bluuebunny/crossref_metadata_2025 huggingface dataset:
On Characterizing the Data Access Complexity of Programs
Authors: Elango Venmugil , Rastello Fabrice , Pouchet Louis-Noël , Ramanujam J. , Sadayappan P.
Published: May 2015

Technology trends will cause data movement to account for the majority of energy expenditure and execution time on emerging computers. Therefore, computational complexity will no longer be a sufficient metric for comparing algorithms, and a fundamental characterization of data access complexity will be increasingly important. The problem of developing lower bounds for data access complexity has been modeled using the formalism of Hong and Kung's red/blue pebble game for computational directed acyclic graphs (CDAGs). However, previously developed approaches to lower bounds analysis for the red/blue pebble game are very limited in effectiveness when applied to CDAGs of real programs, with computations comprised of multiple sub-computations with differing DAG structure. We address this problem by developing an approach for effectively composing lower bounds based on graph decomposition. We also develop a static analysis algorithm to derive the asymptotic data-access lower bounds of programs, as a function of the problem size and cache size.
How to improve the overall quality of cardiac morphometric data
Authors: Gerdes A. Martin
Published: May 2015

By the mid-1990s, experts realized that drugs leading to improved ventricular remodeling were doing something remarkable in cardiac patients. The “age of cardiac remodeling” had begun. This created an experimental need for high-quality assessment of changes in cardiac tissue composition, including myocyte shape, myocardial fibrosis/collagen, and vascular remodeling. Many working in the field today have little or no training related to recognition of fixation artifacts or common errors associated with quantitative morphology. Unfortunately, such skills had become somewhat of a lost art during the ages of cardiac physiology in the mid-20th century and molecular biology, gaining prominence by the mid-1970s. Consequently, cardiac remodeling studies today are often seriously flawed to the point where data are not reproducible and subsequent researchers may be chasing the molecular basis of a nonexistent or erroneous phenotype. The current unacceptably high incidence of irreproducible data is a serious waste of time and resources as recently noted in comments by the National Institutes of Health director. The goal of this “how to” article is to share some lessons I have learned during nearly 40 years of assessing morphological changes in the heart. It is possible for any laboratory to routinely publish highly reproducible morphological data that stand the test of time and contribute to our fundamental knowledge of cardiac remodeling and the molecular mechanisms that drive it.
GABA and glycine receptors in the nucleus ambiguus mediate tachycardia elicited by chemical stimulation of the hypothalamic arcuate nucleus
Authors: Chitravanshi Vineet C. , Kawabe Kazumi , Sapru Hreday N.
Published: May 2015

We have previously reported that stimulation of the hypothalamic arcuate nucleus (ARCN) by microinjections of N-methyl-d-aspartic acid (NMDA) elicits tachycardia, which is partially mediated via inhibition of vagal inputs to the heart. The neuronal pools and neurotransmitters in them mediating tachycardia elicited from the ARCN have not been identified. We tested the hypothesis that the tachycardia elicited from the ARCN may be mediated by inhibitory neurotransmitters in the nucleus ambiguus (nAmb). Experiments were done in urethane-anesthetized, artificially ventilated, male Wistar rats. In separate groups of rats, unilateral and bilateral microinjections of muscimol (1 mM), gabazine (0.01 mM), and strychnine (0.5 mM) into the nAmb significantly attenuated tachycardia elicited by unilateral microinjections of NMDA (10 mM) into the ARCN. Histological examination of the brains showed that the microinjections sites were within the targeted nuclei. Retrograde anatomic tracing from the nAmb revealed direct bilateral projections from the ARCN and hypothalamic paraventricular nucleus to the nAmb. The results of the present study suggest that tachycardia elicited by stimulation of the ARCN by microinjections of NMDA is mediated via GABAAand glycine receptors located in the nAmb.
Role of macrophage migration inhibitory factor in age-related lung disease
Authors: Sauler Maor , Bucala Richard , Lee Patty J.
Published: May 2015

The prevalence of many common respiratory disorders, including pneumonia, chronic obstructive lung disease, pulmonary fibrosis, and lung cancer, increases with age. Little is known of the host factors that may predispose individuals to such diseases. Macrophage migration inhibitory factor (MIF) is a potent upstream regulator of the immune system. MIF is encoded by variant alleles that occur commonly in the population. In addition to its role as a proinflammatory cytokine, a growing body of literature demonstrates that MIF influences diverse molecular processes important for the maintenance of cellular homeostasis and may influence the incidence or clinical manifestations of a variety of chronic lung diseases. This review highlights the biological properties of MIF and its implication in age-related lung disease.
From Plastic to Silicone: The Novelties in Porous Polymer Fabrications
Authors: Berro Soumaya , El Ahdab Ranim , Hajj Hassan Houssein , Khachfe Hassan M. , Hajj-Hassan Mohamad
Published: May 2015

Porous polymers are gaining increased interest in several areas due, in great part, to their large surface area and unique physiochemical properties. Porous polymers are conventionally manufactured using specific processes related to the chemical structure of each polymer. With the wide variety of porous polymers that have been designed, fabricated, and tested to date, this review aims to provide an overview of the advances and recent progress in the preparation processes and fabrication techniques. A detailed comparison between these techniques is also provided. Some of these techniques offer the advantage of controlling the porosity and the possibility to obtain porous 3D polymers. A new generic fabrication process that can be applied to all liquid polymers to texture their outer surfaces with a desired porosity is also presented. The proposed process, which is based on two micromolding steps, offers flexibility in terms of tailoring the texture of the final polymer by simply using porous silicon templates with different pore sizes and configurations. The anticipated process was successfully implemented to texture polyethyl hydrosiloxane (PMHS) using porous silicon and polymethyl methacrylate (PMMA) scaffolds.
Pancreatic and Colonic Abscess Formation Secondary to HELLP Syndrome
Authors: O’Brien James M. , Pursell Nicole , Fumia Fred
Published: May 2015

Preeclampsia and the variant HELLP syndrome are systemic conditions associated with vascular changes resulting in vasoconstriction. Most commonly, patients present with elevated blood pressure and proteinuria, with a background of complaints such as headache, scotoma, and right upper quadrant pain. The systemic vascular changes experienced can target any organ system, oftentimes with more than one organ system being involved. We present the case of a patient admitted with HELLP syndrome who subsequently developed multisystem organ dysfunction, including placental abruption, disseminated intravascular coagulopathy, acute renal failure, colitis, abdominal ascites, pancreatitis, and the development of pancreatic and colonic abscesses.
Cognitive Function and Salivary DHEA Levels in Physically Active Elderly African American Women
Authors: Davis Greggory R. , Gallien Gabrielle J. , Moody Kaitlyn M. , LeBlanc Nina R. , Smoak Peter R. , Bellar David
Published: May 2015

Serum and plasma dehydroepiandrosterone sulfate (DHEAS) concentration has been associated with several health parameters associated with aging including cognitive function, bone mineral density, and muscular strength. However, the effectiveness of salivary DHEA for the prediction of cognitive function, bone mineral density, and muscular strength in older adults is currently unknown. Thirty elderly African American females provided early morning salivary samples and DHEA levels were determined using a commercially available immunoassay. Participants completed testing for psychomotor and executive function via Trail Making Tests (TMT) A and B, respectively. Bone ultrasound attenuation (BUA) was used to bone density and an isometric mid-thigh pull (IMTP) was used to determine isometric strength. Age significantly correlated with time on TMT A (r=0.328) and B (r=0.615) but was not related to DHEA, BUA, or IMTP outcomes. Elevated DHEA was associated with longer time to completion for TMT A (χ2=5.14) but not to TMT B. DHEA levels were not associated with BUA or IMTP outcomes. While elevated levels of DHEA were correlated with impaired psychomotor function, salivary DHEA is not associated with executive function, bone mineral density, or isometric strength in elderly African American women.
Assessment of Macular Parameter Changes in Patients with Keratoconus Using Optical Coherence Tomography
Authors: Sahebjada Srujana , Amirul Islam Fakir M. , Wickremasinghe Sanj , Daniell Mark , Baird Paul N.
Published: May 2015

Keratoconus is typically diagnosed through changes at the anterior ocular surface. However, we wished to assess if macular parameter changes might also occur in these patients. We assessed posterior changes through the use of optical coherence tomography and compared to a nonkeratoconus patient group. All subjects underwent clinical examination including macular thickness measurements. The generalized estimation equation model was used to estimate the means and compare the differences in various measurements between keratoconus and nonkeratoconus patients. A total of 129 keratoconus eyes of 67 cases and 174 nonkeratoconus eyes of 87 controls were analysed. Keratoconus individuals presented with a significantly greater mean retinal thickness in the central fovea, inner, and outer macula compared to the nonkeratoconus group (p<0.05). In addition, individuals presenting with the early signs of keratoconus had significantly greater inner and outer macular volume compared to the nonkeratoconus group (p<0.05). This study indicates the retina appears to thicken at the fovea and macula and had increased macular volume in keratoconus individuals compared to nonkeratoconus individuals. Thus we posit that structural retinal changes exist in keratoconus eyes that are additional to those typically seen in the anterior segment.
A Literature Review on the Progression of Agile Manufacturing Paradigm and Its Scope of Application in Pump Industry
Authors: Thilak V. M. M. , Devadasan S. R. , Sivaram N. M.
Published: May 2015

During the recent years, the manufacturing world has been witnessing the application of agile manufacturing paradigm. The literature review reported in this paper was carried out to study this progression. This literature review was carried out in two phases. In the first phase, the literature was reviewed to trace the origin of agile manufacturing paradigm and identify its enablers. Further, during this phase, the applications of agile manufacturing reported in literature arena were reviewed. It was also discernable that certain research works have been initiated to apply agile manufacturing paradigm in pump industry. During the second phase, the researches reported on applying agile manufacturing in pump industry were reviewed. At the end of this review, it was found that so far the implementation of agile manufacturing in pump industry has been examined by the researchers by considering only certain components of pumps. In fact, the holistic implementation of agile manufacturing in the pump industry is yet to be examined by the researchers. In the context of drawing this inference, this paper has been concluded by stating that high scope exists in examining the infusing of agility characteristics in designing and manufacturing of pumps.
The Multivariate Largest Lyapunov Exponent as an Age-Related Metric of Quiet Standing Balance
Authors: Liu Kun , Wang Hongrui , Xiao Jinzhuang
Published: May 2015

The largest Lyapunov exponent has been researched as a metric of the balance ability during human quiet standing. However, the sensitivity and accuracy of this measurement method are not good enough for clinical use. The present research proposes a metric of the human body’s standing balance ability based on the multivariate largest Lyapunov exponent which can quantify the human standing balance. The dynamic multivariate time series of ankle, knee, and hip were measured by multiple electrical goniometers. Thirty-six normal people of different ages participated in the test. With acquired data, the multivariate largest Lyapunov exponent was calculated. Finally, the results of the proposed approach were analysed and compared with the traditional method, for which the largest Lyapunov exponent and power spectral density from the centre of pressure were also calculated. The following conclusions can be obtained. The multivariate largest Lyapunov exponent has a higher degree of differentiation in differentiating balance in eyes-closed conditions. The MLLE value reflects the overall coordination between multisegment movements. Individuals of different ages can be distinguished by their MLLE values. The standing stability of human is reduced with the increment of age.
Recurrent Syncope Associated with Lung Cancer
Authors: Zhang Dingguo , Wang Liansheng , Yang Zhijian
Published: May 2015

Syncope is an important problem in clinical practice with many possible causes that might be misdiagnosed. We present an unusual case of syncope, which has a normal chest X-ray. Exercise EKG and coronary angioplasty results confirmed the existence of serious coronary heart disease. The patient was treated with coronary stent transplantation. However, scope occurred again and the elevated tumor makers cytokeratin-19-fragment and neuron-specific enolase revealed the bronchogenic carcinoma, which was confirmed by enhanced CT examination. The treatment of carcinoma by chemotherapy was indeed sufficient for prompt elimination of the syncope symptoms.
Clinical Application of Mesenchymal Stem Cells and Novel Supportive Therapies for Oral Bone Regeneration
Authors: Padial-Molina Miguel , O’Valle Francisco , Lanis Alejandro , Mesa Francisco , Dohan Ehrenfest David M. , Wang Hom-Lay , Galindo-Moreno Pablo
Published: May 2015

Bone regeneration is often needed prior to dental implant treatment due to the lack of adequate quantity and quality of the bone after infectious diseases, trauma, tumor, or congenital conditions. In these situations, cell transplantation technologies may help to overcome the limitations of autografts, xenografts, allografts, and alloplastic materials. A database search was conducted to include human clinical trials (randomized or controlled) and case reports/series describing the clinical use of mesenchymal stem cells (MSCs) in the oral cavity for bone regeneration only specifically excluding periodontal regeneration. Additionally, novel advances in related technologies are also described. 190 records were identified. 51 articles were selected for full-text assessment, and only 28 met the inclusion criteria: 9 case series, 10 case reports, and 9 randomized controlled clinical trials. Collectively, they evaluate the use of MSCs in a total of 290 patients in 342 interventions. The current published literature is very diverse in methodology and measurement of outcomes. Moreover, the clinical significance is limited. Therefore, the use of these techniques should be further studied in more challenging clinical scenarios with well-designed and standardized RCTs, potentially in combination with new scaffolding techniques and bioactive molecules to improve the final outcomes.
An Alternative Approach of Dual Response Surface Optimization Based on Penalty Function Method
Authors: Baba Ishaq , Midi Habshah , Rana Sohel , Ibragimov Gafurjan
Published: May 2015

The dual response surface for simultaneously optimizing the mean and variance models as separate functions suffers some deficiencies in handling the tradeoffs between bias and variance components of mean squared error (MSE). In this paper, the accuracy of the predicted response is given a serious attention in the determination of the optimum setting conditions. We consider four different objective functions for the dual response surface optimization approach. The essence of the proposed method is to reduce the influence of variance of the predicted response by minimizing the variability relative to the quality characteristics of interest and at the same time achieving the specific target output. The basic idea is to convert the constraint optimization function into an unconstraint problem by adding the constraint to the original objective function. Numerical examples and simulations study are carried out to compare performance of the proposed method with some existing procedures. Numerical results show that the performance of the proposed method is encouraging and has exhibited clear improvement over the existing approaches.
Anti-Inflammatory Effects of Heparin and Its Derivatives: A Systematic Review
Authors: Mousavi Sarah , Moradi Mandana , Khorshidahmad Tina , Motamedi Maryam
Published: May 2015

Background. Heparin, used clinically as an anticoagulant, also has anti-inflammatory properties. The purpose of this systematic review was to provide a comprehensive review regarding the efficacy and safety of heparin and its derivatives as anti-inflammatory agents.Methods. We searched the following databases up to March 2012: Pub Med, Scopus, Web of Science, Ovid, Elsevier, and Google Scholar using combination of Mesh terms. Randomized Clinical Trials (RCTs) and trials with quasi-experimental design in clinical setting published in English were included. Quality assessments of RCTs were performed using Jadad score and Consolidated Standards of Reporting Trials (CONSORT) checklist.Results. A total of 280 relevant studies were reviewed and 57 studies met the inclusion criteria. Among them 48 studies were RCTs. About 65% of articles had score of 3 and higher according to Jadad score. Twelve studies had a quality score > 40% according to CONSORT items. Asthma (n=7), inflammatory bowel disease (n=5), cardiopulmonary bypass (n=8), and cataract surgery (n=6) were the most studied disease condition. Forty studies use unfractionated heparin (UFH) for intervention; the remaining studies use low molecular weight heparin (LMWH).Conclusion. Despite the conflicting results, heparin seems to be a safe and effective anti-inflammatory agent; although it is shown that heparin can decrease the level of inflammatory biomarkers and improves patient conditions, still more data from larger rigorously designed studies are needed to support use of heparin as an anti-inflammatory agent in clinical setting. However, because of the association between inflammation, atherogenesis, thrombogenesis, and cell proliferation, heparin and related compounds with pleiotropic effects may have greater therapeutic efficacy than compounds acting against a single target.
A Cable-Passive Damper System for Sway and Skew Motion Control of a Crane Spreader
Authors: Viet La Duc , Park Youngjin
Published: May 2015

While the crane control problem is often approached by applying a certain active control command to some parts of the crane, this paper proposes a cable-passive damper system to reduce the vibration of a four-cable suspended crane spreader. The residual sway and skew motions of a crane spreader always produce the angle deflections between the crane cables and the crane spreader. The idea in this paper is to convert those deflections into energy dissipated by the viscous dampers, which connect the cables and the spreader. The proposed damper system is effective in reducing spreader sway and skew motions. Moreover, the optimal damping coefficient can be found analytically by minimizing the time integral of system energy. The numerical simulations show that the proposed passive system can assist the input shaping control of the trolley motion in reducing both sway and skew responses.
Rare Case ofAspergillus ochraceusOsteomyelitis of Calcaneus Bone in a Patient with Diabetic Foot Ulcers
Authors: Babamahmoodi Farhang , Shokohi Tahereh , Ahangarkani Fatemeh , Nabili Mojtaba , Afzalian Ashkezari Elham , Alinezhad Sosan
Published: May 2015

Diabetes is the most common metabolic disease in humans. One of the major complications of the disease is foot ulcer that is prone to infection. The most common causes of infection which have been reported in these patients are bacteria and fungi such asCandida, Aspergillus, and Rhizopusspecies. We report one such rare case with calcaneal osteomyelitis caused byAspergillus ochraceusin a patient with diabetic foot osteomyelitis. The case was a 68-year-old male with a history of type II diabetes for 2 years. The patient had two ulcers on the right heel bones for the past 6 months with no significant improvement. One of the most important predisposing factors to infectious diseases, especially opportunistic fungal infection, is diabetes mellitus.Aspergillusspecies can involve bony tissue through vascular system, direct infection, and trauma. Proper and early diagnosis and treatment of diabetic foot infection can reduce or prevent complications, such as osteomyelitis and amputation. The annual examination of feet for skin and nail lesion, sensation, anatomical changes, and vascular circulation can be useful for prevention and control of infection.
Vibration Sensor Approaches for the Monitoring of Sand Production in Bohai Bay
Authors: Wang Kai , Liu Zhiguo , Liu Gang , Yi Longtao , Yang Kui , Peng Shiqi , Chen Man
Published: May 2015

The real-time monitoring of sand production has always been an important issue during the process of oil production in offshore field. This paper illustrates a new alternative vibration sensor approach to monitor the sand production. A special broadband sensor was selected. Then the time-frequency analysis, characteristic sand frequency band filter method, and peak searching-denoising method were proposed to enhance the detection ability of sand vibration signals in strong background noises of crude oil flow. After that, visible differences in time-frequency domain and power spectrum between sand and nonsand production well can be observed. Four typical wells in Bohai oil production platform were selected to investigate the monitoring effects of sand production. The monitoring findings show that there exists a good correlation between the vibration power spectrum amplitude and the sand production volume, which is consistent with actual results.
Osteogenic Matrix Cell Sheets Facilitate Osteogenesis in Irradiated Rat Bone
Authors: Uchihara Yoshinobu , Akahane Manabu , Shimizu Takamasa , Ueha Tomoyuki , Morita Yusuke , Nakasaki Shintaro , Kura Tomohiko , Tohma Yasuaki , Kido Akira , Kawate Kenji , Tanaka Yasuhito
Published: May 2015

Reconstruction of large bone defects after resection of malignant musculoskeletal tumors is a significant challenge in orthopedic surgery. Extracorporeal autogenous irradiated bone grafting is a treatment option for bone reconstruction. However, nonunion often occurs because the osteogenic capacity is lost by irradiation. In the present study, we established an autogenous irradiated bone graft model in the rat femur to assess whether osteogenic matrix cell sheets improve osteogenesis of the irradiated bone. Osteogenic matrix cell sheets were prepared from bone marrow-derived stromal cells and co-transplanted with irradiated bone. X-ray images at 4 weeks after transplantation showed bridging callus formation around the irradiated bone. Micro-computed tomography images at 12 weeks postoperatively showed abundant callus formation in the whole circumference of the irradiated bone. Histology showed bone union between the irradiated bone and host femur. Mechanical testing showed that the failure force at the irradiated bone site was significantly higher than in the control group. Our study indicates that osteogenic matrix cell sheet transplantation might be a powerful method to facilitate osteogenesis in irradiated bones, which may become a treatment option for reconstruction of bone defects after resection of malignant musculoskeletal tumors.
Development of Castor Oil Based Poly(urethane‐esteramide)/TiO2 Nanocomposites as Anticorrosive and Antimicrobial Coatings
Authors: Shaik Mohammed Rafi , Alam Manawwer , Alandis Naser M.
Published: May 2015

Castor oil based polyesteramide (CPEA) resin has been successfully synthesized by the condensation polymerization of N‐N‐bis (2‐hydroxyethyl) castor oil fatty amide (HECA) with terephthalic acid and further modified with different percentages of 7, 9, 11, and 13 wt.% of toluene‐2,4‐diisocyanate (TDI) to obtain poly(urethane‐esteramide) (UCPEA), via addition polymerization. TiO2 (0.1, 0.2, 0.3, 0.4, and 0.5 wt%) nanoparticles were dispersed in UCPEA resin. The structural elucidation of HECA, CPEA, and UCPEA has been carried out using FT‐IR, 1H‐NMR, and 13C‐NMR spectroscopic techniques while physicochemical and physicomechanical properties were investigated by standard methods. Thermal stability and molecular weight of UCPEA have been assessed by thermogravimetric analysis (TGA) and gel permeation chromatography (GPC), respectively. Furthermore, the corrosion behavior of UCPEA coatings on mild steel has been investigated by potentiodynamic polarization measurements in different corrosive environments (3.5 wt% HCl, 5 wt% NaCl, 3.5 wt% NaOH, and tap water) at room temperature and surface analysis by scanning electron microscope (SEM) and energy dispersive X‐ray (EDX). The antibacterial activities of the UCPEA were tested against bacteria and fungi by agar disc diffusion method. The results of this study have revealed that UCPEA nanocomposite coatings exhibit good physicomechanical, anticorrosion and antimicrobial properties, which can be safely used up to 200°C.
Frequent Self-Weighing and Visual Feedback for Weight Loss in Overweight Adults
Authors: Pacanowski Carly R. , Levitsky David A.
Published: May 2015

Evidence has suggested that self-weighing may be beneficial for weight control in adults, but few studies have independently assessed the contribution of this behavior to weight loss. This study experimentally tested daily self-weighing and visual feedback (the Caloric Titration Method (CTM)) as a weight loss and weight loss maintenance intervention over 2 years. 162 overweight individuals were randomized to the CTM intervention or delayed treatment control group. In year 1, weight change was compared between groups, and in year 2, the control group started using the CTM while the intervention group continued using the CTM for maintenance. A significant difference in weight loss over the first year (CTMn= 70; 2.6 ± 5.9 kg versus controln= 65; 0.5 ± 4.4 kg,p= 0.019) was qualified by a group × gender × time interaction (p= 0.002) such that men lost more weight using the CTM. In year 2, the CTM group maintained their weight and the control group lost an amount similar to the intervention group in year 1. Daily self-weighing and visual feedback facilitated a minimal amount of weight loss and maintenance of this loss. Future research investigating characteristics of those who benefit from this type of self-directed intervention is warranted.
Automated Quantification of Neuropad Improves Its Diagnostic Ability in Patients with Diabetic Neuropathy
Authors: Ponirakis Georgios , Fadavi Hassan , Petropoulos Ioannis N. , Azmi Shazli , Ferdousi Maryam , Dabbah Mohammad A. , Kheyami Ahmad , Alam Uazman , Asghar Omar , Marshall Andrew , Tavakoli Mitra , Al-Ahmar Ahmed , Javed Saad , Jeziorska Maria , Malik Rayaz A.
Published: May 2015

Neuropad is currently a categorical visual screening test that identifies diabetic patients at risk of foot ulceration. The diagnostic performance of Neuropad was compared between the categorical and continuous (image-analysis (Sudometrics)) outputs to diagnose diabetic peripheral neuropathy (DPN). 110 subjects with type 1 and 2 diabetes underwent assessment with Neuropad, Neuropathy Disability Score (NDS), peroneal motor nerve conduction velocity (PMNCV), sural nerve action potential (SNAP), Deep Breathing-Heart Rate Variability (DB-HRV), intraepidermal nerve fibre density (IENFD), and corneal confocal microscopy (CCM). 46/110 patients had DPN according to the Toronto consensus. The continuous output displayed high sensitivity and specificity for DB-HRV (91%, 83%), CNFD (88%, 78%), and SNAP (88%, 83%), whereas the categorical output showed high sensitivity but low specificity. The optimal cut-off points were 90% for the detection of autonomic dysfunction (DB-HRV) and 80% for small fibre neuropathy (CNFD). The diagnostic efficacy of the continuous Neuropad output for abnormal DB-HRV (AUC: 91%,P=0.0003) and CNFD (AUC: 82%,P=0.01) was better than for PMNCV (AUC: 60%). The categorical output showed no significant difference in diagnostic efficacy for these same measures. An image analysis algorithm generating a continuous output (Sudometrics) improved the diagnostic ability of Neuropad, particularly in detecting autonomic and small fibre neuropathy.
Schisandrae Fructus Supplementation Ameliorates Sciatic Neurectomy-Induced Muscle Atrophy in Mice
Authors: Kim Joo Wan , Ku Sae-Kwang , Kim Ki Young , Kim Sung Goo , Han Min Ho , Kim Gi-Young , Hwang Hye Jin , Kim Byung Woo , Kim Cheol Min , Choi Yung Hyun
Published: May 2015

The objective of this study was to assess the possible beneficial skeletal muscle preserving effects of ethanol extract of Schisandrae Fructus (EESF) on sciatic neurectomy- (NTX-) induced hindlimb muscle atrophy in mice. Here, calf muscle atrophy was induced by unilateral right sciatic NTX. In order to investigate whether administration of EESF prevents or improves sciatic NTX-induced muscle atrophy, EESF was administered orally. Our results indicated that EESF dose-dependently diminished the decreases in markers of muscle mass and activity levels, and the increases in markers of muscle damage and fibrosis, inflammatory cell infiltration, cytokines, and apoptotic events in the gastrocnemius muscle bundles are induced by NTX. Additionally, destruction of gastrocnemius antioxidant defense systems after NTX was dose-dependently protected by treatment with EESF. EESF also upregulated muscle-specific mRNAs involved in muscle protein synthesis but downregulated those involved in protein degradation. The overall effects of 500 mg/kg EESF were similar to those of 50 mg/kg oxymetholone, but it showed more favorable antioxidant effects. The present results suggested that EESF exerts a favorable ameliorating effect on muscle atrophy induced by NTX, through anti-inflammatory and antioxidant effects related to muscle fiber protective effects andviaan increase in protein synthesis and a decrease in protein degradation.
Starch Origin and Thermal Processing Affect Starch Digestion in a Minipig Model of Pancreatic Exocrine Insufficiency
Authors: Mößeler Anne , Vagt Sandra , Beyerbach Martin , Kamphues Josef
Published: May 2015

Although steatorrhea is the most obvious symptom of pancreatic exocrine insufficiency (PEI), enzymatic digestion of protein and starch is also impaired. Low praecaecal digestibility of starch causes a forced microbial fermentation accounting for energy losses and meteorism. To optimise dietetic measures, knowledge of praecaecal digestibility of starch is needed but such information from PEI patients is rare. Minipigs fitted with an ileocaecal fistula with (n=3) or without (n=3) pancreatic duct ligation (PL) were used to estimate the rate of praecaecal disappearance (pcD) of starch. Different botanical sources of starch (rice, amaranth, potato, and pea) were fed either raw or cooked. In the controls (C), there was an almost complete pcD (>92%) except for potato starch (61.5%) which was significantly lower. In PL pcD of raw starch was significantly lower for all sources of starch except for amaranth (87.9%). Thermal processing increased pcD in PL, reaching values of C for starch from rice, potato, and pea. This study clearly underlines the need for precise specification of starch used for patients with specific dietetic needs like PEI. Data should be generated in suitable animal models or patients as tests in healthy individuals would not have given similar conclusions.
Rank One Strange Attractors in Periodically Kicked Lorenz System with Time-Delay
Authors: Yang Wenjie , Lin Yiping , Dai Yunxian
Published: May 2015

Rank one strange attractor in periodically kicked Lorenz system with time-delay is investigated. Our discussion is based on the theory of rank one maps formulated by Wang and Young. First, we develop the rank one chaotic theory to delayed systems. It is shown that strange attractors occur when periodically kicked delayed system undergoes a generic Hopf bifurcation. Then we use the theory to the periodically kicked Lorenz system with delay, and derivation of conditions for Hopf bifurcation and rank one chaos along with the results of numerical simulations are presented.
Anterior and Posterior Corneal Astigmatism after Refractive Lenticule Extraction for Myopic Astigmatism
Authors: Kamiya Kazutaka , Shimizu Kimiya , Yamagishi Mayumi , Igarashi Akihito , Kobashi Hidenaga
Published: May 2015

Purpose.To assess the amount and the axis orientation of anterior and posterior corneal astigmatism after refractive lenticule extraction (ReLEx) for myopic astigmatism.Methods.We retrospectively examined 53 eyes of 53 consecutive patients (mean age ± standard deviation, 33.2 ± 6.5 years) undergoing ReLEx to correct myopic astigmatism (manifest cylinder = 0.5 diopters (D)). Power vector analysis was performed with anterior and posterior corneal astigmatism measured with a rotating Scheimpflug system (Pentacam HR, Oculus) and refractive astigmatism preoperatively and 3 months postoperatively.Results.Anterior corneal astigmatism was significantly decreased, measuring 1.42 ± 0.73 diopters (D) preoperatively and 1.11 ± 0.53 D postoperatively (p<0.001, Wilcoxon signed-rank test). Posterior corneal astigmatism showed no significant change, falling from 0.44 ± 0.12 D preoperatively to 0.42 ± 0.13 D postoperatively (p=0.18). Refractive astigmatism decreased significantly, from 0.92 ± 0.51 D preoperatively to 0.27 ± 0.44 D postoperatively (p<0.001). The anterior surface showed with-the-rule astigmatism in 51 eyes (96%) preoperatively and 48 eyes (91%) postoperatively. By contrast, the posterior surface showed against-the-rule astigmatism in all eyes preoperatively and postoperatively.Conclusions.The surgical effects were largely attributed to the astigmatic correction of the anterior corneal surface. Posterior corneal astigmatism remained unchanged even after ReLEx for myopic astigmatism.
An Information Geometric Viewpoint on the Detection of Range Distributed Targets
Authors: Tang Mengjiao , Rong Yao , Zhou Jie
Published: May 2015

The paper adopts the information geometry, to put forward a new viewpoint on the detection of range distributed targets embedded in Gaussian noise with unknown covariance. The original hypothesis test problem is formulated as the discrimination between distributions of the measurements and the noise. The Siegel distance, which is exactly the well-known geodesic distance between images of the original distributions via embedding into a higher-dimensional manifold, is given as an intrinsic measure on the difference between multivariate normal distributions. Without the assumption of uncorrelated measurements, we propose a set of geometric distance detectors, which is designed based on the Siegel distance and different from the generalized likelihood ratio algorithm or other common criterions in statistics. As special cases, the classical optimal matched filter, Rao test, and Wald test, which have been proven to have the CFAR property, belong to the set. Moreover, it is also accessible to an intuitively geometric analysis about how strongly the data contradict the null hypothesis.
Non-Hodgkin Lymphoma, Body Mass Index, and Cytokine Polymorphisms: A Pooled Analysis from the InterLymph Consortium
Authors: Kane Eleanor , Skibola Christine F. , Bracci Paige M. , Cerhan James R. , Costas Laura , Smedby Karin Ekström , Holly Elizabeth A. , Maynadié Marc , Novak Anne J. , Lightfoot Tracy J. , Ansell Stephen M. , Smith Alex G. , Liebow Mark , Melbye Mads , Morton Lindsay , de Sanjosé Silvia , Slager Susan L. , Wang Sophia S. , Zhang Yawei , Zheng Tongzhang , Roman Eve
Published: May 2015

Background: Excess adiposity has been associated with lymphomagenesis, possibly mediated by increased cytokine production causing a chronic inflammatory state. The relationship between obesity, cytokine polymorphisms, and selected mature B-cell neoplasms is reported.

Method: Data on 4,979 cases and 4,752 controls from nine American/European studies from the InterLymph consortium (1988–2008) were pooled. For diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), joint associations of body mass index (from self-reported height and weight) and 12 polymorphisms in cytokines IL1A (rs1800587), IL1B (rs16944, rs1143627), IL1RN (rs454078), IL2 (rs2069762), IL6 (rs1800795, rs1800797), IL10 (rs1800890, rs1800896), TNF (rs1800629), LTA (rs909253), and CARD15 (rs2066847) were investigated using unconditional logistic regression. BMI-polymorphism interaction effects were estimated using the relative excess risk due to interaction (RERI).

Results: Obesity (BMI ≥ 30 kg/m2) was associated with DLBCL risk [OR = 1.33; 95% confidence interval (CI), 1.02–1.73], as was TNF-308GA+AA (OR = 1.24; 95% CI, 1.07–1.44). Together, being obese and TNF-308GA+AA increased DLBCL risk almost 2-fold relative to those of normal weight and TNF-308GG (OR = 1.93; 95% CI, 1.27–2.94), with a RERI of 0.41 (95% CI, −0.05–0.84; Pinteraction = 0.13). For FL and CLL/SLL, no associations with obesity or TNF-308GA+AA, either singly or jointly, were observed. No evidence of interactions between obesity and the other polymorphisms were detected.

Conclusions: Our results suggest that cytokine polymorphisms do not generally interact with BMI to increase lymphoma risk but obesity and TNF-308GA+AA may interact to increase DLBCL risk.

Impact: Studies using better measures of adiposity are needed to further investigate the interactions between obesity and TNF-308G>A in the pathogenesis of lymphoma. Cancer Epidemiol Biomarkers Prev; 24(7); 1061–70. ©2015 AACR.
Polymorphism at 19q13.41 Predicts Breast Cancer Survival Specifically after Endocrine Therapy
Authors: Khan Sofia , Fagerholm Rainer , Rafiq Sajjad , Tapper William , Aittomäki Kristiina , Liu Jianjun , Blomqvist Carl , Eccles Diana , Nevanlinna Heli
Published: May 2015

Purpose: Although most patients with estrogen receptor (ER)–positive breast cancer benefit from endocrine therapies, a significant proportion do not. Our aim was to identify inherited genetic variations that might predict survival among patients receiving adjuvant endocrine therapies.

Experimental Design: We performed a meta-analysis of two genome-wide studies; Helsinki Breast Cancer Study, 805 patients, with 240 receiving endocrine therapy and Prospective study of Outcomes in Sporadic versus Hereditary breast cancer, 536 patients, with 155 endocrine therapy patients, evaluating 486,478 single-nucleotide polymorphisms (SNP). The top four associations from the endocrine treatment subgroup were further investigated in two independent datasets totaling 5,011 patients, with 3,485 receiving endocrine therapy.

Results: A meta-analysis identified a common SNP rs8113308, mapped to 19q13.41, associating with reduced survival among endocrine-treated patients [hazard ratio (HR), 1.69; 95% confidence interval (CI), 1.37–2.07; P = 6.34 × 10−7] and improved survival among ER-negative patients, with a similar trend in ER-positive cases not receiving endocrine therapy. In a multivariate analysis adjusted for conventional prognostic factors, we found a significant interaction between the rs8113308 and endocrine treatment, indicating a predictive, treatment-specific effect of the SNP rs8113308 on breast cancer survival, with the per-allele HR for interaction 2.16 (95% CI, 1.30–3.60; Pinteraction = 0.003) and HR = 7.77 (95% CI, 0.93–64.71) for the homozygous genotype carriers. A biologic rationale is suggested by in silico functional analyses.

Conclusions: Our findings suggest carrying the rs8113308 rare allele may identify patients who will not benefit from adjuvant endocrine treatment. Clin Cancer Res; 21(18); 4086–96. ©2015 AACR.
Dissecting the Dual Role of AMPK in Cancer: From Experimental to Human Studies
Authors: Zadra Giorgia , Batista Julie L. , Loda Massimo
Published: May 2015

The precise role of 5′AMP-activated kinase (AMPK) in cancer and its potential as a therapeutic target is controversial. Although it is well established that activation of this energy sensor inhibits the main anabolic processes that sustain cancer cell proliferation and growth, AMPK activation can confer on cancer cells the plasticity to survive under metabolic stress such as hypoxia and glucose deprivation, which are commonly observed in fast growing tumors. Thus, AMPK is referred to as both a “conditional” tumor suppressor and “contextual” oncogene. To add a further layer of complexity, AMPK activation in human cancer tissues and its correlation with tumor aggressiveness and progression appears to vary in different contexts. The current review discusses the different faces of this metabolic regulator, the therapeutic implications of its modulation, and provides an overview of the most relevant data available on AMPK activation and AMPK-activating drugs in human studies. Mol Cancer Res; 13(7); 1059–72. ©2015 AACR.
Pharmacologically Increasing Mdm2 Inhibits DNA Repair and Cooperates with Genotoxic Agents to Kill p53-Inactivated Ovarian Cancer Cells
Authors: Carrillo Alexia M. , Hicks Mellissa , Khabele Dineo , Eischen Christine M.
Published: May 2015

The Mdm2 oncogene is a negative regulator of the p53 tumor suppressor and recently identified inhibitor of DNA break repair. Nutlin-3 is a small-molecule inhibitor of Mdm2–p53 interaction that can induce apoptosis in cancer cells through activation of p53. Although this is a promising therapy for those cancers with wild-type p53, half of all human cancers have inactivated p53. Here, we reveal that a previously unappreciated effect of Nutlin is inhibition of DNA break repair, stemming from its ability to increase Mdm2 protein levels. The Nutlin-induced increase in Mdm2 inhibited DNA double-strand break repair and prolonged DNA damage response signaling independent of p53. Mechanistically, this effect of Nutlin required Mdm2 and acted through Nbs1 of the Mre11–Rad50–Nbs1 DNA repair complex. In ovarian cancer cells, where >90% have inactivated p53, Nutlin combined with the genotoxic agents, cisplatin or etoposide, had a cooperative lethal effect resulting in increased DNA damage and apoptosis. Therefore, these data demonstrate an unexpected consequence of pharmacologically increasing Mdm2 levels that when used in combination with genotoxic agents induces synthetic lethality in ovarian cancer cells, and likely other malignant cell types, that have inactivated p53.

Implications: Data reveal a therapeutically beneficial effect of pharmacologically increasing Mdm2 levels combined with chemotherapeutic agents for malignancies that have lost functional p53. Mol Cancer Res; 13(8); 1197–205. ©2015 AACR.
PD-1 and CD103 Are Widely Coexpressed on Prognostically Favorable Intraepithelial CD8 T Cells in Human Ovarian Cancer
Authors: Webb John R. , Milne Katy , Nelson Brad H.
Published: May 2015

αE(CD103)β7 is a TGFβ-regulated integrin that mediates retention of lymphocytes in peripheral tissues by binding to E-cadherin expressed on epithelial cells. We recently reported that αE(CD103)β7 specifically demarcates intraepithelial CD8+ tumor-infiltrating lymphocytes (CD8 TIL) in ovarian cancer and that CD103+ TIL have a surface profile consistent with an active effector phenotype (HLA-DR+, Ki67+, and CD127lo). These findings led us to hypothesize that, over time, CD103-mediated retention of CD8 TIL within the tumor epithelium might result in chronic stimulation by tumor antigen, which in turn might lead to an exhausted phenotype. To investigate this possibility, we evaluated PD-1 expression in a large cohort of ovarian tumors (N = 489) with known CD103+ TIL content. PD-1+ cells were present in 38.5% of high-grade serous carcinomas (HGSC), but were less prevalent in other histologic subtypes. PD-1+ TIL were strongly associated with increased disease-specific survival in HGSC (HR, 0.4864; P = 0.0007). Multicolor immunohistochemistry and flow cytometry revealed a high degree of PD-1 and CD103 coexpression, specifically within the CD8 TIL compartment. PD-1+CD103+ CD8 TIL were quiescent when assessed directly ex vivo yet were capable of robust cytokine production after pharmacologic stimulation. Moreover, they showed negligible expression of additional exhaustion-associated markers, including TIM-3, CTLA-4, and LAG-3. Thus, as hypothesized, CD103+ CD8 TIL express PD-1 and appear quiescent in the tumor microenvironment. However, these cells retain functional competence and demonstrate strong prognostic significance. We speculate that, after standard treatment, PD-1+CD103+ CD8 TIL might regain functional antitumor activity, an effect that potentially could be augmented by immune modulation. Cancer Immunol Res; 3(8); 926–35. ©2015 AACR.
Carriage Rates and Characteristics of Enterobacteriaceae Producing Extended-Spectrum Beta-Lactamases in Healthy Individuals: Comparison of Applicants for Long-Term Care and Individuals Screened for Employment Purposes
Authors: Ebrahimi Fatemeh , Mózes Julianna , Mészáros Júlia , Juhász Ágnes , Kardos Gábor
Published: May 2015

Aims: We compared the prevalence of extended-spectrum beta-lactamase (ESBL) producers in the faecal samples of 1,109 healthy individuals screened for employment purposes and in 531 asymptomatic individuals applying for long-term care (LTC). Methods: Eosin-methylene blue agar plates supplemented with 2 mg/l cefotaxime were used to determine which individuals were ESBL producers. ESBL phenotype was confirmed by double-disk synergy test and ESBL genes were identified by sequencing. ESBL producers were characterized by co-resistance and integron carriage. Results: ESBL producers were more frequent in the LTC applicants than in the employment screening individuals (7.2 vs. 2.0%; p < 0.0001), with 43 Escherichia coli, 18 Klebsiella pneumoniae, 1 Klebsiella oxytoca and 1 Proteus mirabilis being found. In the employment screening individuals, only E. coli was found. Most ESBL genes (79.4%, 50/63) were blaCTX-M type; blaCTX-M-15 was more frequent in the LTC applicants (p < 0.001). Regarding ESBL genes and integron diversity, E. coli isolates from the LTC applicants were more similar to K. pneumoniae than to E. coli from the employment screening individuals. Conclusion: These differences in the characteristics of ESBL producers may represent different sources of colonization. Most LTC applicants harboured K. pneumoniae or E. coli that were probably hospital-acquired whereas the E. coli isolates of many healthy individuals showed similarities to environmental E. coli.