bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Microbial Electron Transfer in the Coevolution of the Biosphere and Geosphere
Authors: Jelen Benjamin I. , Giovannelli Donato , Falkowski Paul G.
Published: June 2016

All life on Earth is dependent on biologically mediated electron transfer (i.e., redox) reactions that are far from thermodynamic equilibrium. Biological redox reactions originally evolved in prokaryotes and ultimately, over the first ∼2.5 billion years of Earth's history, formed a global electronic circuit. To maintain the circuit on a global scale requires that oxidants and reductants be transported; the two major planetary wires that connect global metabolism are geophysical fluids—the atmosphere and the oceans. Because all organisms exchange gases with the environment, the evolution of redox reactions has been a major force in modifying the chemistry at Earth's surface. Here we briefly review the discovery and consequences of redox reactions in microbes with a specific focus on the coevolution of life and geochemical phenomena.
Neutrino Mass Models
Authors: de Gouvêa André
Published: June 2016

The discovery of nonzero neutrino masses is among the most important particle physics results of the last two decades: It indicates that the Standard Model of particle physics is incomplete. After 20 years of intense experimental and theoretical research, we still do not know the physics that leads to nonzero neutrino masses. The purpose of this review is to discuss the different models for nonzero neutrino masses. In doing so, I describe the differences between the models, how they connect to other aspects of particle physics, and whether or how one can hope to establish which model—if any—is a faithful description of nature.
Initial-State Quantum Fluctuations in the Little Bang
Authors: Gelis François , Schenke Björn
Published: June 2016

We review recent developments in the ab initio theoretical description of the initial state in heavy-ion collisions. We emphasize the importance of fluctuations, both for the phenomenological description of experimental data from the Relativistic Heavy Ion Collider (RHIC) and the Large Hadron Collider (LHC) and for the theoretical understanding of the nonequilibrium early-time dynamics and thermalization of the medium.
Evolution and Adaptation of Wild Emmer Wheat Populations to Biotic and Abiotic Stresses
Authors: Huang Lin , Raats Dina , Sela Hanan , Klymiuk Valentina , Lidzbarsky Gabriel , Feng Lihua , Krugman Tamar , Fahima Tzion
Published: June 2016

The genetic bottlenecks associated with plant domestication and subsequent selection in man-made agroecosystems have limited the genetic diversity of modern crops and increased their vulnerability to environmental stresses. Wild emmer wheat, the tetraploid progenitor of domesticated wheat, distributed along a wide range of ecogeographical conditions in the Fertile Crescent, has valuable “left behind” adaptive diversity to multiple diseases and environmental stresses. The biotic and abiotic stress responses are conferred by series of genes and quantitative trait loci (QTLs) that control complex resistance pathways. The study of genetic diversity, genomic organization, expression profiles, protein structure and function of biotic and abiotic stress-resistance genes, and QTLs could shed light on the evolutionary history and adaptation mechanisms of wild emmer populations for their natural habitats. The continuous evolution and adaptation of wild emmer to the changing environment provide novel solutions that can contribute to safeguarding food for the rapidly growing human population.
Rice Reoviruses in Insect Vectors
Authors: Wei Taiyun , Li Yi
Published: June 2016

Rice reoviruses, transmitted by leafhopper or planthopper vectors in a persistent propagative manner, seriously threaten the stability of rice production in Asia. Understanding the mechanisms that enable viral transmission by insect vectors is a key to controlling these viral diseases. This review describes current understanding of replication cycles of rice reoviruses in vector cell lines, transmission barriers, and molecular determinants of vector competence and persistent infection. Despite recent breakthroughs, such as the discoveries of actin-based tubule motility exploited by viruses to overcome transmission barriers and mutually beneficial relationships between viruses and bacterial symbionts, there are still many gaps in our knowledge of transmission mechanisms. Advances in genome sequencing, reverse genetics systems, and molecular technologies will help to address these problems. Investigating the multiple interaction systems among the virus, insect vector, insect symbiont, and plant during natural infection in the field is a central topic for future research on rice reoviruses.
Multiple Disease Resistance in Plants
Authors: Wiesner-Hanks Tyr , Nelson Rebecca
Published: June 2016

Many plants, both in nature and in agriculture, are resistant to multiple diseases. Although much of the plant innate immunity system provides highly specific resistance, there is emerging evidence to support the hypothesis that some components of plant defense are relatively nonspecific, providing multiple disease resistance (MDR). Understanding MDR is of fundamental and practical interest to plant biologists, pathologists, and breeders. This review takes stock of the available evidence related to the MDR hypothesis. Questions about MDR are considered primarily through the lens of forward genetics, starting at the organismal level and proceeding to the locus level and, finally, to the gene level. At the organismal level, MDR may be controlled by clusters of R genes that evolve under diversifying selection, by dispersed, pathogen-specific genes, and/or by individual genes providing MDR. Based on the few MDR loci that are well-understood, MDR is conditioned by diverse mechanisms at the locus and gene levels.
Cycles of Sameness and Difference in LGBT Social Movements
Authors: Ghaziani Amin , Taylor Verta , Stone Amy
Published: June 2016

Research on lesbian, gay, bisexual, and transgender (LGBT) movements has accelerated in recent years. We take stock of this literature with a focus on the United States. Our review adopts a historical approach, surveying findings on three protest cycles: gay liberation and lesbian feminism, queer activism, and marriage equality. Existing scholarship focuses primarily on oscillations of the movement's collective identity between emphasizing similarities to the heterosexual mainstream and celebrating differences. We contrast earlier movement cycles mobilized around difference with efforts to legalize same-sex marriage. Our review highlights the turning points that led to shifts in protest cycles, and we trace the consequences for movement outcomes. Scholarship will advance if researchers recognize the path-dependent nature of social movements and that sameness and difference are not oppositional, static, or discrete choices. We conclude by recommending directions for future research.
Religious Studies in Latin America
Authors: de la Torre Renée , Martín Eloisa
Published: June 2016

This article critically reviews recent contributions to religious research in Latin America. Social scientists have long considered religion to be a structuring feature of culture and local society. Owing to the centrality of Catholicism in Latin America, early studies privileged the political influences of the Catholic Church with respect to the state and society at large. The “otherness” of native folk religions received less attention, with scholars undervaluing the presence of indigenous and African religiosities. In Latin America, religions are currently experiencing a diversification and reconfiguration, owing in part to the growing influence of different Christian denominations, particularly Evangelical and Pentecostal churches. Religious change is also occurring at the margins of institutional churches through New Age, neo-pagan, neo-Indian, neo-esoteric, and self-styled religiosities, as well as through popular religious syncretisms, indicating new experiments with what is considered sacred. This dynamism poses theoretical and conceptual challenges to scholars analyzing religious diversity and the renewed role that religions play in contemporary societies with respect to secularization, syncretism, and hybridization as well as the emergence of alternative identities (gender, sexual, ideological and political).
China's Great Migration and the Prospects of a More Integrated Society
Authors: Liang Zai
Published: June 2016

During the last three decades, China has experienced the largest migration in human history. China's great migration has had transformative social, economic, and demographic consequences for China and the world. In this review, first I provide background on China's household registration system (hukou), which has been in existence since the late 1950s and continues to affect the life chances of Chinese people. Then I focus on the great migration by discussing research that has examined its causes, migration trends, the adaptation/assimilation of migrants in urban China, the well-being of migrant children, and migration's impact on rural China. Finally, I identify key areas for future research and argue that China's great migration holds major promise to contribute to the literature on migration studies.
Schedule-Based Passenger Assignment for High-Speed Rail Networks considering the Ticket-Booking Process
Authors: Su Huanyin , Shi Feng , Xu Guangming , Qin Jin , Shan Xinghua
Published: June 2016

This paper proposes a schedule-based passenger assignment method for high-speed rail networks considering the ticket-booking process. Passengers book tickets to reserve seats during the presale period in high-speed rail systems and passengers on trains are determined during the ticket-booking process. The ticket-booking process is modeled as a continuous and deterministic predecision process. A solution algorithm is designed using the discretization of the continuous process by partitioning the ticket-booking time and the optimal paths remain constant in any partition interval. Finally, an application to the Chinese high-speed rail network is presented. A comparison of the numerical results with the reality is conducted to validate the efficiency and precision of the method and algorithm. Based on the results, the operating efficiency of the current train schedule is evaluated and some specific improvement measures are proposed.
Management of Ureterolithiasis in a Patient with Crossed Unfused Renal Ectopia
Authors: Kodama Koichi , Takase Yasukazu , Tatsu Hiroki
Published: June 2016

Crossed renal ectopia is a rare congenital anomaly in which both kidneys are situated on one side and fused together in 85%–90% of cases. The management of urinary calculi in patients with crossed renal ectopia continues to pose challenges to urologists because the aberrant anatomy may make access and clearance of the calculi more difficult to accomplish. Here, we report a case of inferior crossed renal ectopia, without fusion, and a ureteral stone in which the patient was treated successfully by extracorporeal shock wave lithotripsy.
Research Priorities in the Field of Posttraumatic Pain and Disability: Results of a Transdisciplinary Consensus-Generating Workshop
Authors: Walton David M. , Elliott James M. , Lee Joshua , Loh Eldon , MacDermid Joy C. , Schabrun Siobhan , Siqueira Walter L. , Corneil Brian D. , Aal Bill , Birmingham Trevor , Brown Amy , Cooper Lynn K. , Dickey James P. , Dixon S. Jeffrey , Fraser Douglas D. , Gati Joseph S. , Gloor Gregory B. , Good Gordon , Holdsworth David , McLean Samuel A. , Millard Wanda , Miller Jordan , Sadi Jackie , Seminowicz David A. , Shoemaker J. Kevin , Siegmund Gunter P. , Vertseegh Theodore , Wideman Timothy H.
Published: June 2016

Background. Chronic or persistent pain and disability following noncatastrophic “musculoskeletal” (MSK) trauma is a pervasive public health problem. Recent intervention trials have provided little evidence of benefit from several specific treatments for preventing chronic problems. Such findings may appear to argue against formal targeted intervention for MSK traumas. However, these negative findings may reflect a lack of understanding of the causal mechanisms underlying the transition from acute to chronic pain, rendering informed and objective treatment decisions difficult. The Canadian Institutes of Health Research (CIHR) Institute of Musculoskeletal Health and Arthritis (IMHA) has recently identified better understanding of causal mechanisms as one of three priority foci of their most recent strategic plan.Objectives. A 2-day invitation-only active participation workshop was held in March 2015 that included 30 academics, clinicians, and consumers with the purpose of identifying consensus research priorities in the field of trauma-related MSK pain and disability, prediction, and prevention.Methods. Conversations were recorded, explored thematically, and member-checked for accuracy.Results. From the discussions, 13 themes were generated that ranged from a focus on identifying causal mechanisms and models to challenges with funding and patient engagement.Discussion. Novel priorities included the inclusion of consumer groups in research from the early conceptualization and design stages and interdisciplinary longitudinal studies that include evaluation of integrated phenotypes and mechanisms.
Structural and Optical Properties of Zirconia Nanoparticles by Thermal Treatment Synthesis
Authors: Keiteb Aysar S. , Saion Elias , Zakaria Azmi , Soltani Nayereh
Published: June 2016

Zirconium dioxide nanoparticles with monoclinic blended structure were successfully synthesized by thermal treatment method using zirconium (IV) acetate hydroxide as the metal precursor, polyvinylpyrrolidone as the capping agent, and deionized water as a solvent. The chemicals were mixed and stirred to form a homogeneous solution and hereafter directly underwent calcination to attain the pure nanocrystalline powder, which was confirmed by FTIR, EDX, and XRD analyses. The control over the size and optical properties of nanoparticles was achieved through changing in calcination temperatures from 600 to 900°C. The obtained average particle sizes from XRD spectra and TEM images showed that the particle size increased with increasing calcination temperature. The optical properties which were investigated using a UV-Vis spectrophotometer showed a decrease in the band gap energy with increasing calcination temperature due to the enlargement of the particle size. These results prove that, by eliminating drying process (24 h) in the present thermal treatment method, size-controlled zirconia nanoparticles were conveniently manufactured with a reduction of synthesize time and energy consumption, suitable for large-scale fabrication.
Kinematics and Dynamics of a Tensegrity-Based Water Wave Energy Harvester
Authors: Lin Min , Li Tuanjie , Ji Zhifei
Published: June 2016

A tensegrity-based water wave energy harvester is proposed. The direct and inverse kinematic problems are investigated by using a geometric method. Afterwards, the singularities and workspaces are discussed. Then, the Lagrangian method was used to develop the dynamic model considering the interaction between the harvester and water waves. The results indicate that the proposed harvester allows harvesting 13.59% more energy than a conventional heaving system. Therefore, tensegrity systems can be viewed as one alternative solution to conventional water wave energy harvesting systems.
Ibuprofen for Ductus Arteriosus Months after Birth
Authors: Frauenfelder Odile , van Beynum Ingrid M. , Reiss Irwin K. M. , Simons Sinno H. P.
Published: June 2016

Ibuprofen is a well-known agent used to treat patent ductus arteriosus in preterm neonates in the first days of life. In the current case report we illustrate the potential use of ibuprofen in two preterm neonates 60 and 88 days after birth, respectively. To our knowledge, this is the first report on the effects of ibuprofen on patent ductus arteriosus in preterm newborns after months of life. These cases suggest that the ductus arteriosus does not become refractory for ibuprofen after the first days of life. Late closure of the duct with ibuprofen might still improve the cardiorespiratory condition and prevent infants from surgical closure. Controlled trials are necessary to further study these findings.
Automated Bidirectional Languages Localization Testing for Android Apps with Rich GUI
Authors: Ayyal Awwad Aiman M. , Slany Wolfgang
Published: June 2016

Mobile apps are everywhere. The release of apps on a worldwide scale requires them to be made available in many languages, including bidirectional languages. Developers and translators are usually different persons. While automatic testing by itself is important in general in order to be able to develop high quality software, such automatic tests become absolutely essential when developers that do not possess enough knowledge about right-to-left languages need to maintain code that is written for bidirectional languages. A few bidirectional localization tests of mobile applications exist. However, their functionality is limited since they only cover translations and adoption of locales. In this paper we present our approach for automating the bidirectional localization testing for Android applications with a complete consideration for BiDi-languages issues. The objective is to check for any localization defects in the product. The proposed methods are used to test issues of bidirectional apps in general and specifically for the Arabic language. The results show that the methods are able to effectively reveal deficiencies in the app’s design, ensure that the localized app matches all expectations of local users, and guarantee that the product is culturally congruent to local conventions.
Lesion in Scalp and Skull as the First Manifestation of Hepatocellular Carcinoma
Authors: Ferraz V. R. , Vitorino-Araújo J. L. , Sementilli L. , Neto J. F. , Veiga J. C. E.
Published: June 2016

Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and the fifth most common cancer in the world. The lungs, bone, and lymph nodes are frequent sites of metastasis of HCC. The purpose of the present study is show that metastases, although rare, must be among the differential diagnosis of skin lesions and that a diagnostic research based on these findings can be conducted. The authors report a rare case of metastatic hepatocellular injury to the scalp and skull treated by a radical surgical approach. Excision of the lesion in the scalp was performed “en bloc.” The tumor was supplied by the frontal branch of the superficial temporal artery. There are few case reports of metastatic HCC to scalp and skull; treatment of these lesions should be individualized in order to control symptoms, improve quality of life, and promote an increase in survival.
Influence of Trabecular Bone on Peri-Implant Stress and Strain Based on Micro-CT Finite Element Modeling of Beagle Dog
Authors: Liao Sheng-hui , Zhu Xing-hao , Xie Jing , Sohodeb Vikesh Kumar , Ding Xi
Published: June 2016

The objective of this investigation is to analyze the influence of trabecular microstructure modeling on the biomechanical distribution of the implant-bone interface. Two three-dimensional finite element mandible models, one with trabecular microstructure (a refined model) and one with macrostructure (a simplified model), were built. The values of equivalent stress at the implant-bone interface in the refined model increased compared with those of the simplified model and strain on the contrary. The distributions of stress and strain were more uniform in the refined model of trabecular microstructure, in which stress and strain were mainly concentrated in trabecular bone. It was concluded that simulation of trabecular bone microstructure had a significant effect on the distribution of stress and strain at the implant-bone interface. These results suggest that trabecular structures could disperse stress and strain and serve as load buffers.
Collapsing Glomerulopathy in a Child with Galloway-Mowat Syndrome
Authors: Zeybek Cengiz , Basbozkurt Gokalp , Hamcan Salih , Ozcan Ayhan , Gul Davut , Gok Faysal
Published: June 2016

Galloway-Mowat syndrome (GMS) is an autosomal recessive disorder with a poor prognosis that was first defined as a triad of central nervous system involvement, hiatal hernia, and nephrotic syndrome. However, this syndrome is now known to have a heterogeneous clinical presentation. The nephrotic syndrome is steroid resistant and is responsible for the outcome. The combination of collapsing glomerulopathy and GMS is very rare. A 26-month-old boy presented with steroid-resistant nephrotic syndrome associated with neurologic findings, including microcephaly, psychomotor retardation, and nystagmus. Magnetic resonance imaging showed marked cerebral atrophy, optic atrophy, and hypomyelination. A renal biopsy was consistent with collapsing glomerulopathy. If collapsing glomerulopathy is associated with neurological abnormalities, especially with microcephaly, clinicians should consider GMS as a possible underlying cause.
Mathematical Modeling of Local Scour at Slender and Wide Bridge Piers
Authors: Hafez Youssef I.
Published: June 2016

Most existing equations for predicting local scour at bridge piers suffer from overprediction of the scour depths which results in higher foundation costs. To tackle this problem, a mathematical model for predicting bridge pier scour is developed herein based on an energy balance theory. The present study equation was compared to commonly used bridge scour equations using scour field data in USA. The developed equation has several advantages among which we have the following: it adds to the understanding of the physics of bridge pier scour, is valid for slender and wide piers, does not suffer from overprediction of scour depths, addresses clear water and live bed scour, and includes the effects of various characteristics of the bed material such as specific gravity (or density), porosity, size, and angle of repose. In addition, the developed equation accounts for the debris effect and aids in the design of scour mitigation methods such as collars, side bars, slots, and pier protective piles.
JiaWeiDangGui Decoction Ameliorates Proteinuria and Kidney Injury in Adriamycin‐Induced Rat by Blockade of TGF‐β/Smad Signaling
Authors: Wei Ming-gang , He Wei-ming , Lu Xun , Ni Li , Yang Yan-yu , Chen Lin , Xiong Pei-hua , Sun Wei
Published: June 2016

JiaWeiDangGui (JWDG) decoction has anti‐inflammatory and antifibrotic effects, which is used widely for the treatment of various kidney diseases. In previous studies, we have found that JWDG decoction can reduce the quantity of proteinuria, but the mechanism was unknown. Here, we studied the protective effect of JWDG decoction in adriamycin‐induced nephropathy on rat. JWDG decoction, at 10 mL/kg/d, 20 mL/kg/d, and 40 mL/kg/d, was orally administered daily for 12 weeks. Therapeutic effects and mechanisms were further examined. The kidney function related biochemical indexes were measured by automatic biochemistry analyzer. The pathomorphological changes were observed using light and transmission electron microcopies. The proteins expressions of podocin, nephrin, collagen IV, and fibronectin (FN) were examined by immunohistochemical staining, and key proteins involved in TGF‐β/Smad signaling were evaluated by RT‐PCR and western blotting. Compared with vehicle‐treated controls, JWDG decoction decreased the quantity of proteinuria; reduced glomerulosclerotic lesions induced by ADR; and preserved the expression of podocin and nephrin. JWDG decoction also inhibited the expression of the collagen IV, FN, and fibrogenic TGF‐β. Further studies revealed that inhibition of renal fibrosis was associated with the blockade of TGF‐β/Smad signaling and downregulation of snail expression dose dependently. JWDG decoction prevents proteinuria production, podocyte dysfunction, and kidney injury in adriamycin nephropathy by inhibiting TGF‐β/Smad signaling.
Transperitoneal Laparoscopic Pyelopyelostomy for Retrocaval Ureter without Excision of the Retrocaval Segment: Experience on Three Cases
Authors: El Harrech Y. , Ghoundale O. , Kasmaoui E. H. , Touiti D.
Published: June 2016

Introduction. Retrocaval ureter is a rare congenital anomaly. Open surgery was the classic treatment for this condition. Laparoscopy is currently an admitted procedure to treat many urological diseases. The objective of our study is to present our experience and discuss the safety and the feasibility of transperitoneal laparoscopic pyelopyelostomy for treatment of retrocaval ureter (RCU).Materials and Methods. Three symptomatic patients underwent laparoscopic repair for RCU in our department. The diagnosis was suspected on the computed tomography scan (CT) and confirmed on ascending pyelography. After placement of a JJ stent, and, using the transperitoneal approach, the retro peritoneum was exposed; the ureter was identified in both sides of the vena cava. The retrocaval segment was entirely mobilized and pulled from behind of the vena cava after section of renal pelvis. A pyelopyelostomy was done in a normal anatomic position.Results. All operations were achieved laparoscopically without conversion to open surgery. The mean operative time was 140 minutes (110–190). No intraoperative complication occurred. Blood loss was less than 50 mL in all patients. The mean hospital stay was 5 days (4–6 days). All patients were symptom-free after surgery and had reduction of hydronephrosis in control imagery.Conclusion. Laparoscopy seems safe, feasible, and reproducible in managing retrocaval ureter.
Chemokines and Chemokine Receptors in the Development of Lupus Nephritis
Authors: Liao Xiaofeng , Pirapakaran Tharshikha , Luo Xin M.
Published: June 2016

Lupus nephritis (LN) is a major cause of morbidity and mortality in the patients with systemic lupus erythematosus (SLE), an autoimmune disease with damage to multiple organs. Leukocyte recruitment into the inflamed kidney is a critical step to promote LN progression, and the chemokine/chemokine receptor system is necessary for leukocyte recruitment. In this review, we summarize recent studies on the roles of chemokines and chemokine receptors in the development of LN and discuss the potential and hurdles of developing novel, chemokine-based drugs to treat LN.
Arteriovenous Fistula Embolization in Suspected Parauterine Choriocarcinoma
Authors: Alturkistani Husain , Almarzooqi Mohamed-Karji , Oliva Vincent , Gilbert Patrick
Published: June 2016

This is a case of choriocarcinoma that did not regress after chemotherapy treatment. A 30-year-old female patient (gravida 2, para 2), presented to our ER with stroke and persistent mild pelvic pain 2 months after a Caesarean section. Computed tomography (CT) revealed an ischemic left hemicerebellar region and a hypervascular mass in the pelvic region. This mass was not present on routine fetal ultrasound during pregnancy. The lesion was treated by chemotherapy after closure of a foramen ovale and insertion of an inferior vena cava (IVC) filter. After that, 2 courses of EMACO (Etoposide, Methotrexate, Actinomycin D, Cyclophosphamide, and Vincristine) chemotherapy regimen were given. Posttreatment CT showed the hypervascular mass without any changes. Arteriography showed the arteriovenous fistulae that were embolized successfully with plugs, coils, and glue. Embolization was considered due to the risk of acute hemorrhagic life-threatening complications. Eight chemotherapy courses were added after embolization. Treatment by endovascular approach and reduction of the hypervascular mass can be a valuable adjunct to chemotherapy treatment of choriocarcinoma.
A Case of Primary Hepatic Lymphoma and Related Literature Review
Authors: Liu Yonghua , Jiang Jinhong , Wu Qinli , Zhang Qiaolei , Xu Yehui , Qu Zhigang , Ma Guangli , Wang Xiaoqiu , Wang Xiaoli , Jin Weimei , Fang Bingmu
Published: June 2016

Objective. Primary hepatic lymphoma is a rare disease. And the clinical manifestations of this disease are nonspecific. The objective of this paper is to improve clinicians’ understanding of this disease.Methods. We analyzed the clinical characteristics of a case of primary hepatic lymphoma in association with hepatitis B virus infection and reviewed the literature.Conclusion. The clinical manifestations of primary hepatic lymphoma are nonspecific. And it is easily misdiagnosed. Postoperative radiotherapy of patients with early stage was previously speculated to achieve favorable improvement. The application of targeted therapeutic drugs, chemotherapy, or combined local radiotherapy has become the first-line treatment strategy.
Metallothioneins 1 and 2 Modulate Inflammation and Support Remodeling in Ischemic Cardiomyopathy in Mice
Authors: Duerr Georg D. , Dewald Daniela , Schmitz Eva J. , Verfuerth Luise , Keppel Katharina , Peigney Christine , Ghanem Alexander , Welz Armin , Dewald Oliver
Published: June 2016

Aims. Repetitive brief ischemia and reperfusion (I/R) is associated with left ventricular dysfunction during development of ischemic cardiomyopathy. We investigated the role of zinc-donor proteins metallothionein MT1 and MT2 in a closed-chest murine model ofI/R.Methods. Daily 15-minute LAD-occlusion was performed for 1, 3, and 7 days in SV129 (WT)- and MT1/2 knockout (MT-/-)-mice (n= 8–10/group). Hearts were examined with M-mode echocardiography and processed for histological and mRNA studies.Results. Expression of MT1/2 mRNA was transiently induced during repetitiveI/Rin WT-mice, accompanied by a transient inflammation, leading to interstitial fibrosis with left ventricular dysfunction without infarction. In contrast, MT-/--hearts presented with enhanced apoptosis and small infarctions leading to impaired global and regional pump function. Molecular analysis revealed maladaptation of myosin heavy chain isoforms and antioxidative enzymes in MT1/2-/--hearts. Despite their postponed chemokine induction we found a higher total neutrophil density and macrophage infiltration in small infarctions in MT-/--hearts. Subsequently, higher expression of osteopontin 1 and tenascin C was associated with increased myofibroblast density resulting in predominately nonreversible fibrosis and adverse remodeling in MT1/2-/--hearts.Conclusion. Cardioprotective effects of MT1/2 seem to be exerted via modulation of contractile elements, antioxidative enzymes, inflammatory response, and myocardial remodeling.
Pioglitazone Attenuates Drug-Eluting Stent-Induced Proinflammatory State in Patients by Blocking Ubiquitination of PPAR
Authors: Wang Zhongxia , Zhang Tao , Sun Lizhe , Li Ruifeng , Wei Yuanyuan , Fan Xiaojuan , Yuan Zuyi , Liu Junhui , Chen Tao
Published: June 2016

The inflammatory response after polymer-based drug-eluting stent (DES) placement has recently emerged as a major concern. The biologic roles of peroxisome proliferator-activated receptor-γ(PPAR-γ) activators thiazolidinedione (TZD) remain controversial in cardiovascular disease. Herein, we investigated the antiinflammatory effects of pioglitazone (PIO) on circulating peripheral blood mononuclear cells (MNCs) in patients after coronary DES implantation.Methods and Results. Twenty-eight patients with coronary artery disease and who underwent DES implantations were randomly assigned to pioglitazone (30 mg/d; PIO) or placebo (control; Con) treatment in addition to optimal standard therapy. After 12 weeks of treatment, plasma concentrations of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), and matrix metalloproteinase-9 (MMP-9) were significantly decreased in PIO group compared to the Con group (P=0.035, 0.011, 0.008, and 0.012, resp.). DES-induced mRNA expressions of IL-6, TNF-α, and MMP-9 in circulating MNC were significantly blocked by PIO (P=0.031, 0.012, and 0.007, resp.). In addition, PIO markedly inhibited DES-enhanced NF-κB function and DES-blocked PPAR-γactivity. Mechanically, DES induced PPAR-γubiquitination and degradation in protein level, which can be totally reversed by PIO.Conclusion. PIO treatment attenuated DES-induced PPAR loss, NF-κB activation, and proinflammation, indicating that PIO may have a novel direct protective role in modulating proinflammation in DES era.
Atypical Proliferating Trichilemmal Cyst with Malignant Breast Skin Transformation: A Case Report and Review of the Literature
Authors: Capurso-García Marino Antonio , Bautista-Piña Verónica , Pomerantz Alan , Galnares-Olalde Javier Andrés , Blachman-Braun Ruben , Rodríguez-Rodríguez Sergio , Goldberg-Murow Monica
Published: June 2016

Proliferating trichilemmal tumors (PTTs) are benign adnexal skin neoplasms that arise from the outer root sheath of the hair follicle. These tumors are most commonly observed on the scalp and occur, most of the time, in elderly women. Malignant transformation of these neoplasms is a rare event; less than 50 cases have been reported in the English medical literature. We present the case of a 39-year-old Hispanic woman with a tumor located on the skin of one of her breasts that in her third surgical procedure the histologic examination revealed the presence of a malignant proliferating trichilemmal tumor (MPTT). Furthermore, a review of the medical literature and a discussion of the clinical and pathologic features of this rare entity are provided.
Mathematical Analysis on Heat Transfer during Peristaltic Pumping of Fractional Second-Grade Fluid through a Nonuniform Permeable Tube
Authors: Bhatt Siddharth Shankar , Medhavi Amit , Gupta R. S.
Published: June 2016

This mathematical study is related to heat transfer under peristaltic flow of fractional second-grade fluid through nonuniform cylindrical tube with permeable walls. The analysis is performed under low Reynolds number and long wavelength approximation. The analytical solution for pressure gradient, friction force, and temperature field is obtained. The effects of appropriate parameters such as Grashof number, nonuniformity of tube, permeability of tube wall, heat source/sink parameter, material constant, fractional time derivative parameter and amplitude ratio on pressure rise, friction force, and temperature distribution are discussed. It is found that an increase in amplitude ratio and material constant causes increase in pressure but increase in nonuniformity of the tube causes decrease in pressure. It is also observed that variation of friction force against flow rate shows opposite behavior to that of pressure. Increase in temperature is also observed due to increase in heat source/sink parameter at inlet as well as downstream.
Respiratory Changes in Response to Cognitive Load: A Systematic Review
Authors: Grassmann Mariel , Vlemincx Elke , von Leupoldt Andreas , Mittelstädt Justin M. , Van den Bergh Omer
Published: June 2016

When people focus attention or carry out a demanding task, their breathing changes. But which parameters of respiration vary exactly and can respiration reliably be used as an index of cognitive load? These questions are addressed in the present systematic review of empirical studies investigating respiratory behavior in response to cognitive load. Most reviewed studies were restricted to time and volume parameters while less established, yet meaningful parameters such as respiratory variability have rarely been investigated. The available results show that respiratory behavior generally reflects cognitive processing and that distinct parameters differ in sensitivity: While mentally demanding episodes are clearly marked by faster breathing and higher minute ventilation, respiratory amplitude appears to remain rather stable. The present findings further indicate that total variability in respiratory rate is not systematically affected by cognitive load whereas the correlated fraction decreases. In addition, we found that cognitive load may lead to overbreathing as indicated by decreased end-tidal CO2but is also accompanied by elevated oxygen consumption and CO2release. However, additional research is needed to validate the findings on respiratory variability and gas exchange measures. We conclude by outlining recommendations for future research to increase the current understanding of respiration under cognitive load.
Throughput Characterization for Cooperative Wireless Information Transmission with RF Energy Harvesting-Based Relay
Authors: Yao Yuanyuan , Yin Changchuan , Huang Sai
Published: June 2016

The simultaneous wireless information and power transfer (SWIPT) in a cooperative relaying system is investigated, where the relay node is self-sustained by harvesting radiofrequency (RF) energy from the source node. In this paper, we propose a time switching and power splitting (TSPS) protocol for the cooperative system with a mobile destination node. In the first part of the transmission slot, a portion of the received signal power is used for energy transfer, and the remaining power is used for information transmission from the source to the relay. For the remaining time of the transmission slot, information is transmitted from the relay to a mobile destination node. To coordinate the wireless information and power transfer, two transmission modes are investigated, namely, relay-assisted transmission mode and nonrelay mode, respectively. Under these two modes, the outage probability and the network throughput are characterized. By joint optimization of the power splitting and the time switching ratios, we further compare the network throughput under the two transmission modes with different parameters. Results indicate that the relay-assisted transmission mode significantly improves the throughput of the wireless network.
Blocking NF-κB Is Essential for the Immunotherapeutic Effect of Recombinant IL18 in Pancreatic Cancer
Authors: Guo Xingjun , Zheng Lei , Jiang Jianxin , Zhao Yan , Wang Xin , Shen Ming , Zhu Feng , Tian Rui , Shi Chengjian , Xu Meng , Li Xu , Peng Feng , Zhang Hang , Feng Yechen , Xie Yu , Xu Xiaodong , Jia Wei , He Ruizhi , Xie Chencheng , Hu Jun , Ye Dawei , Wang Min , Qin Renyi
Published: June 2016

Purpose: We sought to find new immune-based treatments for pancreatic cancer.

Experimental Design: We detected IL18 expression in plasma and specimens from patients with pancreatic cancer. We then investigated whether IL18 had a therapeutic effect for pancreatic cancer in vitro and in vivo and any underlying mechanisms.

Results: Higher plasma IL18 was associated with longer overall survival (OS), but higher IL18 in pancreatic cancer tissues was associated with shorter OS and increased invasion and metastasis. Recombinant IL18 alone had no antitumor effect in the syngeneic mice with orthotopically transplanted tumors and promoted tumors in immunocompromised mice; it also facilitated immune responses in vitro and in vivo by augmenting the activity of cytotoxic T cells and NK cells in peripheral blood and lymph nodes. However, IL18 promoted the proliferation and invasion of pancreatic cancer cells, in vitro and in vivo, through the NF-κB pathway. Nevertheless, by coadministrating IL18 with BAY11-7082, an NF-κB inhibitor, we were able to prevent the procancerous effects of IL18 and prolong the survival time of the mice.

Conclusions: IL18 has both cancer-promoting and cancer-suppressing functions. Although its single-agent treatment has no therapeutic effect on pancreatic cancer, when combined with the NF-κB pathway inhibitor, IL18 improved survival in a murine pancreatic cancer model. Our study implies the possibility of a combinational immunotherapy that uses IL18 and targets NF-κB pathway. Clin Cancer Res; 22(23); 5939–50. ©2016 AACR.
Targeting RRM2 and Mutant BRAF Is a Novel Combinatorial Strategy for Melanoma
Authors: Fatkhutdinov Nail , Sproesser Katrin , Krepler Clemens , Liu Qin , Brafford Patricia A. , Herlyn Meenhard , Aird Katherine M. , Zhang Rugang
Published: June 2016

The majority of patients with melanoma harbor mutations in the BRAF oncogene, thus making it a clinically relevant target. However, response to mutant BRAF inhibitors (BRAFi) is relatively short-lived with progression-free survival of only 6 to 7 months. Previously, we reported high expression of ribonucleotide reductase M2 (RRM2), which is rate-limiting for de novo dNTP synthesis, as a poor prognostic factor in patients with mutant BRAF melanoma. In this study, the notion that targeting de novo dNTP synthesis through knockdown of RRM2 could prolong the response of melanoma cells to BRAFi was investigated. Knockdown of RRM2 in combination with the mutant BRAFi PLX4720 (an analog of the FDA-approved drug vemurafenib) inhibited melanoma cell proliferation to a greater extent than either treatment alone. This occurred in vitro in multiple mutant BRAF cell lines and in a novel patient-derived xenograft (PDX) model system. Mechanistically, the combination increased DNA damage accumulation, which correlated with a global decrease in DNA damage repair (DDR) gene expression and increased apoptotic markers. After discontinuing PLX4720 treatment, cells showed marked recurrence. However, knockdown of RRM2 attenuated this rebound growth both in vitro and in vivo, which correlated with maintenance of the senescence-associated cell-cycle arrest.

Implications: Inhibition of RRM2 converts the transient response of melanoma cells to BRAFi to a stable response and may be a novel combinatorial strategy to prolong therapeutic response of patients with melanoma. Mol Cancer Res; 14(9); 767–75. ©2016 AACR.
Long-Term Clinical Remission in Biologically Naïve Crohn’s Disease Patients with Adalimumab Therapy, Including Analyses of Switch from Adalimumab to Infliximab
Authors: Mizoshita Tsutomu , Tanida Satoshi , Ozeki Keiji , Katano Takahito , Shimura Takaya , Mori Yoshinori , Kubota Eiji , Kataoka Hiromi , Kamiya Takeshi , Joh Takashi
Published: June 2016

There is little evidence regarding the maintenance of long-term clinical remission by adalimumab (ADA) therapy in Crohn’s disease (CD) patients naïve to anti-tumor necrosis factor treatment (naïve CD patients), since most CD patients are treated with ADA after infliximab (IFX) therapy. The long-term clinical response to ADA was retrospectively analyzed in 17 naïve CD patients for at least 24 months, and the serum trough IFX levels were evaluated in patients switching from ADA to IFX. Of the 17 naïve CD patients, 14 (82.4%) maintained long-term clinical remission with ADA therapy for at least 24 months, without serious adverse events. The clinical condition of 7 patients was observed for more than 36 months, and 3, 1, 1, and 2 cases maintained remission at months 42, 48, 54, and 60 after ADA therapy, respectively. Three patients (17.6%) switched from ADA to IFX less than 24 months after the start of ADA therapy, and they had remission, retaining trough levels of IFX higher than 1 μg/ml, occasionally by dose escalation. In conclusion, maintenance ADA therapy achieves long-term clinical remission in naïve CD patients. Switching from ADA to IFX is an important therapeutic option in CD patients showing loss of response to ADA, occasionally with dose escalation, based on the analysis of serum IFX trough levels.
Infected Urachal Cyst in an Adult: A Laparoscopic Approach
Authors: Kwok Ching-Ming
Published: June 2016

Urachal cysts occur infrequently in adults and are rarely reported in the literature. Laparoscopic excision or robot-assisted laparoscopic excision of urachal cysts has widely been applied in recent years. We present a case of urachal cyst infection treated with antibiotics and two-staged operation. The laparoscopic procedure was performed without any complications. Strong suspicion is the key for early diagnosis.
Understanding the Significance of Mutations in Tumor Suppressor Genes Identified Using Next-Generation Sequencing: A Case Report
Authors: Sorscher Steven
Published: June 2016

Next-generation sequencing (NGS) of tumors has been heralded as a promising tool to identify ‘actionable’ abnormalities susceptible to therapies targeting these mutated genes. Inhibiting the oncoprotein expressed from a single dominant mutated gene (oncogene) forms the basis for the success of most of the targeted gene therapies approved in the last several years. The well over 20 FDA-approved kinase inhibitors for cancer treatment are examples [Janne et al.: Nat Rev Drug Discov 2009;8: 709–723]. These and other similar agents in development might prove effective therapies for tumors originating from tissues other than those for which these drugs are currently approved. Finding such mutations in tumors of patients through NGS is being aggressively pursued by patients and their oncologists. For identified mutated tumor suppressor genes (TSG) the challenge is really the opposite. Rather than inhibiting the action of an oncoprotein, targeting would involve restoring the activity of the wild-type (WT) TSG function [Knudson: Proc Natl Acad Sci USA 1971;249: 912–915]. Here, a case is reported that illustrates the implications of a mutated TSG (BRIP1) identified by NGS as potentially actionable. In such cases, measuring allelic mutation frequency potentially allows for the identification of tumors where the loss of heterozygosity of a TSG exists. Without substantial loss of expression of the WT TSG product, it would seem very unlikely that ‘replacing’ a WT TSG product that is not a lost product would be a useful therapy.
New-Onset Refractory Status Epilepticus: More Investigations, More Questions
Authors: Dillien Philippe , Ferrao Santos Susana , van Pesch Vincent , Suin Vanessa , Lamoral Sophie , Hantson Philippe
Published: June 2016

A 27-year-old previously healthy woman was admitted to the hospital with recurrent seizures. Status epilepticus developed that became refractory to third-line therapy with propofol and barbiturates. The patient had a very extensive diagnostic workup including autoimmune, viral and genetic investigations. A tentative immune therapy was proposed with high doses of steroids and plasma exchanges. Our patient had an inherited heterozygous single nucleotide variant in the sequence c.1280A>G [p.Lys427Arg] of the SMC3 gene that was insufficient to explain the seizures. Surprisingly, IgM antibodies against Japanese encephalitis virus were positive on the serum drawn 11 days after symptom onset, as detected by ELISA and the immunofluorescence antibody (IFA) technique. IgG antibodies were also positive using the IFA technique, but not with ELISA. The same investigations as well as the detection of the viral genome by the q-RT-PCR technique were negative on cerebrospinal fluid. Despite the suspicion of a viral infection, we concluded that our patient had a new-onset refractory status epilepticus of cryptogenic origin. Termination of the status epilepticus was obtained after 47 days, with a possible benefit from the introduction of ketamine.