bluuebunny/crossref_metadata_2025 huggingface dataset:
The two‐way relationship between the Madden–Julian oscillation and anticyclonic wave breaking
Authors: MacRitchie K. , Roundy P. E.
Published: April 2016

The Madden– Julian oscillation (MJO) is the primary mode of intraseasonal variability in the Tropics. The MJO often couples with convection as it moves over the Indian Ocean and decouples as it leaves the west Pacific Ocean. The association between convection coupled to the MJO and the midlatitude flow pattern has been the primary focus of numerous studies. In particular, it has been shown that there is a statistical relationship between the position and strength of the MJO and anticyclonic wave breaking (AWB). This study expands on this statistical relationship by examining the two‐way relationship between the MJO and AWB.

Using a climatology of AWB during an extended boreal cold season, we demonstrate that there is enhanced AWB over the central North Pacific when active MJO convection is over the eastern Indian Ocean and Maritime Continent. Convection associated with the MJO can induce AWB when active MJO convection is over the Indian Ocean. Once the wave breaks over the central North Pacific, the residual cut‐off low phases with the MJO circulation to enhance it as it propagates eastward, resulting in a higher amplitude MJO than when no AWB occurs.
A Novel Approach to Simultaneous Robust Design of Product Parameters and Tolerances Using Quality Loss and Multivariate ANOVA Concepts
Authors: Hazrati‐Marangaloo Hossein , Shahriari Hamid
Published: April 2016

Design and development of high quality products are of utmost importance to any production plant. Product design consists of parameter design and tolerance design, which affect the product performances and the manufacturing costs, respectively. Most products involve more than one quality feature. Design and development of such products raise multi‐response surface problems in which it is necessary to determine the optimal values of parameters and the tolerances for all responses simultaneously. In this research, an approach for simultaneous robust parameter and tolerance design is proposed to deal with multi‐response problems. The proposed method employs quality loss concept and one‐way multivariate analysis of variance. Two simulation studies are performed to validate the applicability of the proposed method. Research findings show that the proposed method performs better in quality improvement as well as in cost reduction than the existing methods. The variances of the responses are also lower than those of the other methods, that is, the proposed method results in a more robust approach to product design. Copyright © 2016 John Wiley & Sons, Ltd.
Bronchial‐pulmonary arterial fistula with primary racemose hemangioma
Authors: Kato Miharu , Morio Yoshiteru , Matsunaga Takeshi , Shiraishi Akihiko , Uekusa Toshimasa , Takahashi Kazuhisa
Published: April 2016

Bronchial‐pulmonary arterial fistula (BPAF) is a rare vascular malformation complicated with racemose hemangioma. We report a case of a 65‐year‐old male with BPAF with primary racemose hemangioma. Bronchial arteriography demonstrated convolution, dilation, and aneurysm connected with pulmonary artery, suggesting the presence of BPAF, in the left upper lobe. Since a 20‐mm sized aneurysm of bronchial artery and BPAF coexisted, he underwent ligation of bronchial arterial aneurysm and left upper lobectomy to prevent hemoptysis. As neither history of prior illness nor histopathologic findings of vascular inflammation was seen, the present case demonstrated BPAF with primary racemose hemangioma. Establishment of non‐invasive treatment strategy for BPAF is urgently required.
Primary ciliary dyskinesia with complex abnormalities including cleavage of B‐subfibers
Authors: Orimo Keisuke , Kondo Mitsuko , Arimura Ken , Takeyama Kiyoshi , Takeuchi Kazuhiko , Tamaoki Jun
Published: April 2016

A 25‐year‐old Japanese woman suffered from repeated respiratory tract infections. Because of her characteristic medical history and imaging findings, we suspected primary ciliary dyskinesia (PCD) and performed a transbronchial biopsy. The biopsy revealed complex abnormalities of the ciliary structure including cleavage of the B‐subfibers observed by transmission electron microscopy analysis and the complete loss of ciliary motion by video analysis. Genetic examinations to diagnose PCD have progressed in recent years. However, in this case, the well‐known genetic mutations in causal genes of PCD were not detected via whole‐exome sequencing of the blood. Cleavage of the B‐subfibers in patients with PCD has never been reported. This case appears to be the first report of this PCD subtype in humans.
Bevacizumab‐induced chronic interstitial pneumonia during maintenance therapy in non‐small cell lung cancer
Authors: Sekimoto Yasuhito , Kato Motoyasu , Shukuya Takehiko , Koyama Ryo , Nagaoka Tetsutaro , Takahashi Kazuhisa
Published: April 2016

Bevacizumab is a monoclonal antibody targeting the vascular endothelial growth factor receptor and a key drug for advanced non‐small cell lung cancer. There are few reports describing bevacizumab‐induced chronic interstitial pneumonia.

A 62‐year‐old man with advanced non‐small cell lung cancer was admitted to our hospital with dyspnea. He previously received four courses of carboplatin plus paclitaxel with bevacizumab combination therapy and thereafter received four courses of maintenance bevacizumab monotherapy. A chest‐computed tomography scan on admission revealed diffuse ground glass opacity. He had not received any other drugs and did not have pneumonia. Thus, he was diagnosed with bevacizumab‐induced chronic interstitial pneumonia and was treated with a high dose of corticosteroids. After steroid treatment, his dyspnea and radiological findings improved.

This case report is the first description of bevacizumab‐induced chronic interstitial pneumonia during maintenance therapy in a patient with non‐small cell lung cancer.
Drivers of Plant Invasion at Broad and Fine Scale in Short Temperate Streams
Authors: Liendo D. , García‐Mijangos I. , Campos J. A. , López‐Muniain U. , Biurrun I.
Published: April 2016

Riparian ecosystems have been described as highly prone to alien plant invasions; thus, disentangling the contributing factors of the invasion process is of utmost importance to conserving and managing these valuable ecosystems. In this study we examined the drivers of riparian plant invasion in 16 Cantabrian river basins (northern Spain) ranging from 100 to ca. 1050 km2. A complete flora was determined for five randomly selected sites within those basins. One hundred and thirty alien plant species were found across the 80 sampling sites, representing 21% of the recorded total flora. At site scale, the level of plant invasion, measured as alien richness (AR) and relative alien richness (RAR), was assessed in relation to a set of explanatory variables by means of Generalised Linear Mixed Models. This level of invasion was influenced by environmental variables such as the thermicity index, the average riverbed width and the number of plant communities and by human‐related variables such as the distance to the nearest town and the proportion of surrounding urban land. At basin scale, industrialised river basins were more heavily invaded than non‐industrialised basins, and they both differed in their alien plant composition. Given that some of the alien species occurring in Cantabrian streams are specially abundant (Crocosmia x crocosmiiflora) and/or form very dense stands (Fallopia japonica, Paspalum distichum), future research should focus on the drivers that influence the presence and distribution of these species of special concern. Copyright © 2016 John Wiley & Sons, Ltd.
The Influence of User Behaviour on Energy Use in European Shopping Centres
Authors: Woods Ruth , Skeie Kristian S. , Haase Matthias
Published: April 2016

European society spends increasing amounts of time in shopping centres. There is an urgent need to reduce energy use and to provide stakeholders with the tools to develop the next generation of sustainable shopping centres. The intention here is to identify how user behaviour, in particular owners, managers, tenants and customers, influences energy performance in European shopping centres. The causes of energy use are often primarily technical; but user behaviour influences whether actions to reduce energy use are implemented and how effective the actions are. Customers are not interested in energy use or sustainability issues when doing their shopping, and this influences how shopping centres act with regard to energy use reductions. This has implications for their sustainability and suggests a design potential in shopping centres, one which lies in considering social and behavioural issues alongside the implementation of more technical aspects associated with energy use in retail environments. Copyright © 2016 John Wiley & Sons, Ltd and ERP Environment
The Economic–Social Performance Relationships of Ports: Roles of Stakeholders and Organizational Tension
Authors: Cheon SangHyun
Published: April 2016

This study examines the mechanisms that shape relationships between port economic and social performance. Based on the concepts of organizational paradox and stakeholder heterogeneity, the study develops a paradox–stakeholder combination matrix to explain context‐ and issue‐specific economic–social performance relationships. Differing economic–social performance links may vary with different stakeholders' roles in relation to ports' sustainable development issues. The empirical evidence from US ports provides crucial implications for quasi‐public organizations, which face complex organizational identities. Copyright © 2016 John Wiley & Sons, Ltd and ERP Environment
The Kerala Tourism Model – An Indian State on the Road to Sustainable Development
Authors: Thimm Tatjana
Published: April 2016

Sustainable tourism in Kerala is on the rise. Therefore, this South Indian state is assessed according to the sustainable tourism criteria of the Strasdas et al. (2007) framework. Kerala as a state does not qualify as a sustainable tourism destination, although individual success stories at the NGO and government level exist. This conceptual paper delivers a detailed analysis of the three dimensions of sustainability, i.e. ecology, economy and socio‐cultural aspects, of the ‘Kerala tourism model’ and discusses the question of whether this model can be transferred to other developing countries. Copyright © 2016 John Wiley & Sons, Ltd and ERP Environment
PSO‐based optimal peer selection approach for highly secure and trusted P2P system
Authors: Nallakannu Senthil Madasamy , Thiagarajan Revathi
Published: April 2016

There is a significant growth of the peer‐to‐peer (P2P) systems over the last few years because of their high potential for sharing file among the peers. Selection of the optimal peer ensures high data transmission rate and reduced network cost. However, it is highly difficult to select the optimal peer because of the variation in the heterogeneous capacity and dynamic capacity of the peers. Efficient peer selection approach is highly required to overcome this difficulty. This paper proposes a particle swarm optimization (PSO)‐based optimal peer selection approach for a highly secure and trusted P2P system, based on the bandwidth and trust level of the peers. File replication is performed to effectively tackle the overloading of the hot files. Replacement of the replicated file is performed, based on their demand rates. The success rate and bandwidth rate of the peer are computed. Bandwidth and trust‐based PSO is applied to select the optimal peer. This improves the success rate for the peer transmission. After selecting the optimal peer, the replicated file is encrypted and transmitted to the selected peer. Finally, the replicated file is decrypted. Our proposed approach achieves minimum average query delay and ensures a highly secure and trusted environment for the P2P systems. The performance of the proposed approach is evaluated by comparing the proposed approach with the existing techniques. From the comparison results, it is clearly evident that the proposed approach achieves higher success rate and lower link stress, delay, communication overhead, finished time and network cost. Copyright © 2016 John Wiley & Sons, Ltd.
Polydopamine‐assisted immobilization of arginine molecules to improve hemocompatibility
Authors: Sun Jiamao , Fu Tao , Sun Jianmin , Wu Feng , Liu Yun
Published: April 2016

TiO2 film containing 20 at% Ta (TaTiO2 film) was sol‐gel coated on NiTi alloy, and polydopamine film was used to immobilize arginine molecules onto the TaTiO2 film surface to improve hemocompatibility of NiTi alloy. X‐ray photoelectron spectroscopy analysis indicated that polydopamine film was formed and then arginine was immobilized onto the surface of TaTiO2‐coated sample. Contact angle measurement showed that the polydopamine film and the arginine molecule layer decreased surface energy and interface tension of the TaTiO2‐coated NiTi sample. The hemocompatibility tests demonstrated that immobilization of arginine molecules improved anti‐thrombogenic activity and anti‐aggregating function of the TaTiO2‐coated NiTi sample. Copyright © 2016 John Wiley & Sons, Ltd.
Efficient One‐Step Production of Microencapsulated Hepatocyte Spheroids with Enhanced Functions
Authors: Chan Hon Fai , Zhang Ying , Leong Kam W.
Published: April 2016

Hepatocyte spheroids microencapsulated in hydrogels can contribute to liver research in various capacities. The conventional approach of microencapsulating spheroids produces a variable number of spheroids per microgel and requires an extra step of spheroid loading into the gel. Here, a microfluidics technology bypassing the step of spheroid loading and controlling the spheroid characteristics is reported. Double‐emulsion droplets are used to generate microencapsulated homotypic or heterotypic hepatocyte spheroids (all as single spheroids <200 μm in diameter) with enhanced functions in 4 h. The composition of the microgel is tunable as demonstrated by improved hepatocyte functions during 24 d culture (albumin secretion, urea secretion, and cytochrome P450 activity) when alginate‐collagen composite hydrogel is used instead of alginate. Hepatocyte spheroids in alginate‐collagen also perform better than hepatocytes cultured in collagen‐sandwich configuration. Moreover, hepatocyte functions are significantly enhanced when hepatocytes and endothelial progenitor cells (used as a novel supporting cell source) are co‐cultured to form composite spheroids at an optimal ratio of 5:1, which could be further boosted when encapsulated in alginate‐collagen. This microencapsulated‐spheroid formation technology with high yield, versatility, and uniformity is envisioned to be an enabling technology for liver tissue engineering as well as biomanufacturing.
Purinergic and Store-Operated Ca2+ Signaling Mechanisms in Mesenchymal Stem Cells and Their Roles in ATP-Induced Stimulation of Cell Migration
Authors: Peng Hongsen , Hao Yunjie , Mousawi Fatema , Roger Sebastien , Li Jing , Sim Joan A. , Ponnambalam Sreenivasan , Yang Xuebin , Jiang Lin-Hua
Published: April 2016

ATP is an extrinsic signal that can induce an increase in the cytosolic Ca2+ level ([Ca2+]c) in mesenchymal stem cells (MSCs). However, the cognate intrinsic mechanisms underlying ATP-induced Ca2+ signaling in MSCs is still contentious, and their importance in MSC migration remains unknown. In this study, we investigated the molecular mechanisms underlying ATP-induced Ca2+ signaling and their roles in the regulation of cell migration in human dental pulp MSCs (hDP-MSCs). RT-PCR analysis of mRNA transcripts and interrogation of agonist-induced increases in the [Ca2+]c support that P2X7, P2Y1, and P2Y11 receptors participate in ATP-induced Ca2+ signaling. In addition, following P2Y receptor activation, Ca2+ release-activated Ca2+ Orai1/Stim1 channel as a downstream mechanism also plays a significant role in ATP-induced Ca2+ signaling. ATP concentration-dependently stimulates hDP-MSC migration. Pharmacological and genetic interventions of the expression or function of the P2X7, P2Y1 and P2Y11 receptors, and Orai1/Stim1 channel support critical involvement of these Ca2+ signaling mechanisms in ATP-induced stimulation of hDP-MSC migration. Taken together, this study provide evidence to show that purinergic P2X7, P2Y1, and P2Y11 receptors and store-operated Orai1/Stim1 channel represent important molecular mechanisms responsible for ATP-induced Ca2+ signaling in hDP-MSCs and activation of these mechanisms stimulates hDP-MSC migration. Such information is useful in building a mechanistic understanding of MSC homing in tissue homeostasis and developing more efficient MSC-based therapeutic applications.
Hispolon suppresses migration and invasion of human nasopharyngeal carcinoma cells by inhibiting the urokinase‐plasminogen activator through modulation of the Akt signaling pathway
Authors: Ho Hsin‐Yu , Ho Yung‐Chuan , Hsieh Ming‐Ju , Yang Shun‐Fa , Chuang Chun‐Yi , Lin Chiao‐Wen , Hsin Chung‐Han
Published: April 2016

Hispolon has been reported to possess antioxidant, antiinflammatory, and antitumor activities. However, the effect of hispolon on the metastasis of nasopharyngeal carcinoma (NPC) remains unclear. In this study, we investigated how the antimetastatic activity and relevant signaling pathways of hispolon affected three NPC cell lines. The results revealed that hispolon significantly reduced the migration and invasion of three NPC cells in a dose‐dependent manner from 0 to 50 µM. Hispolon also significantly inhibited the activity and expression of urokinase‐plasminogen activator (uPA) as well as the phosphorylation of Akt. Moreover, blocking the Akt pathway also enhanced the antimetastatic ability of hispolon in the NPC cells. In conclusion, hispolon inhibited uPA expression and NPC cell metastasis by downregulating Akt signal pathways; therefore, hispolon exerts beneficial effects in chemoprevention. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 645–655, 2017.
What is new in nanoparticle‐based photoacoustic imaging?
Authors: Lemaster Jeanne E. , Jokerst Jesse V.
Published: April 2016

Photoacoustic imaging combines the high temporal and spatial resolution of ultrasound with the good contrast and spectral tuning of optical imaging. Contrast agents are used in photoacoustic imaging to further increase the contrast and specificity of imaging or to image a specific molecular process, e.g., cell‐surface proteins or small molecule biomarkers. Nanoparticle‐based contrast agents are important tools in photoacoustic imaging because they offer intense and stable signal and can be targeted to specific molecular processes. In this review, we describe some of the most interesting and recent advances in nanoparticle‐based photoacoustic imaging including inorganic nanoparticles, organic/polymeric nanoparticles, nanoparticle coatings, multimodality imaging, as well as emerging topics in the field. WIREs Nanomed Nanobiotechnol 2017, 9:e1404. doi: 10.1002/wnan.1404

This article is categorized under:

Diagnostic Tools > In Vivo Nanodiagnostics and Imaging
Exposure–safety–efficacy analysis of single-agent ixazomib, an oral proteasome inhibitor, in relapsed/refractory multiple myeloma: dose selection for a phase 3 maintenance study
Authors: Gupta Neeraj , Labotka Richard , Liu Guohui , Hui Ai-Min , Venkatakrishnan Karthik
Published: April 2016

Background Ixazomib is the first oral, small molecule proteasome inhibitor to reach phase 3 trials. The current analysis characterized the exposure-safety and exposure-efficacy relationships of ixazomib in patients with relapsed/refractory multiple myeloma (MM) with a purpose of recommending an approach to ixazomib dosing for maintenance therapy. Methods Logistic regression was used to investigate relationships between ixazomib plasma exposure (area under the curve/day; derived from individual apparent clearance values from a published population pharmacokinetic analysis) and safety/efficacy outcomes (hematologic [grade ≥ 3 vs ≤ 2] or non-hematologic [grade ≥ 2 vs ≤ 1] adverse events [AEs], and clinical benefit [≥stable disease vs progressive disease]) using phase 1 data in relapsed/refractory MM (NCT00963820; N = 44). Results Significant relationships to ixazomib exposure were observed for five AEs (neutropenia, thrombocytopenia, rash, fatigue, and diarrhea) and clinical benefit (p < 0.05). Dose–response relationships indicated a favorable benefit/risk ratio at 3 mg and 4 mg weekly, which are below the maximum tolerated dose of 5.5 mg. At 3 mg, the model predicted that: 37 % of patients will achieve clinical benefit; incidence of grade ≥ 3 neutropenia and thrombocytopenia will be 10 % and 23 %, respectively; and incidence of grade ≥ 2 rash, fatigue, and diarrhea will be 8 %, 19 %, and 19 %, respectively. Conclusions Based on the findings, patients in the phase 3 maintenance trial will initiate ixazomib at a once-weekly dose of 3 mg, increasing to 4 mg if acceptable tolerability after 4 cycles, to provide maximum clinical benefit balanced with adequate tolerability.
Partial or non-union after triple arthrodesis in children: Does it really matter?
Authors: Wicks Eric D. , Morscher Melanie A. , Newton Meadow , Steiner Richard P. , Weiner Dennis S.
Published: April 2016

Purpose

Triple arthrodesis is a commonly performed salvage procedure to correct hindfoot deformity. Non-union is considered an undesirable radiographic outcome; however, the clinical ramifications of this are not as well defined. The purpose of this study was to determine the incidence of partial or complete radiographic non-union after triple arthrodesis in children and characterize the clinical consequences.

Methods

An IRB-approved retrospective review of triple arthrodesis surgeries in patients less than 16 years of age performed by a single surgeon (DSW) identified 159 cases meeting the inclusion criteria. Plain radiographs were reviewed for bony fusion (defined as over 80 % radiographic bony union of the subtalar, calcaneocuboid, and talonavicular bones) and charts for clinical outcomes (pain, return to activity, and subsequent hindfoot surgeries). Statistics were used to compare the fused and unfused cases, with p < 0.05 considered to be significant.

Results

Of the 159 cases included in the study, 9 % did not achieve at least 80 % plain film radiographic union. The fused and unfused groups had similar clinical outcomes. Only one patient required surgery for sequelae of symptoms arising from a pseudoarthrosis related to the triple arthrodesis. The fused and unfused groups were similar in terms of gender and pin removal time, but differed significantly in surgical age and underlying diagnosis.

Conclusions

This is one of the largest case series of pediatric triple arthrodesis surgery presented in the literature. This study demonstrated that good clinical outcomes can be achieved despite the lack of radiographic union after triple arthrodesis surgery in children.

Level of evidence

IV.
Teacher autonomy support reduces adolescent anxiety and depression: An 18‐month longitudinal study
Authors: Yu Chengfu , Li Xian , Wang Shujun , Zhang Wei
Published: April 2016

Grounded in stage–environment fit theory, this study adopts a longitudinal design to examine the contribution of autonomy support from teachers to reducing adolescent anxiety and depression. A total of 236 Chinese adolescents (57.38% females, Mage = 14.34) completed questionnaires on teacher autonomy support, basic psychological needs satisfaction, school engagement, anxiety, and depression in the fall and spring semesters of their 7th and 8th grade years. The results showed that teacher autonomy support in the fall of 7th grade boosted basic psychological needs satisfaction in the spring of 7th grade; this, in turn, increased school engagement in the fall of 8th grade, which subsequently decreased anxiety and depression in the spring of 8th grade. These findings demonstrated the significant effect of teacher autonomy support on reducing adolescent anxiety and depression; furthermore, it highlighted the mediating roles of basic psychological needs satisfaction and school engagement in this relationship.
Combination therapy induces unfolded protein response and cytoskeletal rearrangement leading to mitochondrial apoptosis in prostate cancer
Authors: Kumar Sandeep , Chaudhary Ajay K. , Kumar Rahul , O'Malley Jordan , Dubrovska Anna , Wang Xinjiang , Yadav Neelu , Goodrich David W. , Chandra Dhyan
Published: April 2016

Development of therapeutic resistance is responsible for most prostate cancer (PCa) related mortality. Resistance has been attributed to an acquired or selected cancer stem cell phenotype. Here we report the histone deacetylase inhibitor apicidin (APC) or ER stressor thapsigargin (TG) potentiate paclitaxel (TXL)‐induced apoptosis in PCa cells and limit accumulation of cancer stem cells. TXL‐induced responses were modulated in the presence of TG with increased accumulation of cells at G1‐phase, rearrangement of the cytoskeleton, and changes in cytokine release. Cytoskeletal rearrangement was associated with modulation of the cytoplasmic and mitochondrial unfolded protein response leading to mitochondrial dysfunction and release of proapoptotic proteins from mitochondria. TXL in combination with APC or TG enhanced caspase activation. Importantly, TXL in combination with TG induced caspase activation and apoptosis in X‐ray resistant LNCaP cells. Increased release of transforming growth factor‐beta (TGF‐β) was observed while phosphorylated β‐catenin level was suppressed with TXL combination treatments. This was accompanied by a decrease in the CD44+CD133+ cancer stem cell‐like population, suggesting treatment affects cancer stem cell properties. Taken together, combination treatment with TXL and either APC or TG induces efficient apoptosis in both proliferating and cancer stem cells, suggesting this therapeutic combination may overcome drug resistance and recurrence in PCa.
Structure of Gremlin-1 and analysis of its interaction with BMP-2
Authors: Kišonaitė Miglė , Wang Xuelu , Hyvönen Marko
Published: April 2016

Bone morphogenetic protein 2 (BMP-2) is a member of the transforming growth factor-β (TGF-β) signalling family and has a very broad biological role in development. Its signalling is regulated by many effectors: transmembrane proteins, membrane-attached proteins and soluble secreted antagonists such as Gremlin-1. Very little is known about the molecular mechanism by which Gremlin-1 and other DAN (differential screening-selected gene aberrative in neuroblastoma) family proteins inhibit BMP signalling. We analysed the interaction of Gremlin-1 with BMP-2 using a range of biophysical techniques, and used mutagenesis to map the binding site on BMP-2. We have also determined the crystal structure of Gremlin-1, revealing a similar conserved dimeric structure to that seen in other DAN family inhibitors. Measurements using biolayer interferometry (BLI) indicate that Gremlin-1 and BMP-2 can form larger complexes, beyond the expected 1:1 stoichiometry of dimers, forming oligomers that assemble in alternating fashion. These results suggest that inhibition of BMP-2 by Gremlin-1 occurs by a mechanism that is distinct from other known inhibitors such as Noggin and Chordin and we propose a novel model of BMP-2–Gremlin-1 interaction yet not seen among any BMP antagonists, and cannot rule out that several different oligomeric states could be found, depending on the concentration of the two proteins.
T-cell involvement in sex differences in blood pressure control
Authors: Crislip G. Ryan , Sullivan Jennifer C.
Published: April 2016

Hypertension affects one-third of adults in the Western world and is the most common independent risk factor for cardiovascular disease, and the leading cause of premature death globally. Despite available therapeutic options, approximately half of the hypertensive population taking medication does not achieve adequate blood pressure (BP) control leaving them at increased risk of chronic kidney disease, renal failure, stroke, congestive heart failure, myocardial infarction, aneurysm and peripheral artery disease. New therapeutic options need to be identified for the treatment of hypertension in order to increase the percentage of individuals with controlled BP. There is a growing basic science literature regarding the role of T-cells in the pathogenesis of hypertension and BP control; however, the majority of this literature has been performed exclusively in males despite the fact that both men and women develop hypertension. This is especially problematic since hypertension is well recognized as having distinct sex differences in the prevalence, absolute BP values and molecular mechanisms contributing to the pathophysiology of the disease. The purpose of this article is to review the available literature regarding sex differences in T-cells in hypertension followed by highlighting the potential pathways that may result in sex-specific effects on T-cell activation and differentiation.
Hormones and sex differences: changes in cardiac electrophysiology with pregnancy
Authors: Bett Glenna C.L.
Published: April 2016

Disruption of cardiac electrical activity resulting in palpitations and syncope is often an early symptom of pregnancy. Pregnancy is a time of dramatic and dynamic physiological and hormonal changes during which numerous demands are placed on the heart. These changes result in electrical remodelling which can be detected as changes in the electrocardiogram (ECG). This gestational remodelling is a very under-researched area. There are no systematic large studies powered to determine changes in the ECG from pre-pregnancy, through gestation, and into the postpartum period. The large variability between patients and the dynamic nature of pregnancy hampers interpretation of smaller studies, but some facts are consistent. Gestational cardiac hypertrophy and a physical shift of the heart contribute to changes in the ECG. There are also electrical changes such as an increased heart rate and lengthening of the QT interval. There is an increased susceptibility to arrhythmias during pregnancy and the postpartum period. Some changes in the ECG are clearly the result of changes in ion channel expression and behaviour, but little is known about the ionic basis for this electrical remodelling. Most information comes from animal models, and implicates changes in the delayed-rectifier channels. However, it is likely that there are additional roles for sodium channels as well as changes in calcium homoeostasis. The changes in the electrical profile of the heart during pregnancy and the postpartum period have clear implications for the safety of pregnant women, but the field remains relatively undeveloped.
Epochs in the depressor/pressor balance of the renin–angiotensin system
Authors: Colafella Katrina M. Mirabito , Hilliard Lucinda M. , Denton Kate M.
Published: April 2016

The renin–angiotensin system (RAS) plays a commanding role in the regulation of extracellular fluid homoeostasis. Tigerstadt and Bergman first identified the RAS more than two centuries ago. By the 1980s a voyage of research and discovery into the mechanisms and actions of this system led to the development of drugs that block the RAS, which have become the mainstay for the treatment of cardiovascular and renal disease. In the last 25 years new components of the RAS have come to light, including the angiotensin type 2 receptor (AT2R) and the angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1–7) [Ang(1–7)]/Mas receptor (MasR) axis. These have been shown to counter the classical actions of angiotensin II (AngII) at the predominant angiotensin type 1 receptor (AT1R). Our studies, and those of others, have demonstrated that targeting these depressor RAS pathways may be therapeutically beneficial. It is apparent that the evolution of both the pressor and depressor RAS pathways is distinct throughout life and that the depressor/pressor balance of the RAS vary between the sexes. These temporal patterns of expression suggest that therapies targeting the RAS could be optimized for discrete epochs in life.
Axial superresolution via multiangle TIRF microscopy with sequential imaging and photobleaching
Authors: Fu Yan , Winter Peter W. , Rojas Raul , Wang Victor , McAuliffe Matthew , Patterson George H.
Published: April 2016

Significance

Superresolution microscopy has made significant progress with molecule localization, stimulated emission depletion, and structured illumination techniques. Here we describe a simple method to achieve ∼20-nm axial resolution based on total internal reflection fluorescence (TIRF) microscopy. In this approach, serial fluorescent images at multiple depths within the normal ∼200-nm TIRF illumination zone are obtained by the serial imaging and photobleaching at multiple TIRF excitation angles. These images with ∼20-nm axial depth intervals are then simply stacked together to differentiate the relative distributions of multiple proteins in the axial direction. Moreover, images collected during the photobleaching step of the experiment can be analyzed using Bayesian analysis of fluorophore blinking and bleaching to generate superresolution images in the lateral direction for each depth.
Unraveling the dynamics and structure of functionalized self-assembled monolayers on gold using 2D IR spectroscopy and MD simulations
Authors: Yan Chang , Yuan Rongfeng , Pfalzgraff William C. , Nishida Jun , Wang Lu , Markland Thomas E. , Fayer Michael D.
Published: April 2016

Significance

Self-assembled monolayers (SAMs) are a form of nanotechnology that enables the functionalization of surfaces with single layers of chemically designed structures having tuned properties. In contrast to the characterization of time-average static structures, it is challenging to measure the dynamic behavior of SAMs on the timescales of molecular motions, i.e. picoseconds. Here we combine 2D IR spectroscopy and molecular dynamics (MD) simulations to investigate alkyl chain monolayers functionalized with a head group. The dynamics reported by the head group are induced by the alkyl chain motions. For example, it was determined that SAMs with higher alkyl chain gauche defect content have faster dynamics caused by more frequent chain conformational fluctuations.
Critical Assessment 17: Mechanisms of hydrogen induced cracking in pipeline steels
Authors: Findley K. O. , O'Brien M. K. , Nako H.
Published: April 2016

Hydrogen induced cracking (HIC) remains a prominent issue for oil and gas exploration in challenging environments. This assessment discusses HIC in light of hydrogen transport through pipeline steel microstructures and crack initiation and propagation processes. While there has been significant research in hydrogen permeation through steel alloys, additional understanding is necessary in microstructures specific to pipeline steels. Furthermore, a standard model for crack initiation and propagation processes needs to be established; a fracture mechanics based model, which has been used by some researchers, is presented in the present paper to predict crack propagation. Advanced characterisation techniques can help elucidate mechanisms of hydrogen induced crack growth. Ultimately, linking hydrogen transport and cracking processes during HIC will enable optimised alloy and microstructure design.
Spatial attention can be biased towards an expected dimension
Authors: Burnett Katherine E. , Close Alex C. , d'Avossa Giovanni , Sapir Ayelet
Published: April 2016

A commonly held view in both exogenous and endogenous orienting is that spatial attention is associated with enhanced processing of all stimuli at the attended location. However, we often search for a specific target at a particular location, so an observer should be able to jointly specify the target identity and expected location. Whether attention can bias dimension-specific processes at a particular location is not yet clear. We used a dual task to examine the effects of endogenous spatial cues on the accuracy of perceptual judgments of different dimensions. Participants responded to a motion target and a colour target, presented at the same or different locations. We manipulated a central cue to predict the location of the motion or colour target. While overall performance in the two tasks was comparable, cueing effects were larger for the target whose location was predicted by the cue, implying that when attending a particular location, processing of the likely dimension was preferentially enhanced. Additionally, an asymmetry between the motion and colour tasks was seen; motion was modulated by attention, and colour was not. We conclude that attention has some ability to select a dimension at a particular location, indicating integration of spatial and feature-based attention.
The coupling between spatial attention and other components of task-set: A task-switching investigation
Authors: Longman Cai S. , Lavric Aureliu , Monsell Stephen
Published: April 2016

Is spatial attention reconfigured independently of, or in tandem with, other task-set components when the task changes? We tracked the eyes of participants cued to perform one of three digit-classification tasks, each consistently associated with a distinct location. Previously we observed, on task switch trials, a substantial delay in orientation to the task-relevant location and tendency to fixate the location of the previously relevant task—“attentional inertia”. In the present experiments the cues specified (and instructions emphasized) the relevant location rather than the current task. In Experiment 1, with explicit spatial cues (arrows or spatial adverbs), the previously documented attentional handicaps all but disappeared, whilst the performance “switch cost” increased. Hence, attention can become decoupled from other aspects of task-set, but at a cost to the efficacy of task-set preparation. Experiment 2 used arbitrary single-letter cues with instructions and a training regime that encouraged participants to interpret the cue as indicating the relevant location rather than task. As in our previous experiments, and unlike in Experiment 1, we now observed clear switch-induced attentional delay and inertia, suggesting that the natural tendency is for spatial attention and task-set to be coupled and that only quasi-exogenous location cues decouple their reconfiguration.
Drug-induced adverse events prediction with the LINCS L1000 data
Authors: Wang Zichen , Clark Neil R. , Ma’ayan Avi
Published: April 2016

Motivation: Adverse drug reactions (ADRs) are a central consideration during drug development. Here we present a machine learning classifier to prioritize ADRs for approved drugs and pre-clinical small-molecule compounds by combining chemical structure (CS) and gene expression (GE) features. The GE data is from the Library of Integrated Network-based Cellular Signatures (LINCS) L1000 dataset that measured changes in GE before and after treatment of human cells with over 20 000 small-molecule compounds including most of the FDA-approved drugs. Using various benchmarking methods, we show that the integration of GE data with the CS of the drugs can significantly improve the predictability of ADRs. Moreover, transforming GE features to enrichment vectors of biological terms further improves the predictive capability of the classifiers. The most predictive biological-term features can assist in understanding the drug mechanisms of action. Finally, we applied the classifier to all  >20 000 small-molecules profiled, and developed a web portal for browsing and searching predictive small-molecule/ADR connections.

Availability and Implementation: The interface for the adverse event predictions for the  >20 000 LINCS compounds is available at http://maayanlab.net/SEP-L1000/.

Contact:  avi.maayan@mssm.edu

Supplementary information: Supplementary data are available at Bioinformatics online.
GenomeRunner web server: regulatory similarity and differences define the functional impact of SNP sets
Authors: Dozmorov Mikhail G. , Cara Lukas R. , Giles Cory B. , Wren Jonathan D.
Published: April 2016

Motivation: The growing amount of regulatory data from the ENCODE, Roadmap Epigenomics and other consortia provides a wealth of opportunities to investigate the functional impact of single nucleotide polymorphisms (SNPs). Yet, given the large number of regulatory datasets, researchers are posed with a challenge of how to efficiently utilize them to interpret the functional impact of SNP sets.

Results: We developed the GenomeRunner web server to automate systematic statistical analysis of SNP sets within a regulatory context. Besides defining the functional impact of SNP sets, GenomeRunner implements novel regulatory similarity/differential analyses, and cell type-specific regulatory enrichment analysis. Validated against literature- and disease ontology-based approaches, analysis of 39 disease/trait-associated SNP sets demonstrated that the functional impact of SNP sets corresponds to known disease relationships. We identified a group of autoimmune diseases with SNPs distinctly enriched in the enhancers of T helper cell subpopulations, and demonstrated relevant cell type-specificity of the functional impact of other SNP sets. In summary, we show how systematic analysis of genomic data within a regulatory context can help interpreting the functional impact of SNP sets.

Availability and Implementation: GenomeRunner web server is freely available at http://www.integrativegenomics.org/.

Contact:  mikhail.dozmorov@gmail.com

Supplementary information:  Supplementary data are available at Bioinformatics online.
Lung inflammation stalls Th17-cell migration en route to the central nervous system during the development of experimental autoimmune encephalomyelitis
Authors: Kanayama Masashi , Danzaki Keiko , He You-Wen , Shinohara Mari L.
Published: April 2016

Recruiting pathogenic T cells to the central nervous system (CNS) is a critical step during the development of experimental autoimmune encephalomyelitis (EAE). Here, we report that the absence of autophagy and microtubule-associated protein 1A/1B-light chain 3-associated phagocytosis significantly delayed the onset of EAE in Atg7 conditional knockout (Atg7 CKO) mice in myeloid cells. T-helper cell-cell priming appeared to be normal in the Atg7 CKO mice, but the mice showed significant accumulation of Th17 cells in the lung. The data suggested that the stalling of Th17 cells in the lung en route to the CNS caused the delay. The lung of Atg7 CKO mice, in which we previously demonstrated spontaneous mild inflammation, showed high expression of CCL20, a chemokine that attracts Th17 cells. We have also shown that LPS intranasal instillation delayed EAE onset, suggesting that pulmonary inflammation has an impact on EAE development. Based on our data, therapeutic immunomodulation targeted to the lung, rather than systemically, might be a possible future option to treat multiple sclerosis.
Compulsory Voting Can Increase Political Inequality: Evidence from Brazil
Authors: Cepaluni Gabriel , Hidalgo F. Daniel
Published: April 2016

One of the most robust findings on political institutions is that compulsory voting (CV) reduces the participation gap between poorer and wealthier voters. We present evidence that in Brazil, the largest country to use such a rule, CVincreasesinequality in turnout. We use individual-level data on 140 million Brazilian citizens and two age-based discontinuities to estimate the heterogeneous effects of CV by educational achievement, a strong proxy for socioeconomic status. Evidence from both thresholds shows that the causal effect of CV on turnout among the more educated is at least twice the size of the effect among those with less education. To explain this result, which is the opposite of what is predicted by the existing literature, we argue that nonmonetary penalties for abstention primarily affect middle- and upper-class voters and thus increase their turnout disproportionately. Survey evidence from a national sample provides evidence for the mechanism. Our results show that studies of CV should consider nonmonetary sanctions, as their effects can reverse standard predictions.
Choice-induced biases in perception
Authors: Luu Long , Stocker Alan A
Published: April 2016

Illusions provide a great opportunity to study how perception is affected by both the observer's expectations and the way sensory information is represented1,2,3,4,5,6. Recently, Jazayeri and Movshon7reported a new and interesting perceptual illusion, demonstrating that the perceived motion direction of a dynamic random dot stimulus is systematically biased when preceded by a motion discrimination judgment. The authors hypothesized that these biases emerge because the brain predominantly relies on those neurons that are most informative for solving the discrimination task8, but then is using the same neural weighting profile for generating the percept. In other words, they argue that these biases are “mistakes” of the brain, resulting from using inappropriate neural read-out weights. While we were able to replicate the illusion for a different visual stimulus (orientation), our new psychophysical data suggest that the above interpretation is likely incorrect: Biases are not caused by a read-out profile optimized for solving the discrimination task but rather by the specific choices subjects make in the discrimination task on any given trial. We formulate this idea as a conditioned Bayesian observer model and show that it can explain the new as well as the original psychophysical data. In this framework, the biases are not caused by mistake but rather by the brain's attempt to remain ‘self-consistent’ in its inference process. Our model establishes a direct connection between the current perceptual illusion and the well-known phenomena of cognitive consistency and dissonance9,10.