bluuebunny/crossref_metadata_2025 huggingface dataset:
Brody curves and mean dimension
Authors: Matsuo Shinichiroh , Tsukamoto Masaki
Published: May 2014

We study the mean dimensions of the systems of Brody curves. In particular we give the formula of the mean dimension of the system of Brody curves in the Riemann sphere. A key notion is a non-degeneracy of Brody curves introduced by Yosida (1934). We develop a deformation theory of non-degenerate Brody curves and apply it to the calculation of the mean dimension. Moreover we show that there are sufficiently many non-degenerate Brody curves by using the method of gluing infinitely many rational curves.
The 14-3-3 protein Bmh1 functions in the spindle position checkpoint by breaking Bfa1 asymmetry at yeast centrosomes
Authors: Caydasi Ayse Koca , Micoogullari Yagmur , Kurtulmus Bahtiyar , Palani Saravanan , Pereira Gislene
Published: May 2014

In addition to their well-known role in microtubule organization, centrosomes function as signaling platforms and regulate cell cycle events. An important example of such a function is the spindle position checkpoint (SPOC) of budding yeast. SPOC is a surveillance mechanism that ensures alignment of the mitotic spindle along the cell polarity axis. Upon spindle misalignment, phosphorylation of the SPOC component Bfa1 by Kin4 kinase engages the SPOC by changing the centrosome localization of Bfa1 from asymmetric (one centrosome) to symmetric (both centrosomes). Here we show that, unexpectedly, Kin4 alone is unable to break Bfa1 asymmetry at yeast centrosomes. Instead, phosphorylation of Bfa1 by Kin4 creates a docking site on Bfa1 for the 14-3-3 family protein Bmh1, which in turn weakens Bfa1–centrosome association and promotes symmetric Bfa1 localization. Consistently, BMH1-null cells are SPOC deficient. Our work thus identifies Bmh1 as a new SPOC component and refines the molecular mechanism that breaks Bfa1 centrosome asymmetry upon SPOC activation.
Gesture, feature, autosegment
Authors: Ladd D. Robert
Published: May 2014

The Prague School concept of feature, which forms part of most mainstream phonological theories, is crucially ambiguous between two interpretations: are features attributes of segments (with segments remaining the primary elements of phonology), or are they autonomous atoms of phonology (with segments being composite or even epiphenomenal)? Early work in autosegmental phonology assumed the first view, and explored the properties of autonomous phonological elements (such as tones) that are neither ordered segments nor attributes of ordered segments. The second view (which is widely held but has never been properly theorized) underlies the ‘naturalness condition’, according to which phonological features must be phonetically definable. This condition is problematical and fails badly in describing the phonological structure of visual communication systems (including signed languages and writing). The naturalness condition should be abandoned and autosegments should be distinguished from features; phonetic description should be quantitative, and features should be seen as symbolic abstractions that characterize phonological segments
Modulations
Authors: Ladd D. Robert
Published: May 2014

Speech simultaneously conveys both propositional and indexical meaning. This is approximately the difference between ‘what you said’ and ‘the way you said it’. Some indexical meaning is conveyed by arbitrary language-specific devices such as lexical choice and sociophonetic variation, but some is conveyed by paralinguistic cues (‘tone of voice’, ‘body language’) that are broadly speaking universal. Describing the universal aspects in terms of gradient ‘modulation’ of the phonetic manifestations of phonological categories expresses their formal similarity to sociophonetic variation. However, in some languages modulation may also be categorical, in phenomena like ideophones and ablaut morphology, and in these it plays a more centrally linguistic or propositional role.
What Makes a Good Decision?
Authors: Chappell Sophie Grace
Published: May 2014

A number of models of how to deliberate are surveyed, deriving from Benjamin Franklin, contemporary consequentialism, causal decision theory, Ignatius of Loyola, and Jeremy Bentham. The question is raised whether there even can be a single model for all deliberation. Another picture of deliberation, Murdoch’s, is introduced, and its stress on imagination and ‘moral vision’ noted. The preconditions of deliberation—what has to be in place for deliberation even to be possible—are explored. Some of these preconditions are ‘outside’ the agent, some of them ‘inside’, and some not clearly either. Determinism and weakness of will come into the picture here, as does the causal nature of the world. The chapter closes by noting three features that agents must have if deliberation is to be an important part of their lives: they must be clever enough to get deliberation right, they must care about getting it right, and they must believe they can get it right.
Platonistic Virtue Ethics
Authors: Chappell Sophie Grace
Published: May 2014

Many philosophers have explored the prospects for an Aristotelian virtue ethics (often on a fairly thin basis of actual Aristotle exegesis). On a not particularly fat basis of Plato exegesis—this chapter explores the prospects for a Platonistic virtue ethics. If the formula for Aristotelian virtue ethics says that ‘Right action is action in accordance with the virtues and contrary to no virtue’, then the formula for Platonistic virtue ethics says that ‘Good agency in the truest and fullest sense presupposes the contemplation of the Form of the Good’. A modest version of Platonistic virtue ethics is explored, which involves no commitment to the theory of Forms; this focuses on contemplation, a term to be explained by reference partly to familiar experiences of attention and study, and partly to Iris Murdoch’s The Sovereignty of Good.
Music Learning Today
Authors: Bauer William I.
Published: May 2014

Grounded in a research-based, conceptual model called Technological Pedagogical and Content Knowledge (TPACK), the essential premise of Music Learning Today:Digital Pedagogy for Creating, Performing, and Responding to Music is that music educators and their students can benefit through use of technology as a tool to support learning in the three musical processes – creating, performing, and responding to music. Insights on how technology can be used to advantage in both traditional and emerging learning environments are provided, and research-based pedagogical approaches that align technologies with specific curricular outcomes are described. Importantly, the book advocates that the decision on whether or not to utilize technology for learning, and the specific technology that might be best suited for a particular learning context, should begin with a consideration of curricular outcomes (music subject matter). This is in sharp contrast to most other books on music technology that are technocentric, organized around specific software applications and hardware. The book also recognizes that knowing how to effectively use the technological tools to maximize learning (pedagogy) is a crucial aspect of the teaching-learning process. Drawing on the research and best practice literature in music education and related fields, pedagogical approaches that are aligned with curricular outcomes and specific technologies are suggested. It is not a “how to” book per se, but rather a text informed by the latest research, theories of learning, and documented best practices, with the goal of helping teachers develop the ability to understand the dynamics of effectively using technology for music learning.
Accurate cell segmentation in microscopy images using membrane patterns
Authors: Dimopoulos Sotiris , Mayer Christian E. , Rudolf Fabian , Stelling Joerg
Published: May 2014

Motivation: Identifying cells in an image (cell segmentation) is essential for quantitative single-cell biology via optical microscopy. Although a plethora of segmentation methods exists, accurate segmentation is challenging and usually requires problem-specific tailoring of algorithms. In addition, most current segmentation algorithms rely on a few basic approaches that use the gradient field of the image to detect cell boundaries. However, many microscopy protocols can generate images with characteristic intensity profiles at the cell membrane. This has not yet been algorithmically exploited to establish more general segmentation methods.

Results: We present an automatic cell segmentation method that decodes the information across the cell membrane and guarantees optimal detection of the cell boundaries on a per-cell basis. Graph cuts account for the information of the cell boundaries through directional cross-correlations, and they automatically incorporate spatial constraints. The method accurately segments images of various cell types grown in dense cultures that are acquired with different microscopy techniques. In quantitative benchmarks and comparisons with established methods on synthetic and real images, we demonstrate significantly improved segmentation performance despite cell-shape irregularity, cell-to-cell variability and image noise. As a proof of concept, we monitor the internalization of green fluorescent protein-tagged plasma membrane transporters in single yeast cells.

Availability and implementation : Matlab code and examples are available at http://www.csb.ethz.ch/tools/cellSegmPackage.zip .

Contact : sotiris.dimopoulos@gmail.com or joerg.stelling@bsse.ethz.ch

Supplementary information:  Supplementary data are available at Bioinformatics online.
MaxLink: network-based prioritization of genes tightly linked to a disease seed set
Authors: Guala Dimitri , Sjölund Erik , Sonnhammer Erik L. L.
Published: May 2014

Summary: MaxLink, a guilt-by-association network search algorithm, has been made available as a web resource and a stand-alone version. Based on a user-supplied list of query genes, MaxLink identifies and ranks genes that are tightly linked to the query list. This functionality can be used to predict potential disease genes from an initial set of genes with known association to a disease. The original algorithm, used to identify and rank novel genes potentially involved in cancer, has been updated to use a more statistically sound method for selection of candidate genes and made applicable to other areas than cancer. The algorithm has also been made faster by re-implementation in C++, and the Web site uses FunCoup 3.0 as the underlying network.

Availability and implementation: MaxLink is freely available at http://maxlink.sbc.su.se both as a web service and a stand-alone application for download.

Contact:  dimitri.guala@scilifelab.se

Supplementary information:  Supplementary materials are available at Bioinformatics online.
The Spread and Control of Norovirus Outbreaks Among Hospitals in a Region: A Simulation Model
Authors: Bartsch Sarah M. , Huang Susan S. , Wong Kim F. , Avery Taliser R. , Lee Bruce Y.
Published: May 2014

Background.  Because hospitals in a region are connected via patient sharing, a norovirus outbreak in one hospital may spread to others.

Methods.  We utilized our Regional Healthcare Ecosystem Analyst software to generate an agent-based model of all the acute care facilities in Orange County (OC), California and simulated various norovirus outbreaks in different locations, both with and without contact precautions.

Results.  At the lower end of norovirus reproductive rate (R0) estimates (1.64), an outbreak tended to remain confined to the originating hospital (≤6.1% probability of spread). However, at the higher end of R0 (3.74), an outbreak spread 4.1%–17.5% of the time to almost all other OC hospitals within 30 days, regardless of the originating hospital. Implementing contact precautions for all symptomatic cases reduced the probability of spread to other hospitals within 30 days and the total number of cases countywide, but not the number of other hospitals seeing norovirus cases.

Conclusions.  A single norovirus outbreak can continue to percolate throughout a system of different hospitals for several months and appear as a series of unrelated outbreaks, highlighting the need for hospitals within a region to more aggressively and cooperatively track and control an initial outbreak.
Titin kinase is an inactive pseudokinase scaffold that supports MuRF1 recruitment to the sarcomeric M-line
Authors: Bogomolovas Julijus , Gasch Alexander , Simkovic Felix , Rigden Daniel J. , Labeit Siegfried , Mayans Olga
Published: May 2014

Striated muscle tissues undergo adaptive remodelling in response to mechanical load. This process involves the myofilament titin and, specifically, its kinase domain (TK; titin kinase) that translates mechanical signals into regulatory pathways of gene expression in the myofibril. TK mechanosensing appears mediated by a C-terminal regulatory tail (CRD) that sterically inhibits its active site. Allegedly, stretch-induced unfolding of this tail during muscle function releases TK inhibition and leads to its catalytic activation. However, the cellular pathway of TK is poorly understood and substrates proposed to date remain controversial. TK's best-established substrate is Tcap, a small structural protein of the Z-disc believed to link TK to myofibrillogenesis. Here, we show that TK is a pseudokinase with undetectable levels of catalysis and, therefore, that Tcap is not its substrate. Inactivity is the result of two atypical residues in TK's active site, M34 and E147, that do not appear compatible with canonical kinase patterns. While not mediating stretch-dependent phospho-transfers, TK binds the E3 ubiquitin ligase MuRF1 that promotes sarcomeric ubiquitination in a stress-induced manner. Given previous evidence of MuRF2 interaction, we propose that the cellular role of TK is to act as a conformationally regulated scaffold that functionally couples the ubiquitin ligases MuRF1 and MuRF2, thereby coordinating muscle-specific ubiquitination pathways and myofibril trophicity. Finally, we suggest that an evolutionary dichotomy of kinases/pseudokinases has occurred in TK-like kinases, where invertebrate members are active enzymes but vertebrate counterparts perform their signalling function as pseudokinase scaffolds.
Cell type-restricted activity of hnRNPM promotes breast cancer metastasis via regulating alternative splicing
Authors: Xu Yilin , Gao Xin D. , Lee Jae-Hyung , Huang Huilin , Tan Haiyan , Ahn Jaegyoon , Reinke Lauren M. , Peter Marcus E. , Feng Yue , Gius David , Siziopikou Kalliopi P. , Peng Junmin , Xiao Xinshu , Cheng Chonghui
Published: May 2014

Tumor metastasis remains the major cause of cancer-related death, but its molecular basis is still not well understood. Here we uncovered a splicing-mediated pathway that is essential for breast cancer metastasis. We show that the RNA-binding protein heterogeneous nuclear ribonucleoprotein M (hnRNPM) promotes breast cancer metastasis by activating the switch of alternative splicing that occurs during epithelial–mesenchymal transition (EMT). Genome-wide deep sequencing analysis suggests that hnRNPM potentiates TGFβ signaling and identifies CD44 as a key downstream target of hnRNPM. hnRNPM ablation prevents TGFβ-induced EMT and inhibits breast cancer metastasis in mice, whereas enforced expression of the specific CD44 standard (CD44s) splice isoform overrides the loss of hnRNPM and permits EMT and metastasis. Mechanistically, we demonstrate that the ubiquitously expressed hnRNPM acts in a mesenchymal-specific manner to precisely control CD44 splice isoform switching during EMT. This restricted cell-type activity of hnRNPM is achieved by competition with ESRP1, an epithelial splicing regulator that binds to the same cis-regulatory RNA elements as hnRNPM and is repressed during EMT. Importantly, hnRNPM is associated with aggressive breast cancer and correlates with increased CD44s in patient specimens. These findings demonstrate a novel molecular mechanism through which tumor metastasis is endowed by the hnRNPM-mediated splicing program.
Earnings management and listing regulations in China
Authors: Li Tao , Luo Mi , Ng David
Published: May 2014

Purpose

– The purpose of this paper is to document earnings management of Chinese firms.

Design/methodology/approach

– The paper takes advantage of the introduction of stringent delisting requirements around 2000 that non-cross-listed firms with consecutive earnings losses for more than two years would be delisted from the mainland Chinese exchanges. The paper examines whether listed firms in Chinese market manage earnings to avoid listings. The paper also examines whether mainland Chinese firms cross-listed in Hong Kong exchanges manage earnings the same way. The measure for earnings management is derived from a kernel density estimate for the return on equity distribution, following Bollen and Pool (2009).

Findings

– The paper finds that the new delisting threats induce rampant earnings management on mainland markets, and cross-listing in Hong Kong has a curbing effect on earnings management. The paper also finds that prices became less value relevant after the implementation of delisting regulations, and investors rationally discounted the reliability of earnings announcements in China. Such market responses were absent for cross-listed firms in Hong Kong.

Originality/value

– There is little conclusive evidence about whether cross-listing in a non-US market has a curbing effect on earnings management. The paper contributes to this literature by using this unique exogenous policy change in China and following a difference-in-difference approach in identifying the potential curbing effect. The particular measure adapted from Bollen and Pool (2009) utilizes information of the whole distribution of return on equity, thus extends earlier crude comparison of nearest two bars around zero and partially deals with the potential endogeneity problem.
A modified lambda algorithm for optimization in electromagnetics
Authors: Alotto Piergiorgio , dos Santos Coelho Leandro , C. Mariani Viviana , da C. Oliveira Camila
Published: May 2014

Purpose

– The purpose of this paper is to show with the help widely used analytical and application-oriented benchmark problems that a novel and relatively uncommon optimization method, lambda optimization, can be successfully applied to the solution of optimization problems in electromagnetics. Furthermore an improvement to the method is proposed and its effectiveness is validated.

Design/methodology/approach

– An adaptive probability factor is used within the framework of lambda optimization.

Findings

– It is shown that in the framework of lambda optimization (LO) the use of an adaptive probability factor can provide high-quality solutions with small standard deviation on the selected benchmark problem.

Research limitations/implications

– Although the chosen benchmarks are considered to be representative of typical electromagnetic problems, different test cases may give less satisfactory results.

Practical implications

– The proposed approach appears to be an efficient general purpose stochastic optimizer for electromagnetic design problems.

Originality/value

– This paper introduces and validates the use of adaptive probability factor in order to improve the balance between the explorative and exploitative characteristics of the LO algorithm.
The challenge of work based learning: a role for academic mentors?
Authors: Stephens Simon , Doherty Oran , Bennett Billy , Margey Michael
Published: May 2014

Purpose

– The purpose of this paper is to explore the key challenge(s) experienced by employers, employees and academics during work based learning (WBL) programmes at undergraduate level. The idea of academic mentors is proposed as an aid to addressing the challenges common to WBL programmes.

Design/methodology/approach

– The case study presented in this paper involves a large multinational organisation and a higher education institution, both of which are based in Ireland. Interviews were used to explore the outcome(s) of a WBL programme.

Findings

– The challenges associated with WBL place demands on the design of curriculum, pedagogy and accreditation. The use of academic mentors can help translate academic knowledge into workplace practice; and address challenges which are common in WBL programmes.

Practical implications

– The understanding of best practice in the design of WBL programmes is enriched. A role for academics as mentors is identified and the implications explored.

Originality/value

– The success of WBL can be linked to the relationships that form between employers, employees and academics. There is evidence that the academic is central to the development of these relationships.
A semiotic analysis of the extendibility of luxury brands
Authors: Veg-Sala Nathalie , Roux Elyette
Published: May 2014

Purpose

– Considering a long-term perspective and the discourse directly emitted by brands, the aim is to study how can brand extension potential be predicted through the analysis of brand contracts?

Design/methodology/approach

– Considering a long-term perspective and the discourse directly emitted by brands, the aim is to study how can brand extension potential be predicted through the analysis of brand contracts?

Findings

– Three groups of brands are identified: brands anchored in both determination and mastery contracts defined as open (high extendibility); brands anchored in a determination contract defined as open, as well as in a mastery contract defined as closed (low extendibility); brands anchored in a mastery contract defined as open as well as in a determination contract defined as not closed (high extendibility, but risks of diluting the brand value).

Research limitations/implications

– Compared with extensions actually developed by these brands, the results are discussed and strategies are proposed to maximize the long-term brand development when the brand extension potential is low. Only studied on products, it would be interesting to complete this analysis in services.

Originality/value

– The main contribution is the focus on brand narratives and contracts to predict the brand extensibility of luxury brands. Structural semiotics provides another original insight.
Brand image and customers' willingness to pay a price premium for food brands
Authors: Anselmsson Johan , Vestman Bondesson Niklas , Johansson Ulf
Published: May 2014

Purpose

– The aim is to understand customers' willingness, or unwillingness, to pay a price premium in the market for consumer packaged food and what kind of images brands can use in order to achieve a price premium.

Design/methodology/approach

– The study is based on a quantitative survey of brand images found in food and branding literature and their impact on loyalty as well as customers' willingness to pay a price premium for consumer packaged food.

Findings

– The survey shows that quality is a significant determinant of price premium, but adding other image dimensions doubles the predictability and understanding about price premium. The strongest determinants of price premium are social image, uniqueness and home country origin. Other significant determinants are corporate social responsibility (CSR) and awareness.

Practical implications

– The results help brand managers to recognise the importance of incorporating price premium and to develop a better understanding of what drives price premium in addition to more traditional dimensions as quality and loyalty.

Originality/value

– In grocery retailing, the competition for customers, margins and price premiums between manufacturer and private labels is fierce. Traditionally, the literature on this competition has focused on quality and product improvements as the main tool for creating distance to low priced competition. This study looks into other more branding related dimensions to distance from price competition.
Big demand(s), small supply – Muslim children in Italian school canteens: a cultural perspective
Authors: Giovine Roberta
Published: May 2014

Purpose

– The paper aims to explore the food needs of a growing Muslim population in Italian kindergartens and primary schools and to provide a basis for further quantitative research.

Design/methodology/approach

– The methodology is essentially qualitative – historical, anthropological, social sources were studied to set the scene for a number of interviews (now 14, eventually 20) with cultural mediators, who know the implications of both cultures, and are trained to see the differences. The results of the interviews were then validated through interactions with anthropologists, food and religious historians, religious authorities and others.

Findings

– The main findings are that: food and food prohibitions bear fundamental religious and identity-related implications for Muslims, that reverberate onto migrants' children of school age and dramatically limit their access to canteen food; halal meat traders exist in Italy, and can provide legally compliant, halal-certified meat, but school/public administrations do not seem to be aware of their interest.

Research limitations/implications

– The number of available mediators is relatively small, although they generally agree on all the basics. The research is qualitative and will require more in-depth analysis.

Practical implications

– Better awareness of the Maghrebi Muslims' food requirements in school canteens. The need to develop a halal meat trade for public institutions and to lobby for the right of these children to bring packed lunches from home.

Originality/value

– The paper has a heuristic value. It could have immediate implications for the stakeholders and, on the other hand, promote quantitative studies.
Identification and characterization of bovine programmed death‐ligand 2
Authors: Nishimori Asami , Konnai Satoru , Ikebuchi Ryoyo , Okagawa Tomohiro , Nakajima Chie , Suzuki Yasuhiko , Mingala Claro N. , Murata Shiro , Ohashi Kazuhiko
Published: May 2014

Previous reports from this group have indicated that the immunoinhibitory programmed death (PD)‐1 receptor and its ligand, PD‐L1, are involved in the mechanism of immune evasion of bovine chronic infection. However, no functional analysis of bovine PD‐L2 in cattle has been reported. Thus, in this study, the molecular function of bovine PD‐L2 was analyzed in vitro. Recombinant PD‐L2 (PD‐L2‐Ig), which comprises an extracellular domain of bovine PD‐L2 fused to the Fc portion of rabbit IgG1, was prepared based on the cloned cDNA sequence for bovine PD‐L2. Bovine PD‐L2‐Ig bound to bovine PD‐1‐expressing cells and addition of soluble bovine PD‐1‐Ig clearly inhibited the binding of PD‐L2‐Ig to membrane PD‐1 in a dose‐dependent manner. Cell proliferation and IFN‐γ production were significantly enhanced in the presence of PD‐L2‐Ig in peripheral blood mononuclear cells (PBMCs) from cattle. Moreover, PD‐L2‐Ig significantly enhanced IFN‐γ production from virus envelope peptides‐stimulated PBMCs derived from bovine leukemia virus‐infected cattle. Interestingly, PD‐L2‐Ig‐induced IFN‐γ production was further enhanced by treatment with anti‐bovine PD‐1 antibody. These data suggest potential applications of bovine PD‐L2‐Ig as a therapy for bovine diseases.
Targeting the Notch signaling pathway in cancer therapeutics
Authors: Guo Huajiao , Lu Yi , Wang Jianhua , Liu Xia , Keller Evan T. , Liu Qian , Zhou Qinghua , Zhang Jian
Published: May 2014

Despite advances in surgery, imaging, chemotherapy, and radiotherapy, the poor overall cancer‐related death rate remains unacceptable. Novel therapeutic strategies are desperately needed. Nowadays, targeted therapy has become the most promising therapy and a welcome asset to the cancer therapeutic arena. There is a large body of evidence demonstrating that the Notch signaling pathway is critically involved in the pathobiology of a variety of malignancies. In this review, we provide an overview of emerging data, highlight the mechanism of the Notch signaling pathway in the development of a wide range of cancers, and summarize recent progress in therapeutic targeting of the Notch signaling pathway.
Tissue near infra red spectroscopy change is not correlated with patients' outcome in elective cardiac surgery
Authors: MOREL J. , BOUCHET J. B. , VOLA M. , BÉRAUD A. M. , CLERC M. , AWAD S. , AUBOYER C. , MOLLIEX S.
Published: May 2014

Background

Microcirculatory disturbances following cardiac surgery with cardiopulmonary bypass (CPB) are thought to be at the origin of organ dysfunction, although few studies have correlated microvascular alterations with outcome. We aimed to assess the microcirculation with near infrared spectroscopy (NIRS) and correlate NIRS parameters with intensive care length of stay and organ dysfunction.

Methods

Forty patients at increased risk of postoperative systemic inflammatory response syndrome after an elective cardiac surgery with CPB were included in this prospective observational study. Microcirculation of the thenar eminence was analysed by NIRS technology, through the tissue oxygen saturation (StO2) and the recovery slope after an ischaemic challenge. Organ dysfunction was assessed with the Sequential Organ Failure Assessment (SOFA) score. Microcirculation parameters were recorded at baseline, at different time points during the surgery and the first 48 postoperative hours.

Results

StO2 at baseline was 82% and decreased significantly until 77% at 2 h after CPB. Recovery slope values were 4.3% per second at baseline and decreased to 2.5% per second during CPB (P < 0.05). From 12 h after CPB time point, both parameters were not statistically different from baseline anymore. We found no correlation between microcirculatory parameters and mean arterial pressure, cardiac index, intensive care unit (ICU) length of stay or SOFA score.

Conclusion

This study confirms, through a non‐invasive technology, a significant but transient alteration of the microcirculation during elective cardiac surgery. However, as these microvascular alterations were not correlated with patient's outcome, NIRS‐derived parameters seem to be of limited interest in the cardiac surgery setting.
Motivational and neurocognitive deficits are central to the prediction of longitudinal functional outcome in schizophrenia
Authors: Fervaha G. , Foussias G. , Agid O. , Remington G.
Published: May 2014

Objective

Functional impairment is characteristic of most individuals with schizophrenia; however, the key variables that undermine community functioning are not well understood. This study evaluated the association between selected clinical variables and one‐year longitudinal functional outcomes in patients with schizophrenia.

Method

The sample included 754 patients with schizophrenia who completed both baseline and one‐year follow‐up visits in the CATIE study. Patients were evaluated with a comprehensive battery of assessments capturing symptom severity and cognitive performance among other variables. The primary outcome variable was functional status one‐year postbaseline measured using the Heinrichs‐Carpenter Quality of Life Scale.

Results

Factor analysis of negative symptom items revealed two factors reflecting diminished expression and amotivation. Multivariate regression modeling revealed several significant independent predictors of longitudinal functioning scores. The strongest predictors were baseline amotivation and neurocognition. Both amotivation and neurocognition also had independent predictive value for each of the domains of functioning assessed (e.g., vocational).

Conclusion

Both motivational and neurocognitive deficits independently contribute to longitudinal functional outcomes assessed 1 year later among patients with schizophrenia. Both of these domains of psychopathology impede functional recovery; hence, it follows that treatments ameliorating each of these symptoms should promote community functioning among individuals with schizophrenia.
Rapid reconstitution of functionally active 6-sulfoLacNAc+ dendritic cells (slanDCs) of donor origin following allogeneic haematopoietic stem cell transplant
Authors: Mimiola E , Marini O , Perbellini O , Micheletti A , Vermi W , Lonardi S , Costantini C , Meneghelli E , Andreini A , Bonetto C , Vassanelli A , Cantini M , Zoratti E , Massi D , Zamo' A , Leso A , Quaresmini G , Benedetti F , Pizzolo G , Cassatella M A , Tecchio C
Published: May 2014

The role of dendritic cells (DCs) and macrophages in allogeneic haematopoietic stem cell transplant (HSCT) is critical in determining the extent of graft-versus-host response. The goal of this study was to analyse slanDCs, a subset of human proinflammatory DCs, in haematopoietic stem cell (HSC) sources, as well as to evaluate their 1-year kinetics of reconstitution, origin and functional capacities in peripheral blood (PB) and bone marrow (BM) of patients who have undergone HSCT, and their presence in graft-versus-host disease (GVHD) tissue specimens. slanDCs were also compared to myeloid (m)DCs, plasmacytoid (p)DCs and monocytes in HSC sources and in patients' PB and BM throughout reconstitution. slanDCs accounted for all HSC sources. In patients' PB and BM, slanDCs were identified from day +21, showing median frequencies comparable to healthy donors, donor origin and kinetics of recovery similar to mDCs, pDCs, and monocytes. Under cyclosporin treatment, slanDCs displayed a normal pattern of maturation, and maintained an efficient chemotactic activity and capacity of releasing tumour necrosis factor (TNF)-α upon lipopolysaccharide (LPS) stimulation. None the less, they were almost undetectable in GVHD tissue specimens, being present only in intestinal acute GVHD samples. slanDCs reconstitute early, being donor-derived and functionally competent. The absence of slanDCs from most of the GVHD-targeted tissue specimens seems to rule out the direct participation of these cells in the majority of the local reactions characterizing GVHD.
Majewski syndrome (short‐rib polydactyly syndrome type II): Prenatal diagnosis and histological features of chondral growth plate, liver and kidneys
Authors: Tonni Gabriele , Palmisano Marcella , Ventura Alessandro , Grisolia Gianpaolo , Baffico Ave Maria , Pattacini Pierpaolo , Bonasoni Maria Paola , De Felice Claudio
Published: May 2014

The Majewski syndrome or short rib‐polydactyly syndrome (SRPS) type II is a lethal skeletal dysplasia characterized by severe IUGR (intrauterine growth restriction) and dysmorphic face, polydactyly, relatively proportionate head size at birth with later progression to microcephaly. A case of second trimester ultrasound diagnosis of SRPS type II is reported with review of the medical record of previous observed cases. Postmortem examination and radiogram confirmed the clinical diagnosis. Histological examination of the femoral epypheseal chondral plate showed an expanded and irregular hypertrophic zone. Moreover, characteristic cortico‐medullary cysts of both kidneys and portal fibrosis were also demonstrated; findings consistent with the broad phenotypic spectrum of this rare skeletal disease.
Genetic testing for sporadic hearing loss using targeted massively parallel sequencing identifies 10 novel mutations
Authors: Gu X. , Guo L. , Ji H. , Sun S. , Chai R. , Wang L. , Li H.
Published: May 2014

The genetic heterogeneity of non‐syndromic hearing loss (NSHL) has hampered the identification of its pathogenic mutations. Several recent studies applied targeted genome enrichment (TGE) and massively parallel sequencing (MPS) to simultaneously screen a large set of known hearing loss (HL) genes. However, most of these studies were focused on familial cases. To evaluate the effectiveness of TGE and MPS on screening sporadic NSHL patients, we recruited 63 unrelated sporadic NSHL probands, who had various levels of HL and were excluded for mutations in GJB2, MT‐RNR1, and SLC26A4 genes. TGE and MPS were performed on 131 known HL genes using the Human Deafness Panel oto‐DA3 (Otogenetics Corporation., Norcross, GA). We identified 14 pathogenic variants in STRC, CATSPER2, USH2A, TRIOBP, MYO15A, GPR98, and TMPRSS3 genes in eight patients (diagnostic rate = 12.7%). Among these variants, 10 were novel compound heterozygous mutations. The identification of pathogenic mutations could predict the progression of HL, and guide diagnosis and treatment of the disease.
Direct Radial LMHF Microvibration Induced Bone Formation and Promoted Implant Osseointegration
Authors: Wang Shirui , Liu Yang , Tang Yi , Zhao Wei , Li Junying , Yang Yang , Du Wen , Yu Haiyang
Published: May 2014

Background

Mechanical loading is known to play an important role in bone remodeling.

Purpose

This study aimed to evaluate the effect of direct low‐magnitude high‐frequency (LMHF) microvibration on dental implant bone formation and osseointegration.

Materials and Methods

Titanium implants were installed in rabbit tibiae. The implants in the left legs were loaded with mechanical vibration (15 μm) at 10, 20, 30, and 40 Hz (10, 20, 30, and 40 Hz groups, respectively) for 30 minutes every day. The implants on the right legs were used as a sham control and did not receive a vibration load.

Results

After 20 days, the 10, 20, and 30 Hz groups showed significantly greater newly formed bone volume, density, ratio of the bone surface area to the trabecular bone surface area, and ratio of the bone surface area in direct contact with osteoclasts versus the total bone surface area in the region of interest compared with the sham control group, especially the 20 Hz group. However, the 40 Hz group did not.

Conclusions

In conclusion, the application of direct LMHF (10, 20, or 30 Hz) vibration on the implants promoted bone formation and osseointegration, especially at 20 Hz; however, the use of 40 Hz did not result in any significant improvement.
The use of an endostapler in the treatment of supralevator abscess of intersphincteric origin
Authors: García‐Granero A. , Granero‐Castro P. , Frasson M. , Flor‐Lorente B. , Carreño O. , Garcia‐Granero E.
Published: May 2014

Aim

This technical note describes the use of an endostapler for the definitive treatment of supralevator abscess upward from an intersphincteric origin.

Method

A two‐stage treatment was performed. First an endoanal drainage was performed by inserting a mushroom catheter in the supralevator abscess cavity. In the second stage transanal unroofing of the fistula was performed with an endostapler.

Results

Since 2011, three patients have been treated in this way. After 2 years of follow up, none of the patients had recurrence of the abscess or been referred for anal incontinence.

Conclusion

The use of an endostapler in the treatment of supralevator abscess of intersphincteric origin may be an alternative to decrease the risk of recurrence and incontinence.
The winners and losers of land use intensification: pollinator community disassembly is non‐random and alters functional diversity
Authors: Rader Romina , Bartomeus Ignasi , Tylianakis Jason M. , Laliberté Etienne
Published: May 2014

Aim

Pollination services are at risk from land use change and intensification, but responses of individual pollinator species are often variable, making it difficult to detect and understand community‐level impacts on pollination. We investigated changes in community composition and functional diversity of insect pollinator communities under land use change in a highly modified landscape.

Location

Canterbury region, South Island, New Zealand.

Methods

We trapped insect pollinators every month for 1 year at 24 sites across four land use types of increasing intensity in New Zealand: gardens with native vegetation, blackcurrant orchards, dairy farms, and rotational cropping farms. We investigated changes in pollinator species and functional richness and differences in species and functional composition.

Results

Under increasing land use intensity, both species and functional richness declined markedly. Changes in functional richness, however, were overall not significantly different than expected based on the observed declines in species richness. Nevertheless, there was a significant trend towards greater than expected functional richness within less‐intensive land use types and lower than expected functional richness within intensive land use types. The order of species loss under increasing land use intensity was non‐random, as pollinators with a narrow diet breadth, large body size, solitary behaviour and a preference for non‐floral larval food resources were lost first.

Main conclusions

Our study shows that pollinator species bearing particular trait attributes are susceptible to differences in land use. Our study suggests that pollination services may be more vulnerable to environmental changes and disturbances in more intensive land use types as a result of lower pollinator functional richness.
MicroRNA expression profiling of the developing murine upper lip
Authors: Warner Dennis R. , Mukhopadhyay Partha , Brock Guy , Webb Cindy L. , Michele Pisano M. , Greene Robert M.
Published: May 2014

Clefts of the lip and palate are thought to be caused by genetic and environmental insults but the role of epigenetic mechanisms underlying this common birth defect are unknown. We analyzed the expression of over 600 microRNAs in the murine medial nasal and maxillary processes isolated on GD10.0–GD11.5 to identify those expressed during development of the upper lip and analyzed spatial expression of a subset. A total of 142 microRNAs were differentially expressed across gestation days 10.0–11.5 in the medial nasal processes, and 66 in the maxillary processes of the first branchial arch with 45 common to both. Of the microRNAs exhibiting the largest percent increase in both facial processes were five members of the Let‐7 family. Among those with the greatest decrease in expression from GD10.0 to GD11.5 were members of the microRNA‐302/367 family that have been implicated in cellular reprogramming. The distribution of expression of microRNA‐199a‐3p and Let‐7i was determined by in situ hybridization and revealed widespread expression in both medial nasal and maxillary facial process, while that for microRNA‐203 was much more limited. MicroRNAs are dynamically expressed in the tissues that form the upper lip and several were identified that target mRNAs known to be important for its development, including those that regulate the two main isoforms of p63 (microRNA‐203 and microRNA‐302/367 family). Integration of these data with corresponding proteomic datasets will lead to a greater appreciation of epigenetic regulation of lip development and provide a better understanding of potential causes of cleft lip.
Implications of Look AHEAD for clinical trials and clinical practice
Authors: Wing R. R. ,   for The Look AHEAD Research Group
Published: May 2014

Look AHEAD (Action for Health in Diabetes) was a randomized clinical trial designed to examine the long‐term health effects of weight loss in overweight and obese individuals with type 2 diabetes. The primary result was that the incidence of cardiovascular events over a median follow‐up of 9.6 years was not reduced in the Intensive Lifestyle Group relative to the control group. This finding is discussed, with emphasis on its implications for design of trials and clinical treatment of obese persons with type 2 diabetes.
Body mass index is related to microvascular vasomotion, this is partly explained by adiponectin
Authors: de Boer Michiel P. , Wijnstok Nienke J. , Serné Erik H. , Eringa Etto C. , Stehouwer Coen D.A. , Flyvbjerg Allan , Hoekstra Trynke , Heymans Martijn W. , Meijer Rick I. , Twisk Jos W. , Smulders Yvo M.
Published: May 2014

Objective

obesity‐related microvascular dysfunction, including alterations in rhythmic changes in vascular diameter, so‐called ‘vasomotion’, may be important in the clustering of obesity with other cardiovascular risk factors. Adipokines have been suggested to play a role in obesity‐related vascular dysfunction. Alterations in vasomotion have been found using extreme body mass index (BMI) phenotypes. Whether these alterations can be translated to the general population is unknown. The aim was to retrospectively investigate relationships between BMI, vasomotion and adipokines in a population‐based cohort.

Methods

Adiposity, vasomotion, adiponectin and leptin were determined in 94 apparently healthy participants (age 42 years, 46 men, mean BMI 25·5 ± 3·8 kg/m2) of the Amsterdam Growth and Health Longitudinal Study (AGHLS). Vasomotion was assessed via wavelet analysis of skin laser Doppler flowmetry (LDF).

Results

BMI was associated with the neurogenic domain of the vasomotion spectrum (β −0·011, P = 0·046), adiponectin (β −0·18, P = 0·028) and leptin (β 2·22, P < 0·0001). Adiponectin was positively associated with the neurogenic domain of vasomotion (β 0·016, P = 0·019). Leptin did not show any significant relationship with vasomotion. The association between BMI and the neurogenic domain of the vasomotion spectrum was partly explained by adiponectin.

Conclusions

The association between adiposity and microvascular vasomotion also applies to the normal population and is partly explained by adiponectin.
Universal hydraulics of the flowering plants: vessel diameter scales with stem length across angiosperm lineages, habits and climates
Authors: Olson Mark E. , Anfodillo Tommaso , Rosell Julieta A. , Petit Giai , Crivellaro Alan , Isnard Sandrine , León‐Gómez Calixto , Alvarado‐Cárdenas Leonardo O. , Castorena Matiss
Published: May 2014

Angiosperm hydraulic performance is crucially affected by the diameters of vessels, the water conducting conduits in the wood. Hydraulic optimality models suggest that vessels should widen predictably from stem tip to base, buffering hydrodynamic resistance accruing as stems, and therefore conductive path, increase in length. Data from 257 species (609 samples) show that vessels widen as predicted with distance from the stem apex across angiosperm orders, habits and habitats. Standardising for stem length, vessels are only slightly wider in warm/moist climates and in lianas, showing that, rather than climate or habit, plant size is by far the main driver of global variation in mean vessel diameter. Terminal twig vessels become wider as plant height increases, while vessel density decreases slightly less than expected tip to base. These patterns lead to testable predictions regarding evolutionary strategies allowing plants to minimise carbon costs per unit leaf area even as height increases.
The case for assessing cannabidiol in epilepsy
Authors: Cilio Maria Roberta , Thiele Elizabeth A. , Devinsky Orrin
Published: May 2014

Intractable epilepsies have an extraordinary impact on cognitive and behavioral function and quality of life, and the treatment of seizures represents a challenge and a unique opportunity. Over the past few years, considerable attention has focused on cannabidiol (CBD), the major nonpsychotropic compound of Cannabis sativa. Basic research studies have provided strong evidence for safety and anticonvulsant properties of CBD. However, the lack of pure, pharmacologically active compounds and legal restrictions have prevented clinical research and confined data on efficacy and safety to anecdotal reports. Pure CBD appears to be an ideal candidate among phytocannabinoids as a therapy for treatment‐resistant epilepsy. A first step in this direction is to systematically investigate the safety, pharmacokinetics, and interactions of CBD with other antiepileptic drugs and obtain an initial signal regarding efficacy at different dosages. These data can then be used to plan double‐blinded placebo‐controlled efficacy trials.

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.