bluuebunny/crossref_metadata_2025_split huggingface dataset:
Force generation by polymerizing filaments revisited: diffusive interaction leads to nonlinear force-number scaling
Authors: Valiyakath Jemseena , Gopalakrishnan Manoj 
Published: April 2017

AbstractPolymers growing against a barrier generate force and push it forward. We study here force generation by a bundle ofNrigid polymers growing in parallel against a diffusing, rigid, flat barrier, resembling a bundle of microtubules. To estimate the polymerization force, the barrier is subjected to a forcefacting against the direction of growth of the polymers and the mean velocityVN(f) of the filament assembly is computed. The maximum polymerization force (aliasstall force)is deduced from the condition. This problem has been studied in the literature earlier, but two important aspects have escaped attention: (a) free diffusion of monomers is hindered by the barrier, even when it is far from the growing tips and (b) parallel filaments could interact through the monomer density field (“diffusive coupling”), leading to negative interference between them. In our model, both these effects are investigated in detail. A mathematical treatment based on a set of continuum Fokker-Planck equations for combined filament-wall dynamics suggests that the barrier reduces the influx of monomers to the growing polymer tip, thereby reducing the growth velocity and also the stall force, but it doesn’t affect the scaling of the stall force with number, i.e.,. However, Brownian dynamics simulations show that the linear scaling holds only when the filaments are far apart; when they are arranged close together, forming a bundle, sublinear scaling of force with number appears. We argue that the nonlinear scaling could be attributed to diffusive interaction between the growing tips which becomes significant when the tips are close together. These conclusions, initially established for simple flat-faced polymers, are also found to hold true for microtubules with their characteristic hollow cylindrical geometry and rugged tip structure. In particular, simulations show conclusively that the stall force of a single microtubule is a fraction of the combined stall force of the 13 protofilaments. This result is supported by a simple analytical estimate of the force using diffusive coupling theory, and is in agreement with earlier experimental observations.
Apremilast, an oral phosphodiesterase 4 inhibitor, in the treatment of Japanese patients with moderate to severe plaque psoriasis: Efficacy, safety and tolerability results from a phase 2b randomized controlled trial
Authors: Ohtsuki Mamitaro , Okubo Yukari , Komine Mayumi , Imafuku Shinichi , Day Robert M. , Chen Peng , Petric Rosemary , Maroli Allan , Nemoto Osamu 
Published: April 2017

AbstractApremilast, an oral, small‐molecule phosphodiesterase 4 inhibitor, works intracellularly within immune cells to regulate inflammatory mediators. This phase 2b randomized, placebo‐controlled study evaluated efficacy and safety of apremilast among Japanese patients with moderate to severe plaque psoriasis. In total, 254 patients were randomized to placebo, apremilast 20 mg b.i.d. (apremilast 20) or apremilast 30 mg b.i.d. (apremilast 30) through week 16; thereafter, all placebo patients were re‐randomized to apremilast 20 or 30 through week 68. Efficacy assessments included achievement of 75% or more reduction from baseline in Psoriasis Area and Severity Index score (PASI‐75; primary) and achievement of static Physician Global Assessment (sPGA; secondary) score of 0 (clear) or 1 (minimal) at week 16. Safety was assessed through week 68. At week 16, PASI‐75 response rates were 7.1% (placebo), 23.5% (apremilast 20; P = 0.0032 vs placebo) and 28.2% (apremilast 30; P = 0.0003 vs placebo); sPGA response rates (score of 0 or 1) were 8.8% (placebo), 23.9% (apremilast 20; P = 0.0165 vs placebo) and 29.6% (apremilast 30; P = 0.0020 vs placebo). Responses were maintained with apremilast through week 68. Most common adverse events (AEs) with placebo, apremilast 20 and apremilast 30 (0–16 weeks) were nasopharyngitis (8.3%, 11.8%, 11.8%), diarrhea (1.2%, 8.2%, 9.4%), and abdominal discomfort (1.2%, 1.2%, 7.1%), respectively. Exposure‐adjusted incidence of these AEs did not increase with continued apremilast treatment (up to 68 weeks). Apremilast demonstrated efficacy and safety in Japanese patients with moderate to severe plaque psoriasis through 68 weeks that was generally consistent with prior studies.
Identification of a heterozygous p.Gly568Val missense mutation in the TRPV3 gene in a Japanese patient with Olmsted syndrome: In silico analysis of TRPV3
Authors: Nagai Hiroshi , Takaoka Yutaka , Sugano Aki , Nakamachi Yuji , Kawano Seiji , Nishigori Chikako 
Published: April 2017

AbstractOlmsted syndrome is a very rare congenital disorder, characterized by palmoplantar keratoderma and periorificial keratotic lesions. Recently, TRPV3 was reported to be a causative gene of Olmsted syndrome. We identified a heterozygous missense mutation of TRPV3, c.1703G>T, p.Gly568Val, in a Japanese patient with Olmsted syndrome. To the best of our knowledge, this is the first report of a Japanese patient with Olmsted syndrome harboring a missense mutation in TRPV3. We conducted in silico analysis of TRPV3 to evaluate whether the p.Gly568Val leads to structural changes in the TRPV3 selectivity filter. The selectivity filter was shown to become dilated and hyperpermeable as a result of genetic mutation (p.Gly573Ser, p.Tr692Gly or p.Gly568Val) as well as after a change in temperature (300 K to 310 K). In silico analysis of TRPV3 could be a useful approach in predicting mutation‐induced activated states of ion channels, and thus enrich our understanding of the pathogenesis of Olmsted syndrome.
Brexit and UK International Development Policy
Authors: Lightfoot Simon , Mawdsley Emma , Szent‐Iványi Balázs 
Published: April 2017

AbstractIn this article we explore the implications of Brexit for the UK and the EU's development policies and strategic directions, focusing on the former. While it is likely that the operational process of disentangling the UK from the various development institutions of the EU will be relatively straightforward, the choices that lie ahead about whether and how to cooperate thereafter are more complex. Aid and development policy touches on a wide range of interests—security, trade, climate change, migration, gender rights, and so on. We argue that Brexit will accelerate existing trends within UK development policy, notably towards the growing priority of private sector‐led economic growth strategies and blended finance tools. There are strong signals that UK aid will be cut, as successive secretaries of state appear unable to persuade a substantial section of the public and media that UK aid and development policy serves UK interests in a variety of ways.
Comparisons of cardioprotective efficacy between fibroblast growth factor 21 and dipeptidyl peptidase‐4 inhibitor in prediabetic rats
Authors: Tanajak Pongpan , Sa‐nguanmoo Piangkwan , Apaijai Nattayaporn , Wang Xiaojie , Liang Guang , Li Xiaokun , Jiang Chao , Chattipakorn Siriporn C. , Chattipakorn Nipon 
Published: April 2017

SummaryAimsComparative efficacy between fibroblast growth factor 21 (FGF21) and vildagliptin on metabolic regulation, cardiac mitochondrial function, heart rate variability (HRV), and left ventricular (LV) function is not known. We hypothesized that FGF21 and vildagliptin share a similar efficacy in improving these parameters in high fat diet (HFD)‐induced obese‐insulin resistant rats.MethodsTwenty‐four male Wistar rats were fed with either a normal diet (ND) or a HFD for 12 weeks. Then, ND rats were received vehicle (NDV). Rats in the HFD group were divided into three subgroups to receive either vehicle (HFV), recombinant human FGF21 (rhFGF21, 0.1 mg/kg/d, ip; HFF), or vildagliptin (3 mg/kg/d, PO; HFVil) for 28 days.ResultsHFV rats developed obese‐insulin resistance, increased serum tumor necrosis factors alpha (TNF‐α) level, impaired heart rate variability (HRV) together with cardiac mitochondrial dysfunction, and LV dysfunction. Cardiac apoptosis was markedly increased in HFV rats indicated by decreased B‐cell lymphoma 2 (Bcl‐2) with increased Bcl2‐associated X‐protein (Bax) and cleaved caspase 3 expression. Cardiac FGF21 signaling pathways were markedly decreased in HFV rats indicated by decreased phosphor‐fibroblast growth factor receptors 1 (p‐FGFR1), phosphor‐extracellular signal‐regulated protein kinases 1 (p‐ERK1/2), proliferator‐activated receptor gamma coactivator 1‐alpha (PGC‐1α), and carnitine palmitoyltransferase‐1 (CPT‐1) expression. Although both FGF21 and vildagliptin similarly attenuated these impairments, only HFF rats had decreased body weight, visceral fat, and serum TNF‐α levels.ConclusionsFGF21 exerts better metabolic regulation and inflammation reduction than vildagliptin. However, FGF21 and vildagliptin shared a similar efficacy for cardioprotection by improving HRV and LV function.
Development Cost Capitalization During R&D Races
Authors: De Waegenaere Anja , Sansing Richard C. , Wielhouwer Jacco L. 
Published: April 2017

AbstractWe investigate the economic effects of capitalizing development costs during a race between two firms to discover and develop a new technology. Winning the race requires success in the research stage and success in the development stage. Development costs are expensed in some settings, but capitalized in others. Capitalization of development costs provides a credible signal regarding progress in the race, allowing the rival to make a more informed decision regarding whether to proceed with development. We study the effects of this signal on the firms’ investment decisions and social welfare. We show that if both firms capitalize instead of expense development costs, aggregate investment in research weakly increases but aggregate investment in development weakly decreases. We also characterize the accounting policies that the two rival firms would adopt if they could freely choose either an expensing policy or a capitalization policy.
Nitric oxide in the pathophysiology of retinopathy: evidences from preclinical and clinical researches
Authors: Opatrilova Radka , Kubatka Peter , Caprnda Martin , Büsselberg Dietrich , Krasnik Vladimir , Vesely Pavol , Saxena Sandeep , Ruia Surabhi , Mozos Ioana , Rodrigo Luis , Kruzliak Peter , dos Santos Katia Goncalves 
Published: April 2017

AbstractRetinopathy is the leading cause of blindness and visual disability in working‐aged people. The pathogenesis of retinopathy is an actual and still open query. Alterations contributing to oxidative and nitrosative stress, including elevated nitric oxide and superoxide production, changes in the expression of different isoforms of nitric oxide synthase or endogenous antioxidant system, have been implicated in the mechanisms how this ocular disease develops. In addition, it was documented that renin–angiotensin system has been implicated in the progression of retinopathy. Based on comprehensive preclinical and clinical researches in this area, the role of above‐mentioned factors in the pathogenesis of diabetic retinopathy, hypertensive retinopathy and ischaemic proliferative retinopathy is reviewed in this study. Moreover, the genetic susceptibility factors involved in the development of the retinopathy and possible strategies that utilize antioxidants as additive therapy are also highlighted here.
Choroidal vascular changes in age‐related macular degeneration
Authors: Koh Lilian Hui Li , Agrawal Rupesh , Khandelwal Neha , Sai Charan Labishetty , Chhablani Jay 
Published: April 2017

AbstractPurposeTo assess the choroidal vascular changes using choroidal vascularity index (CVI) in patients with age‐related macular degeneration (AMD) compared to controls.MethodsEnhanced depth imaging (EDI) optical coherence tomography (OCT) scans of 64 patients with unilateral or bilateral AMD were obtained. Images with a poorly demarcated choroidal–scleral interface (CSI) were excluded from the analysis. Foveal scans of 63 AMD eyes and 35 ‘normal fellow’ eyes were analysed. Images of 30 eyes from 18 age‐matched healthy subjects were included as controls. Choroidal vascularity index (CVI) was derived from binarization of EDI OCT images, using fiji software.ResultsThe mean age was 56.50 ± 5.50 years for AMD patients and 52.25 ± 6.75 years for controls. All patients were treatment naïve. Subfoveal choroidal thickness (SFCT) in AMD, ‘normal fellow’ eyes and controls was 314.02 ± 78.80 μm, 300.88 ± 53.85 μm and 278.5 ± 65.31 μm, respectively. Choroidal vascularity index (CVI) in AMD, ‘normal fellow’ eyes and controls was 64.04 ± 2.43%, 64.66 ± 2.25% and 66.07 ± 1.72%, respectively. Choroidal vascularity index (CVI) of both AMD and ‘normal fellow’ eyes was significantly lower compared to controls (p < 0.0001 and p = 0.007). The SFCT of AMD eye was not found to be significantly different from ‘normal fellow eyes’ (p = 0.45).ConclusionThere was no statistical difference in SFCT, but CVI was significantly lower in patients with AMD. Choroidal vascularity index (CVI) was also lower in ‘normal fellow’ AMD eyes as compared to controls. This suggests possible reduction in choroidal vascularity in eyes with AMD and also to a certain extent in the ‘normal fellow’ eyes without phenotypical manifestations and may suggest underlying choroidal morphological change leading to wet AMD.
Preliminary study of a controllable device for subtenon drug infusion in a rabbit model
Authors: Duan Yiqin , Yang Yezhen , Huang Xuetao , Lin Ding 
Published: April 2017

AbstractBackground and objectiveConventional methods to treat intraocular diseases are invasive or associated with adverse effects. A minimally invasive means of sustained‐release drug delivery to the vitreous is required. This study evaluated a novel device for subtenon drug delivery to the vitreous, relative to a single subconjunctival injection.MethodsSixty adult New Zealand White rabbits were randomly assigned to receive demethylvancomycin (DMV) by continuous subtenon delivery with the flow rate of 0.1 ml/hr for 24 hr, or as a single 0.3 ml subconjunctival injection in the right eyes. Rabbits were killed in subgroups of six at 1, 3, 6, 12 and 24 hr. The DMV concentration of the vitreous humour of the right eye was analysed by high‐performance liquid chromatography.ResultsOverall, the vitreous DMV concentration of the subtenon group was significantly higher than that of the subconjunctival group (F = 25.928, p = 0.001). The DMV concentration of the subtenon group was also significantly higher than that of the subconjunctival group at 3, 6, 12 and 24 hr (t = 2.457, 5.064, 3.085, 4.207; p = 0.04, 0.01, 0.018, 0.004, respectively). In the subtenon group, the DMV concentration reached maximum (2.41 ± 0.67 μg/ml) at 6 hr, and at 24 hr was 2.37 ± 1.23 μg/ml. In the subconjunctival group, the DMV concentration reached maximum (0.48 ± 0.27 μg/ml) at 1 hr and declined to 0.09 ± 0.05 μg/ml at 24 hr.ConclusionSubtenon application with this novel minimally invasive design is an effective method for delivering an appropriate drug to the vitreous in a sustained and controllable amount.
Differential expression and localization of human tissue inhibitors of metalloproteinases in proliferative diabetic retinopathy
Authors: Abu El‐Asrar Ahmed M. , Ahmad Ajmal , Bittoun Emilie , Siddiquei Mohammad Mairaj , Mohammad Ghulam , Mousa Ahmed , De Hertogh Gert , Opdenakker Ghislain 
Published: April 2017

AbstractPurposeTissue inhibitors of metalloproteinases (TIMPs) block the catalysis by matrix metalloproteinases (MMPs) and have additional biologic activities, including regulation of cell growth and differentiation, apoptosis, angiogenesis and oncogenesis. We investigated the expression levels of all the four human TIMPs and correlated these levels with those of MMP‐9 and vascular endothelial growth factor (VEGF) in proliferative diabetic retinopathy (PDR).MethodsVitreous samples from 38 PDR and 21 nondiabetic control patients and epiretinal membranes from 14 patients with PDR and 10 patients with proliferative vitreoretinopathy (PVR) were studied by enzyme‐linked immunosorbent assay, Western blot analysis and immunohistochemistry.ResultsTissue inhibitor of metalloproteinases‐1, TIMP‐4, MMP‐9 and VEGF levels were significantly higher in vitreous samples from PDR patients than in nondiabetic controls (p < 0.0001 for all comparisons), whereas TIMP‐2 and TIMP‐3 levels did not differ significantly. TIMP‐1, TIMP‐4, MMP‐9 and VEGF levels in PDR with active neovascularization were significantly higher than those in inactive PDR (p < 0.0001, 0.001, 0.013, 0.004, respectively). Significant positive correlations existed between levels of TIMP‐1 and levels of TIMP‐4 (r = 0.37; p = 0.004), MMP‐9 (r = 0.65; p < 0.0001) and VEGF (r = 0.59; p < 0.0001), between levels of TIMP‐4 and levels of MMP‐9 (r = 0.61; p < 0.0001) and VEGF (r = 0.62; p < 0.0001) and between levels of MMP‐9 and VEGF (r = 0.62; p < 0.0001). TIMP‐1 and TIMP‐3 were expressed in vascular endothelial cells in PDR epiretinal membranes and in myofibroblasts and leucocytes in PDR and PVR epiretinal membranes.ConclusionThe differential expression of TIMPs in PDR suggests that among the 4 TIMPs, TIMP‐1 and TIMP‐4 may be possible biomarkers of disease activity.
Can the SENSIMED Triggerfish® lens data be used as an accurate measure of intraocular pressure?
Authors: Vitish‐Sharma Parveen , Acheson Austin G. , Stead Richard , Sharp John , Abbas Ali , Hovan Marta , Maxwell‐Armstrong Charles , Guo Boliang , King Anthony J. 
Published: April 2017

AbstractPurposeThe SENSIMED Triggerfish® contact lens sensor (CLS) has an embedded micro‐sensor that captures spontaneous circumferential changes at the corneoscleral junction and transmits them via an antenna to a device where these measurements are stored. During laparoscopic colorectal surgery, patients are placed in Trendelenburg position which has been shown to increase intraocular pressure (IOP). Laparoscopic colorectal surgery requires both pneumoperitoneum and Trendelenburg positioning; therefore, IOP can vary significantly. We aimed to assess whether circumferential changes in the corneoscleral area can be correlated to IOP changes measured using Tono‐pen® XL applanation tonometer during laparoscopic colorectal surgery.MethodPatients undergoing laparoscopic colorectal resections were included. On the day of surgery, baseline IOP was taken and the SENSIMED Triggerfish® CLS was then set up in one eye of the patient. During surgery (whilst under general anaesthetic), IOP measurements were taken in the contralateral eye using a Tono‐pen® XL applanation tonometer every hour and any time the table was moved to record the fluctuations of IOP during surgery and any association with position change. The timings of these readings were documented.ResultsTwenty patients were included in this study (six males, 14 females). Average age was 64.6 years (SD = 16.3). The fluctuation in IOP measured in the reference eye ranged between 6.3 and 46.7 mmHg. The mean correlation coefficient between CLS output measurements and these IOP measurements was r = 0.291 (95% CI).ConclusionOur results showed a weak correlation between the SENSIMED Triggerfish® CLS data output and IOP measurements taken using the Tono‐pen® XL applanation tonometer.
Social anxiety and interpretation bias: examining clinical and subclinical components in adolescents
Authors: Loscalzo Yura , Giannini Marco , Miers Anne C. 
Published: April 2017

BackgroundThis study aimed to examine whether different components of interpretation bias are clinical or dimensional features of adolescent social anxiety. The study analyzed the components of this bias at a subclinical level of Social Anxiety Disorder (SAD) and compared these with a clinical sample of adolescents with SAD.MethodAdolescents in the age range 13–17 years participated. A group with SAD (n = 30) was compared with a group with subclinical SAD (n = 60), and a non‐socially anxious group (n = 95).ResultsNegative interpretation bias for social situations was found to be a dimensional aspect of social anxiety. In contrast, belief in negative interpretations of social situations appears to be a clinical feature. Contrary to expectations, endorsement of positive interpretations did not differ between the three groups.ConclusionsThe results suggest that a screening instrument based on negative interpretations of social situations could be useful to detect adolescents at‐risk of developing SAD. In a clinical setting, the belief in negative interpretations and the presence of the bias in nonsocial situations should also be considered.
Children's experiences of managing Type 1 diabetes in everyday life: a thematic synthesis of qualitative studies
Authors: Rankin D. , Harden J. , Jepson R. , Lawton J. 
Published: April 2017

AbstractAimsTo explore the everyday experiences of children (aged ≤ 12 years) with Type 1 diabetes to identify factors that help or hinder diabetes self‐management practices.MethodsEight databases (Embase, Medline, CINAHL, Web of Science, PsychInfo, ASSIA, ERIC and ProQuest Dissertations) were searched in 2016 to identify qualitative studies exploring children's views about self‐managing diabetes. Data were extracted, coded and analysed using thematic synthesis.ResultsEighteen studies from five countries were included in the review. Synthesis of studies’ findings resulted in the identification of three overarching analytical themes. The first theme, ‘Understandings of diabetes and involvement in self‐management’, outlines ways in which children understand diabetes and develop self‐management responsibilities. The second theme, ‘Disruption to life and getting on with it’, reports children's frustrations at disruptions to everyday life when managing diabetes, and how attempts to appear normal to family and friends affect self‐management practices. The third theme, ‘Friends’ support’, describes how friends’ reactions and responses to diabetes affect children's ability to appear normal and willingness to disclose information about diabetes, and support provided by ‘informed friends’, or peers with diabetes.ConclusionsAlthough the synthesis has identified how children's everyday life experiences inform ways in which they undertake diabetes self‐management, it was not possible to determine new ways to provide support. To help children optimise their glycaemic control, further work should be undertaken to identify their need for support and which takes into account the potential ways in which parents, friends and peers can offer assistance.
Myths and realities about input subsidies in sub‐Saharan Africa
Authors: Ghins Léopold , Mas Aparisi Alban , Balié Jean 
Published: April 2017

AbstractUsing a recent public expenditure dataset, this article proposes a ‘reality check’ of the level and composition of input subsidies in nine African countries between 2006 and 2013. Results show that input subsidies (1) received close to 35% of agricultural‐specific expenditure on average and (2) cover a variety of interventions, including investments in capital, such as on‐farm irrigation, and in on‐farm services, such as inspection or training. Further, the figures show that input subsidies tended to become entrenched in agricultural budgets over time, leading to sub‐optimal execution rates, and were primarily funded by the national taxpayer, while donors invested more in public goods. Findings confirm that input subsidies crowded out other spending categories likely to be more supportive of long‐term agricultural development objectives. The article concludes that the political economy of input subsidies should be directed to making more concrete efforts to attain a better balance of public expenditure on agriculture. Furthermore, policy‐makers should aim to increase the efficiency and policy coherence of input subsidies, since merely abolishing them is likely to be unfeasible in the short term.