bluuebunny/crossref_metadata_2025 huggingface dataset:
Powder Metallurgy Processing of High Strength Turbine Disk Alloys
Authors: Evans D. J.
Published: April 2015

Using vacuum-atomized AF2-1DA and Mar-M432 powders, full-scale gas turbine engine disks were fabricated by hot isostatically pressing (HIP) billets which were then isothermally forged using the Pratt & Whitney Aircraft GATORIZING™ forging process. While a sound forging was produced in the AF2-1DA, a container leak had occurred in the Mar-M432 billet during HIP. This resulted in billet cracking during forging. In-process control procedures were developed to identify such leaks. The AF2-1DA forging was heat treated and metallographic and mechanical property evaluation was performed. Mechanical properties exceeded those of Astroloy, one of the highest temperature capability turbine disk alloys presently used.
Buoyancy Can-Can
Authors: Nelson Jim , Nelson Jane Bray
Published: April 2015

In this paper, a discrepant event is used to initiate a learning cycle1 lesson to help students develop an understanding of the concept and equation for buoyant force. The data are gathered using readily available equipment and then graphically analyzed using a four-step analysis consistent with the modeling instructional approach.2 This laboratory activity is appropriate for high school or first-year college physics, and provides the opportunity for review of free-body diagrams, experimental design, and graphical analysis. We use the “BSCS 5E” version of the Karplus learning cycle idea, popularized by Bybee, in which students are expected to Engage, Explore, Explain, Elaborate, and Evaluate.3
How to Classify Who Experienced Flow from Who Did Not Based on the Flow State Scale-2 Scores: A Pilot Study of Latent Class Factor Analysis
Authors: Kawabata Masato , Evans Rachel
Published: April 2015

The present study examined the extent to which scores on the Flow State Scale-2 (FSS-2) could differentiate individuals who experienced flow characteristics in physical activity from those who did not. A total of 1,048 participants completed the Japanese version of the FSS-2. Latent class factor analysis (LCFA), which combines the strengths of both latent class analysis and factor analysis, was conducted on the FSS-2 responses. Four classes were identified through a series of LCFAs and the patterns of the item-average scores for the nine flow attributes were found parallel among these classes. The top two classes (15.1% and 38.9% of the whole sample) were considered the groups who experienced flow characteristics during their physical activities. These results indicated that individuals who experienced flow attributes in physical activity could be differentiated from those who did not based on their FSS-2 scores. Criteria for classifying individuals into the two groups were proposed.
Psychobehaviorally Based Features of Effective Talent Development in Rugby Union: A Coach’s Perspective
Authors: Hill Andy , MacNamara Áine , Collins Dave
Published: April 2015

Talent development (TD) is widely recognized as a nonlinear and dynamic process, with psychology a key determinant of long-term success in sport. However, given the role that positive characteristics play in the TD process, there is a relative dearth of research examining the psychological characteristics that may derail development. A retrospective qualitative investigation was conducted with academy coaches and directors within rugby union (n = 15), representing nine different elite English rugby union academies, to identify both positive and negative issues that influenced TD. Comprehensive support was found for existing positive constructs as facilitators of effective development. A range of inappropriately applied ‘positive’ characteristics were identified as having a negative impact on development. Potential clinical issues were also recognized by coaches as talent derailers. It is proposed that by incorporating these potentially negative factors into existing formative assessment tools, a more effective development process can be achieved.
Identification of Metabolic Signatures Linked to Anti-Inflammatory Effects of Faecalibacterium prausnitzii
Authors: Miquel Sylvie , Leclerc Marion , Martin Rebeca , Chain Florian , Lenoir Marion , Raguideau Sébastien , Hudault Sylvie , Bridonneau Chantal , Northen Trent , Bowen Benjamin , Bermúdez-Humarán Luis G. , Sokol Harry , Thomas Muriel , Langella Philippe
Published: April 2015

Faecalibacterium prausnitzii
is an anti-inflammatory commensal bacterium identified on the basis of human clinical data. The mechanisms underlying its beneficial effects are still unknown. Gnotobiotic mice harboring
F. prausnitzii
(A2-165) and
Escherichia coli
(K-12 JM105) were subjected to 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute colitis. The inflammatory colitis scores and a gas chromatography-time of flight (GC/TOF) mass spectrometry-based metabolomic profile were monitored in blood, ileum, cecum, colon, and feces in gnotobiotic mice. The potential anti-inflammatory metabolites were tested
in vitro
. We obtained stable
E. coli
and
F. prausnitzii
-diassociated mice in which
E. coli
primed the gastrointestinal tract (GIT), allowing a durable and stable establishment of
F. prausnitzii
. The disease activity index, histological scores, myeloperoxidase (MPO) activity, and serum cytokine levels were significantly lower in the presence of
F. prausnitzii
after TNBS challenge. The protective effect of
F. prausnitzii
against colitis was correlated to its implantation level and was linked to overrepresented metabolites along the GIT and in serum. Among 983 metabolites in GIT samples and serum, 279 were assigned to known chemical reactions. Some of them, belonging to the ammonia (α-ketoglutarate), osmoprotective (raffinose), and phenolic (including anti-inflammatory shikimic and salicylic acids) pathways, were associated with a protective effect of
F. prausnitzii
, and the functional link was established
in vitro
for salicylic acid. We show for the first time that
F. prausnitzii
is a highly active commensal bacterium involved in reduction of colitis through
in vivo
modulation of metabolites along the GIT and in the peripheral blood.

IMPORTANCE
Inflammatory bowel diseases (IBD) are characterized by low proportions of
F. prausnitzii
in the gut microbiome. This commensal bacterium exhibits anti-inflammatory effects through still unknown mechanisms. Stable monoassociated rodents are actually not a reproducible model to decipher
F. prausnitzii
protective effects. We propose a new gnotobiotic rodent model providing mechanistic clues. In this model,
F. prausnitzii
exhibits protective effects against an acute colitis and a protective metabolic profile is linked to its presence along the digestive tract. We identified a molecule, salicylic acid, directly involved in the protective effect of
F. prausnitzii
. Targeting its metabolic pathways could be an attractive therapeutic strategy in IBD.
Extracellular Enzymes Facilitate Electron Uptake in Biocorrosion and Bioelectrosynthesis
Authors: Deutzmann Jörg S. , Sahin Merve , Spormann Alfred M.
Published: April 2015

Direct, mediator-free transfer of electrons between a microbial cell and a solid phase in its surrounding environment has been suggested to be a widespread and ecologically significant process. The high rates of microbial electron uptake observed during microbially influenced corrosion of iron [Fe(0)] and during microbial electrosynthesis have been considered support for a direct electron uptake in these microbial processes. However, the underlying molecular mechanisms of direct electron uptake are unknown. We investigated the electron uptake characteristics of the Fe(0)-corroding and electromethanogenic archaeon
Methanococcus maripaludis
and discovered that free, surface-associated redox enzymes, such as hydrogenases and presumably formate dehydrogenases, are sufficient to mediate an apparent direct electron uptake. In genetic and biochemical experiments, we showed that these enzymes, which are released from cells during routine culturing, catalyze the formation of H
2
or formate when sorbed to an appropriate redox-active surface. These low-molecular-weight products are rapidly consumed by
M. maripaludis
cells when present, thereby preventing their accumulation to any appreciable or even detectable level. Rates of H
2
and formate formation by cell-free spent culture medium were sufficient to explain the observed rates of methane formation from Fe(0) and cathode-derived electrons by wild-type
M. maripaludis
as well as by a mutant strain carrying deletions in all catabolic hydrogenases. Our data collectively show that cell-derived free enzymes can mimic direct extracellular electron transfer during Fe(0) corrosion and microbial electrosynthesis and may represent an ecologically important but so far overlooked mechanism in biological electron transfer.

IMPORTANCE
The intriguing trait of some microbial organisms to engage in direct electron transfer is thought to be widespread in nature. Consequently, direct uptake of electrons into microbial cells from solid surfaces is assumed to have a significant impact not only on fundamental microbial and biogeochemical processes but also on applied bioelectrochemical systems, such as microbial electrosynthesis and biocorrosion. This study provides a simple mechanistic explanation for frequently observed fast electron uptake kinetics in microbiological systems without a direct transfer: free, cell-derived enzymes can interact with cathodic surfaces and catalyze the formation of intermediates that are rapidly consumed by microbial cells. This electron transfer mechanism likely plays a significant role in various microbial electron transfer reactions in the environment.
Endometriosis masquerading as Crohn's disease in a patient with acute small bowel obstruction
Authors: Dong Chaonan , Ngu Wee Sing , Wakefield Simon E
Published: April 2015

A 45-year-old woman, a smoker, presented acutely with subacute small bowel obstruction. Abdominal CT scan showed features of ileocaecal Crohn's disease. She was treated with high dose steroids and her symptoms rapidly settled. A few days later she was discharged on a reducing steroid course in addition to azathioprine. Outpatient colonoscopy was performed and reported as normal but there was failed terminal ileal intubation. Three months later, she represented as an emergency with complete small bowel obstruction. On laparoscopy, a terminal ileal stricture was found resulting in an ileocolic resection. Histopathology reported an endometriotic stricture with no evidence of Crohn's disease. She was advised to stop steroids and azathioprine. A subsequent pelvic MRI scan showed no further endometrial deposits and she remained symptom free. This case highlights that endometriosis should always be considered when women of childbearing age present with bowel obstruction, even if the patient has no other evidence of the disease.
Refractory polymyositis undergoing remission following antitubercular therapy
Authors: Misra Durga Prasanna , Edavalath Sukesh , Chowdhury Abhra Chandra , Agarwal Vikas
Published: April 2015

Opportunistic infections pose a significant problem in patients receiving immunosuppressive therapy for autoimmune diseases. We present a case of a woman with polymyositis refractory to high-dose steroid and methotrexate, as a consequence of which she developed miliary tuberculosis. Her myositis went into remission after initiation of antitubercular therapy, in spite of bringing down the intensity of immunosuppression. This is the first reported case of myositis undergoing remission after treating intercurrent infection, and illustrates the complex relationship between autoimmune disease and host response to infection.
Idiopathic splenic arteriovenous fistula without splenic artery aneurysm
Authors: Ono Shigeshi , Obara Hideaki , Shimoda Masayuki , Kitagawa Yuko
Published: April 2015

Splenic arteriovenous fistula (SAVF) without a splenic arterial aneurysm is a rare entity and may either be congenital or acquired. Acquired SAVFs are commonly due to adjacent splenic arterial aneurysm rupture, trauma or infection. We report a large idiopathic SAVF in a 50-year-old woman who had no symptoms. CT showed that the fistula was around the splenic hilum and no other specific findings. SAVF has a risk of sudden onset of portal hypertension and it should be treated as soon as diagnosed. Endovascular treatment for SAVF is now being performed successfully with increasing frequency, however, there is still no definitive evidence of treatment for SAVF. Treatment options should be determined appropriately depending on individual case characteristics and vascular anatomical variations. Our case was treated successfully with splenectomy, and long-term results are good without need of reintervention.
CEPR
Authors: Lian Defu , Xie Xing , Zheng Vincent W. , Yuan Nicholas Jing , Zhang Fuzheng , Chen Enhong
Published: April 2015

With the growing popularity of location-based social networks, numerous location visiting records (e.g., check-ins) continue to accumulate over time. The more these records are collected, the better we can understand users’ mobility patterns and the more accurately we can predict their future locations. However, due to the personality trait of neophilia, people also show propensities of novelty seeking in human mobility, that is, exploring unvisited but tailored locations for them to visit. As such, the existing prediction algorithms, mainly relying on regular mobility patterns, face severe challenges because such behavior is beyond the reach of regularity. As a matter of fact, the prediction of this behavior not only relies on the forecast of novelty-seeking tendency but also depends on how to determine unvisited candidate locations. To this end, we put forward a Collaborative Exploration and Periodically Returning model (CEPR), based on a novel problem, Exploration Prediction (EP), which forecasts whether people will seek unvisited locations to visit, in the following. When people are predicted to do exploration, a state-of-the-art recommendation algorithm, armed with collaborative social knowledge and assisted by geographical influence, will be applied for seeking the suitable candidates; otherwise, a traditional prediction algorithm, incorporating both regularity and the Markov model, will be put into use for figuring out the most possible locations to visit. We then perform case studies on check-ins and evaluate them on two large-scale check-in datasets with 6M and 36M records, respectively. The evaluation results show that EP achieves a roughly 20% classification error rate on both datasets, greatly outperforming the baselines, and that CEPR improves performances by as much as 30% compared to the traditional location prediction algorithms.
Modeling and Analyzing Dataflow Applications on NoC-Based Many-Core Architectures
Authors: Millo Jean-Vivien , Kofman Emilien , Simone Robert De
Published: April 2015

The advent of chip-level parallel architectures prompted a renewal of interest into dataflow process networks. The trend is to model an application independently from the architecture, then the model is morphed to best fit the target architecture. One downplayed aspect is the mapping of communications through the on-chip topology. The cost of such communications is often prevalent with regard to computations.

This article establishes a dataflow process network called
K-periodically Routed Graph
(KRG), which serves the role of representing the various routing decisions during the transformation of a genuine application into a architecture-aware version for this application.
Optimized and Scalable Co-Processor for McEliece with Binary Goppa Codes
Authors: Massolino Pedro Maat C. , Barreto Paulo S. L. M. , Ruggiero Wilson V.
Published: April 2015

Asymmetric cryptographic primitives are essential to enable secure communications in public networks or public mediums. Such primitives can be deployed as software libraries or hardware co-processors, the latter being more commonly employed in systems on chip (SoC) scenarios, embedded devices, or application-specific servers. Unfortunately, the most commonly available solutions, based on RSA or elliptic curve cryptography (ECC), are highly processing intensive due to the underlying extended-precision modular arithmetic. Consequently, they are not available on highly constrained platforms. Aiming to tackle this issue, we here investigate an alternative asymmetric encryption scheme that relies on lightweight arithmetic: McEliece. This scheme is especially appealing because, being based on error correction codes, it displays a simpler arithmetic and leads to better performance when compared to RSA or ECC. To evaluate the implementation of this scheme in hardware, we propose and analyze a flexible architecture whose security level and time versus area usage characteristics can be reconfigured as desired. The proposed architecture is suitable to all usual security levels, ranging from 80 to 256 bits. It is also very efficient, being able to perform data decryption with binary Goppa codes in 56µs with 3,402 slices on a Xilinx Spartan-3AN FPGA, whereas the best-known result in the literature for the same FPGA is 115µs with 7,331 slices. Alternatively, the architecture can operate with quasi-dyadic Goppa (QD-Goppa) codes, which involves smaller keys than traditional binary Goppa codes. In the latter case, for an 80-bit security level, the decryption operation can take from 1.1ms with 1,129 slices to 68µs with 8,268 sices. By choosing a more hardware-friendly decoding algorithm, focusing hardware resources on most bottleneck operations and sharing hardware resource for two different algorithms, better results than the those in the literature were obtained.
Glucose stimulates neurotensin secretion from the rat small intestine by mechanisms involving SGLT1 and GLUT2, leading to cell depolarization and calcium influx
Authors: Kuhre Rune Ehrenreich , Bechmann Louise Ellegaard , Wewer Albrechtsen Nicolai Jacob , Hartmann Bolette , Holst Jens Juul
Published: April 2015

Neurotensin (NT) is a neurohormone produced in the central nervous system and in the gut epithelium by the enteroendocrine N cell. NT may play a role in appetite regulation and may have potential in obesity treatment. Glucose ingestion stimulates NT secretion in healthy young humans, but the mechanisms involved are not well understood. Here, we show that rats express NT in the gut and that glucose gavage stimulates secretion similarly to oral glucose in humans. Therefore, we conducted experiments on isolated perfused rat small intestine with a view to characterize the cellular pathways of secretion. Luminal glucose (20% wt/vol) stimulated secretion but vascular glucose (5, 10, or 15 mmol/l) was without effect. The underlying mechanisms depend on membrane depolarization and calcium influx, since the voltage-gated calcium channel inhibitor nifedipine and the KATPchannel opener diazoxide, which causes hyperpolarization, eliminated the response. Luminal inhibition of the sodium-glucose cotransporter 1 (SGLT1) (by phloridzin) eliminated glucose-stimulated release as well as secretion stimulated by luminal methyl-α-d-glucopyranoside (20% wt/vol), a metabolically inactive SGLT1 substrate, suggesting that glucose stimulates secretion by initial uptake by this transporter. However, secretion was also sensitive to GLUT2 inhibition (by phloretin) and blockage of oxidative phosphorylation (2-4-dinitrophenol). Direct KATPchannel closure by sulfonylureas stimulated secretion. Therefore, glucose stimulates NT secretion by uptake through SGLT1 and GLUT2, both causing depolarization either as a consequence of sodium-coupled uptake (SGLT1) or by closure of KATPchannels (GLUT2 and SGLT1) secondary to the ATP-generating metabolism of glucose.
Computer-Simulated Biopsy Marking System for Endoscopic Surveillance of Gastric Lesions: A Pilot Study
Authors: Hu Weiling , Wang Bin , Sun Leimin , Chen Shujie , Wang Liangjing , Wang Kan , Wu Jiaguo , Kim John J. , Liu Jiquan , Dai Ning , Duan Huilong , Si Jianmin
Published: April 2015

Endoscopic tattoo with India ink injection for surveillance of premalignant gastric lesions is technically cumbersome and may not be durable. The aim of the study is to evaluate the accuracy of a novel, computer-simulated biopsy marking system (CSBMS) developed for the endoscopic marking of gastric lesions. Twenty-five patients with history of gastric intestinal metaplasia received both CSBMS-guided marking and India ink injection in five points in the stomach at index endoscopy. A second endoscopy was performed at three months. Primary outcome was accuracy of CSBMS (distance between CSBMS probe-guided site and tattoo site measured by CSBMS). The mean accuracy of CSBMS at angularis was5.3±2.2 mm, antral lesser curvature5.7±1.4 mm, antral greater curvature6.1±1.1 mm, antral anterior wall6.9±1.6 mm, and antral posterior wall6.9±1.6 mm. CSBMS (2.3±0.9versus12.5±4.6seconds;P=0.02) required less procedure time compared to endoscopic tattooing. No adverse events were encountered. CSBMS accurately identified previously marked gastric sites by endoscopic tattooing within 1 cm on follow-up endoscopy.
A Novel Scan Architecture for Low Power Scan-Based Testing
Authors: Mojtabavi Naeini Mahshid , Ooi Chia Yee
Published: April 2015

Test power has been turned to a bottleneck for test considerations as the excessive power dissipation has serious negative effects on chip reliability. In scan-based designs, rippling transitions caused by test patterns shifting along the scan chain not only elevate power consumption but also introduce spurious switching activities in the combinational logic. In this paper, we propose a novel area-efficient gating scan architecture that offers an integrated solution for reducing total average power in both scan cells and combinational part during shift mode. In the proposed gating scan structure, conventional master/slave scan flip-flop has been modified into a new gating scan cell augmented with state preserving and gating logic that enables average power reduction in combinational logic during shift mode. The new gating scan cells also mitigate the number of transitions during shift and capture cycles. Thus, it contributes to average power reduction inside the scan cell during scan shifting with low impact on peak power during capture cycle. Simulation results have shown that the proposed gating scan cell saves 28.17% total average power compared to conventional scan cell that has no gating logic and up to 44.79% compared to one of the most common existing gating architectures.
Anti‐Inflammatory Properties of Low and High Doxycycline Doses: An In Vitro Study
Authors: Di Caprio Roberta , Lembo Serena , Di Costanzo Luisa , Balato Anna , Monfrecola Giuseppe
Published: April 2015

Doxycycline is used to treat infective diseases because of its broadspectrum efficacy. High dose administration (100 or 200 mg/day) is often responsible for development of bacterial resistances and endogenous flora alterations, whereas low doses (20–40 mg/day) do not alter bacteria susceptibility to antibiotics and exert anti‐inflammatory activities. In this study, we wanted to assess the efficacy of both low and high doxycycline doses in modulating IL‐8, TNF‐α, and IL‐6 gene expression in HaCaT cells stimulated with LPS. Three experimental settings were used, differing in the timing of doxycycline treatment in respect to the insult induced by LPS: pretreatment, concomitant, and posttreatment. Low doses were more effective than high doses in modulating gene expression of LPS‐induced proinflammatory cytokines (IL‐8, TNF‐α, and IL‐6), when added before (pretreatment) or after (posttreatment) LPS stimulation. This effect was not appreciated when LPS and doxycycline were simultaneously added to cell cultures: in this case high doses were more effective. In conclusion, our in vitro study suggests that low doxycycline doses could be safely used in chronic or acute skin diseases in which the inflammatory process, either constantly in progress or periodically recurring, has to be prevented or controlled.
Initialization by a Novel Clustering for Wavelet Neural Network as Time Series Predictor
Authors: Cheng Rong , Hu Hongping , Tan Xiuhui , Bai Yanping
Published: April 2015

The architecture and parameter initialization of wavelet neural network are discussed and a novel initialization method is proposed. The new approach can be regarded as a dynamic clustering procedure which will derive the neuron number as well as the initial value of translation and dilation parameters according to the input patterns and the activating wavelets functions. Three simulation examples are given to examine the performance of our method as well as Zhang's heuristic initialization approach. The results show that the new approach not only can decide the WNN structure automatically, but also provides superior initial parameter values that make the optimization process more stable and quickly.
Transcriptional Regulation of CYP3A4/2B6/2C9 Mediated via Nuclear Receptor PXR by Helicid and Its Metabolites
Authors: Chen Qun , Xie Hai-tang , Li Yan , Wang Guo , Xu Zhe , Pu Zhi-chen , Hu Hua
Published: April 2015

Objective. This study aims at establishing and validating an in vitro system to screen drug inducers of CYPs mediated via hPXR, as well as studying transcriptional regulation of CYPs mediated via hPXR by helicid and its two metabolites.Methods. Cloning the nuclear receptor hPXR and the promoters of CYP3A4, CYP2B6, CYP2C9, and inserting the trans-element to the upstream of firefly luciferase reporter gene of the pGL4.17 vectors, then cotransfecting the report vectors and hPXR expression plasmid to HepG2 cell line. After 24 hours, the transfected cells were treated with helicid (0.004, 0.04, and 0.4 μmol/L) and its metabolite I and metabolite II (0.0004, 0.004, and 0.04 μmol/L) for 48 h, while rifampin (10 μmol/L) was included as the positive control and 0.1% DMSO as the negative control group. Cells were lysized and luciferase activity was determined using a dual luciferase reporter assay kit.Results. Helicid and its metabolites did not significantly increase promoter activities of CYP3A4, CYP2B6, and CYP2C9 in HepG2 cells transfected with PXR expression plasmid (P>0.05).Conclusion. PXR-expressed CYP3A4, CYP2B6, and CYP2C9 dual luciferase reporter gene platforms were successfully established, and helicid and its metabolites I, II do not significantly induce the transcription of CYP3A4, CYP2B6, and CYP2C9.
Investigation on Nano‐Self‐Lubricant Coating Synthesized by Laser Cladding and Ion Sulfurization
Authors: Li Meiyan , Han Bin , Qi Conghua , Wang Yong , Song Lixin
Published: April 2015

The composite processing between laser cladding and low temperature (300°C) ion sulfurization was applied to prepare wear resistant and self‐lubricating coating. The microstructure, morphology, phase composition, valence states, and wear resistance of the composite coating were investigated by scanning electron microscopy (SEM), atomic force microscope (AFM), X‐ray diffraction (XRD), X‐ray photoelectron spectroscope (XPS), and friction and wear apparatus. The results indicate that the laser cladding Ni‐based coatings and the maximum hardness of 46.5 HRC were obtained when the percent of pure W powder was 10%, composed of columnar dendrites crystals and ultrafine dendritic structure. After ion sulfurization at 300°C for 4 h, the loose and porous composite coating is formed with nanograins and the granularity of all grains is less than 100 nm, which consists of γ‐(Fe, Ni), M23C6 carbides, FeS, FeS2, and WS2. Furthermore, the wear resistance of the composite coating is better than the laser cladding Ni55 + 10%W coating, and the friction coefficient and mass losses under the conditions of dry and oil lubrication are lower than those of laser cladding Ni55 + 10%W coating.
TFF2–CXCR4 Axis Is Associated with BRAF V600E Colon Cancer
Authors: Gala Manish K. , Austin Thomas , Ogino Shuji , Chan Andrew T.
Published: April 2015

Oncogene-induced senescence (OIS), a tumor-suppressive mechanism that is induced by the replicative and metabolic stress of oncogene activation, is a key barrier in the development of BRAF V600E colon cancer. Inhibition of this mechanism has been observed through epigenetic changes observed in sporadic serrated polyps, as well as through the germline mutations associated with those who develop serrated polyposis. We hypothesize that upregulated autocrine factors exist that are specific to the serrated pathway and also promote bypass of oncogene-induced senescence. To identify such autocrine factors, we integrate analyses of microarrays of sessile serrated polyps and two large colon cancer cohorts, the Cancer Genome Atlas (TCGA; n = 153), and French national Cartes d'Identité des Tumeurs (CIT) program (n = 462), with enhanced gene annotation through natural language processing techniques of the existing medical corpus. We reproducibly associate higher expression of the ligand–receptor axis of TFF2 and CXCR4 with BRAF V600E-mutant colon cancer (P = 3.0 × 10−3 and 0.077, respectively for TCGA; P = 3.0 × 10−8 and 5.1 × 10−7 for CIT). Given well-described oncogenic roles of TFF2 and CXCR4 in colon cancer, and availability of CXCR4 inhibitors for other clinical indications, this ligand–receptor axis may represent an actionable target for prevention and treatment of this molecular subtype of colorectal cancer. Cancer Prev Res; 8(7); 614–9. ©2015 AACR.
PolyI:C–Induced, TLR3/RIP3-Dependent Necroptosis Backs Up Immune Effector–Mediated Tumor Elimination In Vivo
Authors: Takemura Ryo , Takaki Hiromi , Okada Seiji , Shime Hiroaki , Akazawa Takashi , Oshiumi Hiroyuki , Matsumoto Misako , Teshima Takanori , Seya Tsukasa
Published: April 2015

Double-stranded RNA directly acts on fibroblast and myeloid lineages to induce necroptosis as in TNFα. Here, we investigated whether this type of cell death occurred in cancer cells in response to polyinosinic–polycytidylic acid (polyI:C) and the pan-caspase inhibitor z-Val-Ala-Asp fluromethyl ketone (zVAD). We found that the colon cancer cell line CT26 is highly susceptible to necroptosis, as revealed by staining with annexin V/propidium iodide. CT26 cells possess RNA sensors, TLR3 and MDA5, which are upregulated by interferon (IFN)-inducing pathways and linked to receptor-interacting protein kinase (RIP) 1/3 activation via TICAM-1 or MAVS adaptor, respectively. Although exogenously added polyI:C alone marginally induced necroptosis in CT26 cells, a combined regimen of polyI:C and zVAD induced approximately 50% CT26 necroptosis in vitro without secondary effects of TNFα or type I IFNs. CT26 necroptosis depended on the TLR3–TICAM-1–RIP3 axis in the tumor cells to produce reactive oxygen species, but not on MDA5, MAVS, or the caspases/inflammasome activation. However, the RNA-derived necroptosis was barely reproduced in vivo in a CT26 tumor–implanted Balb/c mouse model with administration of polyI:C + zVAD. Significant shrinkage of CT26 tumors was revealed only when polyI:C (100 μg) was injected intraperitoneally and zVAD (1 mg) subcutaneously into tumor-bearing mice that were depleted of cytotoxic T lymphocytes and natural killer cells. The results were confirmed with immune-compromised mice with no lymphocytes. Although necroptosis-induced tumor growth retardation appears mechanistically complicated and dependent on the injection routes of polyI:C and zVAD, anti-caspase reagent directed to tumor cells will make RNA adjuvant immunotherapy more effective by modulating the formation of the tumoricidal microenvironment and dendritic cell–inducing antitumor immune system. Cancer Immunol Res; 3(8); 902–14. ©2015 AACR.
Overall Response to First-Line Tyrosine Kinase Inhibitor and Second-Line Chemotherapy Is Predictive of Survival Outcome in Epidermal Growth Factor Receptor-Mutated Adenocarcinoma
Authors: Kuo Scott Chih-Hsi , Hsu Ping-Chih , Chen Chih-Hung , Yu Chih-Teng , Wang Chih-Liang , Chung Fu-Tsai , Lin Shu-Min , Lo Yu-Lun , Chen Tse-Ching , Liu Chien-Ying , Yang Cheng-Ta
Published: April 2015

Background: First-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective for the treatment of lung adenocarcinoma with an EGFR-sensitizing mutation, but resistance is inevitable. Chemotherapy is widely used in the second-line setting. The outcome following this treatment scheme has not been thoroughly evaluated. Methods: From 2007 to 2011, consecutive patients with mutated EGFR receiving first-line TKI and second-line chemotherapy were retrospectively reviewed. The overall response was categorized into double responder, single responder and double nonresponder. Results: Following this treatment scheme, baseline Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (HR 0.60; 95% CI 0.37-0.98; p = 0.041) and double responder (HR 0.24; 95% CI 0.07-0.78; p = 0.018) were independent predictors of overall survival. Absence of pleural metastasis independently predicted the response to first-line TKI (OR 2.60; 95% CI 1.13-5.99; p = 0.025). In TKI responders, ECOG performance status 0-1 before chemotherapy (OR 4.95; 95% CI 1.15-21.28; p = 0.006), an exon 19 deletion (OR 4.74; 95% CI 1.30-17.21; p = 0.018) and progression-free survival (PFS) on first-line TKI (OR 1.02; 95% CI 1.01-1.09; p = 0.049) independently predicted the response to second-line chemotherapy. A moderate linear relationship (Pearson's r = 0.441; p = 0.001) existed between the PFS of this treatment scheme in TKI responders. Conclusion: The status of double responder to first-line TKI and second-line chemotherapy was predictive of improved survival in EGFR-mutated adenocarcinoma.
Overexpression of BDNF and Full-Length TrkB Receptor Ameliorate Striatal Neural Survival in Huntington's Disease
Authors: Silva Ana , Naia Luana , Dominguez Alejandro , Ribeiro Márcio , Rodrigues Joana , Vieira Otília V. , Lessmann Volkmar , Rego Ana Cristina
Published: April 2015

Background: Several cellular mechanisms have been proposed to explain the pathogenesis of Huntington's disease (HD), including the lack of striatal brain-derived neurotrophic factor (BDNF). Thus, by preferentially binding to tropomyosin receptor kinase B (TrkB) receptor, BDNF is an important neurotrophin implicated in striatal neuronal survival. Objective: To study the influence of BDNF and TrkB receptors in intracellular signaling pathways and caspase-3 activation in HD striatal cells. Methods: HD mutant knockin and wild-type striatal cells were transduced with preproBDNF or full-length TrkB receptors to analyze BDNF processing, AKT and extracellular signal-regulated kinase (ERK) activation and the activity of caspase-3 in the absence or presence of staurosporine (STS). Results: HD mutant cells transduced with preproBDNF-mCherry (mCh) expressed similar levels of pro- and mature BDNF compared to WT cells, but HD cells released lower levels of pro- and mature BDNF. Despite this, BDNF-mCh overexpression rescued decreased AKT phosphorylation and reduced the caspase-3 activation observed in HD cells. Activated ERK was also enhanced in HD BDNF-mCh/TrkB-eGFP receptor co-cultures. Of relevance, overexpression of TrkB-eGFP in HD cells decreased caspase-3 activation, and stimulation of TrkB-eGFP-transduced mutant cells with recombinant human BDNF reduced both basal and STS-induced caspase-3 activation. Conclusion: The results highlight the importance of BDNF-induced TrkB receptor signaling in rescuing HD-mediated apoptotic features in striatal cells.
Spatial QT Dispersion Predicts Nonsustained Ventricular Tachycardia and Correlates with Confined Systodiastolic Dysfunction in Hypertrophic Cardiomyopathy
Authors: Magrì Damiano , Piccirillo Gianfranco , Ricotta Agnese , De Cecco Carlo Nicola , Mastromarino Vittoria , Serdoz Andrea , Muscogiuri Giuseppe , Gregori Mario , Casenghi Matteo , Cauti Filippo Maria , Oliviero Giada , Musumeci Maria Beatrice , Maruotti Antonello , Autore Camillo
Published: April 2015

Objectives: An increased dispersion of myocardial repolarization represents one of the mechanisms underlying the arrhythmic risk in hypertrophic cardiomyopathy (HCM). We investigated spatial myocardial repolarization dispersion indices in HCM patients with nonsustained ventricular tachycardia (NSVT) and, contextually, their main clinical determinants. Methods: Fifty-two well-matched HCM outpatients were categorized into two groups according to the presence or the absence of NSVT at 24-hour Holter electrocardiogram (ECG) monitoring. Each patient underwent a clinical examination, including Doppler echocardiogram integrated with tissue Doppler imaging, cardiac magnetic resonance, and 12-lead surface ECG to calculate the dispersion for the following intervals: QRS, Q-Tend (QTe), Q-Tpeak, Tpeak-Tend (TpTe), J-Tpeak, and J-Tend. Results: The NSVT group showed only QTe dispersion and TpTe dispersion values to be significantly higher than their counterparts. NSVT occurrence was independently predicted by late gadolinium enhancement presence (p = 0.021) and QTe Bazett dispersion (p = 0.030), the latter strongly associated with the myocardial performance index (MPI) obtained at the basal segment of the interventricular septum (p = 0.0004). Conclusion: Our data support QTe dispersion as an easy and noninvasive tool for identifying HCM patients with NSVT propensity. The strong relationship between QTe dispersion and MPI allows us to hypothesize an intriguing link between electrical instability and confined myocardial areas of systodiastolic dysfunction.
Effect of Helicobacter pylori Infection on the Composition of Gastric Microbiota in the Development of Gastric Cancer
Authors: Cao Lei , Yu Jun
Published: April 2015

Background: Gastric cancer is one of the most common cancer types worldwide. In China, gastric cancer has become one of the major threats for public health, ranking second on incidence and third on cause of cancer death. Despite the common risk factors that promote the development of gastric cancer, the huge quantity of microorganism colonies within the gastrointestinal tract, particularly Helicobacter pylori infection, demonstrates a correlation with chronic inflammation and gastric carcinogenesis, as epidemiological studies have determined that H. pylori infection confers approximately 75% of the attributable risk for gastric cancer. Summary: The current article draws an overview on the correlation between the microbiota, inflammation and gastric tumorigenesis. H. pylori infection has been identified as the main risk factor as it triggers epithelial barrier disruption, survival signaling as well as genetic/epigenetic modulation. Apart from H. pylori, the existence of a diverse and complex composition of microbiota in the stomach has been identified, which supports a role of microbiota in the development of gastric cancer. Moreover, metagenomics studies focused on the composition and function of the microbiota have associated microbiota with gastric metabolic diseases and even tumorigenesis. Apart from the gastric microbiota, inflammation is another identified contributor to cancer development as well. Key Message: Though H. pylori infection and the non-H. pylori microbiota play a role in gastric cancer, the properties of gastric microbiota and mechanisms by which they participate in the genesis of gastric cancer are still not clearly depicted. Moreover, it remains to be understood how the presence of microbiota along with H. pylori infection affects the progress from gastric disease to cancer. Practical Implications: This article summarized a clue of the current studies on microbiota, H. pylori infection and the progression from gastric disease to cancer.
BMI or BIA: Is Body Mass Index or Body Fat Mass a Better Predictor of Cardiovascular Risk in Overweight or Obese Children and Adolescents?
Authors: Bohn Barbara , Müller Manfred James , Simic-Schleicher Gunter , Kiess Wieland , Siegfried Wolfgang , Oelert Monika , Tuschy Sabine , Berghem Stefan , Holl Reinhard W.
Published: April 2015

Background: Body fat (BF) percentiles for German children and adolescents have recently been published. This study aims to evaluate the association between bioelectrical impedance analysis(BIA)-derived BF and cardiovascular risk factors and to investigate whether BF is better suited than BMI in children and adolescents. Methods: Data of 3,327 children and adolescents (BMI > 90th percentile) were included. Spearman's correlation and receiver operating characteristics (ROCs) were applied determining the associations between BMI or BF and cardiovascular risk factors (hypertension, dyslipidemia, elevated liver enzymes, abnormal carbohydrate metabolism). Area under the curve (AUC) was calculated to predict cardiovascular risk factors. Results: A significant association between both obesity indices and hypertension was present (all p < 0.0001), but the correlation with BMI was stronger (r = 0.22) compared to BF (r = 0.13). There were no differences between BMI and BF regarding their correlation with other cardiovascular risk factors. BF significantly predicted hypertension (AUC = 0.61), decreased HDL-cholesterol (AUC = 0.58), elevated LDL-cholesterol (AUC = 0.59), elevated liver enzymes (AUC = 0.61) (all p < 0.0001), and elevated triglycerides (AUC = 0.57, p < 0.05), but not abnormal carbohydrate metabolism (AUC = 0.54, p = 0.15). For the prediction of cardiovascular risk factors, no significant differences between BMI and BF were observed. Conclusion: BIA-derived BF was not superior to BMI to predict cardiovascular risk factors in overweight or obese children and adolescents.
Recognition of Incident Diabetes Mellitus During an Acute Myocardial Infarction
Authors: Arnold Suzanne V. , Stolker Joshua M. , Lipska Kasia J. , Jones Philip G. , Spertus John A. , McGuire Darren K. , Inzucchi Silvio E. , Goyal Abhinav , Maddox Thomas M. , Lind Marcus , Gumber Divya , Shore Supriya , Kosiborod Mikhail
Published: April 2015

Background—

Diabetes mellitus (DM) is common in patients hospitalized with an acute myocardial infarction (AMI), representing in some cases the first opportunity to recognize and treat DM. We report the incidence of new DM and its recognition among patients with AMI.

Methods and Results—

Patients in a 24-site US AMI registry (2005–08) had glycosylated hemoglobin assessed at a core laboratory, with results blinded to clinicians and local clinical measurements left to the discretion of the treating providers. Among 2854 AMI patients without known DM on admission, 287 patients (10%) met criteria for previously unknown DM, defined by a core laboratory glycosylated hemoglobin of ≥6.5%. Among these, 186 (65%) were unrecognized by treating clinicians, receiving neither DM education, glucose-lowering medications at discharge, nor documentation of DM in the chart (median glycosylated hemoglobin of unrecognized patients, 6.7%; range, 6.5–12.3%). Six months after discharge, only 5% of those not recognized as having DM during hospitalization had been initiated on glucose-lowering medications versus 66% of those recognized (
P
<0.001).

Conclusions—

Underlying DM that has not been previously diagnosed is common among AMI patients, affecting 1 in 10 patients, yet is recognized by the care team only one third of the time. Given its frequency and therapeutic implications, including but extending beyond the initiation of glucose-lowering treatment, consideration should be given to screening all AMI patients for DM during hospitalization. Inexpensive, ubiquitous, and endorsed as an acceptable screen for DM, glycosylated hemoglobin testing should be considered for this purpose.
Evaluating Forecast Impact of Assimilating Microwave Humidity Sounder (MHS) Radiances with a Regional Ensemble Kalman Filter Data Assimilation System
Authors: Newman Kathryn M. , Schwartz Craig S. , Liu Zhiquan , Shao Hui , Huang Xiang-Yu
Published: April 2015

This study examines the impact of assimilating Microwave Humidity Sounder (MHS) radiances in a limited-area ensemble Kalman filter (EnKF) data assimilation system. Two experiments spanning 11 August–13 September 2008 were run over a domain featuring the Atlantic basin using a 6-h full cycling analysis and forecast system. Deterministic 72-h forecasts were initialized at 0000 and 1200 UTC for a comparison of forecast impact. The two experiments were configured identically with the exception of the inclusion of the MHS radiances (AMHS) in the second to isolate the impacts of the MHS radiance data. The results were verified against several sources, and statistical significance tests indicate the most notable differences are in the midlevel moisture fields. Both configurations were characterized by high moisture biases when compared to the European Centre for Medium-Range Weather Forecasts interim reanalysis (ERA-Interim, also known as ERA-I) specific humidity fields, as well as precipitable water vapor from an observationally based product. However, the AMHS experiment has midlevel moisture fields closer to the ERA-I and observation datasets. When reducing the verification domain to focus on the subtropical and easterly wave regions of the North Atlantic Ocean, larger improvements in midlevel moisture at nearly all lead times is seen in the AMHS simulation. Finally, when considering tropical cyclone forecasts, the AMHS configuration shows improvement in intensity forecasts at several lead times as well as improvements at early to intermediate lead times for minimum sea level pressure forecasts.
Ethnic Diversity and Social Trust
Authors: Dinesen Peter Thisted , Sønderskov Kim Mannemar
Published: April 2015

We argue that residential exposure to ethnic diversity reduces social trust. Previous within-country analyses of the relationship between contextual ethnic diversity and trust have been conducted at higher levels of aggregation, thus ignoring substantial variation in actual exposure to ethnic diversity. In contrast, we analyze how ethnic diversity of the immediate micro-context—where interethnic exposure is inevitable—affects trust. We do this using Danish survey data linked with register-based data, which enables us to obtain precise measures of the ethnic diversity of each individual’s residential surroundings. We focus on contextual diversity within a radius of 80 meters of a given individual, but we also compare the effect in the micro-context to the impact of diversity in more aggregate contexts. Our results show that ethnic diversity in the micro-context affects trust negatively, whereas the effect vanishes in larger contextual units. This supports the conjecture that interethnic exposure underlies the negative relationship between ethnic diversity in residential contexts and social trust.
A Dynamic Process Model of Private Politics
Authors: McDonnell Mary-Hunter , King Brayden G , Soule Sarah A.
Published: April 2015

This project explores whether and how corporations become more receptive to social activist challenges over time. Drawing from social movement theory, we suggest a dynamic process through which contentious interactions lead to increased receptivity. We argue that when firms are chronically targeted by social activists, they respond defensively by adopting strategic management devices that help them better manage social issues and demonstrate their normative appropriateness. These defensive devices have the incidental effect of empowering independent monitors and increasing corporate accountability, which in turn increase a firm’s receptivity to future activist challenges. We test our theory using a unique longitudinal dataset that tracks contentious attacks and the adoption of social management devices among a population of 300 large firms from 1993 to 2009.