bluuebunny/crossref_metadata_2025 huggingface dataset:
A note on low energy effective theory of chromo-natural inflation in the light of BICEP2 results
Authors: Bhattacharjee Anindita , Deshamukhya Atri , Panda Sudhakar
Published: March 2015

Recent result of BICEP2, revealing a larger value of tensor to scalar ratio (r), has opened up new investigations of the inflationary models to fit the experimental data. The experiment needs to reconfirm the results, specifically the consistency between Planck and BICEP2. On the other hand, the combined analysis of Planck and BICEP2, including the dust polarization uncertainty, brings down the upper limit on r. In this paper, we re-examine the low energy effective theory of chromo-natural inflation model and its generalization in view of such observational data. We find that the parameter space of the model admits a large value of r as well as other cosmological observables consistent with data.
Dispersive photon propagation in semiclassical higher-derivative gravity
Authors: Accioly Antonio , Helayël-Neto José , Barone F. E. , Giacchini Breno , Herdy Wallace
Published: March 2015

The scattering of a photon by a weak external gravitational field which is solution of the linearized higher-derivative gravity equations sourced by a point-like massive particle located at the origin of the coordinate system, is analyzed. It is shown that the [Formula: see text]-sector of the theory produces dispersive photon propagation. Subsequently, the angle |Δθ|(≡|θ violet -θ red |) at which the visible spectrum would be spread over in the case of a photon passing by the Sun is plotted as a function of the |β|-constant related to the [Formula: see text]-sector. An upper bound on |β| is then found. Interestingly enough, this limit is thirteen orders of magnitude below the accepted upper bound on |β|.
Theoretical remarks on diffraction at the LHC
Authors: Bartels J.
Published: March 2015

We comment on the nonperturbative nature of the total cross-section in pp scattering and on the importance of the survival probability for the understanding of diffractive final states in pp scattering.
Dynamic Response of Railway Vehicles Running on Long-Span Cable-Stayed Bridge Under Uniform Seismic Excitations
Authors: Li Yongle , Zhu Siyu , Cai C. S. , Yang Cheng , Qiang Shizhong
Published: March 2015

In order to evaluate the dynamic response of the train running on long-span cable-stayed bridges under uniform seismic excitations, a time-domain framework of analysis for the train–bridge system is established. The rail irregularities are treated as internal excitation and seismic loads as external excitation considering the inertia forces induced by the 3D seismic waves. The vehicles are modeled as mass-spring-damper systems, and the cable-stayed railway bridge is simulated by finite elements. A comprehensive analysis of the train–bridge system subjected to earthquake is conducted, focused on the effect of seismic ground motions on the dynamic response of the running train. Four kinds of seismic waves, each with three components, are simulated, with their spectral characteristics taken into account. To consider the stochastic characteristic of actual seismic waves, the effect of the incident angle and occurrence time of earthquakes on the bridge and vehicles is analyzed. Moreover, the earthquakes with various occurrence probability levels are also studied and the safety of the train running under the seismic action is evaluated, which may be used as the operation reference for the railway authority. The results demonstrate that the seismic ground motions have significant effects on the dynamic response of railway vehicles running on the long-span cable-stayed bridge under various spectrum characteristics, incident angles, occurrence times, and occurrence probabilities.
OPEN INNOVATION AND OPEN PRODUCTION: A CASE OF A TECHNOLOGY SUPPLIER/USER COLLABORATION IN THE PROCESS INDUSTRIES
Authors: LAGER THOMAS , TANO KENT , ANASTASIJEVIC NIKOLA
Published: March 2015

In the process industries, it is rather uncommon for companies to develop new process technology or even to manufacture new process equipment. As a result, they are highly dependent upon various kinds of equipment suppliers in their effort to acquire new process equipment in order to improve their operating performance. Two previously presented theoretical frameworks for collaboration during the innovation and operations stages have been merged for use as a research instrument in a single case study on the collaboration between a mineral producing company and a supplier of technology and equipment. The evidence from this study shows that it is beneficial for collaborating partners to engage in upfront discussions of pros and cons before entering collaborations. Collaboration during the "innovation stage" was determined to be an interesting avenue to follow for both parties. The need for collaboration during the production stage seemed to be most important during the "start-up" and "optimisation and upgrading" phases. The combined frameworks have proven to be a powerful research instrument for studying the selected kind of collaboration.
Mechanisms and Regulation of Alternative Pre-mRNA Splicing
Authors: Lee Yeon , Rio Donald C.
Published: March 2015

Precursor messenger RNA (pre-mRNA) splicing is a critical step in the posttranscriptional regulation of gene expression, providing significant expansion of the functional proteome of eukaryotic organisms with limited gene numbers. Split eukaryotic genes contain intervening sequences or introns disrupting protein-coding exons, and intron removal occurs by repeated assembly of a large and highly dynamic ribonucleoprotein complex termed the spliceosome, which is composed of five small nuclear ribonucleoprotein particles, U1, U2, U4/U6, and U5. Biochemical studies over the past 10 years have allowed the isolation as well as compositional, functional, and structural analysis of splicing complexes at distinct stages along the spliceosome cycle. The average human gene contains eight exons and seven introns, producing an average of three or more alternatively spliced mRNA isoforms. Recent high-throughput sequencing studies indicate that 100% of human genes produce at least two alternative mRNA isoforms. Mechanisms of alternative splicing include RNA–protein interactions of splicing factors with regulatory sites termed silencers or enhancers, RNA–RNA base-pairing interactions, or chromatin-based effects that can change or determine splicing patterns. Disease-causing mutations can often occur in splice sites near intron borders or in exonic or intronic RNA regulatory silencer or enhancer elements, as well as in genes that encode splicing factors. Together, these studies provide mechanistic insights into how spliceosome assembly, dynamics, and catalysis occur; how alternative splicing is regulated and evolves; and how splicing can be disrupted by cis- and trans-acting mutations leading to disease states. These findings make the spliceosome an attractive new target for small-molecule, antisense, and genome-editing therapeutic interventions.
Application of the Protein Semisynthesis Strategy to the Generation of Modified Chromatin
Authors: Holt Matthew , Muir Tom
Published: March 2015

Histone proteins are subject to a host of posttranslational modifications (PTMs) that modulate chromatin structure and function. Such control is achieved by the direct alteration of the intrinsic physical properties of the chromatin fiber or by regulating the recruitment and activity of a host of trans-acting nuclear factors. The sheer number of histone PTMs presents a formidable barrier to understanding the molecular mechanisms at the heart of epigenetic regulation of eukaryotic genomes. One aspect of this multifarious problem, namely how to access homogeneously modified chromatin for biochemical studies, is well suited to the sensibilities of the organic chemist. Indeed, recent years have witnessed a critical role for synthetic protein chemistry methods in generating the raw materials needed for studying how histone PTMs regulate chromatin biochemistry. This review focuses on what is arguably the most powerful, and widely employed, of these chemical strategies, namely histone semisynthesis via the chemical ligation of peptide fragments.
The Clothes Make the mRNA: Past and Present Trends in mRNP Fashion
Authors: Singh Guramrit , Pratt Gabriel , Yeo Gene W. , Moore Melissa J.
Published: March 2015

Throughout their lifetimes, messenger RNAs (mRNAs) associate with proteins to form ribonucleoproteins (mRNPs). Since the discovery of the first mRNP component more than 40 years ago, what is known as the mRNA interactome now comprises >1,000 proteins. These proteins bind mRNAs in myriad ways with varying affinities and stoichiometries, with many assembling onto nascent RNAs in a highly ordered process during transcription and precursor mRNA (pre-mRNA) processing. The nonrandom distribution of major mRNP proteins observed in transcriptome-wide studies leads us to propose that mRNPs are organized into three major domains loosely corresponding to 5′ untranslated regions (UTRs), open reading frames, and 3′ UTRs. Moving from the nucleus to the cytoplasm, mRNPs undergo extensive remodeling as they are first acted upon by the nuclear pore complex and then by the ribosome. When not being actively translated, cytoplasmic mRNPs can assemble into large multi-mRNP assemblies or be permanently disassembled and degraded. In this review, we aim to give the reader a thorough understanding of past and current eukaryotic mRNP research.
International Trade, Multinational Activity, and Corporate Finance
Authors: Foley C. Fritz , Manova Kalina
Published: March 2015

An emerging new literature brings unique ideas from corporate finance to the study of international trade and investment. Insights about differences in the development of financial institutions across countries, the role of financial constraints, and the use of internal capital markets are proving central in understanding international economics. The ability to access financial capital to pay fixed and variable costs affects choices firms make regarding export entry and operations and, as a consequence, influences aggregate trade patterns. Financial frictions and the use of internal capital markets shape decisions that multinationals make regarding production locations, integration, and corporate governance. This article surveys this recent research with the goal of highlighting the main themes it explores, the key results it establishes, and the leading open questions it raises.
Tax-Exempt Hospitals and Community Benefit: New Directions in Policy and Practice
Authors: Rubin Daniel B. , Singh Simone R. , Young Gary J.
Published: March 2015

The current community benefit standard for nonprofit hospital tax exemption has been the subject of mounting criticism. Many different constituencies have advanced the view that in its present form it fails to ensure that nonprofit hospitals provide adequate benefits to their communities in exchange for their tax exemption. In contrast, hospitals have often expressed the concern that the community benefit standard in its current form is vague and therefore difficult to comply with. Various suggestions have been made regarding how the existing community benefit standard could be improved or even replaced. In this article, we first discuss the historical and legal development of the community benefit standard. We then present the key controversies that have emerged in recent years and the policy responses attempted thus far. Finally, we evaluate possible future policy directions, which reform efforts could follow.
Assessing and Changing Organizational Social Contexts for Effective Mental Health Services
Authors: Glisson Charles , Williams Nathaniel J.
Published: March 2015

Culture and climate are critical dimensions of a mental health service organization's social context that affect the quality and outcomes of the services it provides and the implementation of innovations such as evidence-based treatments (EBTs). We describe a measure of culture and climate labeled Organizational Social Context (OSC), which has been associated with innovation, service quality, and outcomes in national samples and randomized controlled trials (RCTs) of mental health and social service organizations. The article also describes an empirically supported organizational intervention model labeled Availability, Responsiveness, and Continuity (ARC), which has improved organizational social context, innovation, and effectiveness in five RCTs. Finally, the article outlines a research agenda for developing more efficient and scalable organizational strategies to improve mental health services by identifying the mechanisms that link organizational interventions and social context to individual-level service provider intentions and behaviors associated with innovation and effectiveness.
Identifying the Effects of Environmental and Policy Change Interventions on Healthy Eating
Authors: Bowen Deborah J. , Barrington Wendy E. , Beresford Shirley A.A.
Published: March 2015

Obesity has been characterized as a disease. Strategies to change the incidence and prevalence of this disease include a focus on changing physical and social environments, over and above individual-level strategies, using a multilevel or systems approach. We focus our attention on evidence published between 2008 and 2013 on the effectiveness of interventions in nutrition environments, i.e., environmental interventions designed to influence the intake of healthful foods and amount of energy consumed. An overarching socioecological framework that has guided much of this research was used to characterize different types of environmental strategies. Intervention examples in each area of the framework are provided with a discussion of key findings and related conceptual and methodological issues. The emphasis in this review is on adults, but clearly this literature is only one part of the picture. Much research has been focused on child-specific interventions, including environmental interventions. Some evidence suggests effectiveness of policy-based or other types of interventions that aim to regulate or restructure environments to promote healthy dietary choices, and these strategies would apply to both children and adults. Opportunities to evaluate these policy changes in adults' social and physical environments are rare. Much of the existing research has been with children. As conceptual and methodological issues continue to be identified and resolved, we hope that future research in this domain will identify environmental strategies that can be included in intervention toolboxes to build healthy nutrition environments for both adults and children.
Role of VMH ketone bodies in adjusting caloric intake to increased dietary fat content in DIO and DR rats
Authors: Le Foll Christelle , Dunn-Meynell Ambrose A. , Miziorko Henry M. , Levin Barry E.
Published: March 2015

The objective of this study was to determine the potential role of astrocyte-derived ketone bodies in regulating the early changes in caloric intake of diet induced-obese (DIO) versus diet-resistant (DR) rats fed a 31.5% fat high-energy (HE) diet. After 3 days on chow or HE diet, DR and DIO rats were assessed for their ventromedial hypothalamic (VMH) ketone bodies levels and neuronal ventromedial hypothalamic nucleus (VMN) sensing using microdialysis coupled to continuous food intake monitoring and calcium imaging in dissociated neurons, respectively. DIO rats ate more than DR rats over 3 days of HE diet intake. On day 3 of HE diet intake, DR rats reduced their caloric intake while DIO rats remained hyperphagic. Local VMH astrocyte ketone bodies production was similar between DR and DIO rats during the first 6 h after dark onset feeding but inhibiting VMH ketone body production in DR rats on day 3 transiently returned their intake of HE diet to the level of DIO rats consuming HE diet. In addition, dissociated VMN neurons from DIO and DR rats were equally sensitive to the largely excitatory effects of β-hydroxybutyrate. Thus while DR rats respond to increased VMH ketone levels by decreasing their intake after 3 days of HE diet, this is not the case of DIO rats. These data suggest that DIO inherent leptin resistance prevents ketone bodies inhibitory action on food intake.
Compensatory plasticity restores locomotion after chronic removal of descending projections
Authors: Harley Cynthia M. , Reilly Melissa G. , Stewart Christopher , Schlegel Chantel , Morley Emma , Puhl Joshua G. , Nagel Christian , Crisp Kevin M. , Mesce Karen A.
Published: March 2015

Homeostatic plasticity is an important attribute of neurons and their networks, enabling functional recovery after perturbation. Furthermore, the directed nature of this plasticity may hold a key to the restoration of locomotion after spinal cord injury. Here we studied the recovery of crawling in the leech Hirudo verbana after descending cephalic fibers were surgically separated from crawl central pattern generators shown previously to be regulated by dopamine. We observed that immediately after nerve cord transection leeches were unable to crawl, but remarkably, after a day to weeks, animals began to show elements of crawling and intersegmental coordination. Over a similar time course, excessive swimming due to the loss of descending inhibition returned to control levels. Additionally, removal of the brain did not prevent crawl recovery, indicating that connectivity of severed descending neurons was not essential. After crawl recovery, a subset of animals received a second transection immediately below the anterior-most ganglion remaining. Similar to their initial transection, a loss of crawling with subsequent recovery was observed. These data, in recovered individuals, support the idea that compensatory plasticity directly below the site of injury is essential for the initiation and coordination of crawling. We maintain that the leech provides a valuable model to understand the neural mechanisms underlying locomotor recovery after injury because of its experimental accessibility, segmental organization, and dependence on higher-order control involved in the initiation, modulation, and coordination of locomotor behavior.
The Role of Oxidative Stress and Autophagy in Atherosclerosis
Authors: Perrotta Ida , Aquila Saveria
Published: March 2015

Atherosclerosis is a multifactorial, multistep disorder of large- and medium-sized arteries involving, in addition to age, gender and menopausal status, a complex interplay between lifestyle and genetic risk factors. Atherosclerosis usually begins with the diffusion and retention of atherogenic lipoproteins into the subendothelial space of the artery wall where they become oxidized by local enzymes and accumulate, leading to the formation of a cushion called atheroma or atheromatous or fibrofatty plaque, composed of a mixture of macrophages, lymphocytes, smooth muscle cells (SMCs), cholesterol cleft, necrotic debris, and lipid-laden foam cells. The pathogenesis of atherosclerosis still remains incompletely understood but emerging evidence suggests that it may involve multiple cellular events, including endothelial cell (EC) dysfunction, inflammation, proliferation of vascular SMCs, matrix (ECM) alteration, and neovascularization. Actually, a growing body of evidence indicates that autophagy along with the chronic and acute overproduction of reactive oxygen species (ROS) is integral to the development and progression of the disease and may represent fruitful avenues for biological investigation and for the identification of new therapeutic targets. In this review, we give an overview of ROS and autophagy in atherosclerosis as background to understand their potential role in this vascular disease.
Experimental and Numerical Investigation of the Effect of Process Conditions on Residual Wall Thickness and Cooling and Surface Characteristics of Water-Assisted Injection Molded Hollow Products
Authors: Park Hyungpil , Cha Baeg-Soon , Rhee Byungohk
Published: March 2015

Recently, water-assisted injection molding was employed in the automobile industry to manufacture three-dimensional hollow tube-type products with functionalities. However, process optimization is difficult in the case of water-assisted injection molding because of the various rheological interactions between the injected water and the polymer. In this study, the boiling phenomenon that occurs because of the high melt temperature when injecting water and the molding characteristics of the hollow section during the water-assisted injection process were analyzed by a water-assisted injection molding analysis. In addition, the changes in the residual wall thickness accompanying changes in the process conditions were compared with the analysis results by considering water-assisted injection molding based on gas-assisted injection molding. Furthermore, by comparing the cooling characteristics and inner wall surface qualities corresponding to the formation of the hollow section by gas and water injections, a water-assisted injection molding technique was proposed for manufacturing hollow products with functionality.
Immunohistochemical Expression of Survivin and Its Relationship with Cell Apoptosis and Proliferation in Ameloblastomas
Authors: González-González Rogelio , Molina-Frechero Nelly , Damian-Matsumura Pablo , Salazar-Rodriguez Sirced , Bologna-Molina Ronell
Published: March 2015

Ameloblastoma behavior is related to the potential of tumor cells to inhibit apoptosis and to initiate a proliferative phase. This study was performed to compare the immunoexpression of Survivin with Bcl-2, Bax, and Ki-67 and to associate them with the histopathological type of each variant of ameloblastoma.Material and Methods. Using the World Health Organization (WHO) criteria for ameloblastoma, 110 cases were selected. The cases were classified as solid/multicystic and unicystic ameloblastomas. Cellular counts of cytoplasmic immunoexpression were assessed for cytoplasmic Survivin, Bcl-2, and Bax, while the nuclear immunoexpression of Survivin and Ki-67 was assessed using label index.Results. Cytoplasmic Survivin and Bcl-2 showed higher percentages of immunoexpression in solid multicystic ameloblastomas compared to unicystic ameloblastomas (P<0.05). Bax, Ki-67, and nuclear Survivin were expressed in higher percentages in unicystic ameloblastomas.Conclusions. Cytoplasmic Survivin and Bcl-2 immunoexpression levels were elevated in relation to Bax immunoexpression, suggesting aggressive ameloblastoma behavior, while Ki-67 and nuclear Survivin immunoexpression may be associated with the type of tumor morphology that influences cellular counts or with the greater capacity for cellular proliferation and tumor growth.
Hybrid Control of Contention Window and Frame Aggregation for Performance Enhancement in Multirate WLANs
Authors: Adnan Muhammad , Park Eun-Chan
Published: March 2015

The IEEE 802.11 standard has been evolved to support multiple transmission rates in wireless local area networks (WLANs) to cope with diverse channel conditions and to increase throughput. However, when stations with different transmission rates coexist, the basic channel access mechanism of WLAN, distributed coordination function (DCF), not only fails to assure airtime fairness among competing stations but also decreases overall network throughput, because DCF was designed to provide fair opportunity of channel access, regardless of transmission rate. As an effective solution to this problem, we propose a hybrid control mechanism that integrates contention window control and frame aggregation. The former adjusts the size of contention window and differentiates the channel access opportunity depending on the transmission rates of stations. The latter controls the number of packets in the aggregated frame to tightly assure per-station airtime fairness with the reduced channel access overheads. Moreover, we derive an analytical model to evaluate the performance of the proposed mechanism in terms of throughput and fairness. Along with the analysis results, the extensive simulation results confirm that the proposed mechanism significantly increases the overall throughput by about three times compared to the conventional DCF, while assuring airtime fairness strictly.
Roles of Lymphocyte Kv1.3‐Channels in the Pathogenesis of Renal Diseases and Novel Therapeutic Implications of Targeting the Channels
Authors: Kazama Itsuro
Published: March 2015

Delayed rectifier K+‐channels (Kv1.3) are predominantly expressed in T lymphocytes. Based on patch‐clamp studies, the channels play crucial roles in facilitating the calcium influx necessary to trigger lymphocyte activation and proliferation. Using selective channel inhibitors in experimental animal models, in vivo studies then revealed the clinically relevant relationship between the channel expression and the pathogenesis of autoimmune diseases. In renal diseases, in which “chronic inflammation” or “the overstimulation of cellular immunity” is responsible for the pathogenesis, the overexpression of Kv1.3‐channels in lymphocytes promotes their cellular proliferation and thus contributes to the progression of tubulointerstitial fibrosis. We recently demonstrated that benidipine, a potent dihydropyridine calcium channel blocker, which also strongly and persistently inhibits the lymphocyte Kv1.3‐channel currents, suppressed the proliferation of kidney lymphocytes and actually ameliorated the progression of renal fibrosis. Based on the recent in vitro evidence that revealed the pharmacological properties of the channels, the most recent studies have revealed novel therapeutic implications of targeting the lymphocyte Kv1.3‐channels for the treatment of renal diseases.
Influence of Intra-Articular Administration of Trichostatin A on Autologous Osteochondral Transplantation in a Rabbit Model
Authors: Hou Huacheng , Zheng Ke , Wang Guanghu , Ikegawa Shiro , Zheng Minghao , Gao Xiang , Qin Jinzhong , Teng Huajian , Jiang Qing
Published: March 2015

Autologous osteochondral transplantation (AOT) is a method for articular cartilage repair. However, several disadvantages of this method have been reported, such as transplanted cartilage degeneration and the lack of a connection between the grafted and adjacent cartilage tissues. To evaluate the effect of intra-articular administration of trichostatin A (TSA) on AOT, we conducted a case control study in a rabbit model. International Cartilage Repair Society (ICRS) macroscopic scores, the modified O’Driscoll histology scores, and real-time PCR were utilized to evaluate the results. At 4 weeks, both macroscopic and histological assessments showed that there was no significant difference between the TSA and control groups. However, the mean macroscopic and histological scores for the TSA-treated group were significantly higher than the scores for the control group at 12 weeks. TSA was shown to directly reduce collagen type II (COL2), aggrecan, matrix metalloproteinase (MMP), and a disintegrin and metalloproteinase domain with thrombospondin motifs 5 (ADAMTS-5) expression and to simultaneously repress the upregulation of MMP-3, MMP-9, and MMP-13 levels induced by interleukin 1β(IL-1β) in chondrocytes. In conclusion, TSA protects AOT grafts from degeneration, which may provide a benefit in the repair of articular cartilage injury.
The Impact of Incarceration on Obesity: Are Prisoners with Chronic Diseases Becoming Overweight and Obese during Their Confinement?
Authors: Gates Madison L. , Bradford Robert K.
Published: March 2015

Introduction. The association between incarceration and weight gain, along with the public health impact of former prisoners who are overweight or obese, warrants more investigation to understand the impact of prison life. Studies regarding incarceration’s impact on obesity are too few to support assertions that prisons contribute to obesity and comorbid conditions. This study examined a statewide prison population over several years to determine weight gain.Methods. Objective data for weight, height, and chronic diseases, along with demographics, were extracted from an electronic health record. These data were analyzed statistically to determine changes over time and between groups.Results. As a total population, prisoners not only gained weight, but also reflected the distribution of BMIs for the state. There were differences within the population. Male prisoners gained significantly less weight than females. The population with chronic diseases gained less weight than the population without comorbid conditions. Prisoners with diabetes lost weight while hypertension’s impact was negligible.Conclusion. This study found that weight gain was a problem specifically to females. However, this prison system appears to be providing effective chronic disease management, particularly for prisoners with diabetes and hypertension. Additional research is needed to understand the impact incarceration has on the female population.
Immunohistological Analysis of the Jun Family and the Signal Transducers and Activators of Transcription in Thymus
Authors: Papoudou-Bai Alexandra , Barbouti Alexandra , Galani Vassiliki , Stefanaki Kalliopi , Kanavaros Panagiotis
Published: March 2015

The Jun family and the signal transducers and activators of transcription (STAT) are involved in proliferation and apoptosis. Moreover, c-Jun and STAT3 cooperate to regulate apoptosis. Therefore, we used double immunostaining to investigate the immunotopographical distribution of phospho-c-Jun (p-c-Jun), JunB, JunD, p-STAT3, p-STAT5, and p-STAT6 in human thymus.
JunD was frequently expressed by thymocytes with higher expression in medullary compared to cortical thymocytes. p-c-Jun was frequently expressed by cortical and medullary thymic epithelial cells (TEC) and Hassall bodies (HB). p-STAT3 was frequently expressed by TEC with higher expression in cortical compared to medullary TEC and HB. p-c-Jun, JunB, p-STAT3, p-STAT5, and p-STAT6 were rarely expressed by thymocytes. JunB and JunD were expressed by rare cortical TEC with higher expression in medullary TEC. p-STAT5 and p-STAT6 were expressed by rare cortical and medullary TEC. Double immunostaining revealed p-c-Jun and JunD expression in rare CD11c positive dendritic cells. Our findings suggest a notable implication of JunD in the physiology of thymocytes and p-c-Jun and p-STAT3 in the physiology of TEC. The diversity of the immunotopographical distribution and the expression levels of p-c-Jun, JunB, JunD, p-STAT3, p-STAT5, and p-STAT6 indicates that they are differentially involved in the differentiation of TEC, thymocytes, and dendritic cells.
A Hybrid Algorithm for the Permutation Flowshop Scheduling Problem without Intermediate Buffers
Authors: Liu Xiaobo , Li Kun , Ren Huizhi
Published: March 2015

This paper deals with the permutation flowshop scheduling problem without intermediate buffers and presents a hybrid algorithm based on the scatter search and the variable neighborhood search. In the hybrid algorithm, the solutions with good quality and diversity are maintained by a reference set of scatter search, and the search at each generation starts from a solution generated from the reference set so as to improve the search diversity while guaranteeing the quality of the initial solution. In addition, a variable neighbourhood based on the notion of job-block is developed, and the neighbourhood size can adaptively change according to the construction of the job-block. Such a dynamic strategy can help to obtain a balance between search depth and diversity. Extensive experiments on benchmark problems are carried out and the results show that the proposed hybrid algorithm is powerful and competitive with the other powerful algorithms in the literature.
Stability of Intelligent Transportation Network Dynamics: A Daily Path Flow Adjustment considering Travel Time Differentiation
Authors: Hwang Ming-Chorng , Cho Hsun-Jung , Huang You-Heng
Published: March 2015

A theoretic formulation on how traffic time information distributed by ITS operations influences the trajectory of network flows is presented in this paper. The interactions between users and ITS operator are decomposed into three parts: (i) travel time induced path flow dynamics (PFDTT); (ii) demand induced path flow dynamics (PFDD); and (iii) predicted travel time dynamics for an origin-destination (OD) pair (PTTDOD). PFDTT describes the collective results of user’s daily route selection by pairwise comparison of path travel time provided by ITS services. The other two components, PTTDOD and PFDD, are concentrated on the evolutions of system variables which are predicted and observed, respectively, by ITS operators to act as a benchmark in guiding the target system towards an expected status faster. In addition to the delivered modelings, the stability theorem of the equilibrium solution in the sense of Lyapunov stability is also provided. A Lyapunov function is developed and employed to the proof of stability theorem to show the asymptotic behavior of the aimed system. The information of network flow dynamics plays a key role in traffic control policy-making. The evaluation of ITS-based strategies will not be reasonable without a well-established modeling of network flow evolutions.
Methicillin-ResistantStaphylococcus aureusOcular Infection after Corneal Cross-Linking for Keratoconus: Potential Association with Atopic Dermatitis
Authors: Fasciani Romina , Agresta Antonio , Caristia Alice , Mosca Luigi , Scupola Andrea , Caporossi Aldo
Published: March 2015

Purpose. To report the risk of methicillin-resistantStaphylococcus aureus(MRSA) ocular infection after UVA-riboflavin corneal collagen cross-linking in a patient with atopic dermatitis.Methods. A 22-year-old man, with bilateral evolutive keratoconus and atopic dermatitis, underwent UVA-riboflavin corneal cross-linking and presented with rapidly progressive corneal abscesses and cyclitis in the treated eye five days after surgery. The patient was admitted to the hospital and treated with broad-spectrum antimicrobic therapy.Results. The patient had positive cultures for MRSA, exhibiting a strong resistance to antibiotics. Antibiotic therapy was modified and targeted accordingly. The intravitreal reaction is extinguished, but severe damage of ocular structures was unavoidable.Conclusion. Riboflavin/UVA corneal cross-linking is considered a safe procedure and is extremely effective in halting keratoconus’ progression. However, this procedure is not devoid of infectious complications, due to known risk factors and/or poor patients’ hygiene compliance in the postoperative period. Atopic dermatitis is a common disease among patients with keratoconus andStaphylococcus aureuscolonization is commonly found in patients with atopic dermatitis. Therefore, comorbidity with atopic dermatitis should be thoroughly assessed through clinical history before surgery. A clinical evaluation within three days after surgery and the imposition of strict personal hygiene rules are strongly recommended.
The Place of Extensive Surgery in Locoregional Recurrence and Limited Metastatic Disease of Breast Cancer: Preliminary Results
Authors: Berlière M. , Duhoux F. P. , Taburiaux L. , Lacroix V. , Galant C. , Leconte I. , Fellah L. , Lecouvet F. , Bouziane D. , Piette Ph. , Lengele B.
Published: March 2015

The aims of this study were first to clearly define two different entities: locoregional recurrences and limited metastatic disease and secondly to evaluate the place of extensive surgery in these two types of recurrence.Material and Methods. Twenty-four patients were followed from June 2004 until May 2014. All patients underwent surgery but for 1 patient this surgery was stopped because the tumour was unresectable.Results. The median interval between surgery for the primary tumour and the locoregional recurrence or metastatic evolution was 129 months. Eight patients had pure nodal recurrences, 4 had nodal and muscular recurrences, 5 had muscular + skin recurrences, and 8 had metastatic evolution. Currently, all patients are still alive but 2 have liver metastases. Disease free survival was measured at 2 years and extrapolated at 5 years and was 92% at these two time points. No difference was observed for young or older women; limited metastatic evolution and locoregional recurrence exhibited the same disease free survival.Conclusion. Extensive surgery has a place in locoregional and limited metastatic breast cancer recurrences but this option must absolutely be integrated in the multidisciplinary strategy of therapeutic options and needs to be planned with a curative intent.
Nelarabine Associated Myotoxicity and Rhabdomyolysis
Authors: Haider Mahnur , Rizvi Syed Ahsan , Kasi Pashtoon Murtaza
Published: March 2015

Nelarabine (ara-G; Arranon; compound 506U78) is an antineoplastic purine analog used for the treatment of refractory or relapsed T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL). The drug was granted accelerated approval in October 2005 by the US Food and Drug Administration (FDA) given the efficacy (induction of complete responses) noted in 2 single-arm trials (one in pediatric setting and one in adult patient population). The main spectra of toxicities that have been reported in these clinical trials and subsequent studies are hematological and neurological. Nelarabine induced rhabdomyolysis and increased creatinine phosphokinase (CK; CPK) levels apparently have been reported and this side effect has been added as an adverse reaction in the product monograph from the drug company during postmarketing surveillance. However, the true extent and incidence of the myotoxicity from the drug are unclear. In this paper we report a grade IV CK elevation and rhabdomyolysis in a patient with T-ALL treated with nelarabine. Given the reported finding, we examined the literature further for myotoxicity, increased CK, and/or rhabdomyolysis associated with the use of the nelarabine and report our findings.
NADPH Oxidase 4-Derived H2O2Promotes Aberrant Retinal Neovascularization via Activation of VEGF Receptor 2 Pathway in Oxygen-Induced Retinopathy
Authors: Li Jingming , Wang Joshua J. , Zhang Sarah X.
Published: March 2015

NADPH oxidase 4 (Nox4) is a major isoform of NADPH oxidase in retinal endothelial cells. Our previous study suggests that upregulation of Nox4 in retinal endothelial cells contributes to retinal vascular leakage in diabetes. In the current study, we investigated the role and mechanism of Nox4 in regulation of retinal neovascularization (NV), a hallmark of proliferative diabetic retinopathy (PDR), using a mouse model of oxygen-induced retinopathy (OIR). Our results confirmed that Nox4 was expressed predominantly in retinal vasculature of mouse retina. Retinal expression of Nox4 was markedly increased in OIR, in parallel with enhanced phosphorylation of ERK. In human retinal microvascular endothelial cells (HRECs), overexpression of Nox4 by adenovirus significantly increased extracellular H2O2generation, resulting in intensified VEGFR2 activation and exacerbated angiogenesis upon VEGF stimulation. In contrast, silencing Nox4 expression or scavenging H2O2by polyethylene glycol- (PEG-) conjugated catalase inhibited endothelial migration, tube formation, and VEGF-induced activation of VEGFR2 signaling. Importantly, knockdown of retinal Nox4 by adenovirus-delivered siRNA significantly reduced ERK activation and attenuated retinal NV formation in OIR. Taken together, our data indicate that Nox4 promotes retinal NV formation through H2O2/VEGFR2/ERK signaling pathway. Reducing retinal Nox4 expression may represent a promising therapeutic approach for neovascular retinal diseases such as PDR.
Extended Spectrum Beta‐Lactamase Carriage State among Elderly Nursing Home Residents in Beirut
Authors: Jallad M. A. , Naoufal R. , Irani J. , Azar E.
Published: March 2015

Introduction. ESBL‐producing Enterobacteriaceae can cause severe infections, but they are also isolated from the stool of asymptomatic subjects. Faecal carriage of such organism is poorly understood. Methods. First phase of the study was cross‐sectional with prevalence and epidemiology of ESBL faecal carriage in two nursing homes in Beirut: 57 residents in the first (NH1) and 151 residents in the second (NH2). In second phase, faecal swabs from cohort of NH1 residents were examined for carriage at six‐week intervals over three‐month period. Residents’ charts were reviewed to assess carriage risk factors. Results. Over 3 consecutive samplings at NH1, 81% of residents were at least one‐time carriers with 50% at the first round, 60.4% at the second, and 74.5% at the last one. At NH2, 68.2% of residents were carriers. Constipation (in NH1) and antibiotic intake (in NH2) were significantly associated with higher ESBL faecal carriage while the length of stay at the nursing home (in NH2) was associated with less carriage. Conclusion. Faecal carriage of ESBL‐producing Enterobacteriaceae is high among nursing home patients in Beirut. The rate of carriage changes rapidly and significantly over time either with multiple factors playing a possible role like outbreak spreading, antibiotic, and health care system exposure.
The Coordinated Actions of TIM-3 on Cancer and Myeloid Cells in the Regulation of Tumorigenicity and Clinical Prognosis in Clear Cell Renal Cell Carcinomas
Authors: Komohara Yoshihiro , Morita Tomoko , Annan Dorcas A. , Horlad Hasita , Ohnishi Koji , Yamada Sohsuke , Nakayama Toshiyuki , Kitada Shohei , Suzu Shinya , Kinoshita Ichiro , Dosaka-Akita Hirotoshi , Akashi Koichi , Takeya Motohiro , Jinushi Masahisa
Published: March 2015

Clear cell renal cell carcinoma (ccRCC) is one of most common cancers in urogenital organs. Although recent experimental and clinical studies have shown the immunogenic properties of ccRCC as illustrated by the clinical sensitivities to various immunotherapies, the detailed immunoregulatory machineries governing the tumorigenicity of human ccRCC remain largely obscure. In this study, we demonstrated the clinical significance and functional relevance of T-cell immunoglobulin and mucin domain-containing molecule-3 (TIM-3) expressed on tumor cells and myeloid cells in patients with ccRCC. TIM-3 expression was detected on cancer cells and CD204+ tumor-associated macrophages (TAM), and higher expression level of TIM-3 was positively correlated with shorter progression-free survival (PFS) in patients with ccRCC. We found that TIM-3 expression was detected on a large number of tumors, and there was significant correlation between an increased number of TAMs and high expression level of TIM-3 in patients with ccRCC. Furthermore, TIM-3 rendered RCC cells with the ability to induce resistance to sunitinib and mTOR inhibitors, the standard regimen for patients with ccRCC, as well as stem cell activities. TIM-3 expression was induced on CD14+ monocytes upon long-term stimulation with RCC cells, and TIM-3–expressing myeloid cells play a critical role in augmenting tumorigenic activities of TIM-3-negative RCC cells. More importantly, treatment with anti–TIM-3 mAb suppressed its tumorigenic effects in in vitro and in vivo settings. These findings indicate the coordinated action of TIM-3 in cancer cells and in myeloid cells regulates the tumorigenicity of human RCC. Cancer Immunol Res; 3(9); 999–1007. ©2015 AACR.
Regional Ventricular Performance and Exercise Training in Children and Young Adults After Repair of Tetralogy of Fallot
Authors: Duppen Nienke , Geerdink Lianne M. , Kuipers Irene M. , Bossers Sjoerd S.M. , Koopman Laurens P. , van Dijk Arie P.J. , Roos-Hesselink Jolien W. , De Korte Chris L. , Helbing Willem A. , Kapusta Livia
Published: March 2015

Background—

Public-health guidelines recommend patients with congenital heart disease to exercise. Studies have shown that patients with congenital heart disease can improve physical exercise capacity. The effect of training on regional ventricular performance has hardly been studied. We performed a pilot study to assess whether an exercise training program would result in adverse changes of regional ventricular performance in patients with corrected tetralogy of Fallot.

Methods and Results—

Multicenter prospective randomized controlled pilot study in patients with tetralogy of Fallot aged 10 to 25 years. A 12-week standardized aerobic dynamic exercise training program (3 one-hour sessions per week) was used. Pre- and post-training cardiopulmonary exercise tests, MRI, and echocardiography, including tissue-Doppler imaging, were performed. Patients were randomized to the exercise group (n=28) or control group (n=20). One patient in the exercise group dropped out. Change in tissue-Doppler imaging parameters was similar in the exercise group and control group (change in right ventricle free wall peak velocity E′ exercise group, 0.8±2.6 cm/s; control group, 0.9±4.1; peak velocity A′ exercise group, 0.4±2.4 m/s; control group 4.6±18.1 cm/s).

Conclusions—

This randomized controlled pilot study provides preliminary data suggesting that regional ventricular performance is well maintained during 3-month aerobic dynamic exercise training in children and young adults with repaired tetralogy of Fallot. This information might help patients adhere to current public-health guidelines.

Clinical Trial Registration—

URL:
http//:www.trialregister.nl
. Unique identifier: NTR2731.
Establishing the First Mobile Stroke Unit in the United States
Authors: Parker Stephanie A. , Bowry Ritvij , Wu Tzu-Ching , Noser Elizabeth A. , Jackson Kamilah , Richardson Laura , Persse David , Grotta James C.
Published: March 2015

Background and Purpose—

Recently, the Mobile Stroke Unit (MSU) concept was introduced in Germany demonstrating prehospital treatment of more patients within the first hour of symptom onset. However, the details and complexities of establishing such a program in the United States are unknown. We describe the steps involved in setting up the first MSU in the United States.

Methods—

Implementation included establishing leadership, fund-raising, purchase and build-out, knitting a collaborative consortium of community stakeholders, writing protocols to ensure accountability, radiation safety, purchasing supplies, licensing, insurance, establishing a base station, developing a communication plan with city Emergency Medical Services, Emergency Medical Service training, staffing, and designing a research protocol.

Results—

The MSU was introduced after ≈1 year of preparation. Major obstacles to establishing the MSU were primarily obtaining funding, licensure, documenting radiation safety protocols, and establishing a smooth communication system with Emergency Medical Services. During an 8 week run-in phase, ≈2 patients were treated with recombinant tissue-type plasminogen activator per week, one-third within 60 minutes of symptom onset, with no complications. A randomized study to determine clinical outcomes, telemedicine reliability and accuracy, and cost effectiveness was formulated and has begun.

Conclusion—

The first MSU in the United States has been introduced in Houston, TX. The steps needed to accomplish this are described.
Off-label Prescription of Medication
Authors: Vrancken Isabelle
Published: March 2015

Off-label use of medication refers to prescribing a registered medicine outside its approved marketing authorization, purpose, target group, or indication. Off-label prescription is a widely accepted practice. However, no or little regulation can be found. In this article, the legal status of off-label prescription will be examined. Does off-label prescription fall under the therapeutical freedom and is it free from regulation? Or should we equalize off-label prescription with a therapeutical experimentation and should it follow the rules of experimentation? I will also examine whether the patient can give an informed consent. Whether or not this is possible leads to intense discussions. Finally, the potential liability of the prescribing physician is of great importance.