bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting a Nation’s Olympic-Qualifying Swimmers
Authors: Allen Sian V. , Vandenbogaerde Tom J. , Pyne David B. , Hopkins Will G.
Published: October 2014

Talent identification and development typically involve allocation of resources toward athletes selected on the basis of early-career performance.

Purpose:

To compare 4 methods for early-career selection of Australia’s 2012 Olympic-qualifying swimmers.

Methods:

Performance times from 5738 Australian swimmers in individual Olympic events at 101 competitions from 2000 to 2012 were analyzed as percentages of world-record times using 4 methods that retrospectively simulated early selection of swimmers into a talent-development squad. For all methods, squad-selection thresholds were set to include 90% of Olympic qualifiers. One method used each swimmer’s given-year performance for selection, while the others predicted each swimmer’s 2012 performance. The predictive methods were regression and neural-network modeling using given-year performance and age and quadratic trajectories derived using mixed modeling of each swimmer’s annual best career performances up to the given year. All methods were applied to swimmers in 2007 and repeated for each subsequent year through 2011.

Results:

The regression model produced squad sizes of 562, 552, 188, 140, and 93 for the years 2007 through 2011. Corresponding proportions of the squads consisting of Olympic qualifiers were 11%, 11%, 32%, 43%, and 66%. Neural-network modeling produced similar outcomes, but the other methods were less effective. Swimming Australia’s actual squads ranged from 91 to 67 swimmers but included only 50−74% of Olympic qualifiers.

Conclusions:

Large talent-development squads are required to include most eventual Olympic qualifiers. Criteria additional to age and performance are needed to improve early selection of swimmers to talent-development squads.
What Are Athletes' Perceptions of Rehabilitation Outcome 1 Year After Hip Arthroscopy?
Authors: Carter Danielle Lovett , Kennedy Norelee
Published: October 2014

Background:

Hip arthroscopy is a minimally invasive surgical procedure. Femoroacetabular impingement (FAI) is being increasingly recognized as a cause of hip pain in athletes and is a growing indication for arthroscopic surgery. Few studies have attempted to address patient views on outcome after arthroscopy, and no qualitative studies have been carried out to date.

Objectives:

To explore athletes' perceptions of rehabilitation outcome, the rehabilitative process, and return to sport and to gain insight into factors that affected this process.

Methodology:

A retrospective qualitative approach was adopted using semistructured interviews. Eight eligible participants were interviewed. Each had been treated with hip arthroscopy for FAI from September to November 2010. Data were audiotaped, transcribed verbatim, and analyzed using thematic analysis.

Results:

Three main themes emerged. (1) The ability to participate in sport; athletes were relatively satisfied with outcome despite some limitations in sporting ability. (2) Perceptions of hip problems; there was a lack of understanding and an association of hip problems with older people among the general public. (3) Athletes' perception of rehabilitation; athletes were dissatisfied with the rehabilitation and sought greater physiotherapy input.

Conclusions:

Overall, athletes were relatively satisfied with their outcome 1 y after hip arthroscopy, despite some having to adapt their sporting activities. Key areas that need to be addressed in future research include factors affecting outcomes of hip arthroscopy, longer-term outcomes, perception of FAI among the public and health practitioners, and the development of a standardized evidence-based rehabilitation protocol.
Characterization of an in vivo concentration-effect relationship for piperaquine in malaria chemoprevention
Authors: Bergstrand Martin , Nosten François , Lwin Khin Maung , Karlsson Mats O. , White Nicholas J. , Tarning Joel
Published: October 2014

An in vivo concentration-effect relationship for the malaria drug piperaquine can be used for translational simulations of expected therapeutic outcomes in vulnerable populations.
Affinity-based design of a synthetic universal reversal agent for heparin anticoagulants
Authors: Shenoi Rajesh A. , Kalathottukaren Manu Thomas , Travers Richard J. , Lai Benjamin F. L. , Creagh A. Louise , Lange Dirk , Yu Kai , Weinhart Marie , Chew Ben H. , Du Caigan , Brooks Donald E. , Carter Cedric J. , Morrissey James H. , Haynes Charles A. , Kizhakkedathu Jayachandran N.
Published: October 2014

A safe, synthetic anticoagulant-reversal agent based on a dendritic polymer is effective against all the clinical heparin anticoagulants and may be a treatment for bleeding in high-risk surgical procedures.
Pilicide ec240 Disrupts Virulence Circuits in Uropathogenic Escherichia coli
Authors: Greene Sarah E. , Pinkner Jerome S. , Chorell Erik , Dodson Karen W. , Shaffer Carrie L. , Conover Matt S. , Livny Jonathan , Hadjifrangiskou Maria , Almqvist Fredrik , Hultgren Scott J.
Published: October 2014

Chaperone-usher pathway (CUP) pili are extracellular organelles produced by Gram-negative bacteria that mediate bacterial pathogenesis. Small-molecule inhibitors of CUP pili, termed pilicides, were rationally designed and shown to inhibit type 1 or P piliation. Here, we show that pilicide ec240 decreased the levels of type 1, P, and S piliation. Transcriptomic and proteomic analyses using the cystitis isolate UTI89 revealed that ec240 dysregulated CUP pili and decreased motility. Paradoxically, the transcript levels of P and S pilus genes were increased during growth in ec240, even though the level of P and S piliation decreased. In contrast, the most downregulated transcripts after growth in ec240 were from the type 1 pilus genes. Type 1 pilus expression is controlled by inversion of the
fimS
promoter element, which can oscillate between phase on and phase off orientations. ec240 induced the
fimS
phase off orientation, and this effect was necessary for the majority of ec240’s inhibition of type 1 piliation. ec240 increased levels of the transcriptional regulators SfaB and PapB, which were shown to induce the
fimS
promoter phase off orientation. Furthermore, the effect of ec240 on motility was abolished in the absence of the SfaB, PapB, SfaX, and PapX regulators. In contrast to the effects of ec240, deletion of the type 1 pilus operon led to increased S and P piliation and motility. Thus, ec240 dysregulated several uropathogenic
Escherichia coli
(UPEC) virulence factors through different mechanisms and independent of its effects on type 1 pilus biogenesis and may have potential as an antivirulence compound.

IMPORTANCE
CUP pili and flagella play active roles in the pathogenesis of a variety of Gram-negative bacterial infections, including urinary tract infections mediated by UPEC. These are extremely common infections that are often recurrent and increasingly caused by antibiotic-resistant organisms. Preventing piliation and motility through altered regulation and assembly of these important virulence factors could aid in the development of novel therapeutics. This study increases our understanding of the regulation of these virulence factors, providing new avenues by which to target their expression.
Drug-resistant pulmonary tuberculosis presenting as mass lesion
Authors: Chauhan Nishant Kumar , Mishra Mayank , Singh Shelly
Published: October 2014

A 33-year-old woman presented with a 1-month history of dry cough, fever, reduced appetite and weight loss. She had taken antitubercular therapy about a year prior with partial improvement in symptoms. At initial presentation, a plain chest X-ray followed by a contrast-enhanced chest CT scan was advised. The CT scan image was suggestive of a right upper lobe mass lesion. Since the patient had no sputum production, a diagnostic flexible bronchoscopy was performed. The bronchoalveolar lavage fluid analysis along with ultrasonography-guided lung biopsy was diagnostic of multidrug-resistant tuberculosis.
How does a combined preoperative and postoperative rehabilitation programme influence the outcome of ACL reconstruction 2 years after surgery? A comparison between patients in the Delaware-Oslo ACL Cohort and the Norwegian National Knee Ligament Registry
Authors: Grindem H , Granan L P , Risberg M A , Engebretsen L , Snyder-Mackler L , Eitzen I
Published: October 2014

Background

Preoperative knee function is associated with successful postoperative outcome after anterior cruciate ligament reconstruction (ACLR). However, there are few longer term studies of patients who underwent progressive preoperative and postoperative rehabilitation compared to usual care.

Objectives

To compare preoperative and 2 year postoperative patient-reported outcomes (PROs) in patients undergoing progressive preoperative and postoperative rehabilitation at a sports medicine clinic compared with usual care.

Methods

We included patients aged 16–40 years undergoing primary unilateral ACLR. The preoperative and 2 year postoperative Knee Injury and Osteoarthritis Outcome Score (KOOS) of 84 patients undergoing progressive preoperative and postoperative rehabilitation at a sports medicine clinic (Norwegian Research Center for Active Rehabilitation (NAR) cohort) were compared with the scores of 2690 patients from the Norwegian National Knee Ligament Registry (NKLR). The analyses were adjusted for sex, age, months from injury to surgery and cartilage/meniscus injury at ACLR.

Results

The NAR cohort had significantly better preoperative KOOS in all subscales, with clinically relevant differences (>10 points) observed in KOOS Pain, activities of daily living (ADL), Sports and Quality of Life. At 2 years, the NAR cohort still had significantly better KOOS with clinically relevant differences in KOOS Symptoms, Sports and Quality of Life. At 2 years, 85.7–94% of the patients in the NAR cohort scored within the normative range of the different KOOS subscales, compared to 51.4–75.8% of the patients in the NKLR.

Conclusions

Patients in a prospective cohort who underwent progressive preoperative and postoperative rehabilitation at a sports medicine clinic showed superior patient-reported outcomes both preoperatively and 2 years postoperatively compared to patients in the NKLR who received usual care.
Does topical Amethocaine cream increase first-time successful cannulation in children compared with a eutectic mixture of local anaesthetics (EMLA) cream? A systematic review and meta-analysis of randomised controlled trials
Authors: Pywell Alison , Xyrichis Andreas
Published: October 2014

Background

Cannulation of children is often required for administration of intravenous fluids and medications, but can cause pain and anxiety. Amethocaine and a eutectic mixture of local anaesthetics (EMLA) cream are two of the most commonly used local anaesthetic creams.

Objective

To examine the evidence for the superiority of Amethocaine cream compared with EMLA cream in facilitating successful first-time cannulation in children.

Method

A systematic search was undertaken in MEDLINE and EMBASE in June 2014. Studies examining cannulation, undertaken with children and providing data about first-time cannulation success rates were considered for inclusion. Three randomised controlled trials met the inclusion criteria and were included in the meta-analysis. Data extraction was undertaken independently by the two authors using predefined data fields.

Results

Pooled analysis was based on a random effects model. Low statistical heterogeneity was observed. Amethocaine cream increased the likelihood of successful first-time cannulation (RR 1.046, CI 0.975 to 1.122), although this did not reach statistical significance (p=0.211).

Conclusions

Amethocaine cream does not appear to significantly facilitate successful first-time cannulation. Lack of precision and design weaknesses of the included studies hinder the formation of a strong recommendation for either cream.

Implications

Based on the evidence reviewed here and considering analgesic properties and cost-savings associated with both creams, a weak recommendation can be issued in favour of Amethocaine cream for cannulation in children based on high-quality evidence but where the treatment choice will depend on other factors including cost and provider preference.
Gamification as a tool for enhancing graduate medical education
Authors: Nevin Christa R , Westfall Andrew O , Rodriguez J Martin , Dempsey Donald M , Cherrington Andrea , Roy Brita , Patel Mukesh , Willig James H
Published: October 2014

Introduction

The last decade has seen many changes in graduate medical education training in the USA, most notably the implementation of duty hour standards for residents by the Accreditation Council of Graduate Medical Education. As educators are left to balance more limited time available between patient care and resident education, new methods to augment traditional graduate medical education are needed.

Objectives

To assess acceptance and use of a novel gamification-based medical knowledge software among internal medicine residents and to determine retention of information presented to participants by this medical knowledge software.

Methods

We designed and developed software using principles of gamification to deliver a web-based medical knowledge competition among internal medicine residents at the University of Alabama (UA) at Birmingham and UA at Huntsville in 2012–2013. Residents participated individually and in teams. Participants accessed daily questions and tracked their online leaderboard competition scores through any internet-enabled device. We completed focus groups to assess participant acceptance and analysed software use, retention of knowledge and factors associated with loss of participants (attrition).

Results

Acceptance: In focus groups, residents (n=17) reported leaderboards were the most important motivator of participation. Use: 16 427 questions were completed: 28.8% on Saturdays/Sundays, 53.1% between 17:00 and 08:00. Retention of knowledge: 1046 paired responses (for repeated questions) were collected. Correct responses increased by 11.9% (p<0.0001) on retest. Differences per time since question introduction, trainee level and style of play were observed. Attrition: In ordinal regression analyses, completing more questions (0.80 per 10% increase; 0.70 to 0.93) decreased, while postgraduate year 3 class (4.25; 1.44 to 12.55) and non-daily play (4.51; 1.50 to 13.58) increased odds of attrition.

Conclusions

Our software-enabled, gamification-based educational intervention was well accepted among our millennial learners. Coupling software with gamification and analysis of trainee use and engagement data can be used to develop strategies to augment learning in time-constrained educational settings.
Optimal one-parameter observables for the Abelian Z′ in e+e-→μ+μ-process
Authors: Gulov Alexey
Published: October 2014

To detect off-shell Abelian Z′ boson in e+e-→μ+μ-, we propose one-parameter observables with the best value-to-uncertainty ratio. The observables are constructed by angular integration of the differential cross-section with smooth weight functions. The value-to-uncertainty ratio is used as a criterion to select the unique weight function leading to the observable with the best statistical power for data analysis. The observables allow to select either vector or axial-vector Z′ couplings to leptons. The obtained observable can be useful in future experiments at lepton colliders such as the ILC.
Cognitive State Estimation by Effective Feature Extraction and Proper Channel Selection of EEG Signal
Authors: Islam Monira , Ahmed Tazrin , Yusuf Md. Salah Uddin , Ahmad Mohiuddin
Published: October 2014

This paper presents a cognitive state estimation system focused on some effective feature extraction based on temporal and spectral analysis of electroencephalogram (EEG) signal and the proper channel selection of the BIOPAC automated EEG analysis system. In the proposed approach, different frequency components (i) real value; (ii) imaginary value; (iii) magnitude; (iv) phase angle and (v) power spectral density of the EEG data samples during different mental task performed to assess seven types of human cognitive states — relax, mental task, memory related task, motor action, pleasant, fear and enjoying music on the three channels of BIOPAC EEG data acquisition system — EEG, Alpha and Alpha RMS signal. Also the time and time-frequency-based features were extracted to compare the performance of the system. After feature extraction, the channel efficacy is evaluated by support vector machine (SVM) based on the classification rate in different cognitive states. From the experimental results and classification accuracy, it is determined that the overall accuracy for alpha channel shows much improved result for power spectral density than the other frequency based features and other channels. The classification rate is 69.17% for alpha channel whereas for EEG and alpha RMS channel it is found 47.22% and 32.21%, respectively. For statistical analysis standard deviation shows better result for alpha channel and it is found 65.4%. The time-frequency analysis shows much improved result for alpha channel also. For the mean value of DWT coefficients the accuracy is highest and it is 81.3%. Besides the classification accuracy, SVM shows better performance in compare with kNN classifier.
On effective 9-colorings for knots
Authors: Nakamura Takuji , Nakanishi Yasutaka , Satoh Shin
Published: October 2014

For a 1- or 2-dimensional knot, we give a lower bound log 2 n + 1 of the minimum number of distinct colors for all effective n-colorings. In particular, we prove that any effectively 9-colorable 1- or ribbon 2-knot is presented by a diagram where exactly five colors of nine are assigned to the arcs or sheets.
Can a variable gravitational constant resolve the faint young Sun paradox?
Authors: Sahni Varun , Shtanov Yuri
Published: October 2014

Solar models suggest that four billion years ago the young Sun was ~25% fainter than it is today, rendering Earth's oceans frozen and lifeless. However, there is ample geophysical evidence that Earth had a liquid ocean teeming with life 4 Gyr ago. Since [Formula: see text], the Sun's luminosity [Formula: see text] is exceedingly sensitive to small changes in the gravitational constant G. We show that a percent-level increase in G in the past would have prevented Earth's oceans from freezing, resolving the faint young Sun paradox. Such small changes in G are consistent with observational bounds on ΔG/G. Since [Formula: see text], an increase in G leads to fainter supernovae, creating tension between standard candle and standard ruler probes of dark energy. Precisely such a tension has recently been reported by the Planck team.
Remark on nondegeneracy of simple abelian varieties with many endomorphisms
Authors: Sugiyama Rin
Published: October 2014

We investigate a relationship between nondegeneracy of a simple abelian variety A over an algebraic closure of ℚ and of its reduction A0. We prove that under some assumptions, nondegeneracy of A implies nondegeneracy of A0.
A Widening Approach to Multithreaded Program Verification
Authors: Kaiser Alexander , Kroening Daniel , Wahl Thomas
Published: October 2014

Pthread-style multithreaded programs feature rich thread communication mechanisms, such as shared variables, signals, and broadcasts. In this article, we consider the automated verification of such programs where an unknown number of threads execute a given finite-data procedure in parallel. Such procedures are typically obtained as predicate abstractions of recursion-free source code written in C or Java. Many safety problems over finite-data replicated multithreaded programs are decidable via a reduction to the
coverability problem
in certain types of well-ordered infinite-state transition systems. On the other hand, in full generality, this problem is Ackermann-hard, which seems to rule out efficient algorithmic treatment.

We present a novel, sound, and complete yet empirically efficient solution. Our approach is to judiciously
widen
the original set of coverability targets by configurations that involve fewer threads and are thus easier to decide, and whose exploration may well be sufficient: if they turn out uncoverable, so are the original targets. To soften the impact of “bad guesses”—configurations that turn out coverable—the exploration is accompanied by a parallel engine that generates coverable configurations; none of these is ever selected for widening. Its job being merely to prevent bad widening choices, such an engine need not be complete for coverability analysis, which enables a range of existing partial (e.g., nonterminating) techniques. We present extensive experiments on multithreaded C programs, including device driver code from FreeBSD, Solaris, and Linux distributions. Our approach outperforms existing coverability methods by orders of magnitude.
Magnitude of daily energy deficit predicts frequency but not severity of menstrual disturbances associated with exercise and caloric restriction
Authors: Williams Nancy I. , Leidy Heather J. , Hill Brenna R. , Lieberman Jay L. , Legro Richard S. , Souza Mary Jane De
Published: October 2014

We assessed the impact of energy deficiency on menstrual function using controlled feeding and supervised exercise over four menstrual cycles (1 baseline and 3 intervention cycles) in untrained, eumenorrheic women aged 18–30 yr. Subjects were randomized to either an exercising control (EXCON) or one of three exercising energy deficit (ED) groups, i.e., mild (ED1; −8 ± 2%), moderate (ED2; −22 ± 3%), or severe (ED3; −42 ± 3%). Menstrual cycle length and changes in urinary concentrations of estrone-1-glucuronide, pregnanediol glucuronide, and midcycle luteinizing hormone were assessed. Thirty-four subjects completed the study. Weight loss occurred in ED1 (−3.8 ± 0.2 kg), ED2 (−2.8 ± 0.6 kg), and ED3 (−2.6 ± 1.1 kg) but was minimal in EXCON (−0.9 ± 0.7 kg). The overall sum of disturbances (luteal phase defects, anovulation, and oligomenorrhea) was greater in ED2 compared with EXCON and greater in ED3 compared with EXCON AND ED1. The average percent energy deficit was the main predictor of the frequency of menstrual disturbances (f = 10.1, β = −0.48, r2 = 0.23, P = 0.003) even when weight loss was included in the model. The estimates of the magnitude of energy deficiency associated with menstrual disturbances ranged from −22 (ED2) to −42% (ED3), reflecting an energy deficit of −470 to −810 kcal/day, respectively. This is the first study to demonstrate a dose-response relationship between the magnitude of energy deficiency and the frequency of exercise-related menstrual disturbances; however, the severity of menstrual disturbances was not dependent on the magnitude of energy deficiency.
Alteration in rectification of potassium channels in perinatal hypoxia ischemia brain damage
Authors: Chen Penghui , Wang Liyan , Deng Qiyue , Ruan Huaizhen , Cai Wenqin
Published: October 2014

Oligodendrocyte progenitor cells (OPCs) are susceptible to perinatal hypoxia ischemia brain damage (HIBD), which results in infant cerebral palsy due to the effects on myelination. The origin of OPC vulnerability in HIBD, however, remains controversial. In this study, we defined the HIBD punctate lesions by MRI diffuse excessive high signal intensity (DEHSI) in postnatal 7-day-old rats. The electrophysiological functional properties of OPCs in HIBD were recorded by patch-clamp in acute cerebral cortex slices. The slices were intracellularly injected with Lucifer yellow and immunohistochemically labeled with NG2 antibody to identify local OPCs. Passive membrane properties and K+ channel functions in OPCs were analyzed to estimate the onset of vulnerability in HIBD. The resting membrane potential, membrane resistance, and membrane capacitance of OPCs were increased in both the gray and white matter of the cerebral cortex. OPCs in both the gray and white matter exhibited voltage-dependent K+ currents, which consisted of the initiated rectified potassium currents ( IA) and the sustained rectified currents ( IK). The significant alternation in membrane resistance was influenced by the diversity of potassium channel kinetics. These findings suggest that the rectification of IA and IK channels may play a significant role in OPC vulnerability in HIBD.
Lipolytic Potential ofAspergillus japonicusLAB01: Production, Partial Purification, and Characterisation of an Extracellular Lipase
Authors: Souza Lívia Tereza Andrade , Oliveira Jamil S. , dos Santos Vera L. , Regis Wiliam C. B. , Santoro Marcelo M. , Resende Rodrigo R.
Published: October 2014

Lipolytic potential ofAspergillus japonicusLAB01 was investigated by describing the catalytic properties and stability of a secreted extracellular lipase. Enzyme production was considered high under room temperature after 4 days using sunflower oil and a combination of casein with sodium nitrate. Lipase was partially purified by 3.9-fold, resulting in a 44.2% yield using ammonium sulphate precipitation (60%) quantified with Superose 12 HR gel filtration chromatography. The activity of the enzyme was maximised at pH 8.5, and the enzyme demonstrated stability under alkaline conditions. The optimum temperature was found to be 45°C, and the enzyme was stable for up to 100 minutes, with more than 80% of initial activity remaining after incubation at this temperature. Partially purified enzyme showed reasonable stability with triton X-100 and was activated in the presence of organic solvents (toluene, hexane, and methanol). Among the tested ions, only Cu2+, Ni2+, and Al3+showed inhibitory effects. Substrate specificity of the lipase was higher for C14 among various p-nitrophenyl esters assayed. TheKMandVmaxvalues of the purified enzyme for p-nitrophenyl palmitate were 0.13 mM and 12.58 umol/(L·min), respectively. These features render a novel biocatalyst for industrial applications.
The Unfolded Protein Response and Diabetic Retinopathy
Authors: Ma Jacey Hongjie , Wang Josh J. , Zhang Sarah X.
Published: October 2014

Diabetic retinopathy, a common complication of diabetes, is the leading cause of blindness in adults. Diabetes chronically damages retinal blood vessels and neurons likely through multiple pathogenic pathways such as oxidative stress, inflammation, and endoplasmic reticulum (ER) stress. To relieve ER stress, the cell activates an adaptive mechanism known as the unfolded protein response (UPR). The UPR coordinates the processes of protein synthesis, protein folding, and degradation to ensure proteostasis, which is vital for cell survival and activity. Emerging evidence suggests that diabetes can activate all three UPR branches in retinal cells, among which the PERK/ATF4 pathway is the most extensively studied in the development of diabetic retinopathy. X-box binding protein 1 (XBP1) is a major transcription factor in the core UPR pathway and also regulates a variety of genes involved in cellular metabolism, redox state, autophagy, inflammation, cell survival, and vascular function. The exact function and implication of XBP1 in the pathogenesis of diabetic retinopathy remain elusive. Focusing on this less studied pathway, we summarize recent progress in studies of the UPR pertaining to diabetic changes in retinal vasculature and neurons, highlighting the perspective of XBP1 as a potential therapeutic target in diabetic retinopathy.
The Effect of IL-4 Gene Polymorphisms on Cytokine Production in Patients with Chronic Periodontitis and in Healthy Controls
Authors: Bartova Jirina , Borilova Linhartova Petra , Podzimek Stepan , Janatova Tatjana , Svobodova Kazi , Fassmann Antonin , Duskova Jana , Belacek Jaromir , Izakovicova Holla Lydie
Published: October 2014

Chronic periodontitis (CP) is an inflammatory disease of the teeth-supporting tissues in which genetic predisposition, dental plaque bacteria, and immune mechanisms all play important roles. The aim of this study was to evaluate the occurrence of IL-4 gene polymorphisms in chronic periodontitis and to investigate the association between polymorphisms and cytokines production after bacterial stimulation. Sixty-two subjects (47 CP patients and 15 healthy controls) with detected two polymorphisms in the IL-4 gene (-590C/T and intron 3 VNTR) were examined. Production of cytokines (IL-1α, IL-1β, IL-4, IL-5, IL-6, IL-10, IL-17, TNFα, INFγ, and VEGF) was studied afterin vitrostimulation of isolated peripheral blood by mitogens (Pokeweed mitogen, Concanavalin A), dental plaque bacteria (Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Porphyromonas gingivalis, and Prevotella intermedia), and Heat Shock Protein (HSP) 70 by the Luminexmultiplex cytokine analysissystem. The results were correlated with IL-4 genotypes in patients with CP and healthy controls. The mononuclear cells isolated from peripheral blood of CP patients with selected IL-4 polymorphisms significantly altered the production of IFNγ, IL-10, IL-1β, IL-1α, TNFα, and IL-6 after stimulation by HSP 70 or selected bacteria (fromP<0.001toP<0.05). IL-4 gene polymorphisms may influence the function of mononuclear cells to produce not only interleukin-4 but also other cytokines, especially in patients with CP.
Reduction of the In-Band RCS of Microstrip Patch Antenna by Using Offset Feeding Technique
Authors: Xu Weiwei , Wang Junhong , Chen Meie , Zhang Zhan , Li Zheng
Published: October 2014

This paper presents a method for implementing a low in-band scattering design for microstrip patch antennas based on the analysis of structural mode scattering and radiation characteristics. The antenna structure is first designed to have the lowest structural mode scattering in a desired frequency band. The operating frequency band of the antenna is then changed to coincide with that of the lowest structural mode scattering by adjusting the feed position on the antenna (offset feeding) to achieve an antenna with low in-band radar cross section (RCS). In order to reduce the level of cross polarization of the antenna caused by offset feeding, symmetry feeding structures for both single patch antennas and two-patch arrays are proposed. Examples that show the efficiency of the method are given, and the results illustrate that the in-band RCS of the proposed antennas can be reduced by as much as 17 dBsm for plane waves impinging from the normal direction compared to patch antennas fed by conventional methods.
Hepatitis B Infection Awareness among Dental Graduate Students: A Cross Sectional Study
Authors: Mahesh Ramakrishnan , Arthi Chandran , Victor Samuel , Ashokkumar Seiramineni
Published: October 2014

Hepatitis B virus transmission in a dental setting more commonly occurs due to inadequate/improper use of safety measures by the dentist. This particular study evaluated the hepatitis B virus infection related awareness among dental graduate students in a University Dental College, India. A validated questionnaire regarding the awareness about hepatitis infection and various infection control measures was distributed among the students of different year of study in undergraduate bachelor dental graduate program. The data extracted were tabulated and analyzed. Final year students showed an increased awareness when compared to third year students. There is need for improving the knowledge among the nonclinical students, mainly on transmission of virus through salivary contact. The overall awareness among the students is only fairly satisfying, which signifies the need for continued infection control education among the students.
Gradient Learning Algorithms for Ontology Computing
Authors: Gao Wei , Zhu Linli
Published: October 2014

The gradient learning model has been raising great attention in view of its promising perspectives for applications in statistics, data dimensionality reducing, and other specific fields. In this paper, we raise a new gradient learning model for ontology similarity measuring and ontology mapping in multidividing setting. The sample error in this setting is given by virtue of the hypothesis space and the trick of ontology dividing operator. Finally, two experiments presented on plant and humanoid robotics field verify the efficiency of the new computation model for ontology similarity measure and ontology mapping applications in multidividing setting.
Determination of Catechin and Epicatechin Content in Chocolates by High-Performance Liquid Chromatography
Authors: Gottumukkala Raju V. S. S. , Nadimpalli Nareshraju , Sukala Kannababu , Subbaraju Gottumukkala V.
Published: October 2014

A simple and sensitive reversed phase high-performance liquid chromatographic (HPLC) method has been developed for the determination of catechin and epicatechin in cocoa powder and chocolates. The separation was achieved on a reversed phase C 18 column (TARGA) 5 μm by gradient elution with a flow rate of 1.0 mL/minute with an operating temperature of 30°C and detection with a UV-Visible detector was at 280 nm. The method was validated for linearity, precision, intra- and interday precision, and accuracy. The developed method is successfully applied for the determination of catechin and epicatechin content in chocolates. The Godiva brand chocolate contains high concentration of epicatechin.
MAP2K1 (MEK1) Mutations Define a Distinct Subset of Lung Adenocarcinoma Associated with Smoking
Authors: Arcila Maria E. , Drilon Alexander , Sylvester Brooke E. , Lovly Christine M. , Borsu Laetitia , Reva Boris , Kris Mark G. , Solit David B. , Ladanyi Marc
Published: October 2014

Purpose: Genetic alterations affecting the MAPK/ERK pathway are common in lung adenocarcinoma (LAD). Early steps of the signaling pathway are most often affected with EGFR, KRAS, and BRAF mutations encompassing more than 70% of all alterations. Somatic mutations in MEK1, located downstream of BRAF, are rare and remain poorly defined as a distinct molecular subset.

Experimental Design: Tumors harboring MEK1 mutations were identified through targeted screening of a large LAD cohort concurrently interrogated for recurrent mutations in MEK1, EGFR, KRAS, BRAF, ERBB2/HER2, NRAS, PIK3CA, and AKT. Additional cases were identified through a search of publically available cancer genomic datasets. Mutations were correlated with patient characteristics and treatment outcomes. Overall survival was compared with stage-matched patients with KRAS- and EGFR-mutant LADs.

Results: We identified 36 MEK1-mutated cases among 6,024 LAD (0.6%; 95% confidence interval, 0.42–0.85). The majority of patients were smokers (97%, n = 35/36). There was no association with age, sex, race, or stage. The most common mutations were K57N (64%, 23/36) followed by Q56P (19%, 7/36), all mutually exclusive with other driver mutations in the targeted panel. Transversions G:C>T:A were predominant (89%, 31/35), in keeping with smoking-associated DNA damage. Additional less common somatic mutations were identified in the kinase domain, all of which are predicted to converge into a single interaction area based on in silico 3D modeling.

Conclusions: MEK1 mutations define a distinct subset of lung cancers (∼1%) with potential sensitivity to MEK inhibitors. Mutations are predominantly transversions, in keeping with a strong association with smoking. Clin Cancer Res; 21(8); 1935–43. ©2014 AACR.
The NOTCH Ligand JAGGED2 Promotes Pancreatic Cancer Metastasis Independent of NOTCH Signaling Activation
Authors: Hu Yufeng , Su Hexiu , Li Xu , Guo Guoli , Cheng Ling , Qin Renyi , Qing Guoliang , Liu Hudan
Published: October 2014

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal disease with a high rate of metastasis. Numerous signaling events have been implicated in the molecular pathogenesis of this neoplasm. Aberrantly high expression of JAGGED2, one of the NOTCH ligands, often occurs in human PDAC. However, what role JAGGED2 plays in the disease development and whether JAGGED2 executes its function through activating NOTCH signaling remain to be determined. We report here that JAGGED2 plays a critical role in promoting PDAC metastasis in vitro and in vivo. Depletion of JAGGED2, but not its homolog JAGGED1, profoundly inhibited both migration and invasion without influencing cell proliferation. Furthermore, reconstitution of JAGGED2 expression rescued the migratory defect. Surprisingly, neither pharmacologic nor genetic inhibition of NOTCH downstream signaling resulted in obvious defect in metastasis. Instead, depletion of NOTCH1 expression per se gave rise to migratory defects similar to JAGGED2 ablation. Moreover, blockade of ligand–receptor interaction by a specific JAGGED2-Fc fusion protein dramatically inhibited PDAC cell migration, suggesting that tumor metastasis relies on physical interactions of JAGGED2-NOTCH1 but not Notch downstream signaling activation. Taken together, our data reveal a novel role of NOTCH in regulation of PDAC metastasis, and identify JAGGED2 as a critical mediator in this event. These findings also provide rationale for developing small molecules or biologic agents targeting JAGGED2 for therapeutic intervention. Mol Cancer Ther; 14(1); 289–97. ©2014 AACR.
Anticancer Activity of a Novel Selective CYP17A1 Inhibitor in Preclinical Models of Castrate-Resistant Prostate Cancer
Authors: Toren Paul J. , Kim Soojin , Pham Steven , Mangalji Azzra , Adomat Hans , Guns Emma S. Tomlinson , Zoubeidi Amina , Moore William , Gleave Martin E.
Published: October 2014

VT-464 is a novel, nonsteroidal, small-molecule CYP17A1 inhibitor with 17,20-lyase selectivity. This study evaluates the anticancer activity of VT-464 compared with abiraterone (ABI) in castrate-resistant prostate cancer cell lines and xenograft models that are enzalutamide (ENZ)-responsive (C4-2) or ENZ-resistant (MR49C, MR49F). In vitro, androgen receptor (AR) transactivation was assessed by probasin luciferase reporter, whereas AR and AR-regulated genes and steroidogenic pathway enzymes were assessed by Western blot and/or qRT-PCR. The MR49F xenograft model was used to compare effects of oral VT-464 treatment to vehicle and abiraterone acetate (AA). Steroid concentrations were measured using LC-MS chromatography. VT-464 demonstrated a greater decrease in AR transactivation compared with ABI in C4-2 and both ENZ-resistant cell lines. At the gene and protein level, VT-464 suppressed the AR axis to a greater extent compared with ABI. Gene transcripts StAR, CYP17A1, HSD17B3, and SRD5A1 increased following treatment with ABI and to a greater extent with VT-464. In vivo, intratumoral androgen levels were significantly lower after VT-464 or AA treatment compared with vehicle, with the greatest decrease seen with VT-464. Similarly, tumor growth inhibition and PSA decrease trends were greater with VT-464 than with AA. Finally, an AR-antagonist effect of VT-464 independent of CYP17A1 inhibition was observed using luciferase reporter assays, and a direct interaction was confirmed using an AR ligand binding domain biolayer interferometry. These preclinical results suggest greater suppression of the AR axis with VT-464 than ABI that is likely due to both superior selective suppression of androgen synthesis and AR antagonism. Mol Cancer Ther; 14(1); 59–69. ©2014 AACR.
Mast Cells Boost Myeloid-Derived Suppressor Cell Activity and Contribute to the Development of Tumor-Favoring Microenvironment
Authors: Danelli Luca , Frossi Barbara , Gri Giorgia , Mion Francesca , Guarnotta Carla , Bongiovanni Lucia , Tripodo Claudio , Mariuzzi Laura , Marzinotto Stefania , Rigoni Alice , Blank Ulrich , Colombo Mario P. , Pucillo Carlo E.
Published: October 2014

Inflammation plays crucial roles at different stages of tumor development and may lead to the failure of immune surveillance and immunotherapy. Myeloid-derived suppressor cells (MDSC) are one of the major components of the immune-suppressive network that favors tumor growth, and their interaction with mast cells is emerging as critical for the outcome of the tumor-associated immune response. Herein, we showed the occurrence of cell-to-cell interactions between MDSCs and mast cells in the mucosa of patients with colon carcinoma and in the colon and spleen of tumor-bearing mice. Furthermore, we demonstrated that the CT-26 colon cancer cells induced the accumulation of CD11b+Gr1+ immature MDSCs and the recruitment of protumoral mast cells at the tumor site. Using ex vivo analyses, we showed that mast cells have the ability to increase the suppressive properties of spleen-derived monocytic MDSCs, through a mechanism involving IFNγ and nitric oxide production. In addition, we demonstrated that the CD40:CD40L cross-talk between the two cell populations is responsible for the instauration of a proinflammatory microenvironment and for the increase in the production of mediators that can further support MDSC mobilization and tumor growth. In light of these results, interfering with the MDSC:mast cell axis could be a promising approach to abrogate MDSC-related immune suppression and to improve the antitumor immune response. Cancer Immunol Res; 3(1); 85–95. ©2014 AACR.
Congenital Malformations, Chromosomal Abnormalities and Perinatal Results in IVF/ICSI Newborns Resulting from Very Poor Quality Embryos: A Case-Control Study
Authors: Mendoza R. , Perez S. , de los Santos M.J. , Larreategui Z. , Ayerdi F. , Expósito A. , Burgos J. , Martínez Indart L. , Pijoan J.I. , Matorras R.
Published: October 2014

Aims: To explore whether the transfer of very poor quality (VPQ) embryos is associated with an increase in congenital malformations or perinatal problems. Methods: In this retrospective case-control study, 74 children conceived by in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) resulting exclusively from the transfer of VPQ embryos were compared with 1,507 children born after the transfer of top morphological quality (TQ) embryos over the same period of time in the same centers. Results: The prevalence of birth defects in children resulting from VPQ embryos was 1.35% (1/74), similar to the 1.72% (26/1,507) when only TQ embryos were transferred; the rate of chromosomal abnormalities detected was also similar (0.0 vs. 0.4%), as was perinatal mortality. After correcting for multiplicity (higher in the TQ group), the aforementioned parameters remained similar in the two groups. Conclusion: Congenital malformations and perinatal complications do not seem to be more common in children born after transfer of VPQ embryos in IVF/ICSI cycles. Given our preliminary data, which need to be confirmed in much larger studies, when only VPQ embryos are available for transfer in IVF/ICSI cycles, we do not believe that they should be discarded with the intention of avoiding birth defects or perinatal complications.
Model-Based and Model-Free Decisions in Alcohol Dependence
Authors: Sebold Miriam , Deserno Lorenz , Nebe Stefan , Schad Daniel J. , Garbusow Maria , Hägele Claudia , Keller Jürgen , Jünger Elisabeth , Kathmann Norbert , Smolka Michael , Rapp Michael A. , Schlagenhauf Florian , Heinz Andreas , Huys Quentin J.M.
Published: October 2014

Background: Human and animal work suggests a shift from goal-directed to habitual decision-making in addiction. However, the evidence for this in human alcohol dependence is as yet inconclusive. Methods: Twenty-six healthy controls and 26 recently detoxified alcohol-dependent patients underwent behavioral testing with a 2-step task designed to disentangle goal-directed and habitual response patterns. Results: Alcohol-dependent patients showed less evidence of goal-directed choices than healthy controls, particularly after losses. There was no difference in the strength of the habitual component. The group differences did not survive controlling for performance on the Digit Symbol Substitution Task. Conclusion: Chronic alcohol use appears to selectively impair goal-directed function, rather than promoting habitual responding. It appears to do so particularly after nonrewards, and this may be mediated by the effects of alcohol on more general cognitive functions subserved by the prefrontal cortex. © 2014 S. Karger AG, Basel
Integrating Diffusion Tensor Imaging-Based Tractography into Deep Brain Stimulation Surgery: A Review of the Literature
Authors: Torres Cristina V. , Manzanares Rafael , Sola Rafael G.
Published: October 2014

Background: It has been generally accepted that deep brain stimulation (DBS) not only acts in the nucleus where it is being applied, as initially thought, but that chronic stimulation activates axons located in its scope, and that this activation can exert its effects in distant areas. Considering this, DBS target identification should be made based on techniques that identify white matter tracts, such as tractography, rather than only by identifying specific nuclei on conventional magnetic resonance imaging. Methods: In this study, we performed a review of the literature on the use of tractography in DBS surgery and provide an overview of the main results. Results: Tractography has been used in the field of DBS to help clarify relevant aspects in the selection of targets and in evaluating its therapeutic effects in movement disorders, psychiatric diseases and pain. Conclusions: Studies are scarce so far, but they have provided data that, if confirmed, may optimize DBS surgery. Tractography might become a routine tool for DBS surgery in the near future.
Deep Brain Stimulation of the Thalamic Ventral Lateral Anterior Nucleus for DYT6 Dystonia
Authors: Mure Hideo , Morigaki Ryoma , Koizumi Hidetaka , Okita Shinya , Kawarai Toshitaka , Miyamoto Ryosuke , Kaji Ryuji , Nagahiro Shinji , Goto Satoshi
Published: October 2014

Background: A missense mutation of the THAP1 gene results in DYT6 primary dystonia. While deep brain stimulation (DBS) of the internal globus pallidus (GPi) is effective in treating primary dystonia, recent reports indicate that GPi DBS is only mildly effective for DYT6 dystonia. Objective: To describe a patient with DYT6 dystonia who underwent thalamic ventral lateral anterior (VLa) nucleus DBS. Patient: A 35-year-old Japanese man had been experiencing upper limb dystonia and spasmodic dysphonia since the age of 15. His dystonic symptoms progressed to generalized dystonia. He was diagnosed as having DYT6 dystonia with mutations in the THAP1 gene. Because his dystonic symptoms were refractory to pharmacotherapy and pallidal DBS, he underwent thalamic VLa DBS. Results: Continuous bilateral VLa stimulation with optimal parameter settings ameliorated the patient's dystonic symptoms. At the 2-year follow-up, his Burke-Fahn-Marsden Dystonia Rating Scale total score decreased from 71 to 11, an improvement of more than 80%. Conclusions: The thalamic VLa nucleus could serve as an alternative target in DBS therapy for DYT6 dystonia.
Psychopathology of the Bodily Self and the Brain: The Case of Schizophrenia
Authors: Gallese Vittorio , Ferri Francesca
Published: October 2014

In the present paper, we review the recent empirical evidence on the neurobiological basis of a minimal notion of the self, the bodily self. We show the relationship between the body, its motor potentialities and the notion of minimal self. We argue that this approach can shed new light onto self-disturbances and social deficits characterizing schizophrenia. We discuss our approach with other views on the neural correlates of self-disturbances in schizophrenia and propose that cognitive neuroscience can today address the classical topics of psychopathology by adding a new level of description, finally enabling the correlation between the first-person experiential aspects of psychiatric diseases and their neurobiological roots.