bluuebunny/crossref_metadata_2025 huggingface dataset:
A new theory of development: the generation of complexity in ontogenesis
Authors: Barbieri Marcello
Published: February 2016

Today there is a very wide consensus on the idea that embryonic development is the result of a genetic programme and of epigenetic processes. Many models have been proposed in this theoretical framework to account for the various aspects of development, and virtually all of them have one thing in common: they do not acknowledge the presence of organic codes (codes between organic molecules) in ontogenesis. Here it is argued instead that embryonic development is a convergent increase in complexity thatnecessarilyrequires organic codes and organic memories, and a few examples of such codes are described. This is thecode theory of development, a theory that was originally inspired by an algorithm that is capable of reconstructing structuresfrom incomplete information, an algorithm that here is briefly summarized because it makes it intuitively appealing how a convergent increase in complexity can be achieved. The main thesis of the new theory is that the presence of organic codes in ontogenesis is not only a theoretical necessity but, first and foremost, an idea that can be tested and that has already been found to be in agreement with the evidence.
Towards hybrid pixel detectors for energy-dispersive or soft X-ray photon science
Authors: Jungmann-Smith J. H. , Bergamaschi A. , Brückner M. , Cartier S. , Dinapoli R. , Greiffenberg D. , Huthwelker T. , Maliakal D. , Mayilyan D. , Medjoubi K. , Mezza D. , Mozzanica A. , Ramilli M. , Ruder Ch. , Schädler L. , Schmitt B. , Shi X. , Tinti G.
Published: February 2016

JUNGFRAU (adJUstiNg Gain detector FoR the Aramis User station) is a two-dimensional hybrid pixel detector for photon science applications at free-electron lasers and synchrotron light sources. The JUNGFRAU 0.4 prototype presented here is specifically geared towards low-noise performance and hence soft X-ray detection. The design, geometry and readout architecture of JUNGFRAU 0.4 correspond to those of other JUNGFRAU pixel detectors, which are charge-integrating detectors with 75 µm × 75 µm pixels. Main characteristics of JUNGFRAU 0.4 are its fixed gain and r.m.s. noise of as low as 27 e−electronic noise charge (<100 eV) with no active cooling. The 48 × 48 pixels JUNGFRAU 0.4 prototype can be combined with a charge-sharing suppression mask directly placed on the sensor, which keeps photons from hitting the charge-sharing regions of the pixels. The mask consists of a 150 µm tungsten sheet, in which 28 µm-diameter holes are laser-drilled. The mask is aligned with the pixels. The noise and gain characterization, and single-photon detection as low as 1.2 keV are shown. The performance of JUNGFRAU 0.4 without the mask and also in the charge-sharing suppression configuration (with the mask, with a `software mask' or a `cluster finding' algorithm) is tested, compared and evaluated, in particular with respect to the removal of the charge-sharing contribution in the spectra, the detection efficiency and the photon rate capability. Energy-dispersive and imaging experiments with fluorescence X-ray irradiation from an X-ray tube and a synchrotron light source are successfully demonstrated with an r.m.s. energy resolution of 20% (no mask) and 14% (with the mask) at 1.2 keV and of 5% at 13.3 keV. The performance evaluation of the JUNGFRAU 0.4 prototype suggests that this detection system could be the starting point for a future detector development effort for either applications in the soft X-ray energy regime or for an energy-dispersive detection system.
Calibrating the X-ray attenuation of liquid water and correcting sample movement artefacts duringin operandosynchrotron X-ray radiographic imaging of polymer electrolyte membrane fuel cells
Authors: Ge Nan , Chevalier Stéphane , Hinebaugh James , Yip Ronnie , Lee Jongmin , Antonacci Patrick , Kotaka Toshikazu , Tabuchi Yuichiro , Bazylak Aimy
Published: February 2016

Synchrotron X-ray radiography, due to its high temporal and spatial resolutions, provides a valuable means for understanding thein operandowater transport behaviour in polymer electrolyte membrane fuel cells. The purpose of this study is to address the specific artefact of imaging sample movement, which poses a significant challenge to synchrotron-based imaging for fuel cell diagnostics. Specifically, the impact of the micrometer-scale movement of the sample was determined, and a correction methodology was developed. At a photon energy level of 20 keV, a maximum movement of 7.5 µm resulted in a false water thickness of 0.93 cm (9% higher than the maximum amount of water that the experimental apparatus could physically contain). This artefact was corrected by image translations based on the relationship between the false water thickness value and the distance moved by the sample. The implementation of this correction method led to a significant reduction in false water thickness (to ∼0.04 cm). Furthermore, to account for inaccuracies in pixel intensities due to the scattering effect and higher harmonics, a calibration technique was introduced for the liquid water X-ray attenuation coefficient, which was found to be 0.657 ± 0.023 cm−1at 20 keV. The work presented in this paper provides valuable tools for artefact compensation and accuracy improvements for dynamic synchrotron X-ray imaging of fuel cells.
Crystal structure of bis[tetrakis(triphenylphosphane-κP)silver(I)] (nitrilotriacetato-κ4N,O,O′,O′′)(triphenylphosphane-κP)argentate(I) with an unknown amount of methanol as solvate
Authors: Noll Julian , Korb Marcus , Lang Heinrich
Published: February 2016

The structure of the title compound, [Ag(C18H15P)4]2[Ag(C6H6NO6)(C18H15P)], exhibits trigonal (P-3) symmetry, with aC3axis through all three complex ions, resulting in an asymmetric unit that contains one third of the atoms present in the formula unit. The formula unit thus contains two of the cations, one anion and disordered molecules of methanol as the packing solvent. Attempts to refine the solvent model were unsuccessful, indicating uninterpretable disorder. Thus, the SQUEEZE procedure inPLATON[Spek (2015).Acta Cryst. C71, 9–18] was applied, accounting for 670 electrons per unit cell, representing approximately 18 molecules of methanol in the formula unit. The stated crystal data forMr, μetcdo not take these into account.
5-{[1-(2,4-Dichlorophenyl)-1H-1,2,3-triazol-4-yl]methyl}-5H-dibenz[b,f]azepine
Authors: Vinay Kumar K. S. , Chandra  , Rajesh B. M. , Mahendra M. , Sadashiva M. P.
Published: February 2016

In the molecule of the title compound, C23H16Cl2N4, the dihedral angle between the benzene rings fused to the azepine ring is 52.00 (6)°. The plane of the triazole ring makes dihedral angles of 74.40 (5), 25.56 (8) and 44.78 (6)° with the planes of the benzene rings of the dibenzoazepine moiety and the dichlorophenyl ring, respectively. The azepine ring adopts a boat conformation. There are no classical hydrogen bonds in the crystal.
Working capital level influence on SME profitability
Authors: Afrifa Godfred Adjapong , Padachi Kesseven
Published: February 2016

Purpose

– The purpose of this paper is to report the results of an investigation of the relationship between working capital level, measured by the cash conversion cycle (CCC) and profitability of small and medium enterprises (SMEs).

Design/methodology/approach

– The paper employs panel data regression analysis on a sample of 160 Alternative Investment Market (AIM)-listed SMEs for the period from 2005 to 2010.

Findings

– The empirical results show that there is a concave relationship between working capital level and firm profitability and that there is an optimal working capital level at which firms’ profitability is maximised. Furthermore, an examination as to whether or not deviations from the optimal working capital level reduce firm profitability indicate that deviations above or below the optimum decrease profitability.

Research limitations/implications

– The sample is limited to AIM-listed SMEs, and therefore the findings cannot be generalised to all firms.

Practical implications

– Overall, the evidence suggests that firms should strive and attain the optimal working capital level in order to maximise their profitability.

Originality/value

– The results are of importance to both SMEs and policy makers providing insight into the nature of CCC and its relationship to SMEs profitability.
Analysis of SME data readiness: a simulation perspective
Authors: Ivers Anne Marie , Byrne James , Byrne PJ
Published: February 2016

Purpose

– The purpose of this paper is to investigate the data profile of manufacturing small and medium enterprises (SMEs) with specific emphasis on understanding the data readiness of SMEs for discrete event simulation (DES) modelling.

Design/methodology/approach

– Research was conducted through a review of literature and a survey research strategy of manufacturing SMEs.

Findings

– This paper illustrates the data profile of manufacturing SMEs. Insight is provided on the types of data collected by SMEs, the collection methods used and how these data are stored by the SMEs. Additionally size and age effects are considered. Based on this data profile, conclusions are made regarding an indication of data readiness of manufacturing SMEs for DES modelling.

Research limitations/implications

– This research is focused specifically on manufacturing SMEs in Ireland, other countries and sectors are not investigated.

Practical implications

– This paper provides owner-managers and senior management insight into the data profile of manufacturing SMEs and their potential for utilisation of DES for performance improvement and decision support.

Originality/value

– This paper addresses the gaps that exist in the knowledge of the data profile of manufacturing SMEs and consequently the status of this profile with regard to the readiness of SMEs for DES modelling.
Venture creation and award-winning technology through co-produced incubation
Authors: Branstad Are , Saetre Alf Steinar
Published: February 2016

Purpose

– Corporate incubation is a type of business incubation designed to assist small firms to develop using know-how available in large companies. The purpose of this paper is to explicate how incubation services can be co-produced and describe the contributions and conditions influencing learning and firm development.

Design/methodology/approach

– The study used a longitudinal single-case method to analyze a small firm’s development process during four years of incubation. The authors recorded and analyzed interviews with the incubator manager and the entrepreneur, and with incubator staff and external stakeholders.

Findings

– The incubator provided knowledge- and network-based services. These services emphasized the need for the entrepreneurs to be both proactive and receptive to counseling. Although the incubator and the entrepreneurs made progress in developing the company, a dispute over ownership shares threatened to break down the incubation process.

Research limitations/implications

– Taking evidence from a longitudinal case study, this paper exemplifies and emphasizes that incubation can be a process of interdependent service production in which entrepreneurs are active contributors. Future research should explore how managers and entrepreneurs handle the ambiguities of valuation of incubator contributions.

Practical implications

– For managers it is important to take seriously the key task of communicating the value of the incubator’s contribution to the companies they recruit. For entrepreneurs it is important to find ways to estimate potential for value added from the incubator.

Originality/value

– This paper provides a processual understanding of the dynamics of incubator co-production, not found in extant literature.
Forces influencing the speed of internationalisation
Authors: Langseth Henry , O'Dwyer Michele , Arpa Claire
Published: February 2016

Purpose

– This study applies Oviatt and McDougall’s (2005) model of forces influencing the speed of internationalisation to small, export oriented enterprises. The purpose of this paper is to explore the significance of the forces enabling, motivating, mediating and moderating internationalisation in small and medium-sized enterprises (SMEs), and the manner in which these forces manifest themselves in the market.

Design/methodology/approach

– A qualitative research approach utilising eight case studies within Norway and Ireland was adopted in order to facilitate theory building required for this study.

Findings

– The findings demonstrate that four forces in particular are found to be strongly significant to the speed of internationalisation among the case SMEs: the enabling force of technology, the mediating force of entrepreneurial actor perceptions/owner-managers’ global vision and the moderating forces of foreign market knowledge and tie strength in networks.

Practical implications

– The empirical evidence has several implications for managers and policy regarding influencing the speed of internationalisation process. The enabling force (technology) has implications for government in their support of the SME macro environment. The motivating force (competition) has implications for government, in understanding what motivates entrepreneurs to enter international markets. The two moderating forces (foreign market knowledge and network tie strength) have implications for managers and can be leveraged through product innovation, increased focus on intellectual property rights for better protection against copycats, and through active and deliberate international networking.

Originality/value

– The paper suggests adjustments to Oviatt and McDougall’s (2005) model, permitting researchers to gain an in-depth understanding of the complex reality of SME internationalisation.
Sentimental interplay between structured and unstructured user-generated contents
Authors: Zhang Xianfeng , Yu Yang , Li Hongxiu , Lin Zhangxi
Published: February 2016

Purpose

– User-generated content (UGC), i.e. the feedback from consumers in the electronic market, including structured and unstructured types, has become increasingly important in improving online businesses. However, the ambiguity and heterogeneity, and even the conflict between the two types of UGC, require a better understanding from the perspective of human cognitive psychology. By using online feedback on hotel services, the purpose of this paper is to explore the effects of satisfaction level, opinion dispersion and cultural context background on the interrelationship between structured and unstructured UGC.

Design/methodology/approach

– Natural language processing techniques – specifically, topic classification and sentiment analysis on the sentence level – are adopted to retrieve consumer sentiment polarity on five attributes relative to itemized ratings. Canonical correlation analyses are conducted to empirically validate the interplay between structured and unstructured UGC among different populations segmented by the mean-variance approach.

Findings

– The variety of cognitions displayed by individuals affects the general significant interrelationship between structured and unstructured UGC. Extremely dissatisfied consumers or those with heterogeneous opinions tend to have a closer interconnection, and the interaction between valence and dispersion further strengthens or loosens the relationship. The satisfied or neutral consumers tend to show confounding sentiment signals in relation to the two different UGC. Chinese consumers behave differently from non-Chinese consumers, resulting in a relatively looser interplay.

Practical implications

– By identifying consistent opinion providers and promoting more valuable UGC, UGC platforms can raise the quality of information generated. Hotels will then be able to enhance their services through the strategic use of UGC by analyzing reviews with dispersed low-itemized rating and by addressing the differences exhibited by non-Chinese customers. This analytical method can also help to create richly structured sentiment information from unstructured UGC.

Originality/value

– This paper investigates the variety of cognitive behaviors in the process when UGC are contributed by online reviewers, focussing on the consistency between structured and unstructured UGC. The study helps researchers understanding emotion recognition and affective computing in social media analytics, which is achieved by exploring the variety of UGC information and its relationship to the contributors’ cognitions. The analytical framework adopted also improves the prior techniques.
Genetic overexpressing of GPx‐1 attenuates cocaine‐induced renal toxicity via induction of anti‐apoptotic factors
Authors: Mai Huynh Nhu , Jeong Ji Hoon , Kim Dae‐Joong , Chung Yoon Hee , Shin Eun‐Joo , Nguyen Lan Thuy Ty , Nam Yunsung , Lee Yu Jeung , Cho Eun‐Hee , Nah Seung‐Yeol , Jang Choon‐Gon , Lei Xin Gen , Kim Hyoung‐Chun
Published: February 2016

The present study investigates the role of the glutathione peroxidase (GPx)‐1 gene in cocaine‐induced renal damage in mice. Multiple doses of cocaine increased lipid peroxidation, protein oxidation, and glutathione oxidation in the kidney of the non‐transgenic mice (non‐TG mice). The enzymatic activities of GPx and glutathione reductase were significantly decreased in non‐TG mice, whereas superoxide dismutase was increased in the early phase of cocaine exposure. Treatment with cocaine resulted in significant decreases in expression of Bcl‐2 and Bcl‐xl in the kidney of non‐TG mice, which resulted in significant increases in Bax and cleaved‐caspase 3. Consistently, cocaine‐induced tubular epithelial vacuolization and focal tubular necrosis were mainly observed in the proximal tubules in the kidneys of non‐TG mice. These renal pathologic changes were much less pronounced in GPx‐1 TG than in non‐TG mice. These results suggest that the GPx‐1 gene is a protective factor against nephrotoxicity induced by cocaine via interactive modulations between antioxidant and cell survival signaling processes.
Chemical composition of naturally fermented buttermilk
Authors: Gebreselassie Negussie , Abrahamsen Roger K. , Beyene Fekadu , Abay Fetien , Narvhus Judith A.
Published: February 2016

Naturally fermented buttermilk, prepared from soured cream or milk, was collected during two seasons from sixteen farms in northern Ethiopia, to study chemical composition and flavour compounds. Protein, fat, organic acids, carbohydrates and volatile compounds were quantified using Kjeldahl, Gerber, high‐pressure liquid chromatography (HPLC) and headspace GC methods, respectively. Widely differing concentrations of organic acids and volatile compounds among samples indicated variable fermentation in the products. This indicates the need for the introduction of the standardisation of the process to supply the market with homogenous buttermilk products.
Comparison of Dimensional Accuracies Using Two Elastomeric Impression Materials in Casting Three‐dimensional Tool Marks
Authors: Wang Zhen
Published: February 2016

The purpose of this study was to evaluate two types of impression materials which were frequently used for casting three‐dimensional tool marks in China, namely (i) dental impression material and (ii) special elastomeric impression material for tool mark casting. The two different elastomeric impression materials were compared under equal conditions. The parameters measured were dimensional accuracies, the number of air bubbles, the ease of use, and the sharpness and quality of the individual characteristics present on casts. The results showed that dental impression material had the advantage of special elastomeric impression material in casting tool marks in crime scenes; hence, it combined ease of use, dimensional accuracy, sharpness and high quality.
Somnophilia and Sexual Abuse Using Vaginal Administration of Triazolam
Authors: Lauerma Hannu
Published: February 2016

Somnophilia is a rare paraphilia, a form of sexual fetishism which is characterized by the desire to have sex with an unconscious human object who is unable to respond. To the author's knowledge, this is the first case study concerning somnophilic sexual abuse associated with vaginal administration of triazolam. The perpetrator video‐recorded his sexual acts with two unconscious female victims with whom he also had normal sexual intercourse and who were unaware of his paraphilic activities. His Internet conversations with other persons whom he thought to be interested in somnophilic sex and his plans to kidnap a child were recorded by the police. It was evident that sex with an unconscious object played a specific fetishistic role for this man. He obviously used a combination of drugs mixed with alcoholic drinks to make his victims fall sleep and videotaped vaginal administration of triazolam used to deepen the victim's unconscious state.
Clinical utility of multi‐detector cardiac computed tomography in structural heart interventions
Authors: Xu Bo , Gooley Robert , Seneviratne Sujith K , Nasis Arthur
Published: February 2016

In recent years, there have been major advances in structural interventional cardiology, which have revolutionized the practice of cardiology. Appropriate selection and follow‐up of patients undergoing these structural heart interventions is vital. Multi‐detector computed tomography (MDCT) has emerged as a key imaging modality in the peri‐procedural assessment of patients undergoing multiple structural cardiac interventions. The purpose of this review is to provide an evidence‐based clinical update on the roles of MDCT in both established and evolving structural heart interventions, including transcatheter aortic valve replacement (TAVR) and transcatheter mitral valve implantation (TMVI). The utility of MDCT in the peri‐procedural assessment of patients undergoing pulmonary vein isolation (PVI) for atrial fibrillation, cardiac resynchronization therapy (CRT) and left atrial appendage (LAA) closure will also be reviewed.
Megavoltage conebeam CT cine as final verification of treatment plan in lung stereotactic body radiotherapy
Authors: Kudithipudi Vijay , Gayou Olivier , Colonias Athanasios
Published: February 2016

Introduction

To analyse the clinical impact of megavoltage conebeam computed tomography (MV‐CBCT) cine on internal target volume (ITV) coverage in lung stereotactic body radiotherapy (SBRT).

Methods

One hundred and six patients received lung SBRT. All underwent 4D computed tomography simulation followed by treatment via image guided 3D conformal or intensity modulated radiation. Prior to SBRT, all patients underwent MV‐CBCT cine, in which raw projections are displayed as beam's‐eye‐view fluoroscopic series with the planning target volume (PTV) projected onto each image, enabling verification of tumour motion relative to the PTV and assessment of adequacy of treatment margin.

Results

Megavoltage conebeam computed tomography cine was completed 1–2 days prior to SBRT. Four patients (3.8%) had insufficient ITV coverage inferiorly at cine review. All four plans were changed by adding 5 mm on the PTV margin inferiorly. The mean change in PTV volumes was 3.9 cubic centimetres (cc) (range 1.85–6.32 cc). Repeat cine was performed after plan modification to ensure adequate PTV coverage in the modified plans.

Conclusions

PTV margin was adequate in the majority of patients with this technique. MV‐CBCT cine did show insufficient coverage in a small subset of patients. Insufficient PTV margins may be a function of 4D CT simulation inadequacies or deficiencies in visualizing the ITV inferior border in the full‐inhale phase. MV‐CBCT cine is a valuable tool for final verification of PTV margins.
Effects of Ureaplasma urealyticum Infection on Sperm Quality and Concentrations of Nitric Oxide and Cytokine in the Semen of Infertile Males
Authors: Qian Li , Bian Guang‐Rong , Li Hai‐Bo , Zhou Yan , Dong Shu‐De , Wang Wen‐Jun , Song Jie
Published: February 2016

Problem

The relationship between genital infection and two sperm parameters, namely, concentrations of nitric oxide (NO) and cytokines [e.g., interleukin (IL)‐17 and IL‐18], in the semen of infertile males remains undetermined.

Method of study

Semen samples from 81 infertile (with or without Ureaplasma urealyticum infection) and normal males were subjected to semen analysis.

Results

Nitric oxide concentration in the semen of infertile males with genital infection was higher than those of infertile males without genital infection and of normal males (P < 0.05). Sperm density, pH, percentage of forward, movement of sperm, sperm activation rate, sperm survival rate, and normal rate of the sperm morphology of infertile males with U. urealyticum infection were significantly lower than those of infertile males without genital infection and of normal males (P < 0.05). NO concentrations were also positively correlated with IL‐17 and IL‐18 concentrations in the semen of infertile males.

Conclusion

Increased NO concentration and abnormal IL‐17 and IL‐18 expression were induced by genital infection and induced damage to male reproductive capacity, thereby causing male infertility.
Cortical thickness in bipolar disorder: a systematic review
Authors: Hanford Lindsay C , Nazarov Anthony , Hall Geoffrey B , Sassi Roberto B
Published: February 2016

Objectives

Bipolar disorder (BD) is a debilitating illness, the psychopathology of which is associated with aberrant structural and functional differences in the brain. Despite the many advances in psychiatric research, our understanding of the complex neurobiological underpinnings of BD remains incomplete. The aim of this review was to critically examine all available published magnetic resonance imaging (MRI) research reporting cortical thickness in BD with respect to a healthy population and/or other psychiatric samples.

Methods

The systematic search encompassed all relevant studies published until November 2014. Relevant papers were identified through an online search of select databases (MEDLINE and EMBASE) using key terms bipolar disorder or mania, and cortical thickness. Two independent raters determined the eligibility of papers and performed separate data extraction to ensure quality and accuracy of reporting.

Results

A total of 17 papers met the criteria and were included in this review. Compared to a healthy population, the majority of studies reported decreased cortical thickness in the left anterior cingulate/paracingulate and the left superior temporal gyrus, as well as several prefrontal regions bilaterally in patients with BD. Studies also show consistency of cortical thinning in individuals with BD and schizophrenia in frontal and temporal regions, suggesting some common neuropathology.

Conclusions

This systematic review further supports a link between specific structural brain abnormalities and BD. Future studies should investigate cortical thickness with respect to at‐risk populations to determine whether these neuropathologies develop before or after the onset of BD.
Admissions to hospital due to fracture in England in patients with prostate cancer treated with androgen‐deprivation therapy – do we have to worry about the hormones?
Authors: Jefferies Edward R. , Bahl Amit , Hounsome Luke , Eylert Maike F. , Verne Julia , Persad Raj A. ,   the PHONIC collaborative
Published: February 2016

Objective

To investigate the association between androgen‐deprivation therapy (ADT) and fracture risk in men with prostate cancer in England.

Patients and Methods

Using the Hospital Episodes Statistics database, which contains all the information about National Health Service (NHS) and NHS‐funded hospital admissions in England, for the years 2004–2008, 8 902 patients were found to have had prostate cancer and an admission to hospital with a fracture. Of these patients, 3 372 (37.8%) were identified as being treated with ADT, whilst 5 530 (62.2%) were not. There was a total of 228 852 admissions in the background population.

Results

The risk of a fracture requiring hospitalisation increased from 1.12 to 1.41 per 100 person‐years in a man with prostate cancer treated with ADT compared with those without ADT, an absolute increase of only 0.29 per 100 person‐years. When compared with the background population, there was an increase from 0.58 to 1.41 per 100 person‐years, a relative rate ratio increase of 2.4 (P < 0.01) with an absolute increase of 0.83 per 100 person‐years.

Conclusion

In England there was a small but statistically significant increased risk of fracture in men who had been treated with ADT. Men with prostate cancer, with or without ADT, were at an increased risk of fracture compared with the background population. We therefore suggest that if bone health is to be taken seriously in men with prostate cancer that all these men should be risk assessed (FRAX® or Qfracture® tools, as National Institute for Health and Care Excellence advised), as all men with prostate cancer have an increased risk of fracture, with those on ADT having slightly higher risk.
Ensemble‐Based Virtual Screening and Experimental Validation of Inhibitors Targeting a Novel Site of Human DNMT1
Authors: Joshi Manali , Rajpathak Shriram N. , Narwade Santosh C. , Deobagkar Deepti
Published: February 2016

Human DNA methyltransferase1 (hDNMT1) is responsible for preserving DNA methylation patterns that play important regulatory roles in differentiation and development. Misregulation of DNA methylation has thus been linked to many syndromes, life style diseases, and cancers. Developing specific inhibitors of hDNMT1 is an important challenge in the area since the currently targeted cofactor and substrate binding site share structural features with various proteins. In this work, we generated a structural model of the active form of hDNMT1 and identified that the 5‐methylcytosine (5‐mC) binding site of the hDNMT1 is structurally unique to the protein. This site has been previously demonstrated to be critical for methylation activity. We further performed multiple nanosecond time scale atomistic molecular dynamics simulations of the structural model followed by virtual screening of the Asinex database to identify inhibitors targeting the 5‐mC site. Two compounds were discovered that inhibited hDNMT1 in vitro, one of which also showed inhibition in vivo corroborating the screening procedure. This study thus identifies and attempts to validate for the first time a unique site of hDNMT1 that could be harnessed for rationally designing highly selective and potent hypomethylating agents.
Spontaneous and natural cytotoxicity receptor-mediated cytotoxicity are effector functions of distinct natural killer subsets in hepatitis C virus-infected chimpanzees
Authors: Verstrepen B E , Nieuwenhuis I G , Mooij P , Bogers W M , Boonstra A , Koopman G
Published: February 2016

In humans, CD16 and CD56 are used to identify functionally distinct natural killer (NK) subsets. Due to ubiquitous CD56 expression, this marker cannot be used to distinguish between NK cell subsets in chimpanzees. Therefore, functional analysis of distinct NK subsets during hepatitis C virus (HCV) infection has never been performed in these animals. In the present study an alternative strategy was used to identify four distinct NK subsets on the basis of the expression of CD16 and CD94. The expression of activating and inhibiting surface receptors showed that these subsets resemble human NK subsets. CD107 expression was used to determine degranulation of the different subsets in naive and HCV-infected chimpanzees. In HCV-infected chimpanzees increased spontaneous cytotoxicity was observed in CD94high/dimCD16pos and CD94lowCD16pos subsets. By contrast, increased natural cytotoxicity receptor (NCR)- mediated degranulation after NKp30 and NKp44 triggering was demonstrated in the CD94dimCD16neg subset. Our findings suggest that spontaneous and NCR-mediated cytotoxicity are effector functions of distinct NK subsets in HCV-infected chimpanzees.
Unclassifiable arrhythmic cardiomyopathy associated with Emery–Dreifuss caused by a mutation in FHL1
Authors: San Román I. , Navarro M. , Martínez F. , Albert L. , Polo L. , Guardiola J. , García‐Molina E. , Muñoz‐Esparza C. , López‐Ayala J. M. , Sabater‐Molina M. , Gimeno J. R.
Published: February 2016

Emery–Dreifuss muscular dystrophy (EDMD) is a heterogeneous genetic disorder characterized by peripheral muscular weakness often associated with dilated cardiomyopathy. We characterize clinically a large family with a mutation in FHL1 gene (p.Cys255Ser). Penetrance was 44%, 100% for males and 18% for females. The heart was the main organ involved. Affected adult males had mild hypertrophy, systolic dysfunction and restriction with non‐dilated ventricles. Carriers had significant QTc prolongation. The proband presented with resuscitated cardiac arrest. There were two transplants. Pathological study of explanted heart showed fibrofatty replacement and scarring consistent with arrhythmogenic cardiomyopathy and prominent left ventricular trabeculations. Myopathic involvement was evident in all males. Females had no significant neuromuscular disease. Mutations in FHL1 cause unclassifiable cardiomyopathy with coexisting EDMD. Prognosis is poor and systolic impairment and arrhythmias are frequent. Thrombopenia and raised creatine phosphokinase should raise suspicion of an FHL‐1 disorder in X‐linked cardiomyopathy.
A Systematic Review of Outcomes Following Immediate Molar Implant Placement Based on Recently Published Studies
Authors: Ketabi Mohammad , Deporter Douglas , Atenafu Eshetu G.
Published: February 2016

Background

Immediate implant placement in molar extraction sites has become a treatment option for experienced clinicians.

Purpose

The aim of this study was to provide a systematic review and meta‐analysis of outcomes from recent clinical studies with immediate molar implants.

Materials and Methods

A systematic review was undertaken of relevant literature published from November 2008 to May 2015. Data collected included implant survival rates after at least 1 year in function, cumulative crestal bone loss, and implant location (maxilla vs mandible) and diameter. Implant diameters were grouped as “wide” (4–6 mm) or “ultra‐wide” (>6–9 mm). Survival and bone loss with 95% CIs were calculated using a random effects model. Meta‐analysis techniques were used to compare survival rates and cumulative mean bone loss between immediate and delayed placement implants. Survival rates also were computed and compared between wide and ultra‐wide implants using chi‐square testing. The quality of each study was assessed using established criteria.

Results

The literature search provided 15 papers published between November 2008 and May 2015 that satisfied the inclusion criteria. Data on survival were found for a total of 768 immediate molar implants inserted in 757 patients. Meta‐analysis of these data showed an implant survival rate of 98% with no difference between maxilla and mandible. Five studies included delayed molar implants as controls, and no significant differences were detected. A significant difference (p = .048) was found in relation to implant diameter with implant failures being higher (3.67 vs 1.45%) for ultra‐wide (>6–9 mm) versus wide (4–6 mm) implants. The majority of the 15 studies were determined to be either “average” (prospective case series) or “fair” (retrospective) in quality.

Conclusion

While there are still no published reports from double‐blind, randomized, controlled (best quality) clinical trials of immediate molar implant placement, high survival rates have been reported. The present data, however, suggests that there may be an optimal diameter for this implant application. Meta‐analysis of the limited bone loss data reported estimated the overall mean cumulative bone loss after at least 1 year to be 0.57 mm.
Differences in routine esophagogastroduodenoscopy between Japanese and international facilities: A questionnaire survey
Authors: Uedo Noriya , Gotoda Takuji , Yoshinaga Shigetaka , Tanuma Tokuma , Morita Yoshinori , Doyama Hisashi , Aso Akira , Hirasawa Toshiaki , Yano Tomonori , Uchita Norihisa , Ho Shiaw‐Hooi , Hsieh Ping‐Hsin
Published: February 2016

Background and Aim

The mortality rate of gastric cancer (GC) is close to the incidence rate worldwide. However, in Korea and Japan, the mortality rate of GC is less than half of the incidence rate. We hypothesized that good‐quality routine esophagogastroduodenoscopy (EGD) contributes to a high detection rate for early GC (EGC) and improves mortality in these countries.

Methods

To clarify the differences in routine EGD, a questionnaire survey was conducted in 98 Japanese and 53 international institutions.

Results

Prevalence of screening examination among routine EGD was higher in Japanese than in international institutions. Japanese endoscopists noted that endoscopic mucosal atrophy was the most significant risk factor for GC, whereas international endoscopists paid more attention to clinical information such as age, symptoms and family history. Antispasmodics, mucolytics and defoaming agents were used more frequently in Japanese institutions. The examination time was similar (mostly 5–10 min) between Japanese and international institutions. Japanese endoscopists took more pictures (>20 in almost all institutions) than international endoscopists (≤20 in two‐thirds of institutions). In Japanese institutions, biopsy specimens were more frequently taken from areas of mucosal discoloration, unevenness or spontaneous bleeding rather than from obvious endoscopic lesions such as ulceration or polyps. In most Japanese institutions, one or two biopsy specimens were taken per lesion, compared with ≥three in international institutions.

Conclusion

There were some discrepancies between Japanese and international institutions for routine EGD. Thus, standardization is required for adequate risk assessment, proper techniques, and knowledge of endoscopic diagnosis of EGC.
Multi‐color FISH facilitates analysis of cell‐type diversification and developmental gene regulation in the Parasteatoda spider embryo
Authors: Akiyama‐Oda Yasuko , Oda Hiroki
Published: February 2016

The simultaneous and quantitative analysis of the expression of multiple genes helps to shed light on gene regulatory networks. We established a method for multi‐color fluorescence in situ hybridization (mFISH) for the analysis of cell‐type diversification and developmental gene regulation in the embryo of the spider Parasteatoda tepidariorum. This mFISH technique allowed quadruple staining using four types of labels for RNA probes, digoxigenin, fluorescein, biotin, and dinitrophenyl, together with different fluorescent tyramides. To validate the usability of mFISH, we conducted four experiments. First, we distinguished similar gene expression patterns with mFISH, which showed overlaps and differences in the expression domains of anterior patterning hedgehog (hh), orthodenticle (otd), and labial genes at a cellular resolution. Second, we used mFISH to identify early cell types that are internalized on the anterior side. We found that fork head‐positive cells were subdivided into two cell types, 012_A08‐positive endoderm cells and twist‐positive mesoderm cells. Third, we quantified the ratio of expression levels of the odd‐paired (opa) gene in the chelicera and pedipalp segments based on the intensity of mFISH signals. Finally, we combined mFISH with embryonic RNA interference. It was possible to identify opa knockdown cell clones and detect the specific reduction of opa and the upregulation of otd and hh expression levels in the same cell clone that formed in the head region. This study proposes that mFISH is a powerful tool for the cell‐level analysis of gene regulation and quantification in the spider model.
Clinical Relevance of Left Atrial Strain to Predict Recurrence of Atrial Fibrillation after Catheter Ablation: A Meta‐Analysis
Authors: Ma Xin‐Xin , Boldt Leif‐Hendrik , Zhang Yue‐Li , Zhu Meng‐Ruo , Hu Bing , Parwani Abdul , Belyavskiy Evgeny , Radha Krishnan Aravind K. , Krisper Maximilian , Köhncke Clemens , Osmanoglou Engin , Kropf Martin , Lacour Philipp , Blaschke Florian , Edelmann Frank , Tschöpe Carsten , Haverkamp Wilhelm , Pieske‐Kraigher Elisabeth , Pieske Burkert , Morris Daniel A.
Published: February 2016

Background

The purpose of this meta‐analysis was to analyze the clinical relevance of left atrial (LA) strain to predict recurrence of atrial fibrillation (AF) after catheter ablation (CA).

Methods and Results

We searched in different databases (Medline, EMBASE, and Cochrane) prospective studies that analyzed LA strain before CA. Eight studies (2 with only paroxysmal AF and 6 with mixed population of paroxysmal and persistent AF) were included in the final analysis (total patient number = 686). Patients with recurrence of AF were principally characterized by lower LA strain in comparison with those without AF recurrence (mean 18.4% [range 8.8–24.5%] versus 25.3% [13.6–32.7%], weighted mean difference −4.89% [95% CI −5.83% to −3.95%], P < 0.001). In addition, receiver operating curves shown that LA strain was strongly associated with recurrence of AF after CA (weighted mean: AUC 0.798 [95% CI 0.700–0.943], cutoff 22.8% [18.8–30%], sensitivity 78% [65–86%], and specificity 75% [66–100%]). In line, these results were similar using LA strain with QRS‐analysis and P‐analysis as well as using different software package such as Echo‐Pac, QLab, TomTec, and VVI.

Conclusion

In patients with AF candidate for CA, the analysis of the LA using LA strain could be of great usefulness to identify patients with high risk of AF recurrence. Nonetheless, further studies are needed to establish the clinical relevance of LA strain in patients with persistent AF.
Multiple Coronary Artery Aneurysms of the Right Coronary Artery in Neonate with Pulmonary Atresia with Intact Ventricular Septum
Authors: Bremen Carlie , Campbell David N. , Browne Lorna , Jone Pei‐Ni
Published: February 2016

Pulmonary atresia with intact ventricular septum (PA/IVS) with right ventricular‐dependent coronaries is a rare congenital cardiac anomaly. It has been associated with wide range of considerable anomalies including sinusoids, fistulae, coronary stenosis, or complete atresia. Coronary artery aneurysms in a neonate with PA/IVS have not been described. We report a case of neonate with pulmonary atresia with intact ventricular septum with giant coronary artery aneurysms.
Coronary Sinus Orifice Atresia Associated with Persistent Left Superior Vena Cava: A Case Report with Literature Review
Authors: Song Guang , Ren Weidong , Chen Yixin
Published: February 2016

Coronary sinus (CS) orifice atresia is a rare malformation, usually associated with persistent left superior vena cava (PLSVC). The preoperative diagnosis is very challenging. The only clue for diagnosis is the reverse direction of flow through PLSVC. We present the case of a 69‐year‐old woman with CS orifice atresia and PLSVC. Then, we retrospectively study 99 cases of this malformation, including ours. This malformation is usually associated with the “enlarged” CS (>12 mm) and “small” PLSVC (≤5 mm), with the incidence of 81 and 87%, respectively, from the literature review.
Learning from exporting in China
Authors: Hu Cui , Lin Faqin , Wang Xiaosong
Published: February 2016

Do exports increase the firm's productivity causally? Focusing on the matched information of highly disaggregated transaction and firm‐level data from 2000 to 2006 in China, we construct a new measure of firm‐specific demand shock as an instrument for firm exports, based on the GDP growth rate of destination countries. We find that a one percentage point expansion in exports raises firm total factor productivity (estimated by the Olley–Pakes method) by approximately 0.224 percentage points on average. Moreover, we find that exports to high‐income countries, more processing exports and scope expansion about variety contribute to the learning effect.
Where are they now? Psychosocial, educational, and vocational outcomes after epilepsy surgery in childhood
Authors: Puka Klajdi , Smith Mary Lou
Published: February 2016

Objective

To evaluate the social, educational, and vocational outcomes of young adults who underwent resective epilepsy surgery in childhood (4–11 years earlier), and in a comparison group of nonsurgical patients with intractable epilepsy.

Methods

Participants were 78 patients (mean age 22.37, standard deviation [SD] 2.47 years) with childhood onset intractable epilepsy, of whom 51 underwent surgery. At follow‐up, participants were at least 18 years of age. Patients' current education, employment, income, and various social factors, including living arrangements, relationship status, and involvement with friends and community organizations were recorded. In addition, parents of patients completed the Adult Behaviour Checklist (ABCL). Employment status, education, and income were compared with provincial census data.

Results

There was no statistically significant difference in the proportion of surgical and nonsurgical patients who were seizure‐free in the 12 months preceding the study: 53% and 33%, respectively (p = 0.10). Among all patients, 60% were enrolled in, or had completed, postsecondary education and 82% were employed or a student; similar to the general population. However, compared with population data, fewer patients with epilepsy (20%) had an annual income of $10,000 or greater (p < 0.001). Compared to normative data, a greater proportion of patients scored in the abnormal range in some ABCL scales (p < 0.028). Patients with IQs > 85 had significantly better educational, vocational, and psychosocial outcomes compared to patients with IQs ≤ 85. Surgical and nonsurgical patients did not differ on any outcome variable. Compared to patients with seizures, more seizure‐free patients were living independently (p = 0.03), and had a driver's licence (p < 0.001). Other outcomes were similar among patients with and without seizures.

Significance

Overall, patients with intractable epilepsy in childhood attained educational and vocational outcomes similar to that of the general population, but earned a significantly lower income. Seizure freedom, attained through surgery or medication management, was associated with better outcomes in limited psychosocial measures.