bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Direct-Fed Microbials in Conventional Livestock Production
Authors: Buntyn J.O. , Schmidt T.B. , Nisbet D.J. , Callaway T.R.
Published: December 2015

Supplementation of direct-fed microbials (DFM) as a means to improve the health and performance of livestock has generated significant interest over the past 15+ years. A driving force for this increased interest in DFM is to reduce or eliminate the use of low-dose antibiotics in livestock production. This increased attention toward DFM supplementation has generated an extensive body of research. This effort has resulted in conflicting reports. Although there has been considerable variation in the design of these studies, one of the main causes for this lack of consistency may be attributed to the variation in the experimental immune challenge incorporated to evaluate DFM supplementation. Taking into account the experimental immune challenge, there is strong evidence to suggest that DFM supplementation may have an impact on the immune response, overall health, and performance of livestock.
Mechanisms Used by Plants to Cope with DNA Damage
Authors: Hu Zhubing , Cools Toon , De Veylder Lieven
Published: December 2015

Because the genome stores all genetic information required for growth and development, it is of pivotal importance to maintain DNA integrity, especially during cell division, when the genome is prone to replication errors and damage. Although over the last two decades it has become evident that the basic cell cycle toolbox of plants shares several similarities with those of fungi and mammals, plants appear to have evolved a set of distinct checkpoint regulators in response to different types of DNA stress. This might be a consequence of plants' sessile lifestyle, which exposes them to a set of unique DNA damage–inducing conditions. In this review, we highlight the types of DNA stress that plants typically experience and describe the plant-specific molecular mechanisms that control cell division in response to these stresses.
Traumatic Myiasis: A Neglected Disease in a Changing World
Authors: Hall Martin J.R. , Wall Richard L. , Stevens Jamie R.
Published: December 2015

Traumatic myiasis, the parasitic infestation by fly larvae in traumatic lesions of the tissues of living vertebrates, is a serious medical condition in humans and a welfare and economic issue in domestic animals. New molecular studies are providing insights into its evolution and epidemiology. Nevertheless, its incidence in humans is generally underreported, particularly in tropical and subtropical regions. Myiasis in domestic animals has been studied more extensively, but continuous management is difficult and expensive. A key concern is the inadvertent introduction and global spread of agents of myiasis into nonendemic areas, facilitated by climate change and global transport. The incursion of the New World screwworm fly (Cochliomyia hominivorax) into Libya is the most notable of many such range shifts and demonstrates the potential risks of these parasites and the costs of removing them once established in a geographic area. Nevertheless, the insect agents of myiasis can be of societal benefit to forensic science and in medicine as an aid to wound treatment (larval therapy).
Pathophysiology and Mechanisms of Nonalcoholic Fatty Liver Disease
Authors: Haas Joel T. , Francque Sven , Staels Bart
Published: December 2015

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver disorders characterized by abnormal hepatic fat accumulation, inflammation, and hepatocyte dysfunction. Importantly, it is also closely linked to obesity and the metabolic syndrome. NAFLD predisposes susceptible individuals to cirrhosis, hepatocellular carcinoma, and cardiovascular disease. Although the precise signals remain poorly understood, NAFLD pathogenesis likely involves actions of the different hepatic cell types and multiple extrahepatic signals. The complexity of this disease has been a major impediment to the development of appropriate metrics of its progression and effective therapies. Recent clinical data place increasing importance on identifying fibrosis, as it is a strong indicator of hepatic disease–related mortality. Preclinical modeling of the fibrotic process remains challenging, particularly in the contexts of obesity and the metabolic syndrome. Future studies are needed to define the molecular pathways determining the natural progression of NAFLD, including key determinants of fibrosis and disease-related outcomes. This review covers the evolving concepts of NAFLD from both human and animal studies. We discuss recent clinical and diagnostic methods assessing NAFLD diagnosis, progression, and outcomes; compare the features of genetic and dietary animal models of NAFLD; and highlight pharmacological approaches for disease treatment.
Cortico–Basal Ganglia Circuit Function in Psychiatric Disease
Authors: Gunaydin Lisa A. , Kreitzer Anatol C.
Published: December 2015

Circuit dysfunction models of psychiatric disease posit that pathological behavior results from abnormal patterns of electrical activity in specific cells and circuits in the brain. Many psychiatric disorders are associated with abnormal activity in the prefrontal cortex and in the basal ganglia, a set of subcortical nuclei implicated in cognitive and motor control. Here we discuss the role of the basal ganglia and connected prefrontal regions in the etiology and treatment of obsessive-compulsive disorder, anxiety, and depression, emphasizing mechanistic work in rodent behavioral models to dissect causal cortico–basal ganglia circuits underlying discrete behavioral symptom domains relevant to these complex disorders.
Brain-liver connections: role of the preautonomic PVN neurons
Authors: O'Hare James D. , Zsombok Andrea
Published: December 2015

Diabetes mellitus and the coexisting conditions and complications, including hypo- and hyperglycemic events, obesity, high cholesterol levels, and many more, are devastating problems. Undoubtedly, there is a huge demand for treatment and prevention of these conditions that justifies the search for new approaches and concepts for better management of whole body metabolism. Emerging evidence demonstrates that the autonomic nervous system is largely involved in the regulation of glucose homeostasis; however, the underlying mechanisms are still under investigation. Within the hypothalamus, the paraventricular nucleus (PVN) is in a unique position to integrate neural and hormonal signals to command both the autonomic and neuroendocrine outflow. This minireview will provide a brief overview on the role of preautonomic PVN neurons and the importance of the PVN-liver pathway in the regulation of glucose homeostasis.
A 9-wk docosahexaenoic acid-enriched supplementation improves endurance exercise capacity and skeletal muscle mitochondrial function in adult rats
Authors: Le Guen Marie , Chaté Valérie , Hininger-Favier Isabelle , Laillet Brigitte , Morio Béatrice , Pieroni Gérard , Schlattner Uwe , Pison Christophe , Dubouchaud Hervé
Published: December 2015

Decline in skeletal muscle mass and function starts during adulthood. Among the causes, modifications of the mitochondrial function could be of major importance. Polyunsaturated fatty (ω-3) acids have been shown to play a role in intracellular functions. We hypothesize that docosahexaenoic acid (DHA) supplementation could improve muscle mitochondrial function that could contribute to limit the early consequences of aging on adult muscle. Twelve-month-old male Wistar rats were fed a low-polyunsaturated fat diet and were given DHA (DHA group) or placebo (control group) for 9 wk. Rats from the DHA group showed a higher endurance capacity (+56%, P < 0.05) compared with control animals. Permeabilized myofibers from soleus muscle showed higher O2consumptions ( P < 0.05) in the DHA group compared with the control group, with glutamate-malate as substrates, both in basal conditions (i.e., state 2) and under maximal conditions (i.e., state 3, using ADP), along with a higher apparent Kmfor ADP ( P < 0.05). Calcium retention capacity of isolated mitochondria was lower in DHA group compared with the control group ( P < 0.05). Phospho-AMPK/AMPK ratio and PPARδ mRNA content were higher in the DHA group compared with the control group ( P < 0.05). Results showed that DHA enhanced endurance capacity in adult animals, a beneficial effect potentially resulting from improvement in mitochondrial function, as suggested by our results on permeabilized fibers. DHA supplementation could be of potential interest for the muscle function in adults and for fighting the decline in exercise tolerance with age that could imply energy-sensing pathway, as suggested by changes in phospho-AMPK/AMPK ratio.
Effect of blocking tactile information from the fingertips on adaptation and execution of grip forces to friction at the grasping surface
Authors: Bilaloglu Seda , Lu Ying , Geller Daniel , Rizzo John Ross , Aluru Viswanath , Gardner Esther P. , Raghavan Preeti
Published: December 2015

Adaptation of fingertip forces to friction at the grasping surface is necessary to prevent use of inadequate or excessive grip forces. In the current study we investigated the effect of blocking tactile information from the fingertips noninvasively on the adaptation and efficiency of grip forces to surface friction during precision grasp. Ten neurologically intact subjects grasped and lifted an instrumented grip device with 18 different frictional surfaces under three conditions: with bare hands or with a thin layer of plastic (Tegaderm) or an additional layer of foam affixed to the fingertips. The coefficient of friction at the finger-object interface of each surface was obtained for each subject with bare hands and Tegaderm by measuring the slip ratio (grip force/load force) at the moment of slip. We found that the foam layer reduced sensibility for two-point discrimination and pressure sensitivity at the fingertips, but Tegaderm did not. However, Tegaderm reduced static, but not dynamic, tactile discrimination. Adaptation of fingertip grip forces to surface friction measured by the rate of change of peak grip force, and grip force efficiency measured by the grip-load force ratio at lift, showed a proportional relationship with bare hands but were impaired with Tegaderm and foam. Activation of muscles engaged in precision grip also varied with the frictional surface with bare hands but not with Tegaderm and foam. The results suggest that sensitivity for static tactile discrimination is necessary for feedforward and feedback control of grip forces and for adaptive modulation of muscle activity during precision grasp.
Synchronization of Discrete-Time Chaotic Fuzzy Systems by means of Fuzzy Output Regulation Using Genetic Algorithm
Authors: Hernández Cortés Tonatiuh , Curtidor López A. Verónica , Rodríguez Valdez Jorge , Meda Campaña Jesús A. , Tapia Herrera Ricardo , Rubio José de Jesús
Published: December 2015

The synchronization of chaotic systems, described by discrete-time T-S fuzzy models, is treated by means of fuzzy output regulation theory. The conditions for designing a discrete-time output regulator are given in this paper. Besides, when the system does not fulfill the conditions for exact tracking, a new regulator based on genetic algorithms is considered. The genetic algorithms are used to approximate the adequate membership functions, which allow the adequate combination of local regulators. As a result, the tracking error is significantly reduced. Both the Complete Synchronization and the Generalized Synchronization problem are studied. Some numerical examples are used to illustrate the effectiveness of the proposed approach.
Evaluation of Interface Shear Strength Properties of Geogrid Reinforced Foamed Recycled Glass Using a Large-Scale Direct Shear Testing Apparatus
Authors: Arulrajah Arul , Horpibulsuk Suksun , Maghoolpilehrood Farshid , Samingthong Wisanukorn , Du Yan-Jun , Shen Shui-Long
Published: December 2015

The interface shear strength properties of geogrid reinforced recycled foamed glass (FG) were determined using a large-scale direct shear test (DST) apparatus. Triaxial geogrid was used as a geogrid reinforcement. The geogrid increases the confinement of FG particles during shear; consequently the geogrid reinforced FG exhibits smaller vertical displacement and dilatancy ratio than FG at the same normal stress. The failure envelope of geogrid reinforced FG, at peak and critical states, coincides and yields a unique linear line possibly attributed to the crushing of FG particles and the rearrangement of crushed FG after peak shear state. The interface shear strength coefficientαis approximately constant at 0.9. This value can be used as the interface parameter for designing a reinforced embankment and mechanically stabilized earth (MSE) wall when FG is used as a lightweight backfill and triaxial geogrid is used as an extensible earth reinforcement. This research will enable FG, recently assessed as suitable for lightweight backfills, to be used together with geogrids in a sustainable manner as a lightweight MSE wall. The geogrid carries tensile forces, while FG reduces bearing stresses imposed on the in situ soil. The use of geogrid reinforced FG is thus significant from engineering, economical, and environmental perspectives.
The Role of the Multiple Hormonal Dysregulation in the Onset of “Anemia of Aging”: Focus on Testosterone, IGF-1, and Thyroid Hormones
Authors: Maggio Marcello , De Vita Francesca , Fisichella Alberto , Lauretani Fulvio , Ticinesi Andrea , Ceresini Graziano , Cappola Anne , Ferrucci Luigi , Ceda Gian Paolo
Published: December 2015

Anemia is a multifactorial condition whose prevalence increases in both sexes after the fifth decade of life. It is a highly represented phenomenon in older adults and in one-third of cases is “unexplained.” Ageing process is also characterized by a “multiple hormonal dysregulation” with disruption in gonadal, adrenal, and somatotropic axes. Experimental studies suggest that anabolic hormones such as testosterone, IGF-1, and thyroid hormones are able to increase erythroid mass, erythropoietin synthesis, and iron bioavailability, underlining a potential role of multiple hormonal changes in the anemia of aging. Epidemiological data more consistently support an association between lower testosterone and anemia in adult-older individuals. Low IGF-1 has been especially associated with anemia in the pediatric population and in a wide range of disorders. There is also evidence of an association between thyroid hormones and abnormalities in hematological parameters under overt thyroid and euthyroid conditions, with limited data on subclinical statuses. Although RCTs have shown beneficial effects, stronger for testosterone and the GH-IGF-1 axis and less evident for thyroid hormones, in improving different hematological parameters, there is no clear evidence for the usefulness of hormonal treatment in improving anemia in older subjects. Thus, more clinical and research efforts are needed to investigate the hormonal contribution to anemia in the older individuals.
Solution of Turbine Blade Cascade Flow Using an Improved Panel Method
Authors: Lei Zong-qi , Liang Guo-zhu
Published: December 2015

An improved panel method has been developed to calculate compressible inviscid flow through a turbine blade row. The method is a combination of the panel method for infinite cascade, a deviation angle model, and a compressibility correction. The resulting solution provides a fast flexible mesh-free calculation for cascade flow. A VKI turbine blade cascade is used to evaluate the method, and the comparison with experiment data is presented.
Dens Evaginatus: A Problem-Based Approach
Authors: Ayer A. , Vikram M. , Suwal P.
Published: December 2015

Dens evaginatus is an uncommon developmental anomaly of human dentition characterized by the presence of tubercle on the occlusal surface of mandibular premolars and lingual surface of anterior teeth. Due to occlusal trauma this tubercle tends to fracture thus exposing the pathway to the pulp chamber of teeth. This case report is about the presentation of dens evaginatus in mandibular premolars bilaterally; among them tooth 44 was associated with chronic apical periodontitis. Fractured tubercle of three premolars was sealed with composite resin. Root canal treatment was performed with tooth 44. Routine endodontic treatment did not result in remission of infection. Therefore, culture and sensitivity tests were performed to identify the cause and modify treatment plan accordingly. Triple antibiotic paste was used as an intracanal medicament to disinfect the root canal that resulted in remission of infection.
Lights and Shadows about the Effectiveness of IVF in HIV Infected Women: A Systematic Review
Authors: Marques Catarina , Guerreiro Cristina , Soares Sérgio Reis
Published: December 2015

Background. HIV infected women have higher rates of infertility.Objective. The purpose of this literature review is to evaluate the effectiveness of fresh IVF/ICSI cycles in HIV infected women.Materials and Methods. A search of the PubMed database was performed to identify studies assessing fresh nondonor oocyte IVF/ICSI cycle outcomes of serodiscordant couples with an HIV infected female partner.Results and Discussion. Ten studies met the inclusion criteria. Whenever a comparison with a control group was available, with the exception of one case, ovarian stimulation cancelation rate was higher and pregnancy rate (PR) was lower in HIV infected women. However, statistically significant differences in both rates were only seen in one and two studies, respectively. A number of noncontrolled sources of bias for IVF outcome were identified. This fact, added to the small size of samples studied and heterogeneity in study design and methodology, still hampers the performance of a meta-analysis on the issue.Conclusion. Prospective matched case-control studies are necessary for the understanding of the specific effects of HIV infection on ovarian response and ART outcome.
The Progress of Mitophagy and Related Pathogenic Mechanisms of the Neurodegenerative Diseases and Tumor
Authors: Song Ying , Ding Wei , Xiao Yan , Lu Kong-jun
Published: December 2015

Mitochondrion, an organelle with two layers of membrane, is extremely vital to eukaryotic cell. Its major functions are energy center and apoptosis censor inside cell. The intactness of mitochondrial membrane is important to maintain its structure and function. Mitophagy is one kind of autophagy. In recent years, studies of mitochondria have shown that mitophagy is regulated by various factors and is an important regulation mechanism for organisms to maintain their normal state. In addition, abnormal mitophagy is closely related to several neurodegenerative diseases and tumor. However, the related signal pathway and its regulation mechanism still remain unclear. As a result, summarizing the progress of mitophagy and its related pathogenic mechanism not only helps to reveal the complicated molecular mechanism, but also helps to find a new target to treat the related diseases.
Consensus Information Filtering for Large-Scale Systems with Application to Heat Conduction Process
Authors: Zhang Liguo , Lyu Ying
Published: December 2015

For large-scale distributed systems, the evolution of system dynamics is dominated by current states and boundary conditions simultaneously. This work describes a distributed consensus filtering for a class of large-scale distributed systems with unknown boundary conditions, which are monitored by a set of sensors. Because of the difference of spatial positions among the sensor network, only the single state variables or both the states and outside input jointly could be estimates with Kalman information filtering, respectively. On diffusion processing, we fuse the common state estimations of the local information filters using consensus averaging algorithms and algebraic graph theory. Stability and performance analysis is provided for this distributed filtering algorithm. Finally, we consider an application of distributed estimation to a heat conduction process. The performance of the proposed distributed algorithm is compared to the centralized Kalman filtering.
Predictors of a Rapid Decline of Renal Function in Patients with Chronic Kidney Disease Referred to a Nephrology Outpatient Clinic: A Longitudinal Study
Authors: Vigil Ana , Condés Emilia , Camacho Rosa , Cobo Gabriela , Gallar Paloma , Oliet Aniana , Rodriguez Isabel , Ortega Olimpia , Mon Carmen , Ortiz Milagros , Herrero Juan Carlos
Published: December 2015

Background. Predicting the progression of kidney failure in patients with chronic kidney disease is difficult. The aim of this study was to assess the predictors of rapid kidney decline in a cohort of patients referred to a single outpatient nephrology clinic. Design. Longitudinal, prospective cohort study with a median follow-up of 3.39 years. Methods. Data were obtained from 306 patients with chronic renal failure based on serum creatinine-estimated glomerular filtration rate (eGFRcreat) < 90 mL/min/1.73 m2. After excluding patients who died (n=30) and those who developed end-stage renal failure (n=6), 270 patients were included. This population was grouped according to the rate of kidney function decline. Rapid kidney function decline was defined as an annual eGFRcreat loss > 4 mL/min/1.73 m2. We recorded nonfatal cardiovascular events at baseline and during follow-up in addition to biochemical parameters. Results. The mean loss in renal function was 1.22 mL/min/1.73 m2 per year. The mean age was 75 ± 8.8 years old, and the mean baseline eGFRcreat was 42 ± 14 mL/min/1.73 m2. Almost one-fourth of the sample (23.3% [63 patients]) suffered a rapid decline in renal function. In a logistic regression model with rapid decline as the outcome, baseline characteristics, lower serum albumin (OR: 0.313, 95% CI: 0.114–0.859), previous cardiovascular disease (OR: 1.903 95% CI: 1.028–3.523), and higher proteinuria (g/24 h) (OR: 1.817 CI 95%: 1.213–2.723) were the main predictors of rapid kidney decline. On multivariate analysis, including baseline and follow-up data, we obtained similar adjusted associations of rapid kidney decline with baseline serum albumin and proteinuria. The follow-up time was also shorter in the group with rapid rates of decline in renal function. Conclusion. Renal function remained stable in the majority of our population. Previous cardiovascular disease and cardiovascular incidents, lower serum albumin, and higher proteinuria at baseline were the main predictors of rapid kidney decline in our population.
Community Awareness of HPV Screening and Vaccination in Odisha
Authors: Khanna Niharika , Ramaseshan Aparna , Arnold Stephanie , Panigrahi Kalpana , Macek Mark D. , Padhi Bijaya K. , Samanta Diptirani , Senapati Surendra N. , Panigrahi Pinaki
Published: December 2015

Introduction. A number of new technologies including cervical cancer screening and vaccination have introduced new tools in the fight against cervical cancer.Methods. This study was set in Odisha, India, at the Acharya Harihar Regional Cancer Center and study research infrastructure at the Asian Institute of Public Health. IRB approvals were obtained and a research assistant recruited 286 women aged 18–49 years, who provided informed consent and completed a survey tool. Data were entered into EpiData software and statistical analysis was conducted.Results. 76.3% women participants were married, 45.5% had sexual debut at age 21 or greater, 60.5% used contraception, 12.2% reported having a Pap smear in the past, and 4.9% reported having prior genital warts. Most, 68.8% had never heard of HPV and 11.9% were aware that HPV is the main cause of cervical cancer. 82.9% women thought that vaccinations prevent disease, and 74.8% said they make the decision to vaccinate their children.Conclusion. The Odisha community demonstrated a low level of knowledge about cervical cancer prevention, accepted vaccinations in the prevention of disease and screening, and identified mothers/guardians as the key family contacts.
Short-Term Changes in Fertility Attributes and Soil Organic Matter Caused by the Addition of EM Bokashis in Two Tropical Soils
Authors: Lima Carlos Eduardo Pacheco , Fontenelle Mariana Rodrigues , Silva Luciana Rodrigues Borba , Soares Daiane Costa , Moita Antônio Williams , Zandonadi Daniel Basílio , Souza Ronessa Bartolomeu , Lopes Carlos Alberto
Published: December 2015

The present work aimed to evaluate the behavior of ten fertility attributes of soil organic matter physical fractions and total organic carbon upon addition of three EM Bokashis to a Rhodic Ferralsol (FRr) and a Dystric Cambisol (CMd). An experiment was carried out in greenhouse in which the soils were placed into plastic trays and cultivated with tomato. A completely randomized design was used with four repetitions and factorial scheme of 2 × 3 + 2, consisting of two soils (FRr and CMd), three EM Bokashis (Poultry Manure Bokashi (BPM); CNPH Bokashi (BC); and Cattle Manure Bokashi (BCM)), and two controls (both soils without addition of Bokashi). The following fertility attributes were evaluated: pH, Ca2+, Mg2+, K+, Na+, P, SB, H + Al, CEC, andV. Particulate organic carbon (POC) and mineral-associated organic carbon (MOC) and total organic carbon (TOC) were also investigated. Finally, the Principal Component Analysis was conducted in order to identify possible patterns related to soils when fertilized with EM Bokashi. The addition of EM Bokashi increased the soil fertility and contents of POC. Different EM Bokashi presents distinguished effects on each soil. The PCA suggests that BPM presents higher capacity to modify the analyzed chemical attributes.
Imaging Based Methods of Liver Fibrosis Assessment in Viral Hepatitis: A Practical Approach
Authors: Khallafi Hicham , Qureshi Kamran
Published: December 2015

Liver fibrosis represents the repair mechanism in liver injury and is a feature of most chronic liver diseases. The degree of liver fibrosis in chronic viral hepatitis infections has major clinical implications and presence of advanced fibrosis or cirrhosis determines prognosis. Treatment initiation for viral hepatitis is indicated in most cases of advanced liver fibrosis and diagnosis of cirrhosis entails hepatology evaluation for specialized clinical care. Liver biopsy is an invasive technique and has been the standard of care of fibrosis assessment for years; however, it has several limitations and procedure related complications. Recently, several methods of noninvasive assessment of liver fibrosis have been developed which require either serologic testing or imaging of liver. Imaging based noninvasive techniques are reviewed here and their clinical use is described. Some of the imaging based tests are becoming widely available, and collectively they are shown to be superior to liver biopsy in important aspects. Clinical utilization of these methods requires understanding of performance and quality related parameters which can affect the results and provide wrong assessment of the extent of liver fibrosis. Familiarity with the strengths and weaknesses of each modality is needed to correctly interpret the results in appropriate clinical context.
Cadmium Removal from Aqueous Systems UsingOpuntia albicarpaL. Scheinvar as Biosorbent
Authors: Beltrán-Hernández Rosa Icela , Vázquez-Rodríguez Gabriela Alejandra , Juárez-Santillán Luis Felipe , Martínez-Ugalde Ivan , Coronel-Olivares Claudia , Lucho-Constantino Carlos Alexander
Published: December 2015

The aim of this research was to investigate the use of a natural adsorbent like nopal (Opuntia albicarpaL. Scheinvar) for removing cadmium from aqueous solutions with low concentrations of this metal. Two treatments were applied to the cladodes: a dehydration to get dehydrated nopal (DHN) and heating up to 90°C to obtain a thermally treated nopal (TN). After examining the effect of various pH values (2–7), the capacity of each biosorbent was examined in batch sorption tests at different dosages (0, 500, 1000, 1500, 2000, and 3000 mg L−1). The results indicated that adsorption of cadmium to biomass of DHN and TN was highly dependent on pH and biosorbent dosage. The best removal of cadmium (53.3%, corresponding toqeof 0.155 mg g−1) was obtained at pH 4.0 by using the TN sorbent. Infrared and Raman spectra confirmed that cadmium removal occurred via adsorption to –OH functional groups.
Fabrication Improvement of Cold Forging Hexagonal Nuts by Computational Analysis and Experiment Verification
Authors: Hsia Shao-Yi , Chou Yu-Tuan
Published: December 2015

Cold forging has played a critical role in fasteners and has been applied to the automobile industry, construction industry, aerospace industry, and living products so that cold forging presents the opportunities for manufacturing more products. By using computer simulation, this study attempts to analyze the process of creating machine parts, such as hexagonal nuts. The DEFORM-3D forming software is applied to analyze the process at various stages in the computer simulation, and the compression test is also used for the flow stress equation in order to compare the differences between the experimental results and the equation that is built into the computer simulation software. At the same time, the metallography and hardness of experiments are utilized to understand the cold forging characteristics of hexagonal nuts. The research results would benefit machinery businesses to realize the forging load and forming conditions at various stages before the fastener formation. In addition to planning proper die design and production, the quality of the produced hexagonal nuts would be more stable to promote industrial competitiveness.
Management of Long-Segment and Panurethral Stricture Disease
Authors: Martins Francisco E. , Kulkarni Sanjay B. , Joshi Pankaj , Warner Jonathan , Martins Natalia
Published: December 2015

Long-segment urethral stricture or panurethral stricture disease, involving the different anatomic segments of anterior urethra, is a relatively less common lesion of the anterior urethra compared to bulbar stricture. However, it is a particularly difficult surgical challenge for the reconstructive urologist. The etiology varies according to age and geographic location, lichen sclerosus being the most prevalent in some regions of the globe. Other common and significant causes are previous endoscopic urethral manipulations (urethral catheterization, cystourethroscopy, and transurethral resection), previous urethral surgery, trauma, inflammation, and idiopathic. The iatrogenic causes are the most predominant in the Western or industrialized countries, and lichen sclerosus is the most common in India. Several surgical procedures and their modifications, including those performed in one or more stages and with the use of adjunct tissue transfer maneuvers, have been developed and used worldwide, with varying long-term success. A one-stage, minimally invasive technique approached through a single perineal incision has gained widespread popularity for its effectiveness and reproducibility. Nonetheless, for a successful result, the reconstructive urologist should be experienced and familiar with the different treatment modalities currently available and select the best procedure for the individual patient.
Fuzzy State Transition and Kalman Filter Applied in Short-Term Traffic Flow Forecasting
Authors: Ming-jun Deng , Shi-ru Qu
Published: December 2015

Traffic flow is widely recognized as an important parameter for road traffic state forecasting. Fuzzy state transform and Kalman filter (KF) have been applied in this field separately. But the studies show that the former method has good performance on the trend forecasting of traffic state variation but always involves several numerical errors. The latter model is good at numerical forecasting but is deficient in the expression of time hysteretically. This paper proposed an approach that combining fuzzy state transform and KF forecasting model. In considering the advantage of the two models, a weight combination model is proposed. The minimum of the sum forecasting error squared is regarded as a goal in optimizing the combined weight dynamically. Real detection data are used to test the efficiency. Results indicate that the method has a good performance in terms of short-term traffic forecasting.
Update on Medicinal Plants with Potency onMycobacterium ulcerans
Authors: Tsouh Fokou Patrick Valere , Nyarko Alexander Kwadwo , Appiah-Opong Regina , Tchokouaha Yamthe Lauve Rachel , Ofosuhene Mark , Boyom Fabrice Fekam
Published: December 2015

Mycobacterium ulceransdisease has been a serious threat for people living in rural remote areas. Due to poverty or availability of traditional medicine these populations rely on herbal remedies. Currently, data on the anti-Mycobacterium ulceransactivity of plants, so far considered community-based knowledge, have been scientifically confirmed, concomitantly with some medicinal plants used to treat infectious diseases in general. Products derived from plants usually responsible for the biological properties may potentially controlMycobacterium ulceransdisease; numerous studies have aimed to describe the chemical composition of these plant antimicrobials. Thus, the present work provides the first compilation of medicinal plants that demonstrated inhibitory potential onMycobacterium ulcerans. This work shows that the natural products represent potential alternatives to standard therapies for use as curative medicine forMycobacterium ulceransdisease.
An Extension of Wright Function and Its Properties
Authors: El-Shahed Moustafa , Salem Ahmed
Published: December 2015

The paper is devoted to the study of the functionWα,βγ,δ(z), which is an extension of the classical Wright function and Kummer confluent hypergeometric function. The properties ofWα,βγ,δ(z)including its auxiliary functions and the integral representations are proven.
Measurement of Serum Free Thyroxine Index May Provide Additional Case Detection Compared to Free Thyroxine in the Diagnosis of Central Hypothyroidism
Authors: Pantalone Kevin M. , Hatipoglu Betul , Gupta Manjula K. , Kennedy Laurence , Hamrahian Amir H.
Published: December 2015

The diagnosis of central hypothyroidism is often suspected in patients with hypothalamic/pituitary pathology, in the setting of low, normal, or even slightly elevated serum TSH and low free thyroxine (FT4). We present four cases of central hypothyroidism (three had known pituitary pathology) in whom central hypothyroidism was diagnosed after the serum free thyroxine index (FTI) was found to be low. All had normal range serum TSH and free thyroxine levels. This report illustrates that the assessment of the serum FTI may be helpful in making the diagnosis of central hypothyroidism in the appropriate clinical setting and when free T4 is in the low-normal range, particularly in patients with multiple anterior pituitary hormone deficiencies and/or with symptoms suggestive of hypothyroidism.
Stopping Accidents before They Happen: Perceiving Lane-Level Moving Vehicle Danger Regions to Warn Surrounding Drivers and Pedestrians
Authors: Guo Chi , Cao Guangyi , Zeng Jieru , Cui Jinsong , Peng Rong
Published: December 2015

Perceiving the location of dangerous moving vehicles and broadcasting this information to vehicles nearby are essential to achieve active safety in the Internet of Vehicles (IOV). To address this issue, we implement a real-time high-precision lane-level danger region service for moving vehicles. A traditional service depends on static geofencing and fails to deal with dynamic vehicles. To overcome this defect, we devised a new type of IOV service that manages to track dangerous moving vehicles in real time and recognize their danger regions quickly and accurately. Next, we designed algorithms to distinguish the vehicles in danger regions and broadcast the information to these vehicles. Our system can simultaneously manipulate a mass of danger regions for various dangerous vehicles and broadcast this information to surrounding vehicles at a large scale. This new system was tested in Shanghai, Guangzhou, Wuhan, and other cities; the data analysis is presented in this paper as well.
Oral Probiotic VSL#3 Prevents Autoimmune Diabetes by Modulating Microbiota and Promoting Indoleamine 2,3-Dioxygenase-Enriched Tolerogenic Intestinal Environment
Authors: Dolpady Jayashree , Sorini Chiara , Di Pietro Caterina , Cosorich Ilaria , Ferrarese Roberto , Saita Diego , Clementi Massimo , Canducci Filippo , Falcone Marika
Published: December 2015

The gut microbiota modulates the autoimmune pathogenesis of type 1 diabetes (T1D) via mechanisms that remain largely unknown. The inflammasome components are innate immune sensors that are highly influenced by the gut environment and play pivotal roles in maintaining intestinal immune homeostasis. In this study we show that modifications of the gut microbiota induced by oral treatment with Lactobacillaceae-enriched probiotic VSL#3, alone or in combination with retinoic acid (RA), protect NOD mice from T1D by affecting inflammasome at the intestinal level. In particular, we show that VSL#3 treatment inhibits IL-1βexpression while enhancing release of protolerogenic components of the inflammasome, such as indoleamine 2,3-dioxygenase (IDO) and IL-33. Those modifications of the intestinal microenvironment in VSL#3-treated NOD mice modulate gut immunity by promoting differentiation of tolerogenic CD103+DCs and reducing differentiation/expansion of Th1 and Th17 cells in the intestinal mucosa and at the sites of autoimmunity, that is, within the pancreatic lymph nodes (PLN) of VSL#3-treated NOD mice. Our data provide a link between dietary factors, microbiota composition, intestinal inflammation, and immune homeostasis in autoimmune diabetes and could pave the way for new therapeutic approaches aimed at changing the intestinal microenvironment with probiotics to counterregulate autoimmunity and prevent T1D.
Peptide–Drug Conjugate GnRH–Sunitinib Targets Angiogenesis Selectively at the Site of Action to Inhibit Tumor Growth
Authors: Argyros Orestis , Karampelas Theodoros , Asvos Xenophon , Varela Aimilia , Sayyad Nisar , Papakyriakou Athanasios , Davos Constantinos H. , Tzakos Andreas G. , Fokas Demosthenes , Tamvakopoulos Constantin
Published: December 2015

The potential to heighten the efficacy of antiangiogenic agents was explored in this study based on active targeting of tumor cells overexpressing the gonadotropin-releasing hormone receptor (GnRH-R). The rational design pursued focused on five analogues of a clinically established antiangiogenic compound (sunitinib), from which a lead candidate (SAN1) was conjugated to the targeting peptide [d-Lys6]-GnRH, generating SAN1GSC. Conjugation of SAN1 did not disrupt any of its antiangiogenic or cytotoxic properties in GnRH-R–expressing prostate and breast tumor cells. Daily SAN1GSC treatments in mouse xenograft models of castration-resistant prostate cancer resulted in significant tumor growth delay compared with equimolar SAN1 or sunitinib alone. This efficacy correlated with inhibited phosphorylation of AKT and S6, together with reduced Ki-67 and CD31 expression. The superior efficacy of the peptide–drug conjugate was also attributed to the finding that higher amounts of SAN1 were delivered to the tumor site (∼4-fold) following dosing of SAN1GSC compared with equimolar amounts of nonconjugated SAN1. Importantly, treatment with SAN1GSC was associated with minimal hematotoxicity and cardiotoxicity based on measurements of the left ventricular systolic function in treated mice. Our results offer preclinical proof-of-concept for SAN1GSC as a novel molecule that selectively reaches the tumor site and downregulates angiogenesis with negligible cardiotoxicity, thus encouraging its further clinical development and evaluation. Cancer Res; 76(5); 1181–92. ©2015 AACR.
Trends in United States Prostate Cancer Incidence Rates by Age and Stage, 1995–2012
Authors: Hoffman Richard M. , Meisner Angela L.W. , Arap Wadih , Barry Marc , Shah Satyan K. , Zeliadt Steven B. , Wiggins Charles L.
Published: December 2015

Background: The advent of PSA testing in the late 1980s substantially increased prostate cancer incidence rates. Concerns about overscreening and overdiagnosis subsequently led professional guidelines (circa 2000 and later) to recommend against routine PSA testing. We evaluated trends in prostate cancer incidence, including late-stage diagnoses, from 1995 through 2012.

Methods: We used joinpoint regression analyses to evaluate all-, localized/regional-, and distant-stage prostate cancer incidence trends based on Surveillance, Epidemiology, and End Results (SEER) data. We stratified analyses by age (50–69, 70+). We reported incidence trends as annual percent change (APC).

Results: Overall age-adjusted incidence rates for localized/regional stage prostate cancer have been declining since 2001, sharply from 2010 to 2012 [APC, −13.1; 95% confidence intervals (CI), −23.5 to −1.3]. Distant-stage incidence rates have declined since 1995, with greater declines from 1995 to 1997 (APC, −8.4; 95% CI, −2.3 to −14.1) than from 2003 to 2012 (APC, −1.0; 95% CI, −1.7 to −0.4). Distant-stage incidence rates declined for men ages 70+ from 1995 to 2012, but increased in men ages 50 to 69 years from 2004 to 2012 (APC, 1.7; 95% CI, 0.2 to 3.2).

Conclusions: Guidelines discouraging routine prostate cancer screening were temporally associated with declining localized/regional prostate cancer incidence rates; however, incidence rates of distant-stage disease are now increasing in younger men.

Impact: This trend may adversely affect prostate cancer mortality rates. Cancer Epidemiol Biomarkers Prev; 25(2); 259–63. ©2015 AACR.
A Phase I Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Combination Therapy with Refametinib plus Sorafenib in Patients with Advanced Cancer
Authors: Adjei Alex A. , Richards Donald A. , El-Khoueiry Anthony , Braiteh Fadi , Becerra Carlos H.R. , Stephenson Joe J. , Hezel Aram F. , Sherman Morris , Garbo Lawrence , Leffingwell Diane P. , Iverson Cory , Miner Jeffrey N. , Shen Zancong , Yeh Li-Tain , Gunawan Sonny , Wilson David M. , Manhard Kimberly J. , Rajagopalan Prabhu , Krissel Heiko , Clendeninn Neil J.
Published: December 2015

Purpose: To assess the safety and tolerability of the small-molecule allosteric MEK inhibitor refametinib combined with sorafenib, in patients with advanced solid malignancies.

Experimental Design: This phase I dose-escalation study included an expansion phase at the maximum tolerated dose (MTD). Patients received refametinib/sorafenib twice daily for 28 days, from a dose of refametinib 5 mg plus sorafenib 200 mg to a dose of refametinib 50 mg plus sorafenib 400 mg. Plasma levels of refametinib, refametinib metabolite M17, and sorafenib were measured for pharmacokinetic assessments. Tumors were biopsied at the MTD for analysis of MEK pathway mutations and ERK phosphorylation.

Results: Thirty-two patients were enrolled in the dose-escalation cohort. The MTD was refametinib 50 mg twice daily plus sorafenib 400 mg twice daily. The most common treatment-related toxicities were diarrhea and fatigue. Refametinib was readily absorbed following oral administration (plasma half-life of ∼16 hours at the MTD), and pharmacokinetic parameters displayed near-dose proportionality, with less than 2-fold accumulation after multiple dosing. Another 30 patients were enrolled in the MTD cohort; 19 had hepatocellular carcinoma. The combination was associated with significantly reduced ERK phosphorylation in 5 out of 6 patients biopsied, with the greatest reductions in those with KRAS or BRAF mutations. Disease was stabilized in approximately half of patients, and 1 patient with colorectal cancer achieved a partial response at the MTD lasting approximately 1 year.

Conclusions: In this phase I study, refametinib plus sorafenib was well tolerated, with good oral absorption, near-dose proportionality, and target inhibition in a range of tumor types. Clin Cancer Res; 22(10); 2368–76. ©2015 AACR.
The Expression of Markers Related to Ovarian Germline Stem Cells in the Mouse Ovarian Surface Epithelium and the Correlation with Notch Signaling Pathway
Authors: Pan Zezheng , Sun Mengli , Li Jia , Zhou Fangyue , Liang Xia , Huang Jian , Zheng Tuochen , Zheng Liping , Zheng Yuehui
Published: December 2015

Background/Aims: Ovarian germline stem cells (OGSCs) have been shown to mainly exist in the ovarian surface epithelium (OSE), but the activity changes of germline stem cells during different reproductive stages and the potential regulatory signaling pathway are still unknown. The Notch signaling pathway plays a key role in cell development, primordial follicles and stem cell proliferation. However, whether it plays a role in the proliferation of OGSCs is unknown. Here, we analyzed the activity changes of germline stem cells and the correlation between germline stem cells and the Notch signaling pathway. Methods: The expression of germline stem cell markers Mvh, Ooc4 and the Notch molecules Notch1, Hes1, and Hes5 were detected during 3 days (3d), and 2, 12, 20 months (2m, 12m, 20m) mouse ovarian surface epithelium samples. DAPT, a specific inhibitor of the Notch pathway, was used to observe the influence of Notch signaling in the germline stem cells. Results: The results showed that the levels of MVH and OCT4 decreased substantially with reproductive age in ovarian surface epithelium, and the same tendency was detected in the Notch signaling molecules Notch1, Hes1 and Hes5. Dual-IF results showed that the germline stem cell markers were co-expressed with Notch molecules in the ovarian surface epithelium. While, the expression of MVH and OCT4 were reduced when the ovaries were treated with DAPT and the levels were attenuated with increasing dose of DAPT. Conclusion: Taken together, our results indicate that the viability of OGSCs decreased with the age of the mouse ovaries, and the activity of OGSCs in the ovarian surface epithelium may be related to the Notch signaling pathway.
The Prevalence and Management of Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis in China
Authors: Li Zhi-Ying , Ma Tian-Tian , Chen Min , Zhao Ming-Hui
Published: December 2015

Background: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) comprises microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA) and eosinophilic GPA (EGPA). Myeloperoxidase (MPO) and proteinase 3 (PR3) are the main antigens for ANCA. AAV is a common multisystem autoimmune disease and most of the studies on AAV have been conducted in Western countries. Nowadays in China many efforts are made to investigate this disease. Summary: This review highlights the progress in the prevalence, management and outcomes of AAV in Chinese patients. With respect to the prevalence of AAV, though there are no precise data, AAV is not rare in the Chinese population. In Chinese patients with AAV there is a striking preponderance of MPA, and MPO-ANCA is much more common than PR3-ANCA. Even in patients with GPA there is a predominance of MPO-ANCA over PR3-ANCA. Propylthiouracil-induced AAV and ANCA-negative pauci-immune glomerulonephritis are stated in this review as well. With respect to the management of AAV, glucocorticoids in combination with cyclophosphamide remain the mainstay of induction therapy. Besides, we describe predictors of different outcomes in Chinese patients, including mortality, relapse, treatment resistance and end-stage renal disease. Key Messages: AAV is not rare in the Chinese population. The disease spectrum and subtypes of ANCA are different between patients with AAV in China and Western countries. The treatment strategy for AAV in China is in consistency with that in Western countries. Predictors of different clinical outcomes are provided. Facts from East and West: Treatment options for AAV are shared between the East and West, with corticosteroid combined with cyclophosphamide being the standard regimen for inductive therapy and switching to azathioprine after remission. The major cause of death in treated patients is infection related to immunosuppressive therapy within the first year after diagnosis, and this rate might be higher in China than in Western countries. Western studies demonstrated the efficacy and safety of rituximab for induction of remission in cases with relatively mild disease and maintenance therapy, but this agent is rarely used in China.