bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinct Residues Contribute to Motility Repression and Autoregulation in the Proteus mirabilis Fimbria-Associated Transcriptional Regulator AtfJ
Authors: Bode Nadine J. , Chan Kun-Wei , Kong Xiang-Peng , Pearson Melanie M.
Published: June 2016

Proteus mirabilis
contributes to a significant number of catheter-associated urinary tract infections, where coordinated regulation of adherence and motility is critical for ascending disease progression. Previously, the mannose-resistant
Proteus
-like (MR/P) fimbria-associated transcriptional regulator MrpJ has been shown to both repress motility and directly induce the transcription of its own operon; in addition, it affects the expression of a wide range of cellular processes. Interestingly, 14 additional
mrpJ
paralogs are included in the
P. mirabilis
genome. Looking at a selection of MrpJ paralogs, we discovered that these proteins, which consistently repress motility, also have nonidentical functions that include cross-regulation of fimbrial operons. A subset of paralogs, including AtfJ (encoded by the ambient temperature fimbrial operon), Fim8J, and MrpJ, are capable of autoinduction. We identified an element of the
atf
promoter extending from 487 to 655 nucleotides upstream of the transcriptional start site that is responsive to AtfJ, and we found that AtfJ directly binds this fragment. Mutational analysis of AtfJ revealed that its two identified functions, autoregulation and motility repression, are not invariably linked. Residues within the DNA-binding helix-turn-helix domain are required for motility repression but not necessarily autoregulation. Likewise, the C-terminal domain is dispensable for motility repression but is essential for autoregulation. Supported by a three-dimensional (3D) structural model, we hypothesize that the C-terminal domain confers unique regulatory capacities on the AtfJ family of regulators.

IMPORTANCE
Balancing adherence with motility is essential for uropathogens to successfully establish a foothold in their host.
Proteus mirabilis
uses a fimbria-associated transcriptional regulator to switch between these antagonistic processes by increasing fimbrial adherence while simultaneously downregulating flagella. The discovery of multiple related proteins, many of which also function as motility repressors, encoded in the
P. mirabilis
genome has raised considerable interest as to their functionality and potential redundancy in this organism. This study provides an important advance in this field by elucidating the nonidentical effects of these paralogs on a molecular level. Our mechanistic studies of one member of this group, AtfJ, shed light on how these differing functions may be conferred despite the limited sequence variety exhibited by the paralogous proteins.
Toxoplasma gondii Cyclic AMP-Dependent Protein Kinase Subunit 3 Is Involved in the Switch from Tachyzoite to Bradyzoite Development
Authors: Sugi Tatsuki , Ma Yan Fen , Tomita Tadakimi , Murakoshi Fumi , Eaton Michael S. , Yakubu Rama , Han Bing , Tu Vincent , Kato Kentaro , Kawazu Shin-Ichiro , Gupta Nishith , Suvorova Elena S. , White Michael W. , Kim Kami , Weiss Louis M.
Published: June 2016

Toxoplasma gondii
is an obligate intracellular apicomplexan parasite that infects warm-blooded vertebrates, including humans. Asexual reproduction in
T. gondii
allows it to switch between the rapidly replicating tachyzoite and quiescent bradyzoite life cycle stages. A transient cyclic AMP (cAMP) pulse promotes bradyzoite differentiation, whereas a prolonged elevation of cAMP inhibits this process. We investigated the mechanism(s) by which differential modulation of cAMP exerts a bidirectional effect on parasite differentiation. There are three protein kinase A (PKA) catalytic subunits (
Tg
PKAc1 to -3) expressed in
T. gondii
. Unlike
Tg
PKAc1 and
Tg
PKAc2, which are conserved in the phylum Apicomplexa,
Tg
PKAc3 appears evolutionarily divergent and specific to coccidian parasites.
Tg
PKAc1 and
Tg
PKAc2 are distributed in the cytomembranes, whereas
Tg
PKAc3 resides in the cytosol.
Tg
PKAc3 was genetically ablated in a type II cyst-forming strain of
T. gondii
(Pru
Δku80Δhxgprt
) and in a type I strain (RH
Δku80Δhxgprt
), which typically does not form cysts. The Δ
pkac3
mutant exhibited slower growth than the parental and complemented strains, which correlated with a higher basal rate of tachyzoite-to-bradyzoite differentiation. 3-Isobutyl-1-methylxanthine (IBMX) treatment, which elevates cAMP levels, maintained wild-type parasites as tachyzoites under bradyzoite induction culture conditions (pH 8.2/low CO
2
), whereas the Δ
pkac3
mutant failed to respond to the treatment. This suggests that
Tg
PKAc3 is the factor responsible for the cAMP-dependent tachyzoite maintenance. In addition, the Δ
pkac3
mutant had a defect in the production of brain cysts
in vivo
, suggesting that a substrate of
Tg
PKAc3 is probably involved in the persistence of this parasite in the intermediate host animals.

IMPORTANCE
Toxoplasma gondii
is one of the most prevalent eukaryotic parasites in mammals, including humans. Parasites can switch from rapidly replicating tachyzoites responsible for acute infection to slowly replicating bradyzoites that persist as a latent infection. Previous studies have demonstrated that
T. gondii
cAMP signaling can induce or suppress bradyzoite differentiation, depending on the strength and duration of cAMP signal. Here, we report that
Tg
PKAc3 is responsible for cAMP-dependent tachyzoite maintenance while suppressing differentiation into bradyzoites, revealing one mechanism underlying how this parasite transduces cAMP signals during differentiation.
How is the sustainability of chronic disease health programmes empirically measured in hospital and related healthcare services?—a scoping review
Authors: Francis Linda , Dunt David , Cadilhac Dominique A
Published: June 2016

Objectives

Programmes to address chronic disease are a focus of governments worldwide. Despite growth in ‘implementation science’, there is a paucity of knowledge regarding the best means to measure sustainability. The aim of this review was to summarise current practice for measuring sustainability outcomes of chronic disease health programmes, providing guidance for programme planners and future directions for the academic field.

Settings

A scoping review of the literature spanning 1985–2015 was conducted using MEDLINE, CINAHL, PsychINFO and The Cochrane Library limited to English language and adults. Main search terms included chronic disease, acute care, sustainability, institutionalisation and health planning. A descriptive synthesis was required. Settings included primary care, hospitals, mental health centres and community health.

Participants

Programmes included preventing or managing chronic conditions including diabetes, heart disease, depression, respiratory disease, cancer, obesity, dental hygiene and multiple chronic diseases.

Primary and secondary outcome measures

Outcome measures included clarifying a sustainability definition, types of methodologies used, timelines for assessment, criteria levels to determine outcomes and how methodology varies between intervention types.

Results

Among 153 abstracts retrieved, 87 were retained for full article review and 42 included in the qualitative synthesis. Five definitions for sustainability outcome were identified with ‘maintenance of programme activities’ most frequent. Achieving sustainability was dependent on inter-relationships between various organisational and social contexts supporting a broad scale approach to evaluation. An increasing trend in use of mixed methods designs over multiple time points to determine sustainability outcomes was found.

Conclusions

Despite the importance and investment in chronic disease programmes, few studies are undertaken to measure sustainability. Methods to evaluate sustainability are diverse with some emerging patterns in measurement found. Use of mixed methods approaches over multiple time points may serve to better guide measurement of sustainability. Consensus on aspects of standardised measurement would promote the future possibility of meta-analytic syntheses.
Colonic lesion characterisation skills among UK endoscopists and the impact of a brief training intervention
Authors: Basford P , Longcroft-Wheaton G , Higashi Reiji , Uraoka Toshio , Bhandari P
Published: June 2016

Objective

To assess UK gastroenterology registrars' and consultants' competence in in vivo characterisation of polyps, plus the impact of a dedicated colonic lesion characterisation training intervention.

Design

Prospective evaluation of a computer-based colonic lesion training module.

Setting

Three UK general hospitals.

Patients

High-quality endoscopic images obtained during colonoscopy in a previous study.

Interventions

30 min computer-based training module covering in vivo characterisation of colonic lesions viewed under white light, chromoendoscopy and magnification chromoendoscopy.

Main outcome measures

Accuracy of characterisation of colonic lesions (hyperplastic vs adenoma vs cancer) before and after training and differences between groups (bowel cancer screening (BCS) nurses vs gastroenterology trainees vs consultant gastroenterologists).

Results

Mean accuracy pretraining was 61.1%, 67.6% and 60.0% for the trainee, consultant and nurse groups respectively with no significant difference between the groups. Mean accuracy post-training improved significantly to 71.2%, 72.6% and 67.2% for the trainee, consultant and nurse groups (p<0.001 vs pretraining) with no significant difference between the three groups. Mean sensitivity and specificity improved significantly for the 15 participants overall.

Conclusions

The baseline level of colonic lesion characterisation skills is limited for gastroenterology consultants and trainees and does not differ from that of non-endoscopist BCS nurses. Accuracy of lesion characterisation can be modestly improved with a brief computer-based training intervention. Lesion characterisation should become a standard part of training in colonoscopy, and should be learnt alongside technical skills for endoscope handing and therapeutic procedures.
Theoretical study of the structures and chemical ordering of CoPd nanoalloys supported on MgO(001)
Authors: Taran Songul , Garip Ali Kemal , Arslan Haydar
Published: June 2016

Metal nanoalloys on oxide surface are a widely studied topic in surface science and technology. In this study, the structures of CoPd nanoalloys adsorbed on MgO(001) have been searched by basin-hopping global optimization method within an atomistic model. Two different sizes (34 and 38 atom) have been considered for all compositions of CoPd/MgO(001) nanoalloys. Co and Pd atoms, for all the compositions, have cube-on-cube (001) epitaxy with substrate at interface. For both sizes, we have found that Pd rich composition nanoalloys have three layers, Co rich composition nanoalloys have four layers in morphology. Excess energy and second difference in energy analyzes have been performed to investigate the relative stability of nanoalloys with respect to their size and composition.
Productions of J/ψ mesons in p-Pb collisions at 5 TeV
Authors: Liu Fu-Hu , Lao Hai-Ling , Lacey Roy A.
Published: June 2016

The rapidity distributions of [Formula: see text] mesons produced in proton-lead ([Formula: see text]-Pb) collisions at center-of-mass energy per nucleon pair [Formula: see text][Formula: see text]TeV are studied by using a multisource thermal model and compared with the experimental data of the LHCb and ALICE Collaborations. Correspondingly, the pseudorapidity distributions are accurately obtained from the parameters extracted from the rapidity distributions. At the same time, the transverse momentum distributions in the same experiments are described by the simplest Erlang distribution which is the folding result of two exponential distributions which are contributed by the target and projectile partons, respectively.
VALIDATION OF A BONE MINERAL DENSITY CALIBRATION PROTOCOL FOR MICRO-COMPUTED TOMOGRAPHY
Authors: BARUFFALDI FABIO , STOICO ROSSELLA , TASSANI SIMONE , MECOZZI LAURA , FALCIONI STEFANO , FERSINI CHIARA
Published: June 2016

Micro-computed tomography (micro-CT) is widely used for in vitro studies to characterize bone structure at the resolution of 10–100 microns. However, a densitometric calibration protocol is necessary to convert the X-ray attenuation coefficient provided by micro-CT in bone mineral density (BMD). The lastest one has an important role to improve the accuracy of subject-specific finite element models. This work presents a simple calibration protocol based on the use of solid hydroxyapatite phantoms with the correction of the beam hardening effect. The method was validated in comparison to ashing measures of cortical and trabecular human bone. In addition, bone samples tissue mineral density (TMD) was calculated with two different methods. The correlation between ash density and BMD was linear both for cortical ([Formula: see text]) and trabecular bone ([Formula: see text]). The analysis stratified by tissue type versus the pooled analysis confirmed the validity of a common linear model for both types of tissue ([Formula: see text]). Despite its simplicity, the correlation obtained in this work does not depend on the acquisition settings of the micro-CT. TMD was shown to be dependent on the tissue investigated, with values in the range of 1.15–1.21[Formula: see text]mg/mm3 for trabecular bone, and 1.19–1.29[Formula: see text]mg/mm3 for cortical bone. Results are of some interest for generating micro finite elements models.
Quantum cryptography: Theoretical protocols for quantum key distribution and tests of selected commercial QKD systems in commercial fiber networks
Authors: Jacak Monika , Jacak Janusz , Jóźwiak Piotr , Jóźwiak Ireneusz
Published: June 2016

The overview of the current status of quantum cryptography is given in regard to quantum key distribution (QKD) protocols, implemented both on nonentangled and entangled flying qubits. Two commercial R&D platforms of QKD systems are described (the Clavis II platform by idQuantique implemented on nonentangled photons and the EPR S405 Quelle platform by AIT based on entangled photons) and tested for feasibility of their usage in commercial TELECOM fiber metropolitan networks. The comparison of systems efficiency, stability and resistivity against noise and hacker attacks is given with some suggestion toward system improvement, along with assessment of two models of QKD.
Nax signaling evoked by an increase in [Na+] in CSF induces water intake via EET-mediated TRPV4 activation
Authors: Sakuta Hiraki , Nishihara Eri , Hiyama Takeshi Y. , Lin Chia-Hao , Noda Masaharu
Published: June 2016

Water-intake behavior is under the control of brain systems that sense body fluid conditions at sensory circumventricular organs (sCVOs); however, the underlying mechanisms have not yet been elucidated in detail. Nax is a sodium (Na+) level sensor in the brain, and the transient receptor potential vanilloid (TRPV) channels TRPV1 and TRPV4 have been proposed to function as osmosensors. We herein investigated voluntary water intake immediately induced after an intracerebroventricular administration of a hypertonic NaCl solution in TRPV1-, TRPV4-, Na x-, and their double-gene knockout (KO) mice. The induction of water intake by TRPV1-KO mice was normal, whereas intake by TRPV4-KO and Na x-KO mice was significantly less than that by WT mice. Water intake by Na x /TRPV4-double KO mice was similar to that by the respective single KO mice. When TRPV4 activity was blocked with a specific antagonist HC-067047, water intake by WT mice was significantly reduced, whereas intake by TRPV4-KO and Na x-KO mice was not. Similar results were obtained with the administration of miconazole, which inhibits the biosynthesis of epoxyeicosatrienoic acids (EETs), endogenous agonists for TRPV4, from arachidonic acid (AA). Intracerebroventricular injection of hypertonic NaCl with AA or 5,6-EET restored water intake by Na x-KO mice to the wild-type level but not that by TRPV4-KO mice. These results suggest that the Na+ signal generated in Nax-positive glial cells leads to the activation of TRPV4-positive neurons in sCVOs to stimulate water intake by using EETs as gliotransmitters. Intracerebroventricular injection of equiosmolar hypertonic sorbitol solution induced small but significant water intake equally in all the genotypes, suggesting the presence of an unknown osmosensor in the brain.
Myocardial Viability: From Proof of Concept to Clinical Practice
Authors: Bhat Aditya , Gan Gary C. H. , Tan Timothy C. , Hsu Chijen , Denniss Alan Robert
Published: May 2016

Ischaemic left ventricular (LV) dysfunction can arise from myocardial stunning, hibernation, or necrosis. Imaging modalities have become front-line methods in the assessment of viable myocardial tissue, with the aim to stratify patients into optimal treatment pathways. Initial studies, although favorable, lacked sufficient power and sample size to provide conclusive outcomes of viability assessment. Recent trials, including the STICH and HEART studies, have failed to confer prognostic benefits of revascularisation therapy over standard medical management in ischaemic cardiomyopathy. In lieu of these recent findings, assessment of myocardial viability therefore should not be the sole factor for therapy choice. Optimization of medical therapy is paramount, and physicians should feel comfortable in deferring coronary revascularisation in patients with coronary artery disease with reduced LV systolic function. Newer trials are currently underway and will hopefully provide a more complete understanding of the pathos and management of ischaemic cardiomyopathy.
Biobjective Optimization and Evaluation for Transit Signal Priority Strategies at Bus Stop-to-Stop Segment
Authors: Li Rui , Jin Peter J. , Ran Bin
Published: May 2016

This paper proposes a new optimization framework for the transit signal priority strategies in terms of green extension, red truncation, and phase insertion at the stop-to-stop segment of bus lines. The optimization objective is to minimize both passenger delay and the deviation from bus schedule simultaneously. The objective functions are defined with respect to the segment between bus stops, which can include the adjacent signalized intersections and downstream bus stops. The transit priority signal timing is optimized by using a biobjective optimization framework considering both the total delay at a segment and the delay deviation from the arrival schedules at bus stops. The proposed framework is evaluated using a VISSIM model calibrated with field traffic volume and traffic signal data of Caochangmen Boulevard in Nanjing, China. The optimized TSP-based phasing plans result in the reduced delay and improved reliability, compared with the non-TSP scenario under the different traffic flow conditions in the morning peak hour. The evaluation results indicate the promising performance of the proposed optimization framework in reducing the passenger delay and improving the bus schedule adherence for the urban transit system.
A Case of Leukocytoclastic Vasculitis Caused byListeria monocytogenesBacteremia
Authors: Bunker Daniel R. , Sullivan Timothy
Published: May 2016

Importance.Infections can cause leukocytoclastic vasculitis.Observations.We report the case of a patient with a left ventricular assist device who presented with acute kidney injury and biopsy proven leukocytoclastic vasculitis. Blood cultures grewListeria monocytogenes. The patient’s rash improved with treatment of the underlyingListeriainfection.Conclusion.Clinicians should be aware that there are a number of broad categories of disease associated with the histologic finding of vasculitis, including infection. It is important to keep in mind the risk factors of a particular patient when formulating a differential diagnosis. This is the first reported case ofListeriabacteremia causing leukocytoclastic vasculitis.
Impact of Climate Change on Hydrologic Extremes in the Upper Basin of the Yellow River Basin of China
Authors: Wang Jun , Liang Zhongmin , Wang Dong , Liu Tian , Yang Jing
Published: May 2016

To reveal the revolution law of hydrologic extremes in the next 50 years and analyze the impact of climate change on hydrologic extremes, the following main works were carried on: firstly, the long duration (15 d, 30 d, and 60 d) rainfall extremes according to observed time-series and forecast time-series by dynamical climate model product (BCC-CSM-1.1) were deduced, respectively, on the basis that the quantitative estimation of the impact of climate change on rainfall extremes was conducted; secondly, the SWAT model was used to deduce design flood with the input of design rainfall for the next 50 years. On this basis, quantitative estimation of the impact of climate change on long duration flood volume extremes was conducted. It indicates that (1) the value of long duration rainfall extremes for given probabilities (1%, 2%, 5%, and 10%) of the Tangnaihai basin will rise with slight increasing rate from 1% to 6% in the next 50 years and (2) long duration flood volume extremes of given probabilities of the Tangnaihai basin will rise with slight increasing rate from 1% to 6% in the next 50 years. The conclusions may provide technical supports for basin level planning of flood control and hydropower production.
Correlation Assessment between Three-Dimensional Facial Soft Tissue Scan and Lateral Cephalometric Radiography in Orthodontic Diagnosis
Authors: Zecca Piero Antonio , Fastuca Rosamaria , Beretta Matteo , Caprioglio Alberto , Macchi Aldo
Published: May 2016

Purpose. The aim of the present prospective study was to investigate correlations between 3D facial soft tissue scan and lateral cephalometric radiography measurements.Materials and Methods. The study sample comprised 312 subjects of Caucasian ethnic origin. Exclusion criteria were all the craniofacial anomalies, noticeable asymmetries, and previous or current orthodontic treatment. A cephalometric analysis was developed employing 11 soft tissue landmarks and 14 sagittal and 14 vertical angular measurements corresponding to skeletal cephalometric variables. Cephalometric analyses on lateral cephalometric radiographies were performed for all subjects. The measurements were analysed in terms of their reliability and gender-age specific differences. Then, the soft tissue values were analysed for any correlations with lateral cephalometric radiography variables using Pearson correlation coefficient analysis.Results. Low, medium, and high correlations were found for sagittal and vertical measurements. Sagittal measurements seemed to be more reliable in providing a soft tissue diagnosis than vertical measurements.Conclusions. Sagittal parameters seemed to be more reliable in providing a soft tissue diagnosis similar to lateral cephalometric radiography. Vertical soft tissue measurements meanwhile showed a little less correlation with the corresponding cephalometric values perhaps due to the low reproducibility of cranial base and mandibular landmarks.
Endothelial Progenitor Cells in Diabetic Microvascular Complications: Friends or Foes?
Authors: Yu Cai-Guo , Zhang Ning , Yuan Sha-Sha , Ma Yan , Yang Long-Yan , Feng Ying-Mei , Zhao Dong
Published: May 2016

Despite being featured as metabolic disorder, diabetic patients are largely affected by hyperglycemia‐induced vascular abnormality. Accumulated evidence has confirmed the beneficial effect of endothelial progenitor cells (EPCs) in coronary heart disease. However, antivascular endothelial growth factor (anti‐VEGF) treatment is the main therapy for diabetic retinopathy and nephropathy, indicating the uncertain role of EPCs in the pathogenesis of diabetic microvascular disease. In this review, we first illustrate how hyperglycemia induces metabolic and epigenetic changes in EPCs, which exerts deleterious impact on their number and function. We then discuss how abnormal angiogenesis develops in eyes and kidneys under diabetes condition, focusing on “VEGF uncoupling with nitric oxide” and “competitive angiopoietin 1/angiopoietin 2” mechanisms that are shared in both organs. Next, we dissect the nature of EPCs in diabetic microvascular complications. After we overview the current EPCs‐related strategies, we point out new EPCs‐associated options for future exploration. Ultimately, we hope that this review would uncover the mysterious nature of EPCs in diabetic microvascular disease for therapeutics.
Tryon’s Conjecture and Energy and Momentum of Bianchi Type Universes
Authors: Mishra Prajyot Kumar , Panda Bibhudatta , Pattanayak Pradosh Ranjan , Tripathy Sunil Kumar
Published: May 2016

The energy and momentum of some diagonal anisotropic Bianchi type Universes are obtained using different energy-momentum complexes in the framework of General Relativity. The Møller energy is found to be zero for all the Universes considered in the present work. In all other prescriptions, the energy and momentum vanish when the sum of the metric parametersαandβvanishes. This result obviously raises a question: why this specific choice? We have explored Tryon’s conjecture that the Universe must have a zero net value for all conserved quantities to get some ideas on this issue.
Constructing Maximum-Lifetime Data-Gathering Tree in WSNs Based on Compressed Sensing
Authors: Chen Zhengyu , Yang Geng , Chen Lei , Xu Jian
Published: May 2016

Data gathering is one of the most important operations in many wireless sensor networks (WSNs) applications. In order to implement data gathering, a tree structure rooted at the sink is usually defined. In most wireless sensor networks, nodes are powered by batteries with limited energy. Prolonging network lifetime is a critical issue for WSNs. As a technique for signal processing, compressed sensing (CS) is being increasingly applied to wireless sensor networks for saving energy. Compressive sensing can reduce the number of data transmissions and balance the traffic load throughout networks. In this paper, we investigate data gathering in wireless sensor networks using CS and aim at constructing a maximum-lifetime data-gathering tree. The lifetime of the network is defined as the number of data-gathering rounds until the first node depletes its energy. Based on the hybrid-CS data-gathering model, we first construct an arbitrary data-gathering tree and then use the random switching decision and optimal parent node selecting strategy to adjust the load of the bottleneck node and prolong the network lifetime. Simulation results show that the proposed algorithm outperforms several existing approaches in terms of network lifetime.
Valuing the Economic Costs of Allergic Rhinitis, Acute Bronchitis, and Asthma from Exposure to Indoor Dampness and Mold in the US
Authors: Mudarri David H.
Published: May 2016

Two foundational methods for estimating the total economic burden of disease are cost of illness (COI) and willingness to pay (WTP). WTP measures the full cost to society, but WTP estimates are difficult to compute and rarely available. COI methods are more often used but less likely to reflect full costs. This paper attempts to estimate the full economic cost (2014$) of illnesses resulting from exposure to dampness and mold using COI methods and WTP where the data is available. A limited sensitivity analysis of alternative methods and assumptions demonstrates a wide potential range of estimates. In the final estimates, the total annual cost to society attributable to dampness and mold is estimated to be $3.7 (2.3–4.7) billion for allergic rhinitis, $1.9 (1.1–2.3) billion for acute bronchitis, $15.1 (9.4–20.6) billion for asthma morbidity, and $1.7 (0.4–4.5) billion for asthma mortality. The corresponding costs from all causes, not limited to dampness and mold, using the same approach would be $24.8 billion for allergic rhinitis, $13.5 billion for acute bronchitis, $94.5 billion for asthma morbidity, and $10.8 billion for asthma mortality.
Locating Minimal Fault Interaction in Combinatorial Testing
Authors: Zheng Wei , Wu Xiaoxue , Hu Desheng , Zhu Qihai
Published: May 2016

Combinatorial testing (CT) technique could significantly reduce testing cost and increase software system quality. By using the test suite generated by CT as input to conduct black-box testing towards a system, we are able to detect interactions that trigger the system’s faults. Given a test case, there may be only part of all its parameters relevant to the defects in system and the interaction constructed by those partial parameters is key factor of triggering fault. If we can locate those parameters accurately, this will facilitate the software diagnosing and testing process. This paper proposes a novel algorithm named complete Fault Interaction Location (comFIL) to locate those interactions that cause system’s failures and meanwhile obtains the minimal set of target interactions in test suite produced by CT. By applying this method, testers can analyze and locate the factors relevant to defects of system more precisely, thus making the process of software testing and debugging easier and more efficient. The results of our empirical study indicate that comFIL performs better compared with known fault location techniques in combinatorial testing because of its improved effectiveness and precision.
Invisible Victims: Delayed Onset Depression among Adults with Same-Sex Parents
Authors: Sullins D. Paul
Published: May 2016

The relationship of elevated depression risk recently discovered among adult persons raised by same-sex parents with possible precipitating conditions in childhood has not previously been acknowledged. This study tests whether such inattention is supportable. Logistic regression based risk ratios were estimated from longitudinal measures of mental health outcomes observed in three waves (at ages 15, 22, and 28) of the US National Survey of Adolescent to Adult Health (n=15,701). At age 28, the adults raised by same-sex parents were at over twice the risk of depression (CES-D: risk ratio 2.6, 95% CI 1.4–4.6) as persons raised by man-woman parents. These findings should be interpreted with caution. Elevated risk was associated with imbalanced parental closeness and parental child abuse in family of origin; depression, suicidality, and anxiety at age 15; and stigma and obesity. More research and policy attention to potentially problematic conditions for children with same-sex parents appears warranted.
Ischemic Stroke in Confederation with Trivial Head Trauma
Authors: Balachandran Archana , Kalyanshettar Siddarameshwar , Patil Shankargouda , Shegji Vijaykumar
Published: May 2016

Minor head injuries in children are common, resulting in brain concussion, and these injuries mostly end up without complications. Usually head trauma results in hemorrhagic stroke. Here we present a case of ischemic stroke following a trivial head trauma. A 10-month-old girl presented with posttraumatic right sided hemiparesis with right sided facial palsy. MRI brain revealed an area of acute infarct in the left capsuloganglionic region. The child was initially managed conservatively, as the hematological parameters were normal, and was started on anticoagulant therapy. An improvement in the clinical condition was achieved in 12 hrs of treatment with gain in power and resolution of weakness in 10 days. The specific cause for hemiparesis in the child is not elicited; possibility of genetic and environmental factors can be attributable.
Hemispatial Neglect Shows That “Before” Is “Left”
Authors: Bonato Mario , Saj Arnaud , Vuilleumier Patrik
Published: May 2016

Recent research has led to the hypothesis that events which unfold in time might be spatially represented in a left-to-right fashion, resembling writing direction. Here we studied fourteen right-hemisphere damaged patients, with or without neglect, a disorder of spatial awareness affecting contralesional (here left) space processing and representation. We reasoned that if the processing of time-ordered events is spatial in nature, it should be impaired in the presence of neglect and spared in its absence. Patients categorized events of a story as occurring before or after a central event, which acted as a temporal reference. An asymmetric distance effect emerged in neglect patients, with slower responses to events that took place before the temporal reference. The event occurring immediately before the reference elicited particularly slow responses, closely mirroring the pattern found in neglect patients performing numerical comparison tasks. Moreover, the first item elicited significantly slower responses than the last one, suggesting a preference for a left-to-right scanning/representation of events in time. Patients without neglect showed a regular and symmetric distance effect. These findings further suggest that the representation of events order is spatial in nature and provide compelling evidence that ordinality is similarly represented within temporal and numerical domains.
Maximizing Outcomes While Minimizing Morbidity: An Illustrated Case Review of Elbow Soft Tissue Reconstruction
Authors: Ooi Adrian , Ng Jonathan , Chui Christopher , Goh Terence , Tan Bien Keem
Published: May 2016

Background. Injuries to the elbow have led to consequences varying from significant limitation in function to loss of the entire upper limb. Soft tissue reconstruction with durable and pliable coverage balanced with the ability to mobilize the joint early to optimize rehabilitation outcomes is paramount.Methods. Methods of flap reconstruction have evolved from local and pedicled flaps to perforator-based flaps and free tissue transfer. Here we performed a review of 20 patients who have undergone flap reconstruction of the elbow at our institution.Discussion. 20 consecutive patients were identified and included in this study. Flap types include local (n=5), regional pedicled (n=7), and free (n=8) flaps. The average size of defect was 138 cm2(range 36–420 cm2). There were no flap failures in our series, and, at follow-up, the average range of movement of elbow flexion was 100°.Results. While the pedicled latissimus dorsi flap is the workhorse for elbow soft tissue coverage, advancements in microvascular knowledge and surgery have brought about great benefit, with the use of perforator flaps and free tissue transfer for wound coverage.Conclusion. We present here our case series on elbow reconstruction and an abbreviated algorithm on flap choice, highlighting our decision making process in the selection of safe flap choice for soft tissue elbow reconstruction.
Mesenchymal Stem Cells and Metabolic Syndrome: Current Understanding and Potential Clinical Implications
Authors: Matsushita Kenichi
Published: May 2016

Metabolic syndrome is an obesity‐based, complicated clinical condition that has become a global epidemic problem with a high associated risk for cardiovascular disease and mortality. Dyslipidemia, hypertension, and diabetes or glucose dysmetabolism are the major factors constituting metabolic syndrome, and these factors are interrelated and share underlying pathophysiological mechanisms. Severe obesity predisposes individuals to metabolic syndrome, and recent data suggest that mesenchymal stem cells (MSCs) contribute significantly to adipocyte generation by increasing the number of adipocytes. Accordingly, an increasing number of studies have examined the potential roles of MSCs in managing obesity and metabolic syndrome. However, despite the growing bank of experimental and clinical data, the efficacy and the safety of MSCs in the clinical setting are still to be optimized. It is thus hoped that ongoing and future studies can elucidate the roles of MSCs in metabolic syndrome and lead to MSC‐based therapeutic options for affected patients. This review discusses current understanding of the relationship between MSCs and metabolic syndrome and its potential implications for patient management.
Computational Modeling of the Effect of Sulci during Tumor Growth and Cerebral Edema
Authors: Peng Dan , Zhou Zhiheng , Liu Yin , Guo Tianfu , Li Ying , Tang Shan
Published: May 2016

This paper aims at studying the effect of sulci structures during tumor growth and cerebral edema in brain tissues. Motivated by the Intracranial Cerebral Pressure (ICP) monitoring during the brain surgery, a computational model has been created to study macroscopic behaviors of brain tissues with local volume expansion introduced by the tumor growth and cerebral edema. To consider the extra-large deformation during the tumor growth, a nonlinear finite element method has been adopted. Numerical simulation results reveal that sulci structures play significant roles in macroscopic volume expansion and maximum stress of brain tissues. Without considering the sulci structures, predictions on the ICP will be dramatically different from those including sulci structure. Therefore, it is strongly suggested that the sulci structure should be included in future studies on the brain modeling for investigating the space-occupying lesions.
Depressed Mood Differentially Mediates the Relationship between Pain Intensity and Pain Disability Depending on Pain Duration: A Moderated Mediation Analysis in Chronic Pain Patients
Authors: Probst Thomas , Neumeier Susanne , Altmeppen Jürgen , Angerer Michael , Loew Thomas , Pieh Christoph
Published: May 2016

Research has shown that pain is associated with disability and that depressed mood mediates the relationship between pain and disability. The question of whether duration of pain moderates these effects was addressed in this cross-sectional study with 356 chronic pain patients. A simple mediation model replicated the notion that depressed mood explains a significant proportion of the relationship between pain and disability (in the study at hand: 12%). A moderated mediation model revealed that the indirect effect of pain on disability through depressed mood is moderated by pain duration: while depressed mood did not mediate the effect of pain on disability in chronic pain patients with shorter pain duration, depressed mood significantly mediated the effect pain exerts on disability in chronic pain patients with longer pain duration. Pain duration did not moderate the direct effect of pain on disability. Implications of these findings for the treatment of chronic pain might be that targeting depressed mood is especially relevant in chronic pain patients with longer pain duration to reduce the effect of pain on disability.
Electrical Resistivity, Tribological Behaviour of Multiwalled Carbon Nanotubes and Nanoboron Carbide Particles Reinforced Copper Hybrid Composites for Pantograph Application
Authors: Selvakumar N. , Gangatharan K.
Published: May 2016

This work focuses on the influence and contribution of multiwalled carbon-nanotube (MWCNT)–boron carbide (B4C) to the mechanical and tribological properties of copper matrix composites. Different weight fractions of nano- B4C-containing fixed-weight fractions of MWCNT-reinforced copper composites were prepared using the entrenched cold-press sintering method of powder metallurgy. The wear losses of sintered Cu–MWCNT–B4C composites were investigated by conducting sliding tests in a pin-on-disc apparatus. The addition of reinforcements showed enhancements in the hardness and wear properties of the composites due to the uniform dispersion of the secondary reinforcement in the copper matrix and the self-lubricating effect of the MWCNTs. The effects of the nanoparticle distribution in the matrix, the worn surface morphology, and the elemental composition of the composites were characterized using high-resolution scanning electron microscopy and X-ray diffraction analysis. The electrical resistivity of the fabricated copper hybrid composite preforms was evaluated using a four-point probe tester. Our results highlight the use of experiential reinforcing limits of B4C on the wear and electrical and mechanical behaviour of copper composites.
Spinal Intradural, Extramedullary Ependymoma with Astrocytoma Component: A Case Report and Review of the Literature
Authors: Weinstein Gene M. , Arkun Knarik , Kryzanski James , Lanfranchi Michael , Gupta Gaurav K. , Bedi Harprit
Published: May 2016

Ependymomas are common spinal lesions, with the vast majority arising in an intramedullary location. Several cases have been described in the literature of ependymomas in an intradural, extramedullary location. The authors present a case of a 56-year-old female who presented with several weeks of lower back pain and weakness. MRI revealed an intradural, extramedullary enhancing mass at L1-L2. The mass was successfully resected surgically. Pathologic evaluation revealed a low grade glioma with components of both ependymoma and pilocytic astrocytoma with MUTYH G382D mutation. Extramedullary ependymomas are very rare tumors. To the authors’ knowledge, this is the first case of ependymoma/astrocytoma collision tumors described in an extramedullary location.
Overall Survival and Response to Systemic Therapy in Metastatic Extrauterine Leiomyosarcoma
Authors: Shoushtari A. N. , Landa J. , Kuk D. , Sanchez A. , Lala B. , Schmidt N. , Okoli C. , Chi P. , Dickson M. A. , Gounder M. M. , Keohan M. L. , Crago A. M. , Tap W. D. , D’Angelo S. P.
Published: May 2016

Background. Leiomyosarcomas (LMS) represent a heterogeneous subset of soft tissue sarcomas. Factors influencing prognosis for patients with metastatic extrauterine LMS (euLMS) are not well described. Limited data are available regarding responses to systemic therapy.Methods. We collected clinical and pathologic information for all patients with metastatic euLMS seen at Memorial Sloan Kettering Cancer Center between 1989 and 2012. Objective responses to first-line therapy were analyzed for a subset of patients with available baseline and on-treatment imaging using RECIST 1.1.Results. 215 patients with metastatic euLMS had a median overall survival (OS) of 2.6 years from the time of metastasis. Older age, male sex, and ≥3 initial sites of metastasis were associated with worse OS on multivariate analysis. Objective response rate (ORR) inN=113was 19% overall and 25%, 26%, and 25% for gemcitabine, gemcitabine plus docetaxel, and anthracycline-alkylator combinations. Patients whose tumors objectively responded to first-line therapy had a lower risk of death versus those who did not (Hazard Ratio 0.46; 95% CI: 0.26–0.79,p=0.005).Conclusions. Anthracycline- and gemcitabine-based regimens have similar activity in this cohort of euLMS. Prognostic factors for OS include older age, male sex, and ≥3 initial sites.
Ethylene-Induced Vinblastine Accumulation Is Related to Activated Expression of Downstream TIA Pathway Genes inCatharanthus roseus
Authors: Wang Xi , Pan Ya-Jie , Chang Bo-Wen , Hu Yan-Bo , Guo Xiao-Rui , Tang Zhong-Hua
Published: May 2016

We selected different concentrations of ethephon, to stressC. roseus. We used qRT-PCR and HPLC followed by PCA to obtain comprehensive profiling of the vinblastine biosynthesis in response to ethephon. Based on our findings, the results showed that the high concentration of ethephon had a positive effect at both transcriptional and metabolite level. Meanwhile, there was a remarkable decrease of hydrogen peroxide content and a promoted peroxidase activity in leaves. The loading plot combination with correlation analysis suggested thatCrPrx1could be regarded as a positive regulator and interacts with ethylene response factor (ERF) to play a key role in vinblastine content and peroxidase (POD) activity. This study provides the foundation for a better understanding of the regulation and accumulation of vinblastine in response to ethephon.
Comparison of Neuroprotective Effect of Bevacizumab and Sildenafil following Induction of Stroke in a Mouse Model
Authors: Novitzky Ivan , Marianayagam Neelan J. , Weiss Shirel , Muhsinoglu Orkun , Fridman Moran , Leibovitch Tamar Azrad , Goldenberg-Cohen Nitza , Michowiz Shalom
Published: May 2016

To evaluate the effect of bevacizumab and sildenafil on stroke parameters in a mouse model, middle cerebral artery occlusion was induced in male C57Bl/6 mice using an intra-arterial filament method. The filament was removed after 60 minutes, and the mice were immediately given a single intraperitoneal injection of saline, bevacizumab, or sildenafil. An additional group of mice (n=7) received bevacizumab 6 h after MCAO induction. The mice were euthanized 24 hours later and evaluated for infarct area and brain edema using triphenyltetrazolium chloride staining and ImageJ. In the saline-treated mice (n=16), total stroke volume was19.20±6.38 mm3, mean penumbra area was4.5±2.03 mm3, and hemispheric asymmetry was 106.5%. Corresponding values in the bevacizumab group (n=19) were17.79±5.80 mm3,7.3±3.5 mm3, and 108.6%; in the delayed (6 h) bevacizumab injected mice (n=7) they were9.80±8.00 mm3,2.4±2.0 mm3, and 98.2%; and in the sildenafil group (n=16) they were18.42±5.41 mm3,5.7±2.02 mm3, and 109.9%. The bevacizumab group had a significantly larger mean penumbra area when given immediately and smaller total stroke area in both groups than the saline- (p=0.03) and sildenafil-treated (p=0.003) groups. Only delayed bevacizumab group had reduced edema. Bevacizumab, injected immediately or delayed after injury, exerts a neuroprotective/salvage effect, whereas immediate treatment with sildenafil does not. Inflammation may play a role in the neuroprotective effect.
Brain Activation during Memory Encoding in Type 2 Diabetes Mellitus: A Discordant Twin Pair Study
Authors: Wood Amanda G. , Chen Jian , Moran Christopher , Phan Thanh , Beare Richard , Cooper Kimberley , Litras Stacey , Srikanth Velandai
Published: May 2016

Type 2 diabetes mellitus increases the risk of dementia and neuronal dysfunction may occur years before perceptible cognitive decline. We aimed to study the impact of type 2 diabetes on brain activation during memory encoding in middle-aged people, controlling for age, sex, genes, and early-shared environment. Twenty-two twin pairs discordant for type 2 diabetes mellitus (mean age 60.9 years) without neurological disease were recruited from the Australian Twin Registry (ATR) and underwent functional magnetic resonance imaging (fMRI) during a memory encoding task, cognitive tests, and structural MRI. Type 2 diabetes was associated with significantly reduced activation in left hemisphere temporoparietal regions including angular gyrus, supramarginal gyrus, and middle temporal gyrus and significantly increased activation in bilateral posteriorly distributed regions. These findings were present in the absence of within-pair differences in standard cognitive test scores, brain volumes, or vascular lesion load. Differences in activation were more pronounced among monozygotic (MZ) pairs, with MZ individuals with diabetes also displaying greater frontal activation. These results provide evidence for preclinical memory-related neuronal dysfunction in type 2 diabetes. They support the search for modifiable later-life environmental factors or epigenetic mechanisms linking type 2 diabetes and cognitive decline.
Discovery of Novel Biomarkers for Alzheimer’s Disease from Blood
Authors: Long Jintao , Pan Genhua , Ifeachor Emmanuel , Belshaw Robert , Li Xinzhong
Published: May 2016

Blood-based biomarkers for Alzheimer’s disease would be very valuable because blood is a more accessible biofluid and is suitable for repeated sampling. However, currently there are no robust and reliable blood-based biomarkers for practical diagnosis. In this study we used a knowledge-based protein feature pool and two novel support vector machine embedded feature selection methods to find panels consisting of two and three biomarkers. We validated these biomarker sets using another serum cohort and an RNA profile cohort from the brain. Our panels included the proteins ECH1, NHLRC2, HOXB7, FN1, ERBB2, and SLC6A13 and demonstrated promising sensitivity (>87%), specificity (>91%), and accuracy (>89%).