bluuebunny/crossref_metadata_2025 huggingface dataset:
SÃO JOSÉ DO NORTE (RS/BRASIL): MEIO AMBIENTE COMO MERCADORIA/ SÃO JOSÉ DO NORTE (RS/BRAZIL): ENVIRONMENT AS A MERCHANDISE
Authors: Dos Santos Caio Floriano , Puccinelli Vinicius Ramos , Oliveira Cleiton Luiz de , Mascarello Marcela de Avellar , Machado Carlos RS
Published: February 2017

RESUMOSão José do Norte- RS passa por grandes transformações na matriz econômica que marca o cotidiano dos habitantes. Tais transformações são propagandeadas por gestores municipais, empreendedores e jornalistas como a "vinda do progresso". O objetivo deste trabalho é analisar estas mudanças elucidando o discurso neodesenvolvimentista que embasa a aceitação dos Grandes Projetos de Desenvolvimento (GPD's). Para isso, utilizamos textos do sítio eletrônico da prefeitura, reportagens, entre outros. Como metodologia, fizemos a análise de discurso de tais materiais, que revelam o esforço de gestores para vender o município como propício para a instalação de GPD’s.Palavras-chave: Grandes Projetos de Desenvolvimento; mercadoria; progresso. RESUMENSão José do Norte- RS ha pasado por grandes cambios en la matriz económica que marca el cotidiano de los habitantes. Eses cambios son publicitados por gestores municipales, empresarios y periodistas como la “llegada del progreso”. El objetivo del artículo es analizar eses cambios, elucidando el discurso neodesarrollista que basa la aceptación de los Grandes Proyectos de Desarrollo (GPD´s). Para esto, utilizamos textos del sitio electrónico de la intendencia, informes, entre otros. Como metodología, hicimos el análisis de discurso de estos materiales, que revelan el esfuerzo de los gestores para vender la municipalidad como propicio para la instalación de GPD’s.Palabras clave: Grandes Proyectos de Desarrollo; mercancía; progreso. ABSTRACTSão José do Norte-RS goes through great economic changes which cause a direct impact in the everyday-life of the citizens of the city. These changes are publicised by municipal managers, entrepreneurs and journalists as “progress coming for the city”. The aim of this study is to analyze the acceptance of Grandes Projetos de Desenvolvimento (GPD’s). For this, we have used as data, the articles from the website of the City Hall and reports, among others. As the methodology, we have used the discourse analyze of those materials, which reveal the efforts of the managers to sell the city as an auspicious place for the installation of GPD’s.Keywords: Grandes Projetos de Desenvolvimento; merchandise; progress.
Sobre a impossibilidade de se voltar para casa ou a escrita como o lugar possível voltado para o futuro/On the impossibility to back home or written as possible place back to the future
Authors: Marandola Jr. Eduardo
Published: February 2017

RESUMOMeditação sobre o sentido do lugar possível, a escrita, como pensamento voltado para o futuro, o texto se constitui como experiência, composto por interstícios literários de uma tessitura geográfico-política sobre as geometrias do pensamento.Palavras-chave: geometrias do pensamento; literatura; lugar possível RESUMENLa meditación sobre el significado de la posible lugar, la escritura y el pensamiento de vuelta al futuro, el texto se constituye como la experiencia, que consiste en intersticios literarias de un tejido geográfico-política de las geometrías de pensamiento.Palabras clave: la geometría del pensamiento; literatura; lugar posible ABSTRACTMeditation on the meaning of the possible place, writing, and thinking back to the future, the text is as experience, composted by literary interstices of the geographical-political compose of the geometries of thought.Keywords: thinking geometries; literature; possible place
Dynamiques de l’aménagement du territoire et inégalités sociospatiales au Sénégal
Authors: Sène Abdourahmane Mbade , Codjia Claude
Published: February 2017

Cet article s’intéresse à la problématique de l’aménagement du territoire et des inégalités territoriales au Sénégal. Il examine, d’une part, les pratiques courantes d’aménagement du territoire par rapport à la question de la justice spatiale. D’autre part, il montre les effets significatifs de l’aménagement du territoire sur la qualité et le niveau de vie des populations. La méthode porte sur le traitement, l’analyse et la modélisation d’une base de données démographiques, socioéconomiques et d’infrastructures sociales fondamentales des différentes régions. L’analyse en composante principale (ACP) permet d’organiser les 12 variables en deux principaux groupes qui expliquent l’essentiel des données. Elle est suivie d’une cartographie avancée qui montre les spécificités et la dynamique spatiale des processus d’aménagement du territoire, au Sénégal.
Land tenure and conflict propagation: critical geopolitics from the rural grassroots in North Kivu (Democratic Republic of Congo)
Authors: Pottek Elias , Kasisi Robert , Herrmann Thora Martina
Published: February 2017

In its most recent history, the Democratic Republic of Congo (DRC) has taken central stage in two interstate wars and multiple civil conflicts with trans-border dynamics. Somewhat less well known is the fact that the DRC is also a prime example of a different, continent-wide African problematic: the precarity of land rights and resulting conflicts over land tenure. This paper is part of a study that explores interactions between tenure conflicts at the micro-level and the larger ethnic, civil and interstate conflicts of the region. In its first part, the article discusses conflict study approaches from various disciplines and the published literature and makes the case for a multi-scalar critical geopolitical conflict analysis. The second part presents case studies, the survey questionnaire and interview based fieldwork results that reveal the near ubiquity of tenure conflicts in North Kivu and show the causes of these conflicts and how they tend to proliferate at the rural grassroots base and subsequently extend upwards.
Triaging Patients with Multiple Sclerosis in the Emergency Department
Authors: Abboud Hesham , Mente Karin , Seay Meagan , Kim Jeffrey , Ali Ashhar , Bermel Robert , Willis Mary A.
Published: February 2017

Background:

Patients with multiple sclerosis (MS) present to the emergency department (ED) for various reasons. Although true relapse is rarely the underlying culprit, ED visits commonly result in new magnetic resonance imaging (MRI) and neurology admissions. We studied ED visits in patients with MS and evaluated decision making regarding diagnostic/therapeutic interventions and visit outcomes. We identified potential areas for improvement and used the data to propose a triaging algorithm for patients with MS in the ED.

Methods:

We reviewed the medical records from 176 ED visits for patients with MS in 2014.

Results:

Ninety-seven visits in 75 patients were MS related (66.6% female; mean ± SD age, 52.6 ± 13.8 years; mean ± SD disease duration, 18.5 ± 10.5 years). Thirty-three visits were for new neurologic symptoms (category 1), 29 for worsening preexisting symptoms (category 2), and 35 for MS-related complications (category 3). Eighty-nine visits (91.8%) resulted in hospital admission (42.7% to neurology). Only 39% of ordered MRIs showed radiographic activity. New relapses were determined in 27.8% of the visits and were more prevalent in category 1 compared with category 2 (P = .003); however, the two categories had similar rates of ordered MRIs and neurology admissions.

Conclusions:

New relapse is a rare cause of ED visits in MS. Unnecessary MRIs and neurology admissions can be avoided by developing a triaging system for patients with MS based on symptom stratification.
Treatment of Gastric Cancer With Paraaortic Lymph Node Metastasis
Authors: Wang Donghai , Shen Guojie , Shou Chunhui , Zhu Kankai , Chen Chao , Yu Jiren
Published: February 2017

Patients with gastric cancer and paraaortic lymph node (PAN) metastasis suffered poor prognosis. The median survival time of the patients who received palliative chemotherapy was only about 12.8 months. However, the standard treatment strategy for patients with gastric cancer and PAN metastasis was controversial. This study aimed to evaluate the survival benefit of conversion chemotherapy followed by surgery in patients with gastric cancer and radiologically suspicious PAN metastasis compared with palliative chemotherapy alone. Twenty-four patients (19 males and 5 females) between January 1, 2008 and December 31, 2013 were analyzed. Fifteen patients received conversion chemotherapy followed by gastrectomy with D2 lymphadenectomy, and 9 received palliative chemotherapy. The median follow-up was 16.5 months (range: 3–50 months). The estimated median overall survival (OS) of patients who underwent the operation was longer than those who received palliative chemotherapy (44.0 versus 13.0 months; P = 0.007). Cox proportion hazard analysis indicated that surgery was a good prognostic factor for prolonged survival compared with that of palliative chemotherapy (hazard ratio: 0.211; 95% confidence interval, 0.061–0.732; P = 0.014). Moreover, the 1-year OS rate of surgical patients whose PAN shrank to <1 cm was better than those who received palliative chemotherapy (87.5 versus 55.6%; log-rank P = 0.008). In conclusion, patients with gastric cancer and radiologically suspicious PAN metastasis obtained a survival benefit from conversion chemotherapy followed by gastrectomy plus D2 lymphadenectomy.
Insights into the formation of carlactone from in‐depth analysis of theCCD8‐catalyzed reactions
Authors: Bruno Mark , Vermathen Martina , Alder Adrian , Wüst Florian , Schaub Patrick , van der Steen Rob , Beyer Peter , Ghisla Sandro , Al‐Babili Salim
Published: February 2017

Strigolactones are a new class of phytohormones synthesized from carotenoids via carlactone. The complex structure of carlactone is not easily deducible from its precursor, acis‐configured β‐carotene cleavage product, and is thus formed via a poorly understood series of reactions and molecular rearrangements, all catalyzed by only one enzyme, the carotenoid cleavage dioxygenase 8 (CCD8). Moreover, the reactions leading to carlactone are expected to form a second, yet unidentified product. In this study, we used13C and18O‐labeling to shed light on the reactions catalyzed byCCD8. The characterization of the resulting carlactone byLC‐MSandNMR, and the identification of the assumed, less accessible second product allowed us to formulate a minimal reaction mechanism for carlactone generation.
Uptake of 3‐iodothyronamine hormone analogs inhibits the growth and viability of cancer cells
Authors: Rogowski Michael , Gollahon Lauren , Chellini Grazia , Assadi‐Porter Fariba M.
Published: February 2017

3‐Iodothyronamine (T1AM) is a structural analog of thyroid hormone that has been demonstrated to have potent affects on numerous physiological systems. Most studies on T1AM have explored its effects in healthy functional systems; while its potential therapeutic uses and safety, and efficacy in pathological conditions are largely unknown. We sought to evaluate the effects of T1AM and its structural analog SG‐2 on cancer cell growth and viability. We analyzed the cytotoxicity of these analogs on MCF7 breast cancer cells, HepG2 hepatocellular cancer cells as well as normal control cells using primary human foreskin fibroblasts and mouse preadipocytes control cells. The cytotoxicity of T1AM and SG‐2 was determined by cell growth curves, and validated by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide cell viability assays. Cellular uptake analysis was conducted using confocal microscopy. Real‐time (RT)‐PCR was conducted to identify gene pathways affected by SG‐2 in cancer cells. The IC50 of T1AM was approximately double the concentration of its analog SG‐2 in cancer cells. Cytotoxicity studies on normal cells revealed that IC50 concentrations of SG‐2 in cancer cells had no significant impact on cell viability in these cell types. Cell‐imaging experiments demonstrated rapid uptake and localization to the mitochondrial membrane. T1AM and SG‐2 are able to reduce cancer cell growth and viability. These findings support the potential for use of these compounds and related analogs for their antiproliferation properties in cancer cells.
The Tethered Fibrillar Hydrogels Brushes for Underwater Antifouling
Authors: Zhang Ran , Zhang Longzhou , Tian Nan , Ma Shuanhong , Liu Yupeng , Yu Bo , Pei Xiaowei , Zhou Feng
Published: February 2017

The development of antifouling surfaces to prevent bioattachment is an urgent demand for marine coating and biomedical applications. In this paper, two types of anionic and zwitterionic gel fibers are synthesized based on anodic aluminum oxide (AAO) substrate and their antifouling properties against oil and algal attachment are systematically investigated. To begin with, gel surfaces exhibit underwater superoleophoic property and extremely low oil adhesion. The effect of electrolyte on underwater wetting behavior is studied. It is shown that the adhesion of oil droplets on gel fibers significantly increase upon immersing in electrolyte solutions and ionic surfactants, which could be attributed to electrostatic screening effect of salt solution and ion‐pairing interaction. Notably, in regard to Dunaliella tertiolecta and Navicula sp., almost 90% and 95% decrease of fouling algae density are achieved for P(AA/SPMA) and P(AA/SBMA) gel fibers, respectively, comparing with AAO substrate for control. The excellent antifouling property and high structural stability of gel fibers make them effective antifouling surfaces.
Recent Advances of Activatable Molecular Probes Based on Semiconducting Polymer Nanoparticles in Sensing and Imaging
Authors: Lyu Yan , Pu Kanyi
Published: February 2017

Molecular probes that change their signals in response to the target of interest have a critical role in fundamental biology and medicine. Semiconducting polymer nanoparticles (SPNs) have recently emerged as a new generation of purely organic photonic nanoagents with desirable properties for biological applications. In particular, tunable optical properties of SPNs allow them to be developed into photoluminescence, chemiluminescence, and photoacoustic probes, wherein SPNs usually serve as the energy donor and internal reference for luminescence and photoacoustic probes, respectively. Moreover, facile surface modification and intraparticle engineering provide the versatility to make them responsive to various biologically and pathologically important substances and indexes including small‐molecule mediators, proteins, pH and temperature. This article focuses on recent advances in the development of SPN‐based activatable molecular probes for sensing and imaging. The designs and applications of these probes are discussed in details, and the present challenges to further advance them into life science are also analyzed.
Pain management in the Ehlers–Danlos syndromes
Authors: Chopra Pradeep , Tinkle Brad , Hamonet Claude , Brock Isabelle , Gompel Anne , Bulbena Antonio , Francomano Clair
Published: February 2017

Chronic pain in the Ehlers–Danlos syndromes (EDS) is common and may be severe. According to one study, nearly 90% of patients report some form of chronic pain. Pain, which is often one of the first symptoms to occur, may be widespread or localized to one region such as an arm or a leg. Studies on treatment modalities are few and insufficient to guide management. The following is a discussion of the evidence regarding the underlying mechanisms of pain in EDS. The causes of pain in this condition are multifactorial and include joint subluxations and dislocations, previous surgery, muscle weakness, proprioceptive disorders, and vertebral instability. Affected persons may also present with generalized body pain, fatigue, headaches, gastrointestinal pain, temporomandibular joint pain, dysmenorrhea, and vulvodynia. Pain management strategies may be focused around treating the cause of the pain (e.g., dislocation of a joint, proprioceptive disorder) and minimizing the sensation of pain. Management strategies for chronic pain in EDS includes physical therapy, medications, as well as durable medical equipment such as cushions, compressive garments, and braces. The different modalities are discussed in this paper. © 2017 Wiley Periodicals, Inc.
Perceived compliance and barriers to care in sublingual immunotherapy
Authors: Kumar Manvinder S. , Oh Melissa S. , Leader Brittany , Rotella Melissa , Stillman Leisa , DelGaudio John M. , Wise Sarah K.
Published: February 2017

Background

For allergy immunotherapy to be effective, patient compliance is critical. However, aqueous sublingual immunotherapy (SLIT) may be considered demanding for patients, requiring strict daily dosing and refilling of medication at regular intervals. In this study we sought to determine how patients perceive their own compliance with SLIT and identify barriers that may hinder compliance.

Methods

Using a retrospective review, 46 patients currently undergoing aqueous SLIT were identified to have less‐than‐excellent compliance based on frequency of clinic visits for SLIT refills. Twenty‐eight of these patients completed a phone survey regarding symptom improvement, compliance, and barriers to care. In addition, 56 patients who withdrew from therapy before completion were polled about barriers to adherence.

Results

Of the 28 patients participating in the initial phone survey, 24 (86%) reported subjective improvement in symptoms on SLIT, despite less‐than‐excellent compliance. Nineteen (68%) of these patients perceived their own compliance to be excellent. Eighteen patients (65%) reported the inconvenience of scheduling and attending clinic appointments to be the main reason for noncompliance. The most common reasons for withdrawal from therapy were cost (27%), lack of effectiveness (25%), and difficulty with compliance (14%).

Conclusion

The majority of aqueous SLIT patients perceived their compliance to be excellent, although, based on a previous study, these patients did not reach excellent compliance benchmarks. Inconvenience of clinic visits and cost of therapy were found to be the most common barriers to care. Despite what providers perceived as less‐than‐excellent compliance, 82% of patients reported symptom improvement with SLIT.
Cooperative Subunit Refolding of a Light‐Harvesting Protein through a Self‐Chaperone Mechanism
Authors: Laos Alistair J. , Dean Jacob C. , Toa Zi S. D. , Wilk Krystyna E. , Scholes Gregory D. , Curmi Paul M. G. , Thordarson Pall
Published: February 2017

The fold of a protein is encoded by its amino acid sequence, but how complex multimeric proteins fold and assemble into functional quaternary structures remains unclear. Here we show that two structurally different phycobiliproteins refold and reassemble in a cooperative manner from their unfolded polypeptide subunits, without biological chaperones. Refolding was confirmed by ultrafast broadband transient absorption and two‐dimensional electronic spectroscopy to probe internal chromophores as a marker of quaternary structure. Our results demonstrate a cooperative, self‐chaperone refolding mechanism, whereby the β‐subunits independently refold, thereby templating the folding of the α‐subunits, which then chaperone the assembly of the native complex, quantitatively returning all coherences. Our results indicate that subunit self‐chaperoning is a robust mechanism for heteromeric protein folding and assembly that could also be applied in self‐assembled synthetic hierarchical systems.
Selected Mutations Reveal New Intermediates in the Biosynthesis of Mupirocin and the Thiomarinol Antibiotics
Authors: Gao Shu‐Shan , Wang Luoyi , Song Zhongshu , Hothersall Joanne , Stevens Elton R. , Connolly Jack , Winn Peter J. , Cox Russell J. , Crump Matthew P. , Race Paul R. , Thomas Christopher M. , Simpson Thomas J. , Willis Christine L.
Published: February 2017

Thiomarinol and mupirocin are assembled on similar polyketide/fatty acid backbones and exhibit potent antibiotic activity against methicillin‐resistant Staphylococcus aureus (MRSA). They both contain a tetrasubstituted tetrahydropyran (THP) ring that is essential for biological activity. Mupirocin is a mixture of pseudomonic acids (PAs). Isolation of the novel compound mupirocin P, which contains a 7‐hydroxy‐6‐keto‐substituted THP, from a ΔmupP strain and chemical complementation experiments confirm that the first step in the conversion of PA‐B into the major product PA‐A is oxidation at the C6 position. In addition, nine novel thiomarinol (TM) derivatives with different oxidation patterns decorating the central THP core were isolated after gene deletion (tmlF). These metabolites are in accord with the THP ring formation and elaboration in thiomarinol following a similar order to that found in mupirocin biosynthesis, despite the lack of some of the equivalent genes. Novel mupirocin–thiomarinol hybrids were also synthesized by mutasynthesis.
Efficient Difluoromethylation of Alcohols Using TMSCF2Br as a Unique and Practical Difluorocarbene Reagent under Mild Conditions
Authors: Xie Qiqiang , Ni Chuanfa , Zhang Rongyi , Li Lingchun , Rong Jian , Hu Jinbo
Published: February 2017

A general method for the efficient difluoromethylation of alcohols using commercially available TMSCF2Br (TMS=trimethylsilyl) as a unique and practical difluorocarbene source is developed. This method allows primary, secondary, and even tertiary alkyl difluoromethyl ethers to be synthesized under weakly basic or acidic conditions. The reaction mainly proceeds through the direct interaction between a neutral alcohol and difluorocarbene, which is different from the difluoromethylation of phenols. Moreover, alcohols containing other moieties that are also reactive toward difluorocarbene can be transformed divergently by using TMSCF2Br. This research not only solves the synthetic problem of difluorocarbene‐mediated difluoromethylation of alcohols, it also provides new insights into the different reaction mechanisms of alcohol difluoromethylation and phenol difluoromethylation with difluorocarbene species.
A Naphtho‐Fused Double [7]Helicene from a Maleate‐Bridged Chrysene Trimer
Authors: Ferreira Marli , Naulet Guillaume , Gallardo Hugo , Dechambenoit Pierre , Bock Harald , Durola Fabien
Published: February 2017

Perkin condensation of chrysenyl‐6‐acetic acid with chrysenylene‐6,12‐diglyoxylic acid followed by in situ esterification gives a bismaleate, whose conjugated stilbene moieties are efficiently shielded against intermolecular condensations and undergo iodine‐catalyzed oxidative photocyclization in toluene without the need for high dilution. The concentration is limited by the low solubility of the flexible bismaleate at room temperature. The so‐obtained double [7]helicene crystallizes in a nonchiral meso form. It is notably more soluble than its flexible precursor because it cannot fold to optimize π–π stacking.
Flexible epoxy novolac coatings: Use of cardanol‐based flexibilizers
Authors: Gour Rajeshwari S. , Raut Kundalik G. , Badiger Manohar V.
Published: February 2017

Flexible epoxy novolac coatings were developed by reacting an epoxy novolac resin, poly[(phenylglycidyl ether)‐co‐formaldehyde] (PPGEF) with an amine curing agent, 4,4′‐diamino‐3,3′‐dimethyldicyclohexyl methane (BMCHA), cardanol based reactive diluent (Cardolite NC‐513) and two different cardanol‐based flexibilizers (Cardolite NC‐514 and Cardolite NC‐547). The flexibilizer content was varied from 5 to 10% by weight of the resin. These resins were coated onto the stainless steel panels and tested for their gloss, cross‐hatch adhesion, falling weight impact resistance, flexibility, abrasion, scratch hardness, solvent scrub resistance, and chemical resistance. The thermo‐mechanical properties of these coatings were determined by TGA, DSC, DMTA, and tensile strength measurements. The cryofractured specimens were subjected to SEM analysis. The influence of structural differences of two flexibilizers on the coating properties was investigated. These coatings exhibited excellent properties and have great potential in industrial applications. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44920.
Tolerance limits and tolerance intervals for ratios of normal random variables using a bootstrap calibration
Authors: Flouri Marilena , Zhai Shuyan , Mathew Thomas , Bebu Ionut
Published: February 2017

This paper addresses the problem of deriving one‐sided tolerance limits and two‐sided tolerance intervals for a ratio of two random variables that follow a bivariate normal distribution, or a lognormal/normal distribution. The methodology that is developed uses nonparametric tolerance limits based on a parametric bootstrap sample, coupled with a bootstrap calibration in order to improve accuracy. The methodology is also adopted for computing confidence limits for the median of the ratio random variable. Numerical results are reported to demonstrate the accuracy of the proposed approach. The methodology is illustrated using examples where ratio random variables are of interest: an example on the radioactivity count in reverse transcriptase assays and an example from the area of cost‐effectiveness analysis in health economics.
Modulation of the vascular endothelium functioning by dietary components, the role of epigenetics
Authors: Wojtala Martyna , Pirola Luciano , Balcerczyk Aneta
Published: February 2017

Rather than being a passive barrier between circulating blood and smooth muscle cells and the underlying tissues, the endothelium is a fundamental functional component of the vasculature, and could be viewed as the largest human endocrine gland/organ, secreting multiple pro‐/antiangiogenic factors, cytokines and low‐molecular‐weight mediators controlling the vascular tone. The location of endothelium, at the interface between the circulation and the tissues, makes this epithelial layer particularly exposed to physical and chemical cues coming from the bloodstream. In response to such stimuli, the endothelium modulates its morphology and functions to maintain vascular homeostasis. Dietary components significantly affect the proper functioning of the endothelium. High‐calories and high‐fat western diets, in the long term, cause endothelial dysfunction, which is a major contributor to the development of the metabolic syndrome and its pathological consequences, including atherosclerosis, diabetes, and hypertension. On the contrary, plant‐derived antioxidant molecules and polyphenols have been shown to exert beneficial effects on endothelial function. Extensive research in the last decade has clearly shown the close relationship between food intake, dietary habits, and gene expression, which is driven by the action of macro‐ and micronutrients on chromatin regulation. Nutrient‐induced chromatin epigenetic modifications via DNA methylation and histone post‐translational modifications, especially in the context of the western diet, significantly contribute to the dysregulation of endothelial functioning. Here, we review the current understanding on how dietary components (macronutrients, antioxidants), acting on epigenetic mechanisms, regulate endothelial physiology, and physiopathology. © 2016 BioFactors, 43(1):5–16, 2017
Hypothalamic‐pituitary‐adrenal axis and depression symptom effects of an arginine vasopressin type 1B receptor antagonist in a one‐week randomized Phase 1b trial
Authors: Katz David A. , Locke Charles , Greco Nicholas , Liu Wei , Tracy Katherine A.
Published: February 2017

Background

Arginine vasopressin 1B receptor (V1B) antagonists may have utility for the treatment of major depressive disorder (MDD).

Methods

The V1B antagonist ABT‐436 (N = 31) or matching placebo (N = 20) was administered to MDD subjects for 7 days. The main study objectives were to assess the safety and hypothalamic–pituitary–adrenal axis (HPA) effects of ABT‐436 in MDD subjects. MDD symptoms were assessed using the 17‐item Hamilton Depression Rating Scale (HAM‐D‐17) and the subject‐rated Mood and Anxiety Symptom Questionnaire (MASQ).

Results

The most prevalent safety finding associated with ABT‐436 800 mg QD was increased mild‐moderate diarrhea (68% v 5%, p < 0.001). Increased nausea (26% v 5%, p < 0.10), decreased systolic blood pressure (3.15–3.44 mmHg, p < 0.10) and increased heart rate (3.42–4.01 bpm, p < 0.05) were also associated with ABT‐436 800 mg QD. Basal HPA activity measured by 24‐hr urine total glucocorticoids was 25% lower with ABT‐436 than placebo (p < 0.001). The reduction was, on average, larger in subjects with higher baseline urine total glucocorticoids. Results on plasma adrenocorticotrophic hormone (ACTH), urine, serum and saliva cortisol, and saliva cortisone also showed basal HPA attenuation with ABT‐436. Dynamic HPA activity measured by plasma ACTH and serum cortisol responses to corticotrophin releasing hormone (CRH) were 30–46% lower in ABT‐436 subjects (all p < 0.001). Each ABT‐436 subject showed response to CRH in or near the baseline range of responses. ABT‐436 was associated with more favorable symptom changes on two of five MASQ subscales (estimated effect size 1.47–1.86, p < 0.01) but not on HAM‐D‐17.

Conclusions

The results support further clinical study of the antidepressant potential of ABT‐436.
MxA mRNA decrease preceding NAb detection in IFNβ‐treated MS patients
Authors: Libertinova Jana , Meluzinova Eva , Matoska Vaclav , Zajac Miroslav , Kovarova Ivana , Havrdova Eva , Horakova Dana , Tomek Ales , Marusic Petr , Bojar Martin
Published: February 2017

Background

Multiple sclerosis (MS) patients treated with interferon beta (IFNβ) are at risk of a declining response to treatment because of the production of IFNβ‐neutralizing antibodies (NAbs). The expression of Myxovirus resistance protein A (MxA) mRNA is regarded as a marker of IFNβ bioactivity.

Aims

The aim of this study was to analyze the kinetics of MxA mRNA expression during long‐term IFNβ treatment and assess its relationship to NAb production.

Methods

A prospective, observational, open‐label, non‐randomized study was designed in multiple sclerosis patients starting IFNβ treatment. NAbs and MxA mRNA were monitored every six months.

Results

119 patients were consecutively enrolled and 107 were included in the final analysis. Both the presence of NAbs and a decrease in MxA mRNA below the cut off were revealed in 15 patients, however, in six patients (40%) positivity for NAbs was preceded by the decrease in MxA mRNA. In addition, a further six patients showing a decline in MxA mRNA did not have detectable NAbs.

Conclusion

Our data indicate that quantification of MxA mRNA is a more sensitive identifier of loss of IFNβ efficacy than the NAb positivity.
Exploring students’ experiences in using a physical laboratory for computer networks and data security
Authors: Stojanov Zeljko , Dobrilovic Dalibor , Zorić Tamara
Published: February 2017

Data and computer network security issues have become increasingly important in professional engineering practice, requiring educated engineers capable to solve the real security problems. This strongly emphasize the importance of including courses dedicated to data and computer network security in information technology curricula, and providing real first‐hands experiences with physical equipment to students. This article presents a qualitative study aimed at exploring students’ experiences in a physical laboratory for computer network and data security. Identified experiences were organized into a conceptual framework, providing a base for improvement of learning materials and the laboratory. Benefits and implications for students, lecturers, and researchers are also discussed. © 2017 Wiley Periodicals, Inc. Comput Appl Eng Educ 25:290–303, 2017; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.21797
VGLS: A virtual geophysical laboratory system based on C# and viustools and its application for geophysical education
Authors: Xiang Shiming , Wang Lei Chuang
Published: February 2017

It is not hard to find that the forms of traditional education have limitations. The Virtual Laboratory is to provide a virtual experimental environment to the users via computers in controlling engineering by resorting to the virtual reality technology. It was famous for helping students study the complex process of experiments as well as saving time and cost. Therefore, in the new century, it has become more popular as a means of education. In this paper, we present a virtual geophysical laboratory system (VGLS) based on C#, Viustools, and database technology which can make geophysical education more efficient and effective. Besides, practice has proved that VGLS is a kind of flexible, convenient, and interactive system which can help the users understand and master the laboratory equipment and experimental procedures as well as enhance the efficiency of teaching and learning. In general, it was a practical platform that can be an alternative means of traditional experiments in education which can also meet the requirements of geophysical education. © 2017 Wiley Periodicals, Inc. Comput Appl Eng Educ 25:335–344, 2017; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.21801
Conjugate Vaccines from Bacterial Antigens by Squaric Acid Chemistry: A Closer Look
Authors: Xu Peng , Kelly Meagan , Vann Willie F. , Qadri Firdausi , Ryan Edward T. , Kováč Pavol
Published: February 2017

By using O‐SP‐core (O‐SPcNH2) polysaccharide, isolated from Vibrio cholera O1 lipopolysaccharide (LPS) and related synthetic substances, a detailed study of factors that affect conjugation of bacterial polysaccharides to protein carriers through squaric acid chemistry to form conjugate vaccines has been carried out. Several previously unrecognized processes that take place during the squarate labeling of the O‐SPcNH2 and subsequent conjugation of the formed squarate (O‐SPcNH‐SqOMe) have been identified. The efficiency of conjugation at pH 8.5, 9.0, and 9.5 to bovine serum albumin (BSA) and to the recombinant tetanus toxin fragment C (rTT‐Hc) has been determined. The study led to a protocol for more efficient labeling of O‐SPcNH2 antigen with the methyl squarate group, to yield a higher‐quality, more potent squarate conjugation reagent. Its use resulted in about twofold increases in conjugation efficiency (from 23–26 % on BSA to 51 % on BSA and 55 % on rTT‐Hc). The spent conjugation reagent could be recovered and regenerated by treatment with MeI in the absence of additional base. The immunological properties of the experimental vaccine made from the regenerated conjugation reagent were comparable with those of the immunogen made from the parent O‐SPcNH‐SqOMe.
DFT Study of Nickel‐Catalyzed Low‐Temperature Methanol Synthesis
Authors: McGuinness David S. , Patel Jim , Amin Mohamad Hassan , Bhargava Suresh K.
Published: February 2017

Low‐temperature methanol synthesis (CO+2 H2→CH3OH) catalyzed by a homogeneous nickel/alkali metal alkoxide system has been studied theoretically. Two broad mechanistic possibilities, the direct hydrogenation of CO by nickel formyl species and indirect hydrogenation via methyl formate formation, have been examined. The most favorable mechanism involves the methanolysis of CO to methyl formate catalyzed by an ether complex of sodium methoxide followed by the stepwise hydrogenation of methyl formate to formaldehyde and then to a nickel methoxide, in which both steps are mediated by a nickel hydride. In the final step the nickel methoxide is hydrogenated to release methanol. The conversion of methyl formate to the nickel methoxide is predicted to be rate limiting, and the nickel hydride is the most likely catalyst resting state. The theoretical results are discussed in the context of existing experimental observations, and a good agreement with past studies was obtained.
Process Chain for the Fabrication of Nanoparticle Polymer Composites by Laser Ablation Synthesis
Authors: Maurer Elisabeth , Barcikowski Stephan , Gökce Bilal
Published: February 2017

Nanoparticle polymer composites are of growing interest due to their unique properties. However, conventional composite synthesis methods usually require several process steps including steps for cleaning and improving the particle‐matrix dispersion. As an alternative, laser ablation synthesis can be used to prepare tunable composite materials. This method enables an easy process chain, without the need of additional steps. In this status report, the process chain of laser‐based pre‐series fabrication of nanocomposites is visualized, and the increase of the method's technology readiness level is demonstrated. The process steps are demonstrated from the synthesis of the colloid to applicable functional products. The advantages of using laser ablation for nanocomposite synthesis are highlighted.
Th7Fe3‐Type Related Structures in Pd(Pt)‐Cu‐B Systems: Pd6CuB3—A New Structure Type for Borides
Authors: Salamakha Leonid P. , Sologub Oksana , Stöger Berthold , Rogl Peter F. , Waas Monika , Michor Herwig , Bauer Ernst
Published: February 2017

A new member of the series of Th7Fe3‐type derivative structures, h‐(Pd0.86Cu0.14)7B3 (≡Pd6.02Cu0.98B3, unique structure type Pd6CuB3, space group P63cm, a=12.9426(9) Å, c=4.8697(4) Å, single‐crystal X‐ray diffraction (XRD) data) was obtained from as cast alloys and alloys annealed at 600–650 °C. Further substitution of Cu by Pd led to formation of a Mn7C3‐type structure, o‐(Pd0.93Cu0.07)7B3 (≡Pd6.51Cu0.49B3, space group Pnma, a=4.8971(2) Å, b=7.5353(3) Å, c=12.9743(6) Å, single‐crystal XRD). Isotypic LT h‐(Pt0.70Cu0.30)7B3 (≡Pt4.90Cu2.10B3) was observed in the Pt‐Cu‐B system as a low‐temperature (LT) phase (T≤600 °C) (powder XRD), whereas the Th7Fe3‐type (high‐temperature (HT) h‐(Pt0.73Cu0.27)7B3≡Pt5.11Cu1.89B3, space group P63mc, a=7.4671(1) Å, c=4.9039(1) Å, powder XRD) proved to be stable at high temperature. The three structures are built of columns of face connected metal octahedra and columns of metal tetrahedra alternatingly fused by common faces and vertices. Boron atoms are found in trigonal prisms formed by metal atoms. The volumes of the three new Th7Fe3‐type derivative borides relate as 1:2:3. Superconductivity was discovered for Pt4.9Cu2.1B3 (Pd6CuB3‐type) and Pt5.1Cu1.9B3 (Th7Fe3‐type) below 0.67 and 0.66 K, respectively. Despite the close value of the transition temperature the values of the upper critical field at 0 K differ as 0.37 T and 0.27 T for the two compounds.
High‐Efficiency Perovskite Solar Cells Based on New TPE Compounds as Hole Transport Materials: The Role of 2,7‐ and 3,6‐Substituted Carbazole Derivatives
Authors: Zhu Linna , Shan Yahan , Wang Rui , Liu Debei , Zhong Cheng , Song Qunliang , Wu Fei
Published: February 2017

In this work, four tetraphenylethylene (TPE)‐centered hole transport materials (HTMs), with 2,7‐ or 3,6‐substituted carbazole derivatives as periphery groups are deliberately synthesized and characterized. Their photophysical properties, energy levels, and photovoltaic performances are systematically investigated, and their performances as HTMs are discussed with respect to the different substituent positions on the carbazole moiety. It is interesting to find that the TPE‐based HTMs with 2,7‐carbazole substituents rival the 3,6‐carbazole substituents in hole mobility and hole extraction ability. A high power conversion efficiency of up to 16.74 % is achieved for the devices based on the 2,7‐carbazole periphery arms, which is even higher than the one of the “star” HTM Spiro‐OMeTAD (2,2‐7,7‐tetrakis(N,N′‐diparamethoxy‐phenylamine 9,9′‐spirobifluorene) under the same conditions. As far as we know, this is the highest efficiency achieved in tetraphenylethylene derivatives.
Gold‐Catalyzed Formal Cyclisation/Dimerization of Thiophene‐Tethered Diynes
Authors: Tšupova Svetlana , Hansmann Max M. , Rudolph Matthias , Rominger Frank , Hashmi A. Stephen K.
Published: February 2017

A new pathway in dual gold‐catalyzed reaction of thiophene‐tethered diynes has been identified. A series of fully conjugated alkynyl‐substituted benzothiophenes and benzofurans was obtained by a formal cyclisation/dimerization sequence. All the products are fluorescent, owing to their extended conjugation. The mechanistic studies have been carried out, suggesting that gold acetylides take part in this transformation.
Nanosecond Laser‐Assisted Nitrogen Doping of Graphene Oxide Dispersions
Authors: Kepić Dejan , Sandoval Stefania , Pino Ángel Pérez del , György Enikö , Cabana Laura , Ballesteros Belén , Tobias Gerard
Published: February 2017

N‐doped reduced graphene oxide (RGO) has been prepared in bulk form by laser irradiation of graphene oxide (GO) dispersed in an aqueous solution of ammonia. A pulsed Nd:YAG laser with emission wavelengths in the infrared (IR) 1064 nm, visible (Vis) 532 nm, and ultraviolet (UV) 266 nm spectral regions was employed for the preparation of the N‐doped RGO samples. Regardless of the laser energy employed, the resulting material presents a higher fraction of pyrrolic nitrogen compared to nitrogen atoms in pyridinic and graphitic coordination. Noticeably, whereas increasing the laser fluence of UV and Vis wavelengths results in an increase in the total amount of nitrogen, up to 4.9 at. % (UV wavelength at 60 mJ cm−2 fluence), the opposite trend is observed when the GO is irradiated in ammonia solution through IR processing. The proposed laser‐based methodology allows the bulk synthesis of N‐doped reduced graphene oxide in a simple, fast, and cost efficient manner.
A Density Functional Theory Investigation of Nin, Pdn, and Ptn Clusters (n=1–4) Adsorbed on Buckminsterfullerene
Authors: Pham Nguyet N. T. , Le Hung M.
Published: February 2017

In this study, we examine the adsorptions of Ni, Pd, and Pt clusters on C60 by using a computational approach. Our calculation results show that the base structure of C60 can host Nin/Pdn/Ptn (n=1–4) clusters with good adsorption stability and the complexes establish either two or no unpaired electrons. The binding energy of Pd and Pt clusters increases as the number of metal atoms increases, implying that the coverage of C60 with Pd or Pt preferentially establishes a large‐size metal cluster. A single metal atom favorably occupies the C−C bridge site. For dimer clusters, the three metals of interest share a similar binding fashion, in which two metal atoms establish direct interactions with the C−C bridge sites. For trimer adsorptions, the formation of linear and triangular structures is observed. Both Pt3 and Ni3 preferably constitute isosceles triangles on C60, whilst Pd3 favorably establishes a linear shape. Finally, for each of the Ni4 and Pd4 adsorption cases, we observed three stable binding configurations: rhombus, tetrahedron, and Y‐form. Whereas Ni4 establishes a tetrahedral form, Pd4 attains the most stable form with the Y‐shape geometry on C60. Overall, we observe that the trend of Pd binding to C60 tends to go beyond the fashion of Ni and Pt. In terms of magnetic alignment, the Pdn–C60 systems seem to be non‐magnetic in most cases, unlike the Ni and Pt cases, the structures of which possess magnetic moments of 2 μB in their most stable forms.
Optimizing Treatment for Patients With Anaplastic Lymphoma Kinase‐Positive Lung Cancer
Authors: Dagogo‐Jack I , Shaw AT , Riely GJ
Published: February 2017

In the 9 years since the initial discovery of anaplastic lymphoma kinase (ALK) gene rearrangements in non‐small cell lung cancer (NSCLC), there has been tremendous progress, culminating in an ever‐expanding repertoire of agents that have activity in this disease. This review article provides an overview of currently approved ALK inhibitors, other ALK inhibitors in development, and commonly described mechanisms of resistance to ALK inhibitors. We also discuss emerging controversies in treatment of patients with ALK‐positive lung cancer, including the choice of first‐line ALK inhibitor and the role of tyrosine kinase inhibitors in the treatment of central nervous system metastases.
Charting a Course for Precision Oncology
Authors: Kusnezov D , Paragas J
Published: February 2017

The fields of science have undergone dramatic reorganizations as they have come to terms with the realities of the growing complexities of their problem set, the costs, and the breadth of skills needed to make major progress. A field such as particle physics transformed from principal investigator‐driven research supported by an electron synchrotron in the basement of your physics building in the 1950s, to regional centers when costs became prohibitive to refresh technology everywhere, driving larger teams of scientists to cooperate in the 1970s, to international centers where multinational teams work together to achieve progress. The 2013 Nobel Prize winning discovery of the Higgs boson would have been unlikely without such team science. Other fields such as the computational sciences are well on their way through such a transformation. Today, we see precision medicine as a field that will need to come to terms with new organizational principles in order to make major progress, including everyone from individual medical researchers to pharma. Interestingly, the Cancer Moonshot has helped move thinking in that direction for part of the community and now the initiative has been transformed into law.
Collaboration to Accelerate Proteogenomics Cancer Care: The Department of Veterans Affairs, Department of Defense, and the National Cancer Institute's Applied Proteogenomics OrganizationaL Learning and Outcomes (APOLLO) Network
Authors: Fiore LD , Rodriguez H , Shriver CD
Published: February 2017

A tri‐federal initiative arising out of the Cancer Moonshot has resulted in the formation of a program to utilize advanced genomic and proteomic expression platforms on high‐quality human biospecimens in near‐real‐time in order to identify potentially actionable therapeutic molecular targets, study the relationship of molecular findings to cancer treatment outcomes, and accelerate novel clinical trials with biomarkers of prognostic and predictive value.
Antiretroviral Therapy With Efavirenz Accentuates Pregnancy‐Associated Reduction of Dihydroartemisinin‐Piperaquine Exposure During Malaria Chemoprevention
Authors: Kajubi R , Huang L , Jagannathan P , Chamankhah N , Were M , Ruel T , Koss CA , Kakuru A , Mwebaza N , Kamya M , Havlir D , Dorsey G , Rosenthal PJ , Aweeka FT
Published: February 2017

Dihydroartemisinin (DHA)‐piperaquine is promising for malaria chemoprevention in pregnancy. We assessed the impacts of pregnancy and efavirenz‐based antiretroviral therapy on exposure to DHA and piperaquine in pregnant Ugandan women. Intensive sampling was performed at 28 weeks gestation in 31 HIV‐uninfected pregnant women, in 27 HIV‐infected pregnant women receiving efavirenz, and in 30 HIV‐uninfected nonpregnant women. DHA peak concentration and area under the concentration time curve (AUC0‐8hr) were 50% and 47% lower, respectively, and piperaquine AUC0‐21d was 40% lower in pregnant women compared to nonpregnant women. DHA AUC0‐8hr and piperaquine AUC0‐21d were 27% and 38% lower, respectively, in pregnant women receiving efavirenz compared to HIV‐uninfected pregnant women. Exposure to DHA and piperaquine were lower among pregnant women and particularly in women on efavirenz, suggesting a need for dose modifications. The study of modified dosing strategies for these populations is urgently needed.