bluuebunny/crossref_metadata_2025 huggingface dataset:
A global climatology of monsoon low‐pressure systems
Authors: Hurley John V. , Boos William R.
Published: September 2014

The first global climatology of monsoon low‐pressure systems is presented here, based on the ERA‐Interim reanalysis. Low‐pressure systems are classified into three intensity categories and particular focus is given to systems in the category corresponding to a traditional definition of monsoon depressions. Vortex tracks are identified using an automated algorithm applied to the distributions of 850 hPa relative vorticity, sea‐level pressure and surface wind speed for 1979–2012. Roughly two to three times as many monsoon low‐pressure systems form in the Northern Hemisphere as in the Southern Hemisphere during local summer. The frequency of genesis typically peaks in local summer, but low‐pressure systems form throughout the year in every monsoon region. Interannual variability is weak, with standard deviations of summer counts typically being below 10% of the long‐term summer mean. Regional composites reveal that monsoon depressions in India, the western Pacific and northern Australia share a common structure, consisting of a warm‐over‐cold core and a top‐heavy column of potential vorticity that extends from the surface to the upper troposphere. A separate class of monsoon low‐pressure systems develops over dry regions of West Africa and western Australia, with a shallow composite structure having a warm core in the lower troposphere and cyclonic potential vorticity confined to a thin near‐surface layer. Low‐pressure systems in nearly all monsoon regions are estimated to account for a large fraction, from about 40% to more than 80%, of summer precipitation on the poleward edge of the climatological mean precipitation maxima.
The effects of horizontal advection on the urban heat island in Birmingham and the West Midlands, United Kingdom during a heatwave
Authors: Heaviside C. , Cai X.‐M. , Vardoulakis S.
Published: September 2014

Birmingham is the second most populous city in the United Kingdom and observations indicate that it has a pronounced urban heat island (UHI), i.e. higher ambient temperatures in the city centre compared with surrounding suburban and rural areas, particularly at night. The effects of UHIs are often amplified during anticyclonic summer weather conditions, which can cause or exacerbate heatwaves. Enhanced temperatures in highly populated regions can mean that significant numbers of people are at risk from heat‐related illness during hot weather. Climate change projections often do not include the effects of the UHI, which can mean that assessments of heat‐related health effects using these projections underestimate the actual magnitude of future health impacts. We present numerical simulations of the UHI in Birmingham and the West Midlands Metropolitan region during the heatwave of August 2003 using the high‐resolution, regional meteorological Weather Research and Forecasting (WRF) model, with an urban canopy scheme. We evaluated the model using local air‐temperature observations, and found good model performance in capturing the temporal and spatial signature of the UHI. We performed a sensitivity test, replacing urban land categories with rural ones, and found that the difference in temperature between the two model runs throughout the heatwave period (2–11 August 2003) was around 3°C on average, and reached a maximum of 7°C. Finally, we present a novel generic methodology to enable the examination of the extent of horizontal advection of warm air downwind of the conurbation area. We found that during the heatwave, temperatures downwind of Birmingham were up to 2.5°C warmer than those upwind. This methodology has the potential for improvements to, or parametrizations for, diagnostic models that do not explicitly include dynamics and where local conditions are driven largely by land‐surface type.
Adiabatic westward drift of Indian monsoon depressions
Authors: Boos W. R. , Hurley J. V. , Murthy V. S.
Published: September 2014

A large fraction of the rain received by continental India is produced by cyclonic vortices with outer radii of about 1000 km that are contained within the larger scale South Asian monsoon flow. The more intense occurrences of these vortices are called monsoon depressions; these consist of bottom‐heavy columns of relative vorticity that propagate to the northwest in time‐mean low‐level eastward flow. Previous studies have argued that this apparent upstream propagation is caused by dynamical lifting west of the vortex centre, with the resulting ascent producing vortex stretching that shifts the vortex to the west. Here, analysis of over 100 Indian monsoon depressions is used to show that low‐level vortex stretching has a spatial structure inconsistent with the observed propagation and is balanced by other terms in the low‐level vorticity budget. Instead, monsoon depressions are shown to consist of potential vorticity maxima that have peak amplitude in the middle troposphere and propagate westward by nonlinear, horizontal adiabatic advection (i.e. beta drift). The precipitating ascent in monsoon depressions makes a more minor contribution to the total storm motion and primarily acts to maintain the upright structure of the vortex. These results suggest a new view of Indian monsoon depressions as potential vorticity columns that propagate primarily by adiabatic dynamics.
Reptin Regulates Pluripotency of Embryonic Stem Cells and Somatic Cell Reprogramming Through Oct4-Dependent Mechanism
Authors: Do Eun kyoung , Cheon Hyo Cheon , Jang Il Ho , Choi Eun Jung , Heo Soon Chul , Kang Kyung Taek , Bae Kwang Hee , Cho Yee Sook , Seo Jeong Kon , Yoon Jong Hyuk , Lee Taehoon G. , Kim Jae Ho
Published: September 2014

Oct4 has been implicated in regulation of pluripotency in embryonic stem cells (ESCs) and reprogramming of somatic cells into induced pluripotent stem cells. However, the molecular mechanisms involved in Oct4-dependent regulation of pluripotency and reprogramming have not been clear. To gain insight into the mechanism of regulation of Oct4-mediated self-renewal of ESCs and reprogramming of somatic cells, we attempted to identify Oct4-binding proteins using affinity purification and mass spectrometry. We identified Reptin, a key component of ATP-dependent chromatin remodeling complexes, as an Oct4-binding protein. Depletion of endogenous Reptin using lentiviral short hairpin RNA (shRNA) led to a decrease in the number and size of alkaline phosphatase-positive colonies of mouse ESCs. In addition, shRNA-mediated silencing of Reptin resulted in decreased expression of pluripotency-specific marker genes, including Oct4, Sox2, Nanog, and SSEA-1. Results of the Oct4 reporter assay showed synergism between Oct4 and Reptin, and depletion of endogenous Reptin abolished Oct4 transcriptional activity. Results of a chromatin immunoprecipitation assay showed the overlapping interaction of Reptin and Oct4 to CR4 in the Oct4 enhancer in ESCs. Knockdown of Reptin using shRNA suppressed the reprogramming of mouse embryonic fibroblasts to induced pluripotent stem cells, whereas overexpression of Reptin resulted in enhanced efficiency of induced pluripotent stem cell generation. These results strongly suggest that Reptin plays a key role in maintaining the pluripotency of ESCs and in establishing the pluripotency during reprogramming of somatic cells by regulation of Oct4-mediated gene regulation. Stem Cells  2014;32:3126–3136
The Cyclin-Dependent Kinase Inhibitor p27kip1 Regulates Radial Stem Cell Quiescence and Neurogenesis in the Adult Hippocampus
Authors: Andreu Zoraida , Khan Muhammad Amir , González-Gómez Pilar , Negueruela Santiago , Hortigüela Rafael , San Emeterio Juana , Ferrón Sacri R. , Martínez Gloria , Vidal Anxo , Fariñas Isabel , Lie Dieter Chichung , Mira Helena
Published: September 2014

Members of the cyclin-dependent kinase (CDK)-inhibitory protein (CIP)/kinase-inhibitory protein (KIP) family of cyclin-dependent kinase inhibitors regulate proliferation and cell cycle exit of mammalian cells. In the adult brain, the CIP/KIP protein p27kip1 has been related to the regulation of intermediate progenitor cells located in neurogenic niches. Here, we uncover a novel function of p27kip1 in the adult hippocampus as a dual regulator of stem cell quiescence and of cell-cycle exit of immature neurons. In vivo, p27kip1 is detected in radial stem cells expressing SOX2 and in newborn neurons of the dentate gyrus. In vitro, the Cdkn1b gene encoding p27kip1 is transcriptionally upregulated by quiescence signals such as BMP4. The nuclear accumulation of p27kip1 protein in adult hippocampal stem cells encompasses the BMP4-induced quiescent state and its overexpression is able to block proliferation. p27kip1 is also expressed in immature neurons upon differentiation of adult hippocampal stem cell cultures. Loss of p27kip1 leads to an increase in proliferation and neurogenesis in the adult dentate gyrus, which results from both a decrease in the percentage of radial stem cells that are quiescent and a delay in cell cycle exit of immature neurons. Analysis of animals carrying a disruption in the cyclin-CDK interaction domain of p27kip1 indicates that the CDK inhibitory function of the protein is necessary to control the activity of radial stem cells. Thus, we report that p27kip1 acts as a central player of the molecular program that keeps adult hippocampal stem cells out of the cell cycle. Stem Cells  2015;33:219–229
Combination of Systemic Chemotherapy with Local Stem Cell Delivered S-TRAIL in Resected Brain Tumors
Authors: Redjal Navid , Zhu Yanni , Shah Khalid
Published: September 2014

Despite advances in standard therapies, the survival of glioblastoma multiforme (GBM) patients has not improved. Limitations to successful translation of new therapies include poor delivery of systemic therapies and use of simplified preclinical models which fail to reflect the clinical complexity of GBMs. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis specifically in tumor cells and we have tested its efficacy by on-site delivery via engineered stem cells (SC) in mouse models of GBM that mimic the clinical scenario of tumor aggressiveness and resection. However, about half of tumor lines are resistant to TRAIL and overcoming TRAIL-resistance in GBM by combining therapeutic agents that are currently in clinical trials with SC-TRAIL and understanding the molecular dynamics of these combination therapies are critical to the broad use of TRAIL as a therapeutic agent in clinics. In this study, we screened clinically relevant chemotherapeutic agents for their ability to sensitize resistant GBM cell lines to TRAIL induced apoptosis. We show that low dose cisplatin increases surface receptor expression of death receptor 4/5 post G2 cycle arrest and sensitizes GBM cells to TRAIL induced apoptosis. In vivo, using an intracranial resection model of resistant primary human-derived GBM and real-time optical imaging, we show that a low dose of cisplatin in combination with synthetic extracellular matrix encapsulated SC-TRAIL significantly decreases tumor regrowth and increases survival in mice bearing GBM. This study has the potential to help expedite effective translation of local stem cell-based delivery of TRAIL into the clinical setting to target a broad spectrum of GBMs. Stem Cells  2015;33:101–110
The Kynurenine Pathway of Tryptophan Degradation is Activated During Osteoblastogenesis
Authors: Vidal Christopher , Li Wei , Santner-Nanan Brigitte , Lim Chai K. , Guillemin Gilles J. , Ball Helen J. , Hunt Nicholas H. , Nanan Ralph , Duque Gustavo
Published: September 2014

The mechanisms involved in the anabolic effect of interferon gamma (IFNγ) on bone have not been carefully examined. Using microarray expression analysis, we found that IFNγ upregulates a set of genes associated with a tryptophan degradation pathway, known as the kynurenine pathway, in osteogenic differentiating human mesenchymal stem cells (hMSC). We, therefore, hypothesized that activation of the kynurenine pathway plays a role in osteoblastogenesis even in the absence of IFNγ. Initially, we observed a strong increase in tryptophan degradation during osteoblastogenesis with and without IFNγ in the media. We next blocked indoleamine 2,3-dioxygenase-1 (IDO1), the most important enzyme in the kynurenine pathway, using a siRNA and pharmacological approach and observed a strong inhibition of osteoblastogenesis with a concomitant decrease in osteogenic factors. We next examined the bone phenotype of Ido1 knockout (Ido1−/−) mice. Compared to their wild-type littermates, Ido1−/− mice exhibited osteopenia associated with low osteoblast and high osteoclast numbers. Finally, we tested whether the end products of the kynurenine pathway have an osteogenic effect on hMSC. We identified that picolinic acid had a strong and dose-dependent osteogenic effect in vitro. In summary, we demonstrate that the activation of the kynurenine pathway plays an important role during the commitment of hMSC into the osteoblast lineage in vitro, and that this process can be accelerated by exogenous addition of IFNγ. In addition, we found that mice lacking IDO1 activity are osteopenic. These data therefore support a new role for the kynurenine pathway and picolinic acid as essential regulators of osteoblastogenesis and as potential new targets of bone-forming cells in vivo. Stem Cells  2015;33:111–121
Lipid Droplets: A New Player in Colorectal Cancer Stem Cells Unveiled by Spectroscopic Imaging
Authors: Tirinato Luca , Liberale Carlo , Di Franco Simone , Candeloro Patrizio , Benfante Antonina , La Rocca Rosanna , Potze Lisette , Marotta Roberto , Ruffilli Roberta , Rajamanickam Vijayakumar P. , Malerba Mario , De Angelis Francesco , Falqui Andrea , Carbone Ennio , Todaro Matilde , Medema Jan Paul , Stassi Giorgio , Di Fabrizio Enzo
Published: September 2014

The cancer stem cell (CSC) model is describing tumors as a hierarchical organized system and CSCs are suggested to be responsible for cancer recurrence after therapy. The identification of specific markers of CSCs is therefore of paramount importance. Here, we show that high levels of lipid droplets (LDs) are a distinctive mark of CSCs in colorectal (CR) cancer. This increased lipid content was clearly revealed by label-free Raman spectroscopy and it directly correlates with well-accepted CR-CSC markers as CD133 and Wnt pathway activity. By xenotransplantation experiments, we have finally demonstrated that CR-CSCs overexpressing LDs retain most tumorigenic potential. A relevant conceptual advance in this work is the demonstration that a cellular organelle, the LD, is a signature of CSCs, in addition to molecular markers. A further functional characterization of LDs could lead soon to design new target therapies against CR-CSCs. Stem Cells  2015;33:35–44
Glucose Transporter 1-Positive Endothelial Cells in Infantile Hemangioma Exhibit Features of Facultative Stem Cells
Authors: Huang Lan , Nakayama Hironao , Klagsbrun Michael , Mulliken John B. , Bischoff Joyce
Published: September 2014

Endothelial glucose transporter 1 (GLUT1) is a definitive and diagnostic marker for infantile hemangioma (IH), a vascular tumor of infancy. To date, GLUT1-positive endothelial cells in IH have not been quantified nor directly isolated and studied. We isolated GLUT1-positive and GLUT1-negative endothelial cells from IH specimens and characterized their proliferation, differentiation, and response to propranolol, a first-line therapy for IH, and to rapamycin, an mTOR pathway inhibitor used to treat an increasingly wide array of proliferative disorders. Although freshly isolated GLUT1-positive cells, selected using anti-GLUT1 magnetic beads, expressed endothelial markers CD31, VE-Cadherin, and vascular endothelial growth factor receptor 2, they converted to a mesenchymal phenotype after 3 weeks in culture. In contrast, GLUT1-negative endothelial cells exhibited a stable endothelial phenotype in vitro. GLUT1-selected cells were clonogenic when plated as single cells and could be induced to redifferentiate into endothelial cells, or into pericytes/smooth muscle cells or into adipocytes, indicating a stem cell-like phenotype. These data demonstrate that, although they appear and function in the tumor as bona fide endothelial cells, the GLUT1-positive endothelial cells display properties of facultative stem cells. Pretreatment with rapamycin for 4 days significantly slowed proliferation of GLUT1-selected cells, whereas propranolol pretreatment had no effect. These results reveal for the first time the facultative nature of GLUT1-positive endothelial cells in IH. Stem Cells  2015;33:133–145
Focal Adhesion Kinase and Wnt Signaling Regulate Human Ductal Carcinoma In Situ Stem Cell Activity and Response to Radiotherapy
Authors: Williams Kathryn E. , Bundred Nigel J. , Landberg Göran , Clarke Robert B. , Farnie Gillian
Published: September 2014

Cancer stem cells (CSCs) can avoid or efficiently repair DNA damage from radio and chemotherapy, which suggests they play a role in disease recurrence. Twenty percentage of patients treated with surgery and radiotherapy for ductal carcinoma in situ (DCIS) of the breast recur and our previous data show that high grade DCIS have increased numbers of CSCs. Here, we investigate the role of focal adhesion kinase (FAK) and Wnt pathways in DCIS stem cells and their capacity to survive irradiation. Using DCIS cell lines and patient samples, we demonstrate that CSC-enriched populations are relatively radioresistant and possess high FAK activity. Immunohistochemical studies of active FAK in DCIS tissue show high expression was associated with a shorter median time to recurrence. Treatment with a FAK inhibitor or FAK siRNA in nonadherent and three-dimensional matrigel culture reduced mammosphere formation, and potentiated the effect of 2 Gy irradiation. Moreover, inhibition of FAK in vitro and in vivo decreased self-renewal capacity, levels of Wnt3a and B-Catenin revealing a novel FAK-Wnt axis regulating DCIS stem cell activity. Overall, these data establish that the FAK-Wnt axis is a promising target to eradicate self-renewal capacity and progression of human breast cancers. Stem Cells  2015;33:327–341
Methodological Prospects with the Use of Geographic Information Systems and Spatial Statistics for the Evaluation of Alcohol Policy
Authors: Curtin Kevin , Pawloski Lisa
Published: September 2014

There has been increasing recognition that there is a fundamental spatial component to most social phenomena, including health‐related behaviors and outcomes. Health geographics has begun to develop as a significant sub‐discipline within geography, and is strongly influenced by both spatial statistics and medical science. The goal of this field is to increase understanding of the spatial processes underlying health patterns, and thereby contribute to policies for encouraging healthy behavior, and mitigating both individual and public health risks. Unfortunately, the potential contributions to alcohol policy have yet to be comprehensively integrated into health geographics. This article presents a review of potential methodological contributions to alcohol policy by demonstrating the use of geographic information systems techniques and spatial statistics on a dataset comprised of alcohol‐related arrest information. A wide range of outcomes are illustrated, from descriptive spatial statistics of alcohol‐related behavior, to correlative analyses between sources of alcohol and alcohol arrests, and including inferential analyses regarding factors influencing alcohol‐related outcomes. All of these are accompanied by suggestions regarding how policymakers can use the results in developing new policy responses or refining existing ones. Suggestions for the future directions of spatially informed alcohol policy are provided.
Measuring the Strength of State‐Level Alcohol Control Policies
Authors: Erickson Darin J. , Lenk Kathleen M. , Toomey Traci L. , Nelson Toben F. , Jones‐Webb Rhonda , Mosher James F.
Published: September 2014

We describe a multi‐step method of coding the strength of 18 alcohol policies included in the Alcohol Policy Information System for each of the 50 states. After thoroughly reviewing each policy area, we chose components that were most important in categorizing the strength or restrictiveness of the policy using the following criteria: overall reach, enforceability, and implementation. We determined a unique coding scheme for each policy area. The total number of categories per policy area ranged from two to six, with categories numbered in an ordered sequence from least to most restrictive. We provide three examples of our coding schemes: Keg Registration, Underage Possession, and Sunday Sales. We also rank the states on their alcohol policy sum score. This study demonstrates how alcohol policies can be measured quantitatively, an important step for assessing the effects of alcohol policies on various outcomes.
Implementing and Sustaining Effective Alcohol‐Related Policies at the Local Level: Evidence, Challenges, and Next Steps
Authors: Giesbrecht Norman , Bosma Linda M. , Juras Jennifer , Quadri Maria
Published: September 2014

Alcohol‐related problems are experienced most directly at the local level. There have been significant strides in evaluating locally based alcohol policies and prevention strategies. This article draws from this existing body of research to answer three questions: What is known about effective local interventions and policies? What are the main challenges facing local action on alcohol and how can those challenges be addressed? How can local action on alcohol be sustained? This article reviews evaluated local alcohol interventions and policies, focusing on several countries where these initiatives have been evaluated: for example, Australia, Canada, Finland, New Zealand, Norway, Sweden, and the United States. The positive outcomes associated with community‐based initiatives are summarized and features of successful local action are identified. Although current research finds a number of positive outcomes of local alcohol interventions and policies, a number of challenges of this work remain; these challenges include providing adequate training, resources, and tools for local action; building local resource streams and coalitions to sustain expertise; sustaining long‐term commitment to monitor and evaluate the effects of policies; and addressing the vested interests of community stakeholders in alcohol policy efforts. Lessons learned and recommendations for future community‐based alcohol prevention initiatives are drawn from the findings and challenges of current work.
Predicting patterns of intentional introduction of non‐native largemouth bass into farm ponds in northeastern Japan
Authors: Tsunoda Hiroshi , Mitsuo Yoshito , Enari Hiroto
Published: September 2014

Non‐native species are difficult to eradicate or control once established. Thus, the prevention of invasions is a high priority for conserving native ecosystems. Our objective was to determine the factors that influence illegal introductions of non‐native largemouth bass (Micropterus salmoides) and to develop a model that could be used to predict the pattern of future illegal introduction by anglers. We used generalized linear modeling (GLM) to evaluate the relationship between landscape and environmental factors and the presence of bass in farm ponds. Our results suggest that the occurrence of bass was primarily associated with pond size, distance of ponds from the urban center, and the proportion of the pond shoreline covered with a concrete revetment. We conclude that introductions occurred in ponds that were: easier to locate on a map, closer to anglers’ residential areas, and more easily accessible to the pond shore. Last, we suggest our predictive model could be used for preventive measures, such as identifying other ponds most at risk of future illegal introduction of non‐native bass.
Fabrication and tribological properties of superhydrophobic nickel films with positive and negative biomimetic microtextures
Authors: Wang Ying , Yang Jing , Guo Xiaobao , Zhang Qiang , Wang Jingyu , Ding Jianning , Yuan Ningyi
Published: September 2014

Nickel (Ni) films with positive and negative textured surfaces of lotus and rice leaf patterns were fabricated through an inexpensive and effective method. The as-prepared Ni films were superhydrophobic and exhibited excellent tribological properties after chemical treatment. Experimental results indicated that the water contact angles (WCAs) on the surfaces of biomimetic textured Ni films (approximately 120°) were far greater than those on smooth films (65°). The biomimetic textured surfaces became superhydrophobic (WCA of approximately 150°) after perfluoropolyether (PFPE) treatment, which could be due to the combined effects of the special texture and the PFPE. The as-prepared biomimetic-textured Ni films modified with PFPE were improved with a low friction coefficient and excellent antiwear properties, which were due to the combination of the effective lubrication of PFPE and the special textures that served as a good lubricant and a debris reservoir. Moreover, the antiwear properties of the as-prepared Ni films with negative biomimetic microtextures modified with PFPE were much better than those of films with positive biomimetic microtextures modified with PFPE.
Current therapy of granulomatosis with polyangiitis and microscopic polyangiitis: the role of rituximab
Authors: Geetha Duvuru , Kallenberg Cees , Stone John H. , Salama Alan D. , Appel Gerald B. , Duna George , Brunetta Paul , Jayne David
Published: September 2014

Granulomatosis with polyangiitis and microscopic polyangiitis are anti-neutrophil cytoplasmic antibody-associated vasculitides (AAVs) that are prone to cycles of remission and relapse. The introduction of cytotoxic therapy has changed the prognosis for these diseases from typically fatal to manageable chronic illnesses with a relapsing course. Despite improvements in outcomes, recurrence of disease and drug-related toxicity continue to produce significant morbidity and mortality. Better understanding of the pathogenesis of AAV and the mechanism of action of cyclophosphamide has led to investigation of therapies that target B cells. Two randomized controlled trials have shown that rituximab is not inferior to cyclophosphamide for induction of remission in severe AAV, with no significant difference in the incidence of overall adverse events in rituximab- versus cyclophosphamide-treated patients. Data from ongoing clinical trials will determine the role of rituximab in the maintenance of remission.
A decade’s investigation of the stability of erodible stream beds
Authors: Colombini Marco
Published: September 2014

This contribution is a remake of the one published under the same title by Reynolds (Nord. Hydrol., vol. 7, 1976, pp. 161–183). As in that paper, attention is given to the latest developments in the field of river morphodynamics and, in particular, on the formation of bed patterns. Stimulated by the work by Kidanemariam and Uhlmann (J. Fluid Mech., vol. 750, 2014, R2) the opportunity is taken to examine the most recent developments in terms of sediment transport models.
Numerical investigation of the development of three-dimensional wavepackets in a sharp cone boundary layer at Mach 6
Authors: Sivasubramanian Jayahar , Fasel Hermann F.
Published: September 2014

Direct numerical simulations were performed to investigate wavepackets in a sharp cone boundary layer at Mach 6. In order to understand the natural transition process in hypersonic cone boundary layers, the flow was forced by a short-duration (localized) pulse. The pulse disturbance developed into a three-dimensional wavepacket, which consisted of a wide range of disturbance frequencies and wavenumbers. First, the linear development of the wavepacket was studied by forcing the flow with a low-amplitude pulse (0.001 % of the free-stream velocity). The dominant waves within the resulting wavepacket were identified as the second-mode axisymmetric disturbance waves. In addition, weaker first-mode oblique disturbance waves were also observed on the lateral sides of the wavepacket. In order to investigate the nonlinear transition regime, large-amplitude pulse disturbances (0.5 % of the free-stream velocity) were introduced. The response of the flow to the large-amplitude pulse disturbances indicated the presence of a fundamental resonance mechanism. Lower secondary peaks in the disturbance wave spectrum were identified at approximately half the frequency of the high-amplitude frequency band, suggesting the possibility of a subharmonic resonance mechanism. However, the spectrum also indicated that the fundamental resonance was much stronger than the subharmonic resonance. A secondary stability investigation using controlled disturbances confirmed that fundamental resonance is indeed a dominant mechanism compared to subharmonic resonance. Furthermore, strong peaks in the disturbance wave spectrum were also observed for low-azimuthal-wavenumber second-mode oblique waves, hinting at a possible oblique breakdown mechanism. Thus, the wavepacket simulations indicate that the second-mode fundamental resonance and oblique breakdown mechanisms are the strongest for the investigated flow. Hence, both mechanisms are likely to be relevant in the natural transition process for a cone boundary layer at Mach 6.
Multidimensional homophily in friendship networks
Authors: BLOCK PER , GRUND THOMAS
Published: September 2014

Homophily—the tendency for individuals to associate with similar others—is one of the most persistent findings in social network analysis. Its importance is established along the lines of a multitude of sociologically relevant dimensions, e.g. sex, ethnicity and social class. Existing research, however, mostly focuses on one dimension at a time. But people are inherently multidimensional, have many attributes and are members of multiple groups. In this article, we explore such multidimensionality further in the context of network dynamics. Are friendship ties increasingly likely to emerge and persist when individuals have an increasing number of attributes in common? We analyze eleven friendship networks of adolescents, draw on stochastic actor-oriented network models and focus on the interaction of established homophily effects. Our results indicate that main effects for homophily on various dimensions are positive. At the same time, the interaction of these homophily effects is negative. There seems to be a diminishing effect for having more than one attribute in common. We conclude that studies of homophily and friendship formation need to address such multidimensionality further.
Associative learning for host-induced fruit volatiles in Psyttalia concolor (Hymenoptera: Braconidae), a koinobiont parasitoid of tephritid flies
Authors: Canale A. , Geri S. , Benelli G.
Published: September 2014

Parasitic wasps are fascinating organisms that rely on a wide range of communication channels to locate their hosts. Associative learning for foraging kairomones has been demonstrated for various parasitic wasps, but little is known for parasitoids of Tephritidae flies. Psyttalia concolor (Hymenoptera: Braconidae) is a koinobiont parasitoid able to attack at least 14 tephritid pests. Females are innately attracted by some host-induced plant volatiles (HIPVs), whereas others of the same bouquet are unattractive. We hypothesize that females may detect unattractive HIPVs in association with key resources, such as food and hosts, learning to respond favourably to these cues in consecutive experiences. We evaluated associative learning for HIPVs in P. concolor females, testing if they are able to associate a food reward with the presence of different dosages of three HIPVs, thus developing a preference for an odour innately unattractive. Results demonstrated that P. concolor responded favourably to the learned cue in consecutive experiences. For all tested HIPVs (nonanoic acid, decanoic acid and geranyl acetone), regardless of dosage, trained females preferred the reward-associated odour, whereas naïve did not. Both HIPV-trained and naïve females did not show consistent differences in latencies when choosing HIPVs over blank. HIPV-trained and naïve wasps did not spend more time on HIPVs over blank. Odour learning is of adaptive importance for this generalist parasitoid, since it enhances host location efficiency by reducing the time wasted on the decision of where to search for hosts. From an applied perspective, these HIPVs could be used to train mass-reared P. concolor in pre-release, to potentially improve its efficacy in the field.
Histopathological and audiological effects of mechanical trauma associated with the placement of an intracochlear electrode, and the benefit of corticosteroid infusion: prospective animal study
Authors: Malkoc G , Dalgic A , Koc M , Kandogan T , Korkmaz S , Ceylan M E , Inan S , Olgun L
Published: September 2014

Objective:

This study aimed to present the histopathological and audiological effects of mechanical trauma associated with the placement of a model electrode in the scala tympani in rats, and the effects of continuous topical corticosteroid application.

Method:

The study comprised three groups of rats. The round window membrane was perforated in all three groups and a model electrode was inserted in the round window. Group one received no further treatments. Groups two and three also had an intrathecal microcatheter compatible with a mini-osmotic pump inserted; in group two this was used to release normal saline and in group three the pump released 400 µg/ml dexamethasone.

Results:

Dexamethasone infusion given after implantation of the intracochlear model electrode was more effective for preventing hearing loss than the administration of just one dose of dexamethasone.

Conclusion:

The findings suggest that continuous dexamethasone infusion is beneficial for preventing the loss of hair cells and neurons associated with early and late periods of intracochlear electrode trauma.
Bone cement: how effective is it at restoring hearing in isolated incudostapedial erosion?
Authors: Watson G J , Narayan S
Published: September 2014

Objective:

To determine the effectiveness of biocements in rebridging isolated incudostapedial erosion.

Methods:

A review of the use of biocements for isolated incudostapedial joint erosion was performed on publications from 1998 to 2012 available from Medline, Embase and Pubmed. Inclusion criteria were papers published in English, case series or comparative studies with more than 10 patients, isolated incudostapedial erosion through chronic ear disease, minimal air-bone gap less than 20 dB (or air-bone gap less than 10 dB) and follow up for at least one year.

Results:

In 108 patients, rebridging ossiculoplasty was performed using hydroxyapatite cement. Closure of air-bone gaps less than 20 dB and less than 10 dB was achieved in 80–94.4 per cent and 29–75 per cent, respectively. Glass ionomer cement was used in 318 patients. Closure of air-bone gaps less than 20 dB and less than 10 dB was achieved in 74–94 per cent and 40–76 per cent, respectively.

Conclusion:

Biocements can be successfully used to close isolated incudostapedial erosions. Larger comparative prospective studies documenting the length of eroded incus and types of reformation of the incudostapedial joint, with standardised reporting, are needed in the future.
Guy of Saint-Denis on the tones: thinking about chant for Saint-Denis c.1300
Authors: MEWS CONSTANT J. , CROSSLEY JOHN N. , WILLIAMS CAROL
Published: September 2014

This article examines the thinking of Guy of Saint-Denis about plainchant tones as formulated in his Tractatus de Tonis (c.1300), preserved as the final item in an anthology of texts that he prepared (British Library, MS Harley 281). It examines his attitude to each of the major theorists singled out in this anthology. It argues that Guy's approach to chant combines the practically oriented writings of Guido of Arezzo with the Aristotelian perspective formulated by Johannes de Grocheio, but takes that perspective a step further by reflecting on the ways different types of chant impact on the emotions. Guy was also much influenced by Peter of Auvergne, a philosopher in the Arts Faculty at Paris committed to developing the teaching of Thomas Aquinas. Careful corrections to the Tractatus in Harley 281 reflect this ongoing concern to refine his thinking, possibly stimulated by Jerome of Moravia. His core conviction is that chant modes each have an affective attribute, and need to be chosen according to the subject matter of the text being sung. Guy criticised the practice of choosing modes sequentially in liturgical offices composed by those he calls ‘moderns’. Guy argues his case by drawing on examples of chant from Saint-Denis. A case can be made, on palaeographic grounds, for identifying him with Guy of Châtres, abbot of Saint-Denis (1326–42) and author of a Sanctilogium that updates the traditional monastic martyrology by reference to more recent Dominican collections of saints' lives in order to make them more accessible for liturgical use.
Nation-building Modernism and European post-war debates: Glikson's ‘Integral Habitational Unit’ and Team 10 discourse
Authors: Kallus Rachel
Published: September 2014

The September 1965 meeting of Team 10 in Berlin was another occasion on which the ‘family’ gathered to present and discuss projects and ideas. Like other Team 10 meetings, issues of modernisation, inhabitation, post-war reconstruction, the welfare state, consumer society and the role of the architect were subjects of heated debate. After the famous 1959 meeting in Otterlo at which Team 10 emerged out of CIAM, the core group members were still trying to determine the character and size of their group, which would enable them to reach some kind of unity while maintaining a diversified outlook. The list of 30 invitees included familiar names alongside a few newcomers, among them the Israeli, German-born planner-architect Artur Glikson, who had been invited to join the meeting by Aldo van Eyck. The gathering was to be informal but, unlike invitations to previous meetings, this one, sent by Shadrach Woods, did not propose any specific theme. The meeting was motivated partly by the establishment of the new branch office of Candilis-Josic-Woods in Berlin, set up to supervise construction of the Free University. Presentations took place at the Akademie der Künste, in the Hansaviertel, the showcase district for modern architecture built in the latter half of the 1950s [1, 2].
Poetic measures of architecture: Martin Heidegger’s ‘…Poetically Man Dwells…’
Authors: Hill Glen
Published: September 2014

Martin Heidegger begins his lecture ‘… Poetically Man Dwells …’ by denying poetry is a marginal practice whose imaginings are ‘mere fancies and illusions’. ‘[T]he poetic’, he states, is not ‘merely an ornament and bonus added on to dwelling’. On the contrary, Heidegger boldly claims that poetry is the source of all human dwelling on earth: ‘[…] poetry first causes dwelling to be dwelling. Poetry is what really lets us dwell.’

The connective tissue of Heidegger's argument in ‘… Poetically Man Dwells …’ is the concept of ‘measure’. In the English translation of the lecture, permutations of the term ‘measure’ (Maß/messen) appear a remarkable ninety-four times, not including dozens more uses of its synonyms: ‘dimension’, ‘span’, ‘meter’ and ‘gauge’. What seems surprising, given that the set-up of the lecture revolves around poetry and measure, is that the commonest understanding of measure related to poetry – poetic measure itself – is not discussed thematically by Heidegger. Rather, Heidegger's incessant word play produces meanings that include ‘measuring against’ in the sense of comparing to a standard, ‘measuring up’ a space by ‘stepping-out’ (durchmessen), ‘measuring out’ in the sense of dividing-up or apportioning (das Zu-Gemessene), ‘being measured’ in the sense of having propriety, ‘taking measures’ (die Maß-Nahme) in response to a situation, and ‘measuring between’ as a distance or span. These meanings are of course related to common poetic measure, and might even be claimed to be its ground.
Suizidalität im Alter – was kann der Hausarzt tun?
Authors: Haas Sebastian , Minder Jacqueline , Harbauer Gregor
Published: September 2014

Die Suizidraten der älteren Bevölkerung sind in der Schweiz und den meisten anderen Ländern höher als in der gesamten Bevölkerung. Suizidalität im Alter kommt meistens im Zusammenhang mit psychischen Erkrankungen v.a. Depression vor. Ärzte in der medizinischen Grundversorgung haben besondere Bedeutung im Erkennen und Erfassen suizidaler Zustände bei älteren Menschen wegen derer oft langjährigen, vertrauensvollen Beziehung und der Tatsache, dass Suizidalität sich oft hinter Somatisierung oder anderen medizinischen Beschwerden «verbirgt». Ein neuer praxisnaher Ansatz, das «PRISM-S Instrument», ermöglicht das Erfassen des Suizidalitätsausmasses in weniger als fünf Minuten mithilfe eines einfachen visuellen Verfahrens. Neben der Bedeutung öffentlicher Massnahmen im Bereich der psychischen Gesundheit, bietet PRISM-S eine zeitsparende und einfach anzuwendende Methode die von allen Gesundheitsfachpersonen zum Erfassen von Suizidalität bei Erwachsenen (18–65 Jahre) genutzt werden kann. Weitere noch ausstehende Untersuchungen werden den spezifischen Nutzen bei älteren Menschen (über 65 Jahren) untersuchen.
Gender Differences in Cognitive Performance in Old Age
Authors: Praetorius Marcus , Thorvaldsson Valgeir , Johansson Boo , Hassing Linda B.
Published: September 2014

Objective: To examine gender differences in level and change of cognitive performance in the oldest old while accounting for gender differences in longevity. Method: 574 individuals, aged 80 years and older, from the OCTO Twin Study. Five cognitive domains were administered at five occasions at 2-year intervals. Results: There were no cognitive differences between men and women, with the exception that men showed a steeper rate of decline in semantic memory. This effect was driven by men who had developed dementia and declined at a faster rate than women. Conclusion: Our results support previous findings showing minor to nonexisting gender differences in cognition among nondemented individuals in very old age when taking gender differences in longevity into account.
Non-Invasive Diagnostic Biomarkers for Estimating the Onset Time of Permanent Cerebral Ischemia
Authors: Berthet Carole , Xin Lijing , Buscemi Lara , Benakis Corinne , Gruetter Rolf , Hirt Lorenz , Lei Hongxia
Published: September 2014

The treatments for ischemic stroke can only be administered in a narrow time-window. However, the ischemia onset time is unknown in ∼ 30% of stroke patients (wake-up strokes). The objective of this study was to determine whether MR spectra of ischemic brains might allow the precise estimation of cerebral ischemia onset time. We modeled ischemic stroke in male ICR-CD1 mice using a permanent middle cerebral artery filament occlusion model with laser Doppler control of the regional cerebral blood flow. Mice were then subjected to repeated MRS measurements of ipsilateral striatum at 14.1 T. A striking initial increase in γ-aminobutyric acid (GABA) and no increase in glutamine were observed. A steady decline was observed for taurine (Tau), N-acetylaspartate (NAA) and similarly for the sum of NAA+Tau+glutamate that mimicked an exponential function. The estimation of the time of onset of permanent ischemia within 6 hours in a blinded experiment with mice showed an accuracy of 33 ± 10 minutes. A plot of GABA, Tau, and neuronal marker concentrations against the ratio of acetate/NAA allowed precise separation of mice whose ischemia onset lay within arbitrarily chosen time-windows. We conclude that 1H-MRS has the potential to detect the clinically relevant time of onset of ischemic stroke.
Towards Practical Application of Paper based Printed Circuits: Capillarity Effectively Enhances Conductivity of the Thermoplastic Electrically Conductive Adhesives
Authors: Wu Haoyi , Chiang Sum Wai , Lin Wei , Yang Cheng , Li Zhuo , Liu Jingping , Cui Xiaoya , Kang Feiyu , Wong Ching Ping
Published: September 2014

Direct printing nanoparticle-based conductive inks onto paper substrates has encountered difficulties e.g. the nanoparticles are prone to penetrate into the pores of the paper and become partially segmented and the necessary low-temperature-sintering process is harmful to the dimension-stability of paper. Here we prototyped the paper-based circuit substrate in combination with printed thermoplastic electrically conductive adhesives (ECA), which takes the advantage of the capillarity of paper and thus both the conductivity and mechanical robustness of the printed circuitsweredrastically improved without sintering process. For instance, the electrical resistivity of the ECA specimen on a pulp paper (6 × 10−5Ω·cm, with 50 wt% loading of Ag) was only 14% of that on PET film than that on PET film. This improvement has been found directly related to the sizing degree of paper, in agreement with the effective medium approximation simulation results in this work. The thermoplastic nature also enables excellent mechanical strength of the printed ECA to resist repeated folding. Considering the generality of the process and the wide acceptance of ECA technique in the modern electronic packages, this method may find vast applications in e.g. circuit boards, capacitive touch pads and radio frequency identification antennas, which have been prototyped in the manuscript.
High-Throughput Screening
Authors: Böcker Alexander , Schaertl Sabine , Hess Stephen D.
Published: September 2014

Ion channels are a class of proteins that are attractive human, animal, and crop health targets. Ion channels can be considered high-gain (physiologically speaking), high-reward (therapeutic benefit) and high technology (difficult assay development) drug targets. Ion channels are attractive therapeutic targets because they often have high control gain in physiological systems; opening or blocking many of the ion channels studied to date has a large effect on the function of the muscle, nerve, or cell containing the channels. The major issue confronting ion channel drug development teams is safety as the same or closely-related ion channels are often widely distributed in the heart and CNS, and activity at these channels needs to be minimal. This chapter reviews the history of ion channel HTS techniques, using examples from the authors’ work to illustrate how the necessary approaches yield good results, and describing in numerical detail their approach to assay development and full library HTS for selected examples in as much detail as possible.
Structural Understanding of Ion Channels in Atomic Detail
Authors: Stansfeld Phillip J.
Published: September 2014

The first ion channel crystal structure was resolved nearly 15 years ago, in 1998, an achievement acknowledged by the award of the Nobel Prize for Chemistry to Rod MacKinnon, in 2003. Although these proteins remain difficult to crystallise there are an increasing number of structures available. This chapter discusses the history of the field, outlines some of the recent structural successes and describes the development of novel methods that have rendered ion channels, and membrane proteins in general, more tractable to structural biology. The wealth of information provided by all these structures enhances our understanding of channel structure and by inference allows us to understand their functional influence on the associated physiological processes. While many of the ion channel structures are bacterial in nature, recent developments have led to the structural elucidation of eukaryotic proteins that should facilitate future ion channel drug discovery.
Open Access to the KCNQ Channel: Retigabine and Second Generation M-current Openers
Authors: Krupp Johannes , Rush Anthony M. , Swahn Britt-Marie , Main Martin
Published: September 2014

In 2011, Retigabine (Ezogabine; Valeant Pharmaceuticals/GlaxoSmithKline), an opener of KCNQ (Kv7) potassium channels, was approved for the adjunctive treatment of partial-onset seizures in adult patients. In this chapter, we review the story of retigabine, from identification as a novel anticonvulsant through to clinical testing, and detail the ongoing work to identify a second generation of KCNQ channel openers.