bluuebunny/crossref_metadata_2025 huggingface dataset:
Age-Related Shifts in the Density and Distribution of Genetic Marker Water Quality Indicators in Cow and Calf Feces
Authors: Shanks Orin C. , Kelty Catherine A. , Peed Lindsay , Sivaganesan Mano , Mooney Thomas , Jenkins Michael
Published: December 2013

Calves make up about 16% of the current bovine population in the United States and can excrete high levels of human pathogens in their feces. We describe the density and distribution of genetic markers from 9 PCR- and real-time quantitative PCR-based assays, including CF128, CF193, CowM2, CowM3, GenBac3, Entero1, EC23S857, CampF2, and ttr-6, commonly used to help assess ambient surface water quality. Each assay was tested against a collection of 381 individual bovine fecal samples representing 31 mother and calf pairings collected over a 10-month time period from time of birth through weaning. Genetic markers reported to be associated with ruminant and/or bovine fecal pollution were virtually undetected in calves for up to 115 days from birth, suggesting that physiological changes in calf ruminant function impact host-associated genetic marker shedding. In addition, general fecal indicator markers for
Bacteroidales
,
Escherichia coli
, and
Enterococcus
spp. exhibited three separate trends across time, indicating that these bacteria respond differently to age-related physiological and dietary changes during calf development. The results of this study suggest that currently available PCR-based water quality indicator technologies can under- or overestimate fecal pollution originating from calves and identify a need for novel calf-associated source identification methods.
Immune Evasion, Stress Resistance, and Efficient Nutrient Acquisition Are Crucial for Intracellular Survival of Candida glabrata within Macrophages
Authors: Seider Katja , Gerwien Franziska , Kasper Lydia , Allert Stefanie , Brunke Sascha , Jablonowski Nadja , Schwarzmüller Tobias , Barz Dagmar , Rupp Steffen , Kuchler Karl , Hube Bernhard
Published: December 2013

Candida glabrata
is both a human fungal commensal and an opportunistic pathogen which can withstand activities of the immune system. For example,
C. glabrata
can survive phagocytosis and replicates within macrophages. However, the mechanisms underlying intracellular survival remain unclear. In this work, we used a functional genomic approach to identify
C. glabrata
determinants necessary for survival within human monocyte-derived macrophages by screening a set of 433 deletion mutants. We identified 23 genes which are required to resist killing by macrophages. Based on homologies to
Saccharomyces cerevisiae
orthologs, these genes are putatively involved in cell wall biosynthesis, calcium homeostasis, nutritional and stress response, protein glycosylation, or iron homeostasis. Mutants were further characterized using a series of
in vitro
assays to elucidate the genes' functions in survival. We investigated different parameters of
C. glabrata
-phagocyte interactions: uptake by macrophages, replication within macrophages, phagosomal pH, and recognition of mutant cells by macrophages as indicated by production of reactive oxygen species and tumor necrosis factor alpha (TNF-α). We further studied the cell surface integrity of mutant cells, their ability to grow under nutrient-limited conditions, and their susceptibility to stress conditions mirroring the harsh environment inside a phagosome. Additionally, resistance to killing by neutrophils was analyzed. Our data support the view that immune evasion is a key aspect of
C. glabrata
virulence and that increased immune recognition causes increased antifungal activities by macrophages. Furthermore, stress resistance and efficient nutrient acquisition, in particular, iron uptake, are crucial for intraphagosomal survival of
C. glabrata
.
Molecular Components of Nitrate and Nitrite Efflux in Yeast
Authors: Cabrera Elisa , González-Montelongo Rafaela , Giraldez Teresa , de la Rosa Diego Alvarez , Siverio José M.
Published: December 2013

Some eukaryotes, such as plant and fungi, are capable of utilizing nitrate as the sole nitrogen source. Once transported into the cell, nitrate is reduced to ammonium by the consecutive action of nitrate and nitrite reductase. How nitrate assimilation is balanced with nitrate and nitrite efflux is unknown, as are the proteins involved. The nitrate assimilatory yeast
Hansenula polymorpha
was used as a model to dissect these efflux systems. We identified the sulfite transporters Ssu1 and Ssu2 as effective nitrate exporters, Ssu2 being quantitatively more important, and we characterize the Nar1 protein as a nitrate/nitrite exporter. The use of strains lacking either
SSU2
or
NAR1
along with the nitrate reductase gene
YNR1
showed that nitrate reductase activity is not required for net nitrate uptake. Growth test experiments indicated that Ssu2 and Nar1 exporters allow yeast to cope with nitrite toxicity. We also have shown that the well-known
Saccharomyces cerevisiae
sulfite efflux permease Ssu1 is also able to excrete nitrite and nitrate. These results characterize for the first time essential components of the nitrate/nitrite efflux system and their impact on net nitrate uptake and its regulation.
Role of Retrograde Trafficking in Stress Response, Host Cell Interactions, and Virulence of Candida albicans
Authors: Liu Yaoping , Solis Norma V. , Heilmann Clemens J. , Phan Quynh T. , Mitchell Aaron P. , Klis Frans M. , Filler Scott G.
Published: December 2013

In
Saccharomyces cerevisiae
, the vacuolar protein sorting complexes Vps51/52/53/54 and Vps15/30/34/38 are essential for efficient endosome-to-Golgi complex retrograde transport. Here we investigated the function of Vps15 and Vps51, representative members of these complexes, in the stress resistance, host cell interactions, and virulence of
Candida albicans
. We found that
C. albicans
vps15
Δ/Δ and
vps51
Δ/Δ mutants had abnormal vacuolar morphology, impaired retrograde protein trafficking, and dramatically increased susceptibility to a variety of stressors. These mutants also had reduced capacity to invade and damage oral epithelial cells
in vitro
and attenuated virulence in the mouse model of oropharyngeal candidiasis. Proteomic analysis of the cell wall of the
vps51
Δ/Δ mutant revealed increased levels of the Crh11 and Utr2 transglycosylases, which are targets of the calcineurin signaling pathway. The transcript levels of the calcineurin pathway members
CHR11
,
UTR2
,
CRZ1
,
CNA1
, and
CNA2
were elevated in the
vps15
Δ/Δ and
vps51
Δ/Δ mutants. Furthermore, these strains were highly sensitive to the calcineurin-specific inhibitor FK506. Also, deletion of
CHR11
and
UTR2
further increased the stress susceptibility of these mutants. In contrast, overexpression of
CRH11
and
UTR2
partially rescued their defects in stress resistance, but not host cell interactions. Therefore, intact retrograde trafficking in
C. albicans
is essential for stress resistance, host cell interactions, and virulence. Aberrant retrograde trafficking stimulates the calcineurin signaling pathway, leading to the increased expression of Chr11 and Utr2, which enables
C. albicans
to withstand environmental stress.
Using Aspergillus nidulans To Identify Antifungal Drug Resistance Mutations
Authors: He Xiaoxiao , Li Shengnan , Kaminskyj Susan G. W.
Published: December 2013

Systemic fungal infections contribute to at least 10% of deaths in hospital settings. Most antifungal drugs target ergosterol (polyenes) or its biosynthetic pathway (azoles and allylamines), or beta-glucan synthesis (echinocandins). Antifungal drugs that target proteins are prone to the emergence of resistant strains. Identification of genes whose mutations lead to targeted resistance can provide new information on those pathways. We used
Aspergillus nidulans
as a model system to exploit its tractable sexual cycle and calcofluor white as a model antifungal agent to cross-reference our results with other studies. Within 2 weeks from inoculation on sublethal doses of calcofluor white, we isolated 24
A. nidulans
adaptive strains from sectoring colonies. Meiotic analysis showed that these strains had single-gene mutations. In each case, the resistance was specific to calcofluor white, since there was no cross-resistance to caspofungin (echinocandin). Mutation sites were identified in two mutants by next-generation sequencing. These were confirmed by reengineering the mutation in a wild-type strain using a gene replacement strategy. One of these mutated genes was related to cell wall synthesis, and the other one was related to drug metabolism. Our strategy has wide application for many fungal species, for antifungal compounds used in agriculture as well as health care, and potentially during protracted drug therapy once drug resistance arises. We suggest that our strategy will be useful for keeping ahead in the drug resistance arms race.
Relative bioequivalence of amoxicillin dissolved in breast milk
Authors: Yazdani-Brojeni Parvaneh , Garcia-Bournissen Facundo , Fujii Hisaki , Tanoshima Reo , Ito Shinya
Published: December 2013

Background

Oral antibiotics use in infants in developing countries is challenging because liquid formulations are often unavailable. However, dissolving solid formulation of drugs in water poses a risk of gastrointestinal infection. Although mother's milk may be a potential vehicle, no evidence exists to indicate that antibiotics dissolved in human milk are bioequivalent to those dissolved in water. Therefore, we compared pharmacokinetic parameters of an orally administered antibiotic, amoxicillin, dissolved in human milk, to those of water-dissolved amoxicillin.

Methods

A pharmacokinetic study was conducted in 16 healthy adult volunteers in a randomised crossover design. Marketed amoxicillin powder for suspension was dissolved in either human milk or water at a final concentration of 50 mg/mL, and 10 mL was given orally in a fasting state. Timed blood samples were obtained and plasma amoxicillin was quantified using liquid chromatography-mass spectrometry.

Findings

Results showed that pharmacokinetic parameters, including area-under-the-curve, Cmax and half-life of the water-based and milk-based amoxicillin administration were not significantly different. 90% CIs of the ratios of these parameters in concomitant breast milk administration to those of water were within 89% and 116%, suggesting they are bioequivalent (defined as a range between 80% and 125%).

Interpretation

We conclude that oral administration of amoxicillin dissolved in human milk at 50 mg/mL results in pharmacokinetics profiles comparable to amoxicillin dissolved in water. Pharmaceutical interactions between amoxicillin and breast milk are unlikely, suggesting no need to modify dosing schedules.
What are effective approaches to increasing rates of organ donor registration among ethnic minority populations: a systematic review
Authors: Deedat Sarah , Kenten Charlotte , Morgan Myfanwy
Published: December 2013

Objectives

To identify effective interventions to increase organ donor registration and improve knowledge about organ donation among ethnic minorities in North America and the UK.

Design

Systematic review.

Data Sources

MEDLINE, EMBASE, PsycINFO, CINAHL and Cochrane Central searched up to November 2012, together with four trials databases and the grey literature.

Review methods

A systematic search followed by assessment of eligibility and quality. An interpretive and thematic approach to synthesis was undertaken. This examined the nature and delivery of interventions in relation to a range of outcomes: verified registration, changing knowledge and a measured shift towards greater readiness.

Results

18 studies were included in the review, comprising educational and mass media interventions. Mass media interventions alone reported no significant change in the intention or willingness to register. Educational interventions either alone or combined with mass media approaches were more effective in increasing registration rates, with a strong interpersonal component and an immediate opportunity to register identified as important characteristics in successful change.

Conclusions

Effective interventions need to be matched to the populations’ stage of readiness to register. Measured outcomes should include registration and shifts along the pathway towards this behavioural outcome.
Diagnostic workup for fever of unknown origin: a multicenter collaborative retrospective study
Authors: Naito Toshio , Mizooka Masafumi , Mitsumoto Fujiko , Kanazawa Kenji , Torikai Keito , Ohno Shiro , Morita Hiroyuki , Ukimura Akira , Mishima Nobuhiko , Otsuka Fumio , Ohyama Yoshio , Nara Noriko , Murakami Kazunari , Mashiba Kouichi , Akazawa Kenichiro , Yamamoto Koji , Senda Shoichi , Yamanouchi Masashi , Tazuma Susumu , Hayashi Jun
Published: December 2013

Objective

Fever of unknown origin (FUO) can be caused by many diseases, and varies depending on region and time period. Research on FUO in Japan has been limited to single medical institution or region, and no nationwide study has been conducted. We identified diseases that should be considered and useful diagnostic testing in patients with FUO.

Design

A nationwide retrospective study.

Setting

17 hospitals affiliated with the Japanese Society of Hospital General Medicine.

Participants

This study included patients ≥18 years diagnosed with ‘classical fever of unknown origin’ (axillary temperature ≥38°C at least twice over a ≥3-week period without elucidation of a cause at three outpatient visits or during 3 days of hospitalisation) between January and December 2011.

Results

A total of 121 patients with FUO were enrolled. The median age was 59 years (range 19–94 years). Causative diseases were infectious disease in 28 patients (23.1%), non-infectious inflammatory disease in 37 (30.6%), malignancy in 13 (10.7%), other in 15 (12.4%) and unknown in 28 (23.1%). The median interval from fever onset to evaluation at each hospital was 28 days. The longest time required for diagnosis involved a case of familial Mediterranean fever. Tests performed included blood cultures in 86.8%, serum procalcitonin in 43.8% and positron emission tomography in 29.8% of patients.

Conclusions

With the widespread use of CT, FUO due to deep-seated abscess or solid tumour is decreasing markedly. Owing to the influence of the ageing population, polymyalgia rheumatica was the most frequent cause (9 patients). Four patients had FUO associated with HIV/AIDS, an important cause of FUO in Japan. In a relatively small number of cases, cause remained unclear. This may have been due to bias inherent in a retrospective study. This study identified diseases that should be considered in the differential diagnosis of FUO.
Lower gastrointestinal endoscopy: guidance on indications for biopsy
Authors: Bateman A C , Patel P
Published: December 2013

Lower gastrointestinal endoscopy is a commonly undertaken procedure and has assumed even greater prominence with the inception of the NHS Bowel Cancer Screening Programme (BCSP). Workloads are also constantly increasing within histopathology departments and this has led to a need for workload management by laboratories. Advanced endoscopic techniques now allow for targeted biopsies within settings such as inflammatory bowel disease surveillance and the BCSP. In this article, we provide guidance to the endoscopist for optimal biopsy protocols that are designed to maximise the chance of a subsequent histopathological examination providing definitive results and to reduce the number of unnecessary biopsies, in which histopathology is unlikely to deliver clinically useful information. The majority of the article focuses on biopsy taking within a defined range of clinical situations that are commonly encountered by endoscopists.
Targeted antibiotic treatment of lame sheep with footrot using either oxytetracycline or gamithromycin
Authors: Strobel H. , Lauseker M. , Forbes A. B.
Published: December 2013

A study on parenteral antibiotic treatment in sheep footrot was conducted on 10 farms in southern Germany to obtain information on the efficacy of gamithromycin under practical use conditions compared with a positive control. On each farm, 20 (10 on one farm) lame sheep were clinically evaluated and divided into two groups. On day 1, sheep were treated once according to group with either long‐acting oxytetracycline (OTC) at 20 mg/kg bodyweight or gamithromycin at 6 mg/kg; clinical responses were assessed 21 days later. When compared with day 1, both treatments reduced clinical lameness, as reflected in the reduction in the number of footrot‐affected feet (OTC: 79.3 per cent; gamithromycin: 93.7 per cent) and in the severity of the lesions. The difference between the two treatments was significant (P<0.01) with an OR of 6.1 in favour of gamithromycin. Of the 33 sheep that were still lame on day 21, nine mildly affected animals were not re‐treated and the remaining 24 sheep were re‐treated with gamithromycin. On day 42, all but two (on the same farm) of the 33 sheep were cured, giving an overall response rate in this study to one or two parenteral antibiotic treatments of 99 per cent.
Failures of sand tailings dams in a highly seismic country
Authors: Villavicencio Gabriel , Espinace Raúl , Palma Juan , Fourie Andy , Valenzuela Pamela
Published: December 2013

Chile is one of the main copper producers in the world. It is located in a geographical area where mega-earthquakes occur and this fact, together with the development of larger and higher sand tailings dams (with some facilities currently under development having final heights in excess of 250 m), requires that careful attention be paid to the safety and security of these facilities. In this paper, the main failure mechanisms of these sand tailings dams that have generated incidents of different magnitude involving loss of human life, significant environmental damage, and economic losses are described. Some key characteristics of reported incidents in Chile are presented, including failures resulting from the mega-earthquake that occurred on 27 February 2010 (Maule Region, Chile). Finally, the engineering practice and present Chilean regulatory framework, which have allowed progressive improvements in the construction, operation, and closure of such deposits, are described.
Perfusion territories subtended by penetrating coronary arteries increase in size and decrease in number toward the subendocardium
Authors: van Horssen P. , van den Wijngaard J. P. H. M. , Brandt M. J. , Hoefer I. E. , Spaan J. A. E. , Siebes M.
Published: December 2013

Blood flow distribution within the myocardium and the location and extent of areas at risk in case of coronary artery disease are dependent on the distribution and morphology of intramural vascular crowns. Knowledge of the intramural vasculature is essential in novel multiscale and multiphysics modeling of the heart. For this study, eight canine hearts were analyzed with an imaging cryomicrotome, developed to acquire high-resolution spatial data on three-dimensional vascular structures. The obtained vasculature was skeletonized, and for each penetrating artery starting from the epicardium, the dependent vascular crown was defined. Three-dimensional Voronoi tessellation was applied with the end points of the terminal segments as center points. The centroid of end points in each branch allowed classification of the corresponding perfusion territories in subendocardial, midmyocardial, and subepicardial. Subendocardial regions have relatively few territories of about 0.5 ml in volume having their own penetrating artery at the epicardium, whereas the subepicardium is perfused by a multitude of small perfusion territories, in the order of 0.01 ml. Vascular volume density of small arteries up till 400 μm was 3.2% at the subendocardium territories but only 0.8% in the subepicardium territories. Their higher volume density corresponds to compensation for flow impeding forces by cardiac contraction. These density differences result in different scaling law properties of vascular volume and tissue mass per territory type. This novel three-dimensional quantitative analysis may form the basis for patient-specific computational models on coronary perfusion and aid the interpretation of image-based clinical methods for assessing the transmural perfusion distribution.
Apelin gene therapy increases myocardial vascular density and ameliorates diabetic cardiomyopathy via upregulation of sirtuin 3
Authors: Zeng Heng , He Xiaochen , Hou Xuwei , Li Lanfang , Chen Jian-Xiong
Published: December 2013

Microvascular insufficiency contributes to cardiac hypertrophy and worsens heart dysfunction in diabetic cardiomyopathy. Our recent study shows that apelin may protect ischemic heart failure via upregulation of sirtuin 3 (Sirt3) and angiogenesis. This study investigated whether apelin promotes angiogenesis and ameliorates diabetic cardiomyopathy via activation of Sirt3. Wild-type (WT) and diabetic db/db mice were administrated with adenovirus-apelin to overexpressing apelin. In WT mice, overexpression of apelin increased Sirt3, VEGF/VEGFR2, and angiopoietin-1 (Ang-1)/Tie-2 expression in the heart. In vitro, treatment of endothelial cells (EC) with apelin increased VEGF and Ang-1 expression. In EC isolated from Sirt3KO mice, however, apelin treatment did not upregulate VEGF and Ang-1 expression. Moreover, apelin-induced angiogenesis was diminished in Sirt3KO mice. In db/db mice, the basal levels of apelin and Sirt3 expression were significantly reduced in the heart. This was accompanied by a significant reduction of capillary and arteriole densities in the heart. Overexpression of apelin increased Sirt3, VEGF/VEGFR2, and Ang-1/Tie-2 expression together with improved vascular density in db/db mice. Overexpression of apelin further improved cardiac function in db/db mice. Treatment with apelin significantly attenuated high glucose (HG)-induced reactive oxygen species (ROS) formation and EC apoptosis. The protection of apelin against HG-induced ROS formation and EC apoptosis was diminished in Sirt3KO-EC. We conclude that apelin gene therapy increases vascular density and alleviates diabetic cardiomyopathy by a mechanism involving activation of Sirt3 and upregulation of VEGF/VEGFR2 and Ang-1/Tie-2 expression.
On an Invariant Set in the Heat Conductivity Problem with Time Lag
Authors: Tukhtasinov M. , Ibragimov G. I. , Mamadaliev N. O.
Published: December 2013

The problems of weak and strong invariance of a constant multivalued mapping with respect to the heat conductivity equation with time lag are studied. Sufficient conditions of weak and strong invariance of a given multivalued mapping are obtained.
Torque Ripple Suppression in an External-Meshed Magnetic Gear Train
Authors: Wu Yi-Chang , Tseng Wan-Tsun , Chen Yueh-Tung
Published: December 2013

Magnetic gear trains transmit torque through noncontact magnetic couplings rather than conjugate gear teeth; they have the unique advantages of reduced maintenance and improved reliability, inherent overload protection, high efficiency, precise peak torque transmission, and tolerance for misalignment. Smooth and steadily transmitted torque is an important characteristic for a magnetic gear train. It is necessary for the reduction of possible mechanical vibration, position inaccuracy, and acoustic noise. This paper investigates the transmitted torque characteristics, especially torque ripple reduction, of an external-meshed magnetic gear train using finite-element analysis (FEA). The topological structure and working principles of a simple magnetic gear train with parallel axes are introduced. With the aid of a commercial FEA package, the transmitted torque waveform of a magnetic gear train is numerically calculated. The effects of geometrical parameters on the maximum transmitted torque and torque ripple are further discussed in terms of obtaining a magnetic gear train with high transmitted torque or low torque ripple. This examination offers insights beneficial to future magnetic gear mechanism design.
Protective Effect ofThunbergia laurifolia(Linn.) on Lead Induced Acetylcholinesterase Dysfunction and Cognitive Impairment in Mice
Authors: Phyu Moe Pwint , Tangpong Jitbanjong
Published: December 2013

Thunbergia laurifolia(linn., TL), a natural phenolic compound, has been reported to have many benefits and medicinal properties. The current study ascertains the total phenolic content present in TL aqueous leaf extract and also examines the antioxidant ability of the extract in preserving acetylcholinesterase (AChE) activity of mice exposed to leadin vivoandin vitromodel. Mice were given lead acetate (Pb) in drinking water (1 g/L) together with TL 100 and 200 mg/kg/day. The result showed that Pb induced AChE dysfunction in bothin vitroandin vivostudies. TL significantly prevented Pb induced neurotoxicity in a dose-dependent manner which was indicated by comparatively better performance of TL treated mice in Morris Water Maze Swimming Test and increased AChE activity in the tissue sample collected from the brains of these mice. TL also exhibited the greatest amount of phenolic content, which has a significant positive correlation with its antioxidant capacity (P<0.05). Taken together, these data suggested that the total phenolic compounds in TL could exhibit antioxidant and in part neuroprotective properties. It may play a potential treatment strategy for Pb contamination.
Comparison of Electric Vehicle’s Energy Consumption Factors for Different Road Types
Authors: Yao Enjian , Yang Zhiqiang , Song Yuanyuan , Zuo Ting
Published: December 2013

Energy-optimal route planning for electric vehicle (EV) is highly required for the wide-spread use of EV, which is hindered by limited battery capacity and relative short cruising range. Obtaining the cost for each link (i.e., link energy consumption) in road networks plays a key role in energy-optimal route planning process. The link energy consumption depends mainly on energy consumption factor, which is related to not only vehicle speed but also road type. This study aims to analyze the difference of EV’s energy consumption factors for different road types. According to the floating car data (FCD) collected from the road network in Beijing, the vehicle specific power (VSP) distributions under different average travel speeds for different road types are analyzed firstly, and then the EV’s energy consumption rates under different VSP-Bins are calculated. By using VSP as an intermediate variable, EV’s energy consumption factor models for different road types are established and the difference of EV’s energy consumption factors is analyzed. The results show that road type-based energy consumption factor should be used in EV’s energy-optimal route planning process.
Management of Gastric Varices Unsuccessfully Treated by Balloon‐Occluded Retrograde Transvenous Obliteration: Long‐Term Follow‐Up and Outcomes
Authors: Uchiyama Fumio , Murata Satoru , Onozawa Shiro , Nakazawa Ken , Sugihara Fumie , Yasui Daisuke , Narahara Yoshiyuki , Uchida Eiji , Amano Yasuo , Kumita Shin-ichiro
Published: December 2013

Our aim was to evaluate the long‐term efficacy and safety of percutaneous transhepatic obliteration (PTO) alone and combined with balloon‐occluded retrograde transvenous obliteration (BRTO) for gastroesophageal varices refractory to BRTO alone. Between July 1999 and December 2010, 13 patients with gastroesophageal varices refractory to BRTO were treated with PTO (n = 6) or a combination of PTO and BRTO (n = 7). We retrospectively investigated the rates of survival, recurrence, or worsening of the varices; hepatic function before and after the procedure; and complications. The procedure achieved complete obliteration or significant reduction of the varices in all 13 patients without major complications. During follow‐up, the varices had recurred in 2 patients, of which one had hepatocellular carcinoma, and the other died suddenly from variceal rebleeding 7 years after PTO. The remaining 11 patients did not experience worsening of the varices and showed significant improvements in the serum ammonia levels and prothrombin time. The mean follow‐up period was 90 months, and the cumulative survival rate at 1, 3, and 5 years was 92.9%, 85.7%, and 85.7%, respectively. Both PTO and combined PTO and BRTO seem as safe and effective procedures for the treatment of gastroesophageal varices refractory to BRTO alone.
Slope Stability Analysis Based on Measured Strains along Soil Nails Using FBG Sensing Technology
Authors: Pei Hua-Fu , Li Chao , Zhu Hong-Hu , Wang Yu-Jie
Published: December 2013

In the past few decades, slope stability analysis using numerical methods is becoming a hot issue, but it is based on extremely ideal assumptions. Soil nailing technique, as one of the most cost-effective reinforcing methods, has already been widely used for reinforcing slopes. In this study, to evaluate the safety factor of a slope, the strains on soil nails were measured by fiber Bragg grating (FBG) sensor. Strains along soil nails in the same cross section of a slope can be computed using the measured wavelength shifts of FBG sensors. In order to evaluate the stability of a slope, an optimal model was proposed to search the potential slip surfaces based on measured strain values. Maximum sum of strains on soil nails at different elevations of the same cross section was taken as the objective. Positions of soil nails, circular slip surface, and boundary conditions of the soil nails were summarized and taken as constraints. Finally, safety factors can be computed using the searched slip surface regarding the axial stress of soil nails. This method combines the limit equilibrium methods with measured axial strains on site which can reflect the actual condition of field slopes.
Reliable, Efficient, and Power Optimized Control-Channel Selection Scheme for Cognitive Radio Networks
Authors: Aslam Saleem , Shahid Adnan , Lee Kyung Geun
Published: December 2013

This paper presents a centralized control-channel selection scheme for cognitive radio networks (CRNs) by exploiting the variation in the spectrum across capacity, occupancy, and error rate. We address the fundamental challenges in the design of the control-channel for CRNs: (1) random licensed users (LUs) activity and (2) the economical and vulnerability concerns for a dedicated control-channel. We develop a knapsack problem (KP) based reliable, efficient, and power optimized (REPO) control-channel selection scheme with an optimal data rate, bit error rate (BER), and idle time. Moreover, we introduce the concept of the backup channels in the context of control-channel selection, which assists the CRs to quickly move on to the next stable channel in order to cater for the sudden appearance of LUs. Based on the KP and its dynamic programming solution, simulation results show that the proposed scheme is highly adaptable and resilient to random LU activity. The REPO scheme reduces collisions with the LUs, minimizes the alternate channel selection time, and reduces the bit error rate (BER). Moreover, it reduces the power consumed during channel switching and provides a performance, that is, competitive with those schemes that are using a static control-channel for the management of control traffic in CRNs.
Protective Effect of Theaflavin on Erythrocytes Subjected toIn VitroOxidative Stress
Authors: Fatima Mahejabeen , Kesharwani Rajesh Kumar , Misra Krishna , Rizvi Syed Ibrahim
Published: December 2013

Antioxidant and free radical scavenging effect of black tea theaflavins has been shown in many epidemiological studies. In the present work we report the protective mechanism of tea theaflavins on biomarkers of oxidative stress, which are elevated during stress conditions. We hereby report thein vitroeffect of theaflavins on erythrocyte malondialdehyde (MDA), intracellular reduced glutathione (GSH), and plasma membrane redox system (PMRS) of rats. The effect of theaflavin on PMRS has also been validated through anin silicodocking simulation study using Molegro Virtual Docker (MVD). We report that theaflavins show significant protection to erythrocyte against oxidative stress induced bytert-butyl hydroperoxide (t-BHP). The findings suggest a possible protective role of theaflavins as antioxidant.
Delay Adjustment Method at Transfer Station of High-Speed Railway
Authors: Xiaojuan Li , Baoming Han , Qi Zhang
Published: December 2013

Passenger transfer is one of the important research contents after the network operation of high-speed railway. Due to the high operation speed and high frequency, delays at transfer stations may occur frequently, leading to some potential safety problems. Main influence factors such as schedule time, transfer buffer time, waiting time, and delay time of delay and passengers classification during transfer were analyzed. A delay adjustment model of passengers at a transfer station was presented with minimal delay cost, waiting time cost, and adjustment cost as the optimization goal. Two adjustment strategies were proposed, including transfer passengers departure time adjustment and connecting trains departure time adjustment. And a delay adjustment algorithm at transfer station was designed for the optimal adjustment scheme. A case study proves the effectiveness of the method on optimal scheme design for passengers transferbased on the lowest delay cost of all passengers.
Transport Turnover with Spatial Econometric Perspective under the Energy Conservation and Emissions Reduction in China
Authors: Yang Zhongzhen , Wang Wensi , Bao Hongli , Kong Lu , Yu Bin
Published: December 2013

The method of spatial econometrics model is used to study the space correlation of road turnover (freight and passenger) among the 31 provinces (municipalities and autonomous regions) in China. Since some factors (such as the level of economic development, industrial structure, and population) may impact the road turnover (freight and passenger), these indexes are used as variables to reflect the influence in this model. The data of 31 provinces (municipalities and autonomous regions) in China in 2012 is collected to analyze the method. The results show that when the characteristics of turnover in a region are analyzed, it is necessary to consider the influence of its surrounding areas in space. Different scenarios were established according to different economic growth and degree of emission reduction to analyze the influence of the reduction of road turnover in regions with high spatial cluster effect to the whole country. We also carried out how to use the space effect of road turnover to the energy saving and emission reduction in the transportation industry.
Model Predictive Control of Piecewise Affine System with Constrained Input and Time Delay
Authors: Liu Zhilin , Liu Lutao , Zhang Jun , Yuan Xin
Published: December 2013

A model predictive control (MPC) is proposed for the piecewise affine (PWA) systems with constrained input and time delay. The corresponding operating region of the considered systems in state space is described as ellipsoid which can be characterized by a set of vector inequalities. And the constrained control input of the considered systems is solved in terms of linear matrix inequalities (LMIs). An MPC controller is designed that will move the PWA system with time delay from the current operating point to the desired one. Multiple objective functions are used to relax the monotonically decreasing condition of the Lyapunov function when the control algorithm switches from a quasi-infinite horizon to an infinite horizon strategy. The simulation results verify the effectiveness of the proposed method. It is shown that, based on LMI constraints, it is easy to get the MPC for the PWA systems with time delay. Moreover, it is suitable for practical application.
Tumor Suppressor VHL Functions in the Control of Mitotic Fidelity
Authors: Hell Michael P. , Duda Maria , Weber Thomas C. , Moch Holger , Krek Wilhelm
Published: December 2013

The von Hippel–Lindau (VHL) tumor suppressor protein pVHL is commonly mutated in clear cell renal cell carcinoma (ccRCC) and has been implicated in the control of multiple cellular processes that might be linked to tumor suppression, including promoting proper spindle orientation and chromosomal stability. However, it is unclear whether pVHL exerts these mitotic regulatory functions in vivo as well. Here, we applied ischemic kidney injury to stimulate cell division in otherwise quiescent mouse adult kidneys. We show that in the short term (5.5 days after surgery), Vhl-deficient kidney cells demonstrate both spindle misorientation and aneuploidy. The spindle misorientation phenotype encompassed changes in directed cell division, which may manifest in the development of cystic lesions, whereas the aneuploidy phenotype involved the occurrence of lagging chromosomes but not chromosome bridges, indicative of mitotic checkpoint impairment. Intriguingly, in the long term (4 months after the ischemic insult), Vhl-deficient kidneys displayed a heterogeneous pattern of ccRCC precursor lesions, including cysts, clear cell–type cells, and dysplasia. Together, these data provide direct evidence for a key role of pVHL in mediating oriented cell division and faithful mitotic checkpoint function in the renal epithelium, emphasizing the importance of pVHL as a controller of mitotic fidelity in vivo. Cancer Res; 74(9); 2422–31. ©2013 AACR.
Bioavailable Insulin-like Growth Factor-I Inversely Related to Weight Gain in Postmenopausal Women Regardless of Exogenous Estrogen
Authors: Jung Su Yon , Hursting Stephen D. , Guindani Michele , Vitolins Mara Z. , Paskett Electra , Chang Shine
Published: December 2013

Background: Weight gain, insulin-like growth factor-I (IGF-I) levels, and excess exogenous steroid hormone use are putative cancer risk factors, yet their interconnected pathways have not been fully characterized. This cross-sectional study investigated the relationship between plasma IGF-I levels and weight gain according to body mass index (BMI), leptin levels, and exogenous estrogen use among postmenopausal women.

Methods: This study included 794 postmenopausal women who enrolled in an ancillary study of the Women's Health Initiative Observational Study between February 1995 and July 1998. The relationship between IGF-I levels and weight gain was analyzed using ordinal logistic regression. We used the molar ratio of IGF-I to IGF binding protein-3 (IGF-I/IGFBP-3) or circulating IGF-I levels adjusting for IGFBP-3 as a proxy of bioavailable IGF-I. The plasma concentrations were expressed as quartiles.

Results: Among the obese group, women in the third quartile (Q3) of IGF-I and highest quartile of IGF-I/IGFBP-3 were less likely to gain weight (>3% from baseline) than were women in the first quartiles (Q1). Among the normal-weight group, women in Q2 and Q3 of IGF-I/IGFBP-3 were 70% less likely than those in Q1 to gain weight. Among current estrogen users, Q3 of IGF-I/IGFBP-3 had 0.5 times the odds of gaining weight than Q1.

Conclusions: Bioavailable IGF-I levels were inversely related to weight gain overall.

Impact: Although weight gain was not consistent with increases in IGF-I levels among postmenopausal women in this report, avoidance of weight gain as a strategy to reduce cancer risk may be recommended. Cancer Epidemiol Biomarkers Prev; 23(3); 534–44. ©2013 AACR.
Knockdown of CABYR-a/b Increases Chemosensitivity of Human Non–Small Cell Lung Cancer Cells through Inactivation of Akt
Authors: Qian Zunlei , Li Min , Wang Rui , Xiao Qianqian , Wang Jing , Li Mingying , He Dacheng , Xiao Xueyuan
Published: December 2013

CABYR is a calcium-binding tyrosine phosphorylation–regulated protein that was identified as a novel cancer testis antigen in lung cancer in our previous study. However, the role of CABYR as a driver of disease progression or as a chemosensitizer is poorly understood. This study sought to investigate the relationship between the expression levels of CABYR-a/b, which are the two predominant isoforms of the five isoform proteins encoded by CABYR, and chemosensitivity in non–small cell lung cancer cells. We found that the short hairpin RNA–mediated knockdown of CABYR-a/b significantly inhibited the proliferation of NCI-H460 and A549 cells and resulted in the attenuation of Akt phosphorylation, which is constitutively active in lung cancer cells. The silencing of CABYR-a/b expression notably impacted the downstream components of the Akt pathways: decreasing the phospho-GSK-3β (Ser9) levels and increasing the expression of the p53 and p27 proteins. Furthermore, CABYR-a/b knockdown led to a significant increase in chemosensitivity in response to chemotherapeutic drugs and drug-induced apoptosis, both in vitro and in vivo. Conversely, the transient transfection of CABYR-a/b–depleted cells with constitutively active Akt partially restored the resistance to cisplatin and paclitaxel and significantly decreased the activation of GSK-3β and cleaved PARP. Taken together, our results suggest that the inhibition of CABYR-a/b is a novel method to improve the apoptotic response and chemosensitivity in lung cancer and that this cancer testis antigen is an attractive target for lung cancer drug development.

Implications: Suppression of CABYR-a/b expression increases chemosensitivity of lung cancer cells by inhibiting Akt activity. Mol Cancer Res; 12(3); 335–47. ©2013 AACR.
MEK-Dependent Negative Feedback Underlies BCR–ABL-Mediated Oncogene Addiction
Authors: Asmussen Jennifer , Lasater Elisabeth A. , Tajon Cheryl , Oses-Prieto Juan , Jun Young-wook , Taylor Barry S. , Burlingame Alma , Craik Charles S. , Shah Neil P.
Published: December 2013

The clinical experience with BCR–ABL tyrosine kinase inhibitors (TKI) for the treatment of chronic myelogenous leukemia (CML) provides compelling evidence for oncogene addiction. Yet, the molecular basis of oncogene addiction remains elusive. Through unbiased quantitative phosphoproteomic analyses of CML cells transiently exposed to BCR–ABL TKI, we identified persistent downregulation of growth factor receptor (GF-R) signaling pathways. We then established and validated a tissue-relevant isogenic model of BCR–ABL-mediated addiction, and found evidence for myeloid GF-R signaling pathway rewiring that profoundly and persistently dampens physiologic pathway activation. We demonstrate that eventual restoration of ligand-mediated GF-R pathway activation is insufficient to fully rescue cells from a competing apoptotic fate. In contrast to previous work with BRAFV600E in melanoma cells, feedback inhibition following BCR–ABL TKI treatment is markedly prolonged, extending beyond the time required to initiate apoptosis. Mechanistically, BCR–ABL-mediated oncogene addiction is facilitated by persistent high levels of MAP–ERK kinase (MEK)-dependent negative feedback.

Significance: We found that BCR–ABL can confer addiction in vitro by rewiring myeloid GF-R signaling through establishment of MEK-dependent negative feedback. Our findings predict that deeper, more durable responses to targeted agents across a range of malignancies may be facilitated by maintaining negative feedback concurrently with oncoprotein inhibition. Cancer Discov; 4(2); 200–15. ©2013 AACR.

This article is highlighted in the In This Issue feature, p. 131
Genetic Characteristics of Children and Adolescents With Long-QT Syndrome Diagnosed by School-Based Electrocardiographic Screening Programs
Authors: Yoshinaga Masao , Kucho Yu , Sarantuya Jav , Ninomiya Yumiko , Horigome Hitoshi , Ushinohama Hiroya , Shimizu Wataru , Horie Minoru
Published: December 2013

Background—

A school-based electrocardiographic screening program has been developed in Japan. However, few data are available on the genetic characteristics of pediatric patients with long-QT syndrome who were diagnosed by this program.

Methods and Results—

A total of 117 unrelated probands aged ≤18 years were the subjects who were referred to our centers for genetic testing. Of these, 69 subjects diagnosed by the program formed the screened group. A total of 48 subjects were included in the clinical group and were diagnosed with long-QT syndrome–related symptoms, familial study, or by chance. Mutations were classified as radical, of high probability of pathogenicity, or of uncertain significance. Two subjects in the clinical group died. Genotypes were identified in 50 (72%) and 23 (48%) of subjects in the screened and clinical groups, respectively. Of the
KCNQ1
or
KCNH2
mutations, 31 of 33 (94%) in the screened group and 14 of 15 (93%) in the clinical group were radical and of high probability of pathogenicity. Prevalence of symptoms before (9/69 versus 31/48;
P
<0.0001) and after (12/69 versus 17/48;
P
=0.03) diagnosis was significantly lower in the screened group when compared with that in the clinical group although the QTc values, family history of long-QT syndrome, sudden death, and follow-up periods were not different between the groups.

Conclusions—

These data suggest that the screening program may be effective for early diagnosis of long-QT syndrome that may allow intervention before symptoms. In addition, screened patients should have follow-up equivalent to clinically identified patients.
Reentrant Ventricular Tachycardia Originating From the Periaortic Region in the Absence of Overt Structural Heart Disease
Authors: Nagashima Koichi , Tedrow Usha B. , Koplan Bruce A. , Michaud Gregory F. , John Roy M. , Epstein Laurence M. , Tokuda Michifumi , Inada Keiichi , Reichlin Tobias R. , Ng Justin P. , Barbhaiya Chirag R. , Nof Eyal , Tadros Thomas M. , Stevenson William G.
Published: December 2013

Background—

In the absence of overt structural heart disease, most left ventricular outflow tract ventricular tachycardias (VTs) have a focal origin and are benign. We hypothesized that multiple morphologies (MMs) of inducible left ventricular outflow tract VT may indicate a scar-related VT that can mimic idiopathic VT.

Methods and Results—

Of 54 consecutive patients referred for ablation of sustained outflow tract VT without overt structural heart disease, 24 had left ventricular outflow tract VT, 10 had MM VT, and 14 had a single VT (SM). The MM group were older (70.3±4.3 versus 53.9±15.9 years;
P
=0.004), had more hypertension (100% versus 29%;
P
=0.0006), and had longer PR intervals and QRS durations compared with the SM group. In contrast to the SM group, the MM group VTs had features consistent with reentry, including induction by programmed stimulation without isoproterenol, entrainment in some, and abnormal electrograms in the periaortic area. Periaortic region voltages suggested scar in the MM group, but not in the SM group. MRI in 2 MM patients was consistent with scar, but not in 10 SM patients. Longer radiofrequency applications were required in the MM group than in the SM group. At a median follow-up of 9.7 (3.0–32.0) months, recurrences tended to be more frequent in the MM group than in the SM group (70% versus 22%;
P
=0.07).

Conclusions—

VTs from small regions of periaortic scar can mimic idiopathic VT but are suggested by multiple VT morphologies and are more difficult to ablate. Whether these patients are at greater risk, as feared for other scar-related VTs, warrants further study.