weight loss, while asparagine increased after weight maintenance. These changes were validated in the replication cohort. Scores that were constructed based on obesity-associated amino acids and known risk factors decreased in the ≥10% weight loss group with an associated change in BMI (R2=0.16–0.22,p<0.002), whereas the scores increased in the <10% weight loss group (p<0.0004).Conclusions. Weight loss followed by weight maintenance leads to differential changes in amino acid levels associated with obesity. Treatment modifiable scores based on epidemiological and interventional data may be used to evaluate the potential metabolic benefit of weight loss.
Optimal Keratoplasty for the Correction of Presbyopia and Hypermetropia
Authors: Veritti Daniele , Sarao Valentina , Lanzetta Paolo
Published: April 2017

Purpose.To evaluate prospectively the safety and efficacy of optimal keratoplasty for the correction of hyperopia and presbyopia.Methods. Consecutive patients undergoing bilateral optimal keratoplasty for refractive presbyopic and hypermetropic corrections were enrolled. Each patient received a complete ophthalmologic examination at baseline, 1 hour, 1 day, 1 week, 1 month, 3 months, and 6 months after treatment.Results. The study included 40 consecutive eyes of 20 patients. All patients reached the 6-month follow-up. No serious intra- or postoperative complications were recorded. Monocular and binocular uncorrected near visual acuities improved significantly during the follow-up (p<0.001). Binocular uncorrected distance visual acuity in presbyopic patients improved from 0.28 logMAR to a maximum of 0.04 logMAR (from 20/38 to 20/22 Snellen equivalent) the day after the treatment and remained significantly better than baseline until the end of the follow-up. A significant improvement of patient satisfaction for near (p<0.001) and distance (p=0.007) activities was seen the day after treatment and was maintained throughout the follow-up.Conclusions.Optimal keratoplasty is a safe, noninvasive, rapid, pain-free, office-based procedure. It offers low to moderate hyperopes and presbyopes an improvement in uncorrected near visual acuity while maintaining or improving their distance visual acuity.
Organic Compounds Based on (E)-N-Aryl-2-ethene-sulfonamide as Microtubule Targeted Agents in Prostate Cancer: QSAR Study
Authors: Hadaji El Ghalia , Bourass Mohamed , Ouammou Abdelkarim , Bouachrine Mohammed
Published: April 2017

(E)-N-Aryl-2-ethene-sulfonamide and its derivatives are potent anticancer agents; these compounds inhibit cancer cells proliferation. A study of quantitative structure-activity relationship (QSAR) has been applied on 40 compounds based on (E)-N-Aryl-2-ethene-sulfonamide, in order to predict their anticancer biological activity. The principal components analysis is used for minimizing the base matrix and the multiple linear regression (MLR) and multiple nonlinear regression have been used to design the relationships between the molecular descriptor and anticancer properties of the sulfonamide derivatives. The validation of the models MLR and MNLR has been done by dividing the dataset into training and test set, the external validation of multiple correlation coefficients was RpIC50 = 0.81 for MLR and RpIC50 = 0.91 for MNLR. The artificial neural network (ANN) showed a correlation coefficient close to 0.96, which concluded that this latter model is more effective and much better than the other models. This obtained model (ANN) has been confirmed by two methods of LOO cross-validation and scrambling (or Y-randomization). The high correlation between experimental and predicted activity values was observed, indicating the validation and the good quality of the derived QSAR model.
Performance Analysis of Buffer-Aided Relaying System Based on Data and Energy Coupling Queuing Model for Cooperative Communication Networks
Authors: Liang Guangjun , Zhu Qi , Xin Jianfang , Tang Jiashan , Zhang Tianjiao
Published: April 2017

We focus on the performance analysis of the buffer-aided relaying system which allows data and energy packets to arrive independently and depart interactively. First, we profile the cooperative relaying system model as a data arrival and energy arrival coupling queuing model. Considering the influence of channel condition on the data departure rate, a new relay transmit protocol which permits exhausting more energy packet to send one data packet in the bad channel environment is proposed. Second, the joint data packet and energy packet handling problem is ascribed to a Coupled Processor Queuing Model which could achieve its steady state transition probability by Quasi-Birth and Death method. Third, the expressions of throughput, delay, and packet drop rate for both data queue and energy queue are also derived. Simulations are demonstrated to verify the analytical results under different data arrival rate, energy arrival rate, and relaying strategy.
Preclinical Characterization of BET Family Bromodomain Inhibitor ABBV-075 Suggests Combination Therapeutic Strategies
Authors: Bui Mai H. , Lin Xiaoyu , Albert Daniel H. , Li Leiming , Lam Lloyd T. , Faivre Emily J. , Warder Scott E. , Huang Xiaoli , Wilcox Denise , Donawho Cherrie K. , Sheppard George S. , Wang Le , Fidanze Steve , Pratt John K. , Liu Dachun , Hasvold Lisa , Uziel Tamar , Lu Xin , Kohlhapp Fred , Fang Guowei , Elmore Steven W. , Rosenberg Saul H. , McDaniel Keith F. , Kati Warren M. , Shen Yu
Published: April 2017

ABBV-075 is a potent and selective BET family bromodomain inhibitor that recently entered phase I clinical trials. Comprehensive preclinical characterization of ABBV-075 demonstrated broad activity across cell lines and tumor models, representing a variety of hematologic malignancies and solid tumor indications. In most cancer cell lines derived from solid tumors, ABBV-075 triggers prominent G1 cell-cycle arrest without extensive apoptosis. In this study, we show that ABBV-075 efficiently triggers apoptosis in acute myeloid leukemia (AML), non-Hodgkin lymphoma, and multiple myeloma cells. Apoptosis induced by ABBV-075 was mediated in part by modulation of the intrinsic apoptotic pathway, exhibiting synergy with the BCL-2 inhibitor venetoclax in preclinical models of AML. In germinal center diffuse large B-cell lymphoma, BCL-2 levels or venetoclax sensitivity predicted the apoptotic response to ABBV-075 treatment. In vivo combination studies uncovered surprising benefits of low doses of ABBV-075 coupled with bortezomib and azacitidine treatment, despite the lack of in vitro synergy between ABBV-075 and these agents. The in vitro/in vivo activities of ABBV-075 described here may serve as a useful reference to guide the development of ABBV-075 and other BET family inhibitors for cancer therapy. Cancer Res; 77(11); 2976–89. ©2017 AACR.
Molecular Genetic Analysis of Normosmic Hypogonadotropic Hypogonadism in a Turkish Population: Identification and Detailed Functional Characterization of a Novel Mutation in the Gonadotropin-Releasing Hormone Receptor Gene
Authors: Topaloglu A. Kemal , Lu Zhi-Liang , Farooqi I. Sadaf , Mungan Neslihan O. , Yuksel Bilgin , O'Rahilly Stephen , Millar Robert P.
Published: April 2017

Background/Aims: Currently known mutations account for less than 15% of cases with normosmic hypogonadotropic hypogonadism (nIHH). The objective of the study was to identify novel hereditary associations in the pathogenesis of nIHH. Methods: We investigated 26 Turkish patients with nIHH (21 males and 5 females) from 22 families. The coding regions of the GnRH receptor, GnRH1, GPR54, and KISS1 genes were directly sequenced. Results: In two sisters, a novel homozygous missense mutation, R139C, located in the conserved DRS motif at the junction of the third transmembrane and the second intracellular loop of the GnRH receptor was identified. The R139C mutation almost completely abolished plasma membrane expression while having little effect on GnRH-binding affinity. The mutant receptor expression was rescued by a membrane-permeant, non-peptide GnRH receptor antagonist IN3. Conclusions: Consistent with the previous studies we were able to find mutations in only 7.6% of a well-defined group of patients with nIHH, which further suggests that yet unidentified genetic associations to explain nIHH exist.
Methylation Status of Genes Upregulated by Demethylating Agent 5-aza-2′-Deoxycytidine in Hepatocellular Carcinoma
Authors: Hirasawa Yuichi , Arai Makoto , Imazeki Fumio , Tada Motohisa , Mikata Rintaro , Fukai Kenichi , Miyazaki Masaru , Ochiai Takenori , Saisho Hiromitsu , Yokosuka Osamu
Published: April 2017

Background/Aims: To determine the clinical significance of gene promoter methylation in hepatocellular carcinoma (HCC), we examined in clinical samples the methylation status of those promoters that showed elevated activity in hepatoma cell lines after 5-aza-2′-deoxycytidine treatment. Methods: Regarding the genes with promoter hypermethylation in the cell lines, their expression levels and methylation status in HCC and non-HCC tissues were assessed by semiquantitive RT-PCR and methylation-specific PCR. To confirm the result, the expression levels and methylation status in 16 additional HCC and non-HCC tissues were assessed. Results: The promoter regions of caveolin 1 (CAV1), cysteine and glycine-rich protein 1 (CSRP1), Kruppel-like factor 6 (KLF6), myosin (light polypeptide 9) (MYL9), and transgelin (TAGLN) were highly methylated in the cell lines. CAV1 and CSRP1 were methylated in HCC more frequently than in non-HCC. KLF6, MYL9, and TAGLN were fully methylated in both HCC and non-HCC. Using additional clinical samples, downregulation of CAV1 and CSRP1 was observed in 38 and 56%, respectively, of the 16 HCC samples and aberrant methylation of CAV1 and CSRP1 was observed in 56% of HCC in both cases. Conclusion:CAV1 and CSRP1 were inactivated in HCC by aberrant methylation and they may serve as important biomarkers of malignancy.
Intravascular Ultrasound Correlates with Coronary Flow Reserve and Predicts the Survival in Angiographically Normal Cardiac Transplant Recipients
Authors: Lee Chii-Ming , Wu Yen-Wen , Jui Hsiang-Yiang , Yen Ruoh-Fang , Tzen Kai-Yuan , Chou Nai-Kuan , Wang Shoei-Shen
Published: April 2017

Objectives: We aimed to determine whether epicardial and intramyocardial arteries were involved concordantly in early cardiac allograft vasculopathy. Methods: Thirty consecutive recipients who had received cardiac transplantation more than 1 year before and had a normal coronary angiogram were enrolled for intravascular ultrasound (IVUS), fractional flow reserve, coronary flow reserve and dipyridamole thallium-201 single photon emission computed tomography. Graft failure including cardiac death and retransplantation served as the primary outcome. Results: Plaque volume index and maximum area stenosis calculated from IVUS measurements correlated with coronary flow reserve deterioration in a subgroup of patients with normal fractional flow reserve (n = 13; r = –0.80, p = 0.001 and r = –0.91, p <0.0001, respectively). After follow-up for 18.4 ± 7.6 months, maximum area stenosis was found to be an independent predictor of graft failure (hazard ratio 1.43, 95% confidence interval 1.08–1.89, p = 0.012). Conclusion: In patients with physiologically normal epicardial coronary arteries, impairment of microvascular integrity correlates with the plaque burden measured by IVUS, suggesting the concordant involvement of both epicardial and resistant vessels in early cardiac allograft vasculopathy. Evident epicardial coronary narrowing on IVUS may predict graft failure in spite of normal coronary angiograms.
Beta-2-Adrenergic Receptor Polymorphisms and Changes in Lipids Induced by Metoprolol
Authors: Isaza Carlos A. , Henao Julieta , Sánchez Julio C. , Porras Gloria L. , Cardona J. , Bedoya G.
Published: April 2017

Polymorphisms Arg16Gly and Gln27Glu of the gene of adrenoreceptor β2(ADRB2) are associated with altered sympathetic responses. This study evaluated the relationship between these polymorphisms and changes in lipids induced by metoprolol in hypertensive patients. 105 adults were enrolled. After serum lipid levels and genotype had been determined, metoprolol was administered orally. Genotyping was performed using a mini-sequencing technique. Allelic and genotypic frequencies were: Arg16 (49.5%); Gly16 (50.5%); Gln27 (89%); Glu27 (11%); Arg16Arg (28.6%); Arg16Gly (41.9%); Gly16Gly (29.5%); Gln27Gln (81%); Gln27Glu (16.1%), and Glu27Glu (2.9%). Ninety patients concluded the study. There were no significant differences between the demographic, pharmacological and biochemical variables evaluated, grouped by their genotype in positions 16 and 27 of the ADRB2 gene. We did not find differences in lipid profiles in the whole group, but when we compared these profiles within each genotypic subgroup, we found that total cholesterol diminished (p = 0.03) in the patients with the native Gln27Gln genotype, whereas in the Gln27Glu heterozygous triglycerides increased (p = 0.025). We only found 3 patients homozygous for Glu27Glu and 2 of them were treated with diet and antidyslipidemic drugs. These results suggest that the polymorphism of codon 27 constitutes the target of the changes in lipids induced by β-adrenergic receptor antagonists.
Costs and Effects of Prenatal Screening Methods for Down Syndrome and Neural Tube Defects
Authors: Hoogendoorn Mirjam , Evers Silvia M.A.A. , Schielen Peter C.J.I. , van Genugten Marianne L.L. , de Wit G. Ardine , Ament André J.H.A.
Published: April 2017

Objectives: To evaluate prenatal screening methods for Down syndrome and neural tube defects (NTD) with regard to costs per detected case and the number of screening-related miscarriages. Methods: The screening methods compared were risk assessment tests, i.e. serum tests and nuchal translucency measurement (NT), and invasive testing through chorionic villus sampling (CVS) or amniocentesis. Costs, the number of cases detected and screening-related miscarriages were calculated using a decision tree model. Results: The costs per detected case of Down syndrome ranged from EUR 98,000 for the first-trimester (serum) double test to EUR 191,000 for invasive testing. If NTD detection was included, the (serum) triple test had the lowest costs, EUR 73,000, per detected case of Down syndrome or NTD. The number of screening-related miscarriages due to invasive diagnostic tests varied from 13 per 100,000 women for the (serum) first- and second-trimester combined test to 914 per 100,000 women for invasive testing. Conclusions: Considering screening for both Down syndrome and NTD favors the triple test in terms of costs per detected case. Compared to invasive testing, risk assessment tests in general substantially lower screening-related miscarriages, which raises the question of whether invasive testing should still be offered in a screening program for Down syndrome.
Toll-Like Receptors in Endocrine Disease and Diabetes
Authors: Kanczkowski W. , Ziegler C.G. , Zacharowski K. , Bornstein S.R.
Published: April 2017

The body’s ability to keep a steady homeostatic state is crucial to health and life. This involves providing an adequate response to a variety of challenges both physical and mental, such as microbial invasion and emotional distress. Interplay between the neuroendocrine and immune systems is essential in either case. Studies have demonstrated that toll-like receptors, or TLRs, play a regulatory role in both systems, and have been proposed as a possible link between the immune, hormonal and metabolic systems. As part of the innate immune system, these receptors control the identification by the body of microbial invaders and its immediate reaction in immune and inflammatory response. What are referred to as pattern recognition receptors are mostly expressed by cells involved in hematopoietic linkage, but an increasing number of studies have demonstrated their expression in other cell types such as neurons and endocrine cells on the hypothalamic-pituitary-adrenal (HPA) axis, thyrocytes, adipocytes and islets of Langerhans. Together with endocrine and metabolic dysregulation, immune system overreaction is often associated with infection and autoimmunity, clearly indicating TLR involvement at organ level which affects organ function. Several diseases such as autoimmune thyroid and pancreatic diseases, septic dysregulation of the HPA axis, diabetes and the metabolic syndrome have been linked to TLR activation and polymorphism. To gain insight into stress response and adaptation, we need to know more about TLRs and the specific physiological role they play in the endocrine and metabolic system and its processes.
Increased Serum Levels of Inflammatory Markers in Chronic Institutionalized Patients with Schizophrenia
Authors: Coelho Fernanda Matos , Reis Helton José , Nicolato Rodrigo , Romano-Silva Marco Aurélio , Teixeira Mauro Martins , Bauer Moisés Evandro , Teixeira Antonio Lucio
Published: April 2017

Activation of the cytokine systems may be involved in the neuropathological changes occurring in the central nervous systems of schizophrenic patients. However, associations between the levels of cytokines and the severity of symptoms have not been completely established. Objective: It was the aim of this study to evaluate serum levels of tumor necrosis factor (TNF)-α and their soluble receptors (sTNFR) in schizophrenic patients and healthy controls. Methods: Forty male institutionalized schizophrenic patients (mean age ± SD, 52.3 ± 9.9 years) and 20 asymptomatic matched controls were recruited. The severity of symptoms was assessed using the Brief Psychiatric Rating Scale, the Positive and Negative Syndrome Scale and the Abnormal Involuntary Movement Scale. Serum levels of cytokines were measured by ELISAs. Results: Serum levels of sTNFR1 and sTNFR2 were increased in schizophrenic patients when compared with controls (all p < 0.05), but there was no difference in TNF-α levels. There was no correlation between the length of disease/hospitalization or the severity of symptoms and the serum levels of these molecules. Conclusion: Inflammatory markers are increased in schizophrenia but they do not correlate with symptom severity.
Temporary Unilateral Neurogenic Blepharoptosis after Orbital Medial Wall Reconstruction: 3 Cases
Authors: Jung Jee Woong , Chi Mi Jung
Published: April 2017

Purpose: We report 3 cases of unilateral blepharoptosis after orbital medial wall reconstruction and describe the cause and clinical outcome. Methods: Observational case series. Results: Three previously healthy patients underwent reconstruction for orbital medial wall fracture. All 3 patients had complete unilateral upper eyelid ptosis with no levator palpebrae superioris muscle function immediately after their recovery from anesthesia. Additional findings included minimal eyelid ecchymosis, eyelid edema and subconjunctival hemorrhage, which all presented preoperatively. All 3 patients had full conjugated ocular motility in the entire field of gaze and no anisocoria. With oral steroid therapy, all 3 patients recovered completely with normal symmetric lid height and levator function within 1 month. Conclusion: Isolated neurogenic blepharoptosis after medial orbital wall reconstruction is a rare but favorable disease that may result from ischemic damage at the end portion of the superior branch of the oculomotor nerve in the orbit. High-dose steroid therapy early in the course of the disease was effective, and complete resolution was achieved within 1 month.
Amino Acid Substitutions in Glycoprotein D Mediate the Ability of ‘Fusion from Without’-Positive Herpes Simplex Virus Type 1 Strains to Penetrate at 4° and in the Presence of Soluble Glycoprotein D
Authors: Lingen M. , Seck T. , Dehoust U. , Weise K. , Falke D.
Published: April 2017

In former studies, we described herpes simplex virus type 1 (HSV-1) strains ANG, ANG path and HSZP as strains with special fusion activities, caused by mutations in the syn 3 locus. In this report, we describe the special penetration properties of these strains: their ability to penetrate at 4° and to overcome the infection block caused by soluble glycoprotein D-1 (gD-1) in the medium. Using intertypic recombinants of HSV-1 strains ANG path and KOS, we showed that these penetration properties are the result of two mutations in amino acids 25 (Leu-Pro) and 27 (Gln-Arg) in the N-terminal part of the mature gD-1 glycoprotein.
Prolonged-Release Nicotinic Acid in Patients with Atherosclerotic Disease in The Netherlands
Authors: Poldermans D. , Dunkelgrun M. , Schouten O. , Hostalek U.
Published: April 2017

Objectives: High-density lipoprotein (HDL) cholesterol elevation is associated with an improved outcome in patients with atherosclerotic disease. Niaspan®, a prolonged-release nicotinic acid, was evaluated during the Niaspan-Induced HDL Elevation for Optimizing Risk Control (NEMO) study in The Netherlands. Methods: NEMO was a 6-month, prospective, observational, multicentre, open-label study. Niaspan was prescribed in statin-treated patients with known or suspected atherosclerotic disease. The main outcome measures were treatment-related adverse drug reactions (ADRs) and effects on lipids and cardiovascular-risk score based on the algorithm derived from the Prospective Cardiovascular Münster study. Results: 612 patients were included in The Netherlands. Flushing was the most common ADR (29% of patients during the first month of treatment). The main reasons for treatment discontinuation were flushing (10.5%), patient request (8.0%) and being lost to follow-up (6.0%). About half of all patients (52%) continued treatment after the study. Tolerability was rated ‘good’ or ‘very good’ in 54% of these patients. HDL cholesterol increased by 23% from baseline, and triglycerides were reduced by 16%, with little change in low-density lipoprotein or total cholesterol. Cardiovascular risk score was reduced by 3.3 points. Conclusions: The use of the prolonged-release nicotinic acid Niaspan in patients with or at risk for atherosclerotic disease showed good tolerability, a marked increase in HDL cholesterol and a reduced cardiovascular risk score.
Quality of Life following Colorectal Cancer Surgery: The Role of Alexithymia
Authors: Ripetti V. , Ausania F. , Bruni R. , Campoli G. , Coppola R.
Published: April 2017

Background: Alexithymia refers to a set of cognitive and emotional deficits. Its effect on surgical outcome has been demonstrated but no studies have been published on colorectal cancer patients. Study Design: A series of 60 consecutive colorectal cancer patients were enrolled in a 3-year prospective study on quality of life by using the SF-36 test and Toronto Alexithymia Scale questionnaires. Patients were investigated pre- and postoperatively (before discharge and then 1 and 3 months thereafter). The control group consisted of patients undergoing laparoscopic cholecystectomy for cholelithiasis. These two groups were divided into two subsets: high-level alexithymia (HA) and low-level alexithymia (LA). The prevalence of HA was 34% in colorectal patients and 35% in cholelithiasis patients. Results: During the postoperative period, in the colorectal group the SF-36 score was significantly higher in HA than in LA subsets. This result was confirmed in the cholelithiasis group. During follow-up, a progressive reduction of the SF-36 score was observed in both HA populations. Discussion: Results emerging from this investigation demonstrate that surgery significantly improves the quality of life in HA patients. These findings suggest that alexithymia might be advantageous in evaluating the adaptation after surgery in the short follow-up period.
Foraging and Ranging Patterns in White-Bellied Spider Monkeys
Authors: Nunes A.
Published: April 2017

Ranging and foraging patterns observed during a field study of the behavioral ecology of Ateles belzebuth belzebuth are analysed in the context of temporal and spatial variation in the distribution of plant resources at the study site. The study group exhibited two basic patterns of foraging behaviour and habitat exploitation, which appeared to correlate with the observed variation in resource availability. During the dry season, when the relative abundance of fruit decreased, the spider monkeys ranged over a smaller area, repeatedly visiting a few intensively used fruiting and sleeping trees. As fruit abundance increased during the course of the wet season, the study group expanded its range, and both the daily path length and the number of fruiting trees visited increased daily. These patterns are analysed and evaluated in relation to foraging strategies.