bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutations inash1andtrxenhanceP-element-dependent silencing inDrosophila melanogaster
Authors: McCracken Allen , Locke John
Published: May 2016

In Drosophila melanogaster, the mini-w+transgene in Pci is normally expressed throughout the adult eye; however, when other P or KP elements are present, a variegated-eye phenotype results, indicating random w+silencing during development called P-element-dependent silencing (PDS). Mutant Su(var)205 and Su(var)3-7 alleles act as haplo-suppressors/triplo-enhancers of this variegated phenotype, indicating that these heterochromatic modifiers act dose dependently in PDS. Previously, we recovered a spontaneous mutation of P{lacW}ciDplaccalled P{lacW}ciDplacE1(E1) that variegated in the absence of P elements, presumably due to the insertion of an adjacent gypsy element. From a screen for genetic modifiers of E1 variegation, we describe here the isolation of five mutations in ash1 and three in trx that enhance the E1 variegated phenotype in a dose-dependent and cumulative manner. These mutant alleles enhance PDS at E1, and in E1/P{lacW}ciDplac, but suppress position effect variegation (PEV) at In(1)wm4. This opposite action is consistent with a model where ASH1 and TRX mark transcriptionally active chromatin domains. If ASH1 or TRX function is lost or reduced, heterochromatin can spread into these domains creating a sink that diverts heterochromatic proteins from other variegating locations, which then may express a suppressed phenotype.
Identification of the genomic mutation inEpha4rb-2J/rb-2Jmice
Authors: Mohd-Zin Siti W. , Abdullah Nor-Linda , Abdullah Aminah , Greene Nicholas D.E. , Cheah Pike-See , Ling King-Hwa , Yusof Hadri , Marwan Ahmed I. , Williams Sarah M. , York Kerri T. , Ahmad-Annuar Azlina , Abdul-Aziz Noraishah M.
Published: May 2016

The EphA4 receptor tyrosine kinase is involved in numerous cell-signalling activities during embryonic development. EphA4 has the ability to bind to both types of ephrin ligands, the ephrinAs and ephrinBs. The C57BL/6J-Epha4rb-2J/GrsrJ strain, denoted Epha4rb-2J/rb-2J, is a spontaneous mouse mutant that arose at The Jackson Laboratory. These mutants exhibited a synchronous hind limb locomotion defect or “hopping gait” phenotype, which is also characteristic of EphA4 null mice. Genetic complementation experiments suggested that Epha4rb-2Jcorresponds to an allele of EphA4, but details of the genomic defect in this mouse mutant are currently unavailable. We found a single base-pair deletion in exon 9 resulting in a frame shift mutation that subsequently resulted in a premature stop codon. Analysis of the predicted structure of the truncated protein suggests that both the kinase and sterile α motif (SAM) domains are absent. Definitive determination of genotype is needed for experimental studies of mice carrying the Epha4rb-2Jallele, and we have also developed a method to ease detection of the mutation through RFLP. Eph-ephrin family members are reportedly expressed as numerous isoforms. Hence, delineation of the specific mutation in EphA4 in this strain is important for further functional studies, such as protein–protein interactions, immunostaining and gene compensatory studies, investigating the mechanism underlying the effects of altered function of Eph family of receptor tyrosine kinases on phenotype.
Can fractional quantum Hall effect be due to the formation of coherent wave structures in a 2D electron gas?
Authors: Mirza Babur M.
Published: May 2016

A microscopic theory of integer and fractional quantum Hall effects is presented here. In quantum density wave representation of charged particles, it is shown that, in a two-dimensional electron gas coherent structures form under the low temperature and high density conditions. With a sufficiently high applied magnetic field, the combined [Formula: see text] particle quantum density wave exhibits collective periodic oscillations. As a result the corresponding quantum Hall voltage function shows a step-wise change in multiples of the ratio [Formula: see text]. At lower temperatures further subdivisions emerge in the Hall resistance, exhibiting the fractional quantum Hall effect.
Many Rivers to Cross : Evaluating the Benefits and Limitations of Strategic Environmental Assessment for the Koshi River Basin
Authors: King Hugh , Smith Laurence
Published: May 2016

This paper assesses the value of using Strategic Environmental Assessment (SEA) to account for the spatially and temporally diverse and diffuse potential impacts of hydropower development in South Asia’s Koshi basin. A policy and practice review and key stakeholder interviews identified opportunities for SEA to improve existing planning procedures, and also barriers to effective adoption. Whilst stakeholders are interested in employing SEA to evaluate cumulative impacts, institutional blockages and an economic development imperative for power generation leave little space for consideration of alternative scenarios as part of SEA. The analysis is conducted through the formulation and application of a conceptual framework (CFW) for SEA best practice which is then used to identify priority next-steps for a more dynamic application of SEA in the region.
My Text in Your Handwriting
Authors: Haines Tom S. F. , Mac Aodha Oisin , Brostow Gabriel J.
Published: May 2016

There are many scenarios where we wish to imitate a specific author’s pen-on-paper handwriting style. Rendering new text in someone’s handwriting is difficult because natural handwriting is highly variable, yet follows both intentional and involuntary structure that makes a person’s style self-consistent. The variability means that naive example-based texture synthesis can be conspicuously repetitive.

We propose an algorithm that renders a desired input string in an author’s handwriting. An annotated sample of the author’s handwriting is required; the system is flexible enough that historical documents can usually be used with only a little extra effort. Experiments show that our glyph-centric approach, with learned parameters for spacing, line thickness, and pressure, produces novel images of handwriting that look hand-made to casual observers, even when printed on paper.
Management of chronic hepatitis C: Consensus guidelines
Authors: Sherman Morris , Shafran Stephen , Burak Kelly , Doucette Karen , Wong Winnie , Girgrah Nigel , Yoshida Eric , Renner Eberhard , Wong Philip , Deschenes Marc
Published: May 2016

Since the last consensus conference on the management of chronic viral hepatitis, a number of studies looking at modifications of the standard course of treatment have been published. These changes have been sufficiently substantive to warrant review to determine whether any changes in the recommended treatment algorithms are needed. A consensus development conference was held in January 2007, and the present document highlights the results of the presentations and discussion about these issues. It reviews the epidemiology of hepatitis C in Canada, treatment of acute hepatitis C and new algorithms in chronic hepatitis C, including retreatment of previous treatment failures. In addition, sections on management of hepatitis C in special populations have been updated. There is also a section on the use of hematopoietic growth factors to help manage patients on therapy. The document should be read in conjunction with the previous document to identify changes. Some recommendations made in the previous document remain and are not discussed here.
Cancer Care Ontario Colonoscopy Standards: Standards and Evidentiary Base
Authors: Rabeneck L , Rumble RB , Axler J , Smith A , Armstrong D , Vinden C , Belliveau P , Rhodes K , Zwaal C , Mai V , Dixon P ,   for Cancer Care Ontario’s Colonoscopy Standards Expert Panel
Published: May 2016

Colorectal cancer (CRC) is the most common cause of non-tobaccorelated cancer deaths in Canadian men and women, accounting for 10% of all cancer deaths. An estimated 7800 men and women will be diagnosed with CRC, and 3250 will die from the disease in Ontario in 2007. Given that CRC incidence and mortality rates in Ontario are among the highest in the world, the best opportunity to reduce this burden of disease would be through screening. The present report describes the findings and recommendations of Cancer Care Ontario’s Colonoscopy Standards Expert Panel, which was convened in March 2006 by the Program in Evidence-Based Care. The recommendations will form the basis of the quality assurance program for colonoscopy delivered in support of Ontario’s CRC screening program.
Chronic Constipation: Current Management and Challenges
Authors: Storr Martin
Published: May 2016

Many challenges are associated with the diagnosis and management of patients with chronic constipation. Some of these challenges arise from the currently incomplete understanding of what causes constipation and from the difficulties in diagnosing and classifying the heterogeneous group of patients with chronic constipation. Despite the availability of different treatment options for constipation, an unmet need for drugs in the treatment of patients with chronic constipation remains. This holds especially true for patients who fail an initial treatment. With promising novel drugs either close to approval for the Canadian market or on the horizon, many of these unmet needs may be addressed. The present supplement toThe Canadian Journal of Gastroenterologyprovides an educational overview of the current understanding of the diagnosis, epidemiology, pathophysiology and management of chronic constipation, and summarizes current treatment options in light of current and newly available drugs.
New Treatment Options for Chronic Constipation: Mechanisms, Efficacy and Safety
Authors: Camilleri Michael
Published: May 2016

The present review has several objectives, the first of which is to review the pharmacology and selectivity of serotonergic agents to contrast the older serotonergic agents (which were withdrawn because of cardiac or vascular adverse effects) with the newer generation serotonin receptor subtype 4 agonists. Second, the chloride ion secretagogues that act through the guanylate cyclase C receptor are appraised and their pharmacology is compared with the approved medication, lubiprostone. Third, the efficacy and safety of the application of bile acid modulation to treat constipation are addressed. The long-term studies of surgically induced excess bile acid delivery to the colon are reviewed to ascertain the safety of this therapeutic approach. Finally, the new drugs for opiate-induced constipation are introduced. Assuming these drugs are approved, practitioners will have a choice; however, patient responsiveness will be based on trial and error. Nevertheless, the spectrum of mechanisms and demonstrated efficacy and safety augur well for satisfactory treatment outcomes.
Chronic Constipation: Current Treatment Options
Authors: Liu Louis Wing
Published: May 2016

Chronic constipation is a common functional gastrointestinal disorder that affects patients of all ages. In 2007, a consensus group of 10 Canadian gastroenterologists developed a set of recommendations pertaining to the management of chronic constipation and constipationdominant irritable bowel syndrome. Since then, tegaserod has been withdrawn from the Canadian market. A new, highly selective serotonin receptor subtype 4 agonist, prucalopride, has been examined in several large, randomized, placebo-controlled trials demonstrating its efficacy and safety in the management of patients with chronic constipation. Additional studies evaluating the use of stimulant laxatives, polyethylene glycol and probiotics in the management of chronic constipation have also been published. The present review summarizes the previous recommendations and new evidence supporting different treatment modalities – namely, diet and lifestyle, bulking agents, stool softeners, osmotic and stimulant laxatives, prucalopride and probiotics in the management of chronic constipation. A brief summary of lubiprostone and linaclotide is also presented. The quality of evidence is presented by adopting the Grading of Recommendations, Assessment, Development and Evaluation system. Finally, a management pyramid for patients with chronic constipation is proposed based on the quality of evidence, impact of each modality on constipation and on general health, and their availabilities in Canada.
The Role of Rhizobial ACC Deaminase in the Nodulation Process of Leguminous Plants
Authors: Nascimento Francisco X. , Brígido Clarisse , Glick Bernard R. , Rossi Márcio J.
Published: May 2016

Symbiotic rhizobia-legumes associations are extremely important in terms of sustainable agricultural practices. This symbiosis involves a complex interaction between both partners, plant and bacterium, for bacterial infection and the formation of symbiotic N-fixing nodules. In this regard, the phytohormone ethylene plays a significant role in nodule formation, acting as an inhibitor of the nodulation process. Ethylene not only regulates nodule development but also regulates many other plant developmental cues, including various stress responses that inhibit overall plant growth. Some rhizobia produce the enzyme 1-aminocyclopropane-1-carboxylate (ACC) deaminase, thus, being able to decrease ACC and, consequently, decrease deleterious ethylene levels that affect the nodulation process. This occurs because ACC is the immediate precursor of ethylene in all higher plants. Hence, rhizobia that express this enzyme have an increased symbiotic potential. In addition to the direct role that ACC deaminase plays in the nodulation processper se, in a limited number of instances, ACC deaminase can also modulate nodule persistence. This review focuses on the important role of rhizobial ACC deaminase during the nodulation process, emphasizing its significance to legume growth promotion.
Chiral Perturbation Theory for Three-Flavour Lattice QCD with Isospin Splitting
Authors: Engelnkemper S. , Münster G.
Published: May 2016

An important tool for the analysis of results of numerical simulations of lattice QCD is chiral perturbation theory. In the Wilson chiral perturbation theory the effects of the finite lattice spacingaare taken into account. In recent years the effects of isospin splitting on the masses of hadrons have been investigated in the Monte Carlo simulations. Correspondingly, in this paper we derive the expansions of the masses of the pseudoscalar mesons in chiral perturbation theory at next-to-leading order for twisted mass lattice QCD with three light quark flavours, taking the mass difference between the up- and downquarks into account. The results include terms up to ordersmq2in the quark masses,Δm2in the mass splitting between up- and downquarks, anda2in the lattice spacing, respectively.
Environmental Determinants Influencing Fish Community Structure and Diversity in Two Distinct Seasons among Wetlands of Northern Region (Ghana)
Authors: Nsor Collins Ayine , Obodai Edward Adzesiwor
Published: May 2016

Fish community structure was assessed in six wetlands using cast nets, to correlate with environmental variables with diversity and distribution patterns, from 2010 to 2012. A total of 2,239 individuals belonging to 44 species and 1,938 individuals belonging to 40 species were sampled in the dry and wet seasons. Mochokid and Mormyrid families dominated fish community and constituted 14.8%, respectively, followed by Alestids (12.9%) and Chlariids (11.1%). Rarer taxons were centropomids, channids, malapteruds, and oesteoglossids and represented 1.9%, respectively. Overall, CPUE per net did not vary significantly (Tukey HSD test,p=0.27) in the dry and wet seasons. Wuntori marsh consistently showed dominance in mean monthly CPUE per net (dry =115±4.5; wet =107±7.7seasons), while Bunglung constructed wetland was the least recorded (dry =56.5±6.2; wet =58.3±4.1seasons). Fish diversity and richness differed significantly (F=0.11,p=0.03) among seasons. Environmental disturbances were season-specific and did not differ significantly (F=0.16,df=14,p=0.97) among sites. A DCA ordination explained 69% variability in fish distribution patterns, while PCA showed that 81.8% of nitrate-nitrogen, phosphate, and grazing intensity on axis 1 and conductivity, temperature, and turbidity on axis 2 influenced fish community structure. Wetland conservation must be promoted to sustain fish abundance and overall ecosystem stability.
Diurnal Variation of Soil Heat Flux at an Antarctic Local Area during Warmer Months
Authors: Alves Marco , Soares Jacyra
Published: May 2016

Soil heat flux (G) is one term in the energy balance equation, and it can be particularly important in regions with arid, bare, or thinly vegetated soil surfaces. However, in remote areas such as the Antarctic, this measurement is not routinely performed. The analysis of observational data collected by the ETA Project at the Brazilian Antarctic Station from December 2013 to March 2014 showed that, for the total daily energy flux, the surface soil flux heats the deeper soil layers during December and January andGacts as a heat source to the outer soil layers during February and March. With regard to daytime energy flux,Gacts as a source of heat to the deeper layers. During the night-time, the soil is a heat source to the shallower soil layers and represents at least 29% of the net night-time radiation. A relatively simple method—the objective hysteresis method (OHM)—was successfully applied to determine the surface soil heat flux using net radiation observations.A priori, the OHM coefficients obtained in this study may only be used for short-time parameterizations and for filling data gaps at this specific site.
Modeling Age-Friendly Environment, Active Aging, and Social Connectedness in an Emerging Asian Economy
Authors: Lai Ming-Ming , Lein Shi-Ying , Lau Siok-Hwa , Lai Ming-Ling
Published: May 2016

This paper empirically tested eight key features of WHO guidelines to age-friendly community by surveying 211 informal caregivers and 402 self-care adults (aged 45 to 85 and above) in Malaysia. We examined the associations of these eight features with active aging and social connectedness through exploratory and confirmatory factor analyses. A structural model with satisfactory goodness-of-fit indices (CMIN/df = 1.11, RMSEA = 0.02, NFI = 0.97, TLI = 1.00, CFI = 1.00, and GFI = 0.96) indicates that transportation and housing, community support and health services, and outdoor spaces and buildings are statistically significant in creating an age-friendly environment. We found a statistically significant positive relationship between an age-friendly environment and active aging. This relationship is mediated by social connectedness. The results indicate that built environments such as accessible public transportations and housing, affordable and accessible healthcare services, and elderly friendly outdoor spaces and buildings have to be put into place before social environment in building an age-friendly environment. Otherwise, the structural barriers would hinder social interactions for the aged. The removal of the environmental barriers and improved public transportation services provide short-term solutions to meet the varied and growing needs of the older population.
A Guiding Evolutionary Algorithm with Greedy Strategy for Global Optimization Problems
Authors: Cao Leilei , Xu Lihong , Goodman Erik D.
Published: May 2016

A Guiding Evolutionary Algorithm (GEA) with greedy strategy for global optimization problems is proposed. Inspired by Particle Swarm Optimization, the Genetic Algorithm, and the Bat Algorithm, the GEA was designed to retain some advantages of each method while avoiding some disadvantages. In contrast to the usual Genetic Algorithm, each individual in GEA is crossed with the current global best one instead of a randomly selected individual. The current best individual served as a guide to attract offspring to its region of genotype space. Mutation was added to offspring according to a dynamic mutation probability. To increase the capability of exploitation, a local search mechanism was applied to new individuals according to a dynamic probability of local search. Experimental results show that GEA outperformed the other three typical global optimization algorithms with which it was compared.
Screening for Nephropathy in Diabetes Mellitus: Is Micral-Test Valid among All Diabetics?
Authors: Afifa Koubaa , Belguith Asma Sriha , Nabil Harzallah , Ahlem Bellaleh , Mounira Sahtout , Kawthar Younes , Sonia Triki , Ilhem Hellara , Fadoua Neffati , Fadhel Najjar , Mohamed Soltani
Published: May 2016

Background.Using Micral-test (MT) for screening microalbuminuria (MA) among type 2 diabetics (T2D) is helpful. We aimed at determining prevalence of MA and at describing the MT validity.Methods.We studied 182 T2D followed up in family medicine. Two 24-hour urinary quantitative assays of MA had been used as a gold standard.Results. Prevalence of MA was 23%, CI 95%: 16.9–29.1. MT validity was 77% for sensitivity, 88% for negative predictive value, and 0.2 for Kappa coefficient (p=0.001). Among subjects having a blood pressure ≥130/80 mmHg, having a CHT/HDL ratio ≥ 3, being a T2D for more than 5 years, and being women, negative predictive values were, respectively, 91%, 89%, 95%, and 91%. The area under the ROC curve was 0.81 in men (p=0.008) and 0.80 when diabetes duration exceeds 5 years (p=0.001). The MA value at 100% Sp for MT was 35 mg/L.Conclusion.The use of MT in primary healthcare for yearly screening for MA in T2D must be accentuated especially when diabetes duration exceeds 5 years or when associated with other cardiovascular risks.
Graphene-Based FET Detector forE. coliK12 Real-Time Monitoring and Its Theoretical Analysis
Authors: Zhu Jieyi , Niu Fuzhou , Zhu Changan , Yang Jie , Xi Ning
Published: May 2016

This paper presents a theoretical analysis for a graphene-based FET real-time detector of the target bacteriaE. coliK12. The motivation for this study is to design a sensor device for detection of bacteria in food and water in order to guarantee food safety. Graphene is chosen as our material for sensor design, which has outstanding electrical, physical, and optical performance. In our sensor structure, graphene-based solution gate field effect transistor (FET) is the device model; fabrication and functionalization protocol are presented together in this paper. What is more, a real-time signal display system is the accompanied equipment for our designed biosensor device. In this system, the sensor bias current signalIdswould change obviously when the target bacteria are attached to the sensor surface. And the bias currentIdsincreases when theE. coliconcentration increases. In the latter part, a theoretical interpretation of the sensor signal is to explain the bias currentIdsincreasing after theE. coliK12 attachment.
Diagnosing and Treating Inflammatory Myofibroblastic Tumor of the Bladder
Authors: Alam Ridwan , Johnson Michael H. , Caldwell Trevor , Pavlovich Christian P. , Bivalacqua Trinity J. , Tosoian Jeffrey J.
Published: May 2016

Inflammatory myofibroblastic tumor (IMT) is an uncommon condition that is rarely encountered in the urinary tract. In this report, we present a case of IMT of the bladder in a woman with multiple previous pelvic surgeries. We further review the relevant literature to highlight this rare but important clinical presentation.
A Novel Quantum-Behaved Bat Algorithm with Mean Best Position Directed for Numerical Optimization
Authors: Zhu Binglian , Zhu Wenyong , Liu Zijuan , Duan Qingyan , Cao Long
Published: May 2016

This paper proposes a novel quantum-behaved bat algorithm with the direction of mean best position (QMBA). In QMBA, the position of each bat is mainly updated by the current optimal solution in the early stage of searching and in the late search it also depends on the mean best position which can enhance the convergence speed of the algorithm. During the process of searching, quantum behavior of bats is introduced which is beneficial to jump out of local optimal solution and make the quantum-behaved bats not easily fall into local optimal solution, and it has better ability to adapt complex environment. Meanwhile, QMBA makes good use of statistical information of best position which bats had experienced to generate better quality solutions. This approach not only inherits the characteristic of quick convergence, simplicity, and easy implementation of original bat algorithm, but also increases the diversity of population and improves the accuracy of solution. Twenty-four benchmark test functions are tested and compared with other variant bat algorithms for numerical optimization the simulation results show that this approach is simple and efficient and can achieve a more accurate solution.
The Emerging Role of HMGB1 in Neuropathic Pain: A Potential Therapeutic Target for Neuroinflammation
Authors: Wan Wenbin , Cao Lan , Khanabdali Ramin , Kalionis Bill , Tai Xiantao , Xia Shijin
Published: May 2016

Neuropathic pain (NPP) is intolerable, persistent, and specific type of long-term pain. It is considered to be a direct consequence of pathological changes affecting the somatosensory system and can be debilitating for affected patients. Despite recent progress and growing interest in understanding the pathogenesis of the disease, NPP still presents a major diagnostic and therapeutic challenge. High mobility group box 1 (HMGB1) mediates inflammatory and immune reactions in nervous system and emerging evidence reveals that HMGB1 plays an essential role in neuroinflammation through receptors such as Toll-like receptors (TLR), receptor for advanced glycation end products (RAGE), C-X-X motif chemokines receptor 4 (CXCR4), and N-methyl-D-aspartate (NMDA) receptor. In this review, we present evidence from studies that address the role of HMGB1 in NPP. First, we review studies aimed at determining the role of HMGB1 in NPP and discuss the possible mechanisms underlying HMGB1-mediated NPP progression where receptors for HMGB1 are involved. Then we review studies that address HMGB1 as a potential therapeutic target for NPP.
Systemic Administration of Proteoglycan Protects BALB/c Retired Breeder Mice from Experimental Arthritis
Authors: Ishikawa Larissa Lumi Watanabe , Colavite Priscila Maria , Fraga-Silva Thais Fernanda de Campos , Mimura Luiza Ayumi Nishiyama , França Thais Graziela Donegá , Zorzella-Pezavento Sofia Fernanda Gonçalves , Chiuso-Minicucci Fernanda , Marcolino Larissa Doddi , Marques Camila , Ikoma Maura Rosane Valerio , Sartori Alexandrina
Published: May 2016

This study was undertaken to evaluate the prophylactic potential of proteoglycan (PG) administration in experimental arthritis. Female BALB/c retired breeder mice received two (2xPG50 and 2xPG100 groups) or three (3xPG50 group) intraperitoneal doses of bovine PG (50 μg or 100 μg) every three days. A week later the animals were submitted to arthritis induction by immunization with three i.p. doses of bovine PG associated with dimethyldioctadecylammonium bromide adjuvant at intervals of 21 days. Disease severity was daily assessed after the third dose by score evaluation. The 3xPG50 group showed significant reduction in prevalence and clinical scores. This protective effect was associated with lower production of IFN-γand IL-17 and increased production of IL-5 and IL-10 by spleen cells restimulatedin vitrowith PG. Even though previous PG administration restrained dendritic cells maturation this procedure did not alter the frequency of regulatory Foxp3+T cells. Lower TNF-αand IL-6 levels and higher expression of ROR-γand GATA-3 were detected in the paws of protected animals. A delayed-type hypersensitivity reaction confirmed specific tolerance induction. Taken together, these results indicate that previous PG inoculation determines a specific tolerogenic effect that is able to decrease severity of subsequently induced arthritis.
Efficacy of Mitochondrial Antioxidant Plastoquinonyl‐decyl‐triphenylphosphonium Bromide (SkQ1) in the Rat Model of Autoimmune Arthritis
Authors: Andreev-Andrievskiy Alexander A. , Kolosova Nataliya G. , Stefanova Natalia A. , Lovat Maxim V. , Egorov Maxim V. , Manskikh Vasily N. , Zinovkin Roman A. , Galkin Ivan I. , Prikhodko Anastasia S. , Skulachev Maxim V. , Lukashev Alexander N.
Published: May 2016

Rheumatoid arthritis is one of the most common autoimmune diseases. Many antioxidants have been tested in arthritis, but their efficacy was, at best, marginal. In this study, a novel mitochondria‐targeted antioxidant, plastoquinonyl‐decyl‐triphenylphosphonium bromide (SkQ1), was tested in vivo to prevent and cure experimental autoimmune arthritis. In conventional Wistar rats, SkQ1 completely prevented the development of clinical signs of arthritis if administered with food before induction. Further, SkQ1 significantly reduced the fraction of animals that developed clinical signs of arthritis and severity of pathological lesions if administration began immediately after induction of arthritis or at the onset of first symptoms (day 14 after induction). In specific pathogen‐free Wistar rats, SkQ1 administered via gavage after induction of arthritis did not reduce the fraction of animals with arthritis but decreased the severity of lesions upon pathology examination in a dose‐dependent manner. Efficacious doses of SkQ1 were in the range of 0.25–1.25 nmol/kg/day (0.13–0.7 μg/kg/day), which is much lower than doses commonly used for conventional antioxidants. SkQ1 promoted apoptosis of neutrophils in vitro, which may be one of the mechanisms underlying its pharmacological activity. Considering its low toxicity and the wide therapeutic window, SkQ1 may be a valuable additional therapy for rheumatoid arthritis.
An Approach of Tracking Control for Chaotic Systems
Authors: Xing Jin , Zhang Fangfang
Published: May 2016

Combining the ergodicity of chaos and the Jacobian matrix, we design a general tracking controller for continuous and discrete chaotic systems. The control scheme has the ability to track a bounded reference signal. We prove its globally asymptotic stability and extend it to generalized projective synchronization. Numerical simulations verify the effectiveness of the proposed scheme.
Downregulation of the TGFβ Pseudoreceptor BAMBI in Non–Small Cell Lung Cancer Enhances TGFβ Signaling and Invasion
Authors: Marwitz Sebastian , Depner Sofia , Dvornikov Dmytro , Merkle Ruth , Szczygieł Magdalena , Müller-Decker Karin , Lucarelli Philippe , Wäsch Marvin , Mairbäurl Heimo , Rabe Klaus F. , Kugler Christian , Vollmer Ekkehard , Reck Martin , Scheufele Swetlana , Kröger Maren , Ammerpohl Ole , Siebert Reiner , Goldmann Torsten , Klingmüller Ursula
Published: May 2016

Non–small cell lung cancer (NSCLC) is characterized by early metastasis and has the highest mortality rate among all solid tumors, with the majority of patients diagnosed at an advanced stage where curative therapeutic options are lacking. In this study, we identify a targetable mechanism involving TGFβ elevation that orchestrates tumor progression in this disease. Substantial activation of this pathway was detected in human lung cancer tissues with concomitant downregulation of BAMBI, a negative regulator of the TGFβ signaling pathway. Alterations of epithelial-to-mesenchymal transition (EMT) marker expression were observed in lung cancer samples compared with tumor-free tissues. Distinct alterations in the DNA methylation of the gene regions encoding TGFβ pathway components were detected in NSCLC samples compared with tumor-free lung tissues. In particular, epigenetic silencing of BAMBI was identified as a hallmark of NSCLC. Reconstitution of BAMBI expression in NSCLC cells resulted in a marked reduction of TGFβ-induced EMT, migration, and invasion in vitro, along with reduced tumor burden and tumor growth in vivo. In conclusion, our results demonstrate how BAMBI downregulation drives the invasiveness of NSCLC, highlighting TGFβ signaling as a candidate therapeutic target in this setting. Cancer Res; 76(13); 3785–801. ©2016 AACR.
mTORC1-Driven Tumor Cells Are Highly Sensitive to Therapeutic Targeting by Antagonists of Oxidative Stress
Authors: Li Jing , Shin Sejeong , Sun Yang , Yoon Sang-Oh , Li Chenggang , Zhang Erik , Yu Jane , Zhang Jianming , Blenis John
Published: May 2016

mTORC1 is a central signaling node in controlling cell growth, proliferation, and metabolism that is aberrantly activated in cancers and certain cancer-associated genetic disorders, such as tuberous sclerosis complex (TSC) and sporadic lymphangioleiomyomatosis. However, while mTORC1-inhibitory compounds (rapamycin and rapalogs) attracted interest as candidate therapeutics, clinical trials have not replicated the promising findings in preclinical models, perhaps because these compounds tend to limit cell proliferation without inducing cell death. In seeking to address this issue, we performed a high-throughput screen for small molecules that could heighten the cytotoxicity of mTORC1 inhibitors. Here we report the discovery that combining inhibitors of mTORC1 and glutamate cysteine ligase (GCLC) can selectively and efficiently trigger apoptosis in Tsc2-deficient cells but not wild-type cells. Mechanistic investigations revealed that coinhibition of mTORC1 and GCLC decreased the level of the intracellular thiol antioxidant glutathione (GSH), thereby increasing levels of reactive oxygen species, which we determined to mediate cell death in Tsc2-deficient cells. Our findings offer preclinical proof of concept for a strategy to selectively increase the cytotoxicity of mTORC1 inhibitors as a therapy to eradicate tumor cells marked by high mTORC1 signaling, based on cotargeting a GSH-controlled oxidative stress pathway. Cancer Res; 76(16); 4816–27. ©2016 AACR.
Circulating Cancer-Associated Macrophage-Like Cells Differentiate Malignant Breast Cancer and Benign Breast Conditions
Authors: Adams Daniel L. , Adams Diane K. , Alpaugh R. Katherine , Cristofanilli Massimo , Martin Stuart S. , Chumsri Saranya , Tang Cha-Mei , Marks Jeffrey R.
Published: May 2016

Background: Blood-based testing can be used as a noninvasive method to recover and analyze circulating tumor-derived cells for clinical use. Circulating cancer-associated macrophage-like cells (CAML) are specialized myeloid cells found in peripheral blood and associated with the presence of solid malignancies. We measured CAMLs prospectively in peripheral blood to ascertain their prevalence, specificity, and sensitivity in relation to breast disease status at clinical presentation.

Methods: We report on two related but separate studies: 1) CellSieve microfilters were used to isolate CAMLs from blood samples of patients with known malignant disease (n = 41). Prevalence and specificity was compared against healthy volunteers (n = 16). 2) A follow-up double-blind pilot study was conducted on women (n = 41) undergoing core-needle biopsy to diagnose suspicious breast masses.

Results: CAMLs were found in 93% of known malignant patients (n = 38/41), averaging 19.4 cells per sample, but none in the healthy controls. In subjects undergoing core biopsy for initial diagnosis, CAMLs were found in 88% of subjects with invasive carcinoma (n = 15/17) and 26% with benign breast conditions (n = 5/19).

Conclusion: These preliminary pilot studies suggest that the presence of CAMLs may differentiate patients with malignant disease, benign breast conditions, and healthy individuals.

Impact: We supply evidence that this previously unidentified circulating stromal cell may have utility as a screening tool to detect breast cancer in various malignancies, irrespective of disease stage. Cancer Epidemiol Biomarkers Prev; 25(7); 1037–42. ©2016 AACR.
Tumor-Infiltrating Lymphocytes: A Predictive and Prognostic Biomarker in Neoadjuvant-Treated HER2-Positive Breast Cancer
Authors: Ingold Heppner Barbara , Untch Michael , Denkert Carsten , Pfitzner Berit M. , Lederer Bianca , Schmitt Wolfgang , Eidtmann Holger , Fasching Peter A. , Tesch Hans , Solbach Christine , Rezai Mahdi , Zahm Dirk M. , Holms Frank , Glados Manfred , Krabisch Petra , Heck Esther , Ober Angelika , Lorenz Petra , Diebold Kurt , Habeck Jörg-Olaf , Loibl Sibylle
Published: May 2016

Purpose: We elucidated the value of tumor-infiltrating lymphocytes (TIL) as an independent predictor for pathologic complete response (pCR) rate and as a prognostic marker for disease-free survival (DFS) in patients with HER2-positive breast cancer in the neoadjuvant setting.

Experimental Design: We evaluated stromal TILs in 498 HER2-positive breast cancer samples of the neoadjuvant GeparQuattro (G4) and GeparQuinto (G5) trials. Levels of TILs were determined as a continuous parameter per 10% increase and as lymphocyte-predominant breast cancer (LPBC; ≥ 60% TILs), and correlated with pCR rate and DFS.

Results: In the complete cohort, HER2-positive LPBC cases had a significantly increased pCR rates compared with non-LPBC types. They were significant predictors for pCR in univariate (10% TILs: OR 1.12, P = 0.002; LPBC: OR 2.02, P = 0.002) and multivariate analyses (10% TILs: OR 1.1, P = 0.014; LPBC: OR 1.87, P = 0.009). This effect was also detectable in the trastuzumab-treated (10% TILs: OR 1.12, P = 0.018; LPBC: OR 2.08, P = 0.013) but not in the lapatinib-treated subgroup. We identified a low-risk (pCR/LPBC) and a high-risk group (no pCR/no LPBC) regarding DFS. In triple-positive breast cancer, TILs are of more prognostic relevance than pCR.

Conclusions: We could demonstrate the predictive and prognostic impact of TILs in HER2-positive breast cancer in the neoadjuvant setting. In combination with pCR rate, TILs may help to stratify prognostic subgroups, thereby guiding future therapy decisions. Clin Cancer Res; 22(23); 5747–54. ©2016 AACR.
Macular Retinal Ganglion Cell Layer Thickness Is Not Reduced in Patients with Obstructive Sleep Apnea
Authors: Ferrandez Blanca , Ferreras Antonio , Calvo Pilar , Abadia Beatriz , Pajarin Ana B. , Marin Jose M. , Iester Michele
Published: May 2016

Purpose: To evaluate macular ganglion cell layer (GCL) and ganglion cell-inner plexiform layer (GCIPL) thicknesses in patients with obstructive sleep apnea (OSA) syndrome. Methods: 73 OSA patients and 67 age-matched controls were consecutively and prospectively enrolled. All participants underwent at least one reliable standard automated perimetry (SAP) and were imaged with spectral-domain optical coherence tomography (OCT) using two different devices. The OCT parameters were compared between groups, and Pearson correlations between main indices of SAP and OCT parameters were calculated. Results: The pattern standard deviation of SAP was higher in the OSA group (p = 0.001). Mean GCIPL thickness was 82.99 ± 10.30 and 80.78 ± 12.15 µm in the control and OSA groups, respectively (p = 0.25), and GCL thickness was 44.93 ± 11.42 µm in the control group and 48.81 ± 10.85 µm in OSA individuals (p = 0.47). Pearson correlations between the GCIPL-GCL measurements and the main indices of SAP were not significant. Conclusions: Neither GCIPL nor GCL thickness were reduced in OSA subjects compared with healthy individuals. Retinal sensitivity evaluated with SAP was however decreased in OSA patients.
Amyotrophic Lateral Sclerosis in Northern Spain 40 Years Later: What Has Changed?
Authors: Riancho Javier , Lozano-Cuesta Pablo , Santurtún Ana , Sánchez-Juan Pascual , López-Vega José Manuel , Berciano José , Polo José Miguel
Published: May 2016

Background: In the last years different studies have reported an increase of amyotrophic lateral sclerosis (ALS) incidence, highlighting the role of the environment in this disease. This prompted us to review ALS cases diagnosed at our hospital in the last decade and to compare them with a previous ALS series reported in our region 30 years ago. Methods: We reviewed those ALS cases diagnosed at our centre between 2004 and 2013. Subsequently, we compared them with the previous series regarding clinical and epidemiological features. Results: A total of 53 patients (30 males, 23 females) were included. The annual incidence was 1.7 cases per 100,000 inhabitants (2.2 and 1.2 per 100,000 in males and females, respectively), which was significantly higher than in the previous series (1 case per 100,000 inhabitants). Otherwise, the clinical and epidemiological features were similar in both series. The median age at symptom onset was 67 years, with a median diagnosis delay of 6 months. About two thirds of the patients presented with systemic ALS, whereas the remaining had a bulbar onset. Weakness, dysphagia, and dysarthria were the most common clinical symptoms at diagnosis. The median survival from symptom onset was 22 months. Conclusion: After 3 decades, the annual incidence of ALS has almost doubled in our region. We did not find significant differences regarding other clinical or epidemiological features.
Abnormal Epigenetic Modifications in Peripheral T Cells from Patients with Abdominal Aortic Aneurysm Are Correlated with Disease Development
Authors: Jiang Han , Xia Qian , Xin Shijie , Lun Yun , Song Jianbo , Tang Dianjun , Liu Xun , Ren Jiancong , Duan Zhiquan , Zhang Jian
Published: May 2016

Background: Increasing evidence suggests that abdominal aortic aneurysm (AAA) is a T-cell-mediated autoimmune condition. This study investigates the epigenetic modifications that occur in the T cells of AAA patients and evaluates the correlation of these modifications with disease development. Methods and Results: Peripheral T cells were collected from 101 AAA patients and 102 healthy controls (HCs). DNA methylation and histone acetylation levels were measured by ELISA. Methyl-CpG-binding domain, DNA methyltransferase (DNMT) and histone deacetylase (HDAC) mRNA levels were determined by real-time PCR. DNA from the T cells of the AAA patients exhibited significant hypomethylation compared with the HCs (1.6-fold, p < 0.0001). Expression of DNMT1 at the mRNA level in the T cells of the AAA patients was 1.52-fold lower than that of the HCs (p < 0.0001). The extent of DNA methylation in the AAA patients was negatively correlated with the corresponding aortic diameter (r = -0.498, p < 0.0001). H3 (1.59-fold, p < 0.0001) and H3K14 (2.15-fold, p < 0.0001) acetylation levels in the T cells of the AAA patients were higher than those of the HCs, but the HDAC1 mRNA level was 2.33-fold lower than that of the HCs (p < 0.0001). Conclusions: DNA methylation and the histone modification status are significantly altered in the T cells of AAA patients. These changes could play a pivotal role in the activation of pathological immune responses and may influence AAA development.
Does More Accurate Knowledge of Course Grade Impact Teaching Evaluation?
Authors: Cho Donghun , Cho Joonmo
Published: May 2016

Students’ different standards may yield different kinds of bias, such as self-directed (higher than their past performance) bias and peer-directed (higher than their classmates) bias. Utilizing data obtained from a natural experiment where some students were able to see their grades prior to teacher evaluations, and to investigate possible sources of bias, we empirically analyzed the role of information (such as the actual grade students received in their current course and their previous grade point average), and the average grade of the course, on the student evaluation of teaching. Because bias is sensitive to the accuracy of grade information, the randomized data examined in this paper are a valuable source for estimating both self-directed and peer-directed bias. We identify the existence of the two kinds of biases and demonstrate that the influence of peer-directed bias tends to increase after the accurate information on the course grade is revealed.
ACT for All: The Effect of Mandatory College Entrance Exams on Postsecondary Attainment and Choice
Authors: Hyman Joshua
Published: May 2016

This paper examines the effects of requiring and paying for all public high school students to take a college entrance exam, a policy adopted by eleven states since 2001. I show that prior to the policy, for every ten poor students who score college-ready on the ACT or SAT, there are an additional five poor students who would score college-ready but who take neither exam. I use a difference-in-differences strategy to estimate the effects of the policy on postsecondary attainment and find small increases in enrollment at four-year institutions. The effects are concentrated among students less likely to take a college entrance exam in the absence of the policy and students in the poorest high schools. The students induced by the policy to enroll persist through college at approximately the same rate as their inframarginal peers. I calculate that the policy is more cost-effective than traditional student aid at boosting postsecondary attainment.
Emancipatory Intercultural Hermeneutics: Interpreting Theo Sundermeier’s Differenzhermeneutik
Authors: Congdon David W.
Published: May 2016

This article introduces and assesses Sundermeier’s “hermeneutic of difference” (Differenzhermeneutik). Though he is not well-known in English-speaking circles, the pioneering work of Theo Sundermeier has contributed to a hermeneutical and intercultural turn within the field of missiology, as well as a missiological and practical turn within hermeneutics. He criticizes the western hermeneutical tradition for being text-centric and egocentric, and he replaces the standard hermeneutical models with one that is focused on the practical problem of understanding the stranger. I summarize the four-step process he provides for learning how to understand and coexist with another person, reflect on its missiological implications, and offer a constructive critique in the direction of a distinctively emancipatory intercultural hermeneutic.
Taxonomic studies on Zingiber (Zingiberaceae) in China III: Z. ventricosum, a new species from Yunnan, and notes on three closely related species
Authors: BAI LIN , LEONG-ŠKORNIČKOVÁ JANA , XIA NIAN-HE , YE YU-SHI
Published: May 2016

A new species, Zingiber ventricosum, endemic to Yunnan Province of southwestern China, is described and illustrated. It is similar to Z. oligophyllum, Z. thorelii and Z. xishuangbannaense in having much-reduced ligules, usually elongated petioles, flower shape and glabrous ovaries. Zingiber ventricosum, however, is readily distinguished from its three relatives by having erect peduncles and convex bracts that are inflated at their bases and acuminate and wide-spreading at their apices. These four species belong to Zingiber sect. Cryptanthium and together compose the informal “Z. oligophyllum complex”. This complex has a rather wide geographic distribution that extends from southern China to Thailand, Laos and southern Vietnam and to Taiwan, China. The three previously described species are revised based on a study of herbarium specimens, as well as living plants. Zingiber xishuangbannaense, previously regarded as conspecific with Z. thorelii, is resurrected here. Some of the previous records of Z. thorelii from Thailand are assigned to Z. xishuangbannaense, while the remaining records represent an as-yet unidentified taxon. Zingiber oligophyllum, previously reported as endemic to Taiwan, is now recorded for southeastern mainland China and Hong Kong. Descriptions, colour plates, distribution maps and preliminary IUCN conservations assessments for the four species are provided, together with a key to these species. Lectotypes for Z. oligophyllum and Z. xishuangbannaense are designated here, and the previous lectotypification of Z. thorelii is narrowed to a single specimen. Based on the latest IUCN criteria, Z. ventricosum is proposed to be Critically Endangered (CR), while the other three species qualify as least concern (LC).
Typification of the name Pteris multifida (Pteridaceae subfamily Pteridoideae)
Authors: MAZUMDAR JAIDEEP , ARANA MARCELO D.
Published: May 2016

Pteris multifida, sometimes called ‘spider fern’, ‘spider brake’, ‘Chinese brake’, or ‘Huguenot fern’, is characterized by its distal pinnae of mature leaves being simple, adnate and decurrent to the rachis in at least the distal ½ of the leaf, and the venation is entirely free. The species is native to subtropical Asia and was probably first collected from China. The species is commonly cultivated as an ornamental and has become naturalized in many parts of tropical Africa (Verdcourt 2002) and America (Prado & Windisch 2000, Christenhusz 2010, Martínez 2011). It grows terrestrially or epiphytically in moist, open, disturbed places.