bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Cytomegalovirus gH/gL/gO Promotes the Fusion Step of Entry into All Cell Types, whereas gH/gL/UL128-131 Broadens Virus Tropism through a Distinct Mechanism
Authors: Zhou Momei , Lanchy Jean-Marc , Ryckman Brent J.
Published: June 2015

Interaction between gH/gL and the fusion protein gB is likely a conserved feature of the entry mechanism for all herpesviruses. Human cytomegalovirus (HCMV) gH/gL can be bound by gO or by the set of proteins UL128, UL130, and UL131, forming gH/gL/gO and gH/gL/UL128-131. The mechanisms by which these complexes facilitate entry are poorly understood. Mutants lacking UL128-131 replicate well on fibroblasts but fail to enter epithelial/endothelial cells, and this has led to the general assumption that gH/gL/UL128-131 promotes gB-mediated fusion on epithelial/endothelial cells whereas gH/gL/gO provides this function on fibroblasts. This was challenged by observations that gO-null mutants were defective on all of these cell types, suggesting that entry into epithelial/endothelial cells requires both of the gH/gL complexes, but the severe replication defect of the gO mutants precluded detailed analysis. We previously reported that the ratio of gH/gL/gO and gH/gL/UL128-131 in the virion envelope varied dramatically among HCMV strains. Here, we show that strains not only differ in the ratio, but also vary in the total amount of gH/gL in the virion. Cell-type-specific particle-to-PFU ratios of HCMV strains that contained different amounts of gH/gL/gO and gH/gL/UL128-131 were determined. Infection of both fibroblasts and epithelial cells was generally correlated with the abundance of gH/gL/gO, but not with that of gH/gL/UL128-131. The low infectivity of virions rich in gH/gL/UL128-131 but low in gH/gL/gO could be overcome by treatment with the chemical fusogen polyethylene glycol (PEG), strongly arguing that gH/gL/gO provides the conserved herpesvirus gH/gL entry function of promoting gB-mediated fusion for entry into all cell types, whereas gH/gL/UL128-131 acts through a distinct mechanism to allow infection of select cell types.

IMPORTANCE
The functions of HCMV gH/gL complexes in entry are unclear. Unlike the well-studied Epstein-Barr virus (EBV), where gH/gL and gH/gL/gp42 complexes both seem capable of promoting gB fusion during entry into different cell types, our studies here suggest that for HCMV, gH/gL/gO promotes gB fusion on all cell types, whereas gH/gL/UL128-131 broadens virus tropism through a distinct, as yet unknown mechanism. To our knowledge, this is the first suggestion of a herpesvirus gH/gL that does not act by promoting gB fusion, which might make HCMV a useful model to study the fundamental mechanisms by which herpesvirus gH/gL regulates gB fusion. Moreover, gH/gL/UL128-131 is a candidate vaccine target. Our findings help to explain the cell-type-dependent virus neutralization exhibited by anti-gH/gL/UL128-131 antibodies and underscore the importance of gH/gL/gO as another important part of vaccine or therapeutic strategies.
Atypical Henoch-Schonlein purpura? Consider polyarteritis nodosa!
Authors: Braungart Sarah , Campbell Alison , Besarovic Sanja
Published: June 2015

We describe the case of a previously healthy 12-year-old boy admitted to a tertiary paediatric centre with the clinical diagnosis of Henoch-Schonlein purpura (HSP). Symptoms on admission included a generalised rash, colicky abdominal pain, hypertension, proteinuria and fresh rectal bleeding. Abdominal pain and distension worsened and serial ultrasounds suggested bowel ischaemia. He underwent repeat laparotomy and bowel resection, with slow improvement after the second laparotomy. The severity of systemic involvement (gastrointestinal, cardiac, renal and skin) made the initial diagnosis of HSP questionable. Immunohistochemistry of skin biopsies was negative for HSP. Histopathology of the bowel specimen revealed features of necrotising small and medium vessel vasculitis in keeping with polyarteritis nodosa.
Fungal keratitis presenting as radial keratoneuritis
Authors: Kapoor Aditya , Jain Rajat , Sahu Srikant , Sangwan Virender
Published: June 2015

A 44-year-old man presented with severe pain, redness, watering and photophobia for 10 days in the right eye without any history of trauma. Diagnosis of herpes simplex disciform keratitis was made and he was prescribed topical steroids. The patient showed clinical worsening and presented with ring infiltrate, diffuse stromal oedema and radial keratoneuritis, a finding pathognomic of acanthamoeba keratitis. With two inconclusive corneal scrapings and the patient showing clinical worsening, an urgent therapeutic penetrating keratoplasty was carried out. Histopathological and microbiological examination of the excised corneal button revealed the presence of fungus. At 5 weeks follow-up, the patient has best-corrected visual acuity 20/40 with no recurrence of infection.
A differential for right iliac fossa pain and the importance of consenting properly
Authors: Gray Sarah Yu Weng , Kang Peter
Published: June 2015

A 39-year-old man presented with a 2-day history of central abdominal pain which had subsequently localised to the right iliac fossa, with clinical signs of tenderness with guarding in the right iliac fossa. With these classical signs, he was diagnosed with probable appendicitis and a laparoscopy with a view to appendicectomy was arranged. At laparoscopy, a torted, dusky-looking ischaemic greater omentum was found and resected. When performing laparoscopy for suspected appendicitis, it is important to look for other unexpected pathology and treat it as the situation requires, if the appendix is normal at the time of laparoscopy. The possibility of other pathologies to account for the patient's symptoms must not be overlooked.
Use of an oscillatory PEP device to enhance bronchial hygiene in a patient of post-H1NI pneumonia and acute respiratory distress syndrome with pneumothorax
Authors: Narula Deepali , Nangia Vivek
Published: June 2015

A 26-year-old, 14 week pregnant woman was admitted to our hospital with pneumonia with acute respiratory distress syndrome in an intubated and mechanically ventilated state. She was diagnosed to have polymicrobial infection and left-sided pneumothorax and was put on a ventilator for 2 weeks. Postextubation, she found it difficult to clear her respiratory secretions despite aggressive routine chest physiotherapy. She was planned to undergo a mini-tracheostomy for tracheobronchial toileting. However, before that, she was given a trial of Acapella, a hand-held oscillatory positive expiratory pressure (OPEP) therapy device, for facilitating airway clearance, with the aim to speed up the recovery. The patient found it easy to use and clear the secretions optimally, thus averting a mini-tracheostomy. This case report highlights the advantages of the OPEP therapy device in effective management of bronchial hygiene in patients with poor respiratory effort.
The risk of copper deficiency in patients prescribed zinc supplements
Authors: Duncan Andrew , Yacoubian Calum , Watson Neil , Morrison Ian
Published: June 2015

Aims

In high doses zinc may cause copper deficiency, a diagnosis that is often missed resulting in anaemia, neutropenia and irreversible neurological symptoms. The aim of this study was to assess if zinc deficiency is erroneously diagnosed by misinterpretation of plasma zinc concentrations and whether copper deficiency is induced in patients prescribed zinc.

Methods

Casenotes of 70 patients prescribed zinc were scrutinised. Plasma concentrations of zinc, copper, C reactive protein and albumin were recorded from the laboratory database.

Results

62% of patients were prescribed zinc at doses sufficient to cause copper deficiency. In 48% of the patients, plasma zinc concentrations were low as a probable result of hypoalbuminaemia or the systemic inflammatory response rather than deficiency. Awareness of copper deficiency was lacking; it was only documented as a possible side effect in one patient and plasma copper was measured in only two patients prescribed zinc. 9% of patients developed unexplained anaemia and 7% developed neurological symptoms typical of copper deficiency.

Conclusions

Zinc deficiency is frequently misdiagnosed on the basis of low plasma zinc concentrations. The potential risk of copper deficiency developing in patients prescribed high doses of zinc is apparently infrequently considered. It is probable that a significant minority of patients prescribed with high doses of zinc develop iatrogenic copper deficiency.
National surveillance for type 1, type 2 diabetes and prediabetes among children and adolescents: a population-based study (SAUDI-DM)
Authors: Al-Rubeaan Khalid
Published: June 2015

Background

There is a paucity of data on the national prevalence of diabetes and prediabetes among youth. The Saudi Abnormal Glucose Metabolism and Diabetes Impact Study (SAUDI-DM) was used to assess the prevalence of type 1 and type 2 diabetes as well as impaired fasting glucose (IFG) among children and adolescents.

Methods

Sociodemographic, anthropometric and clinical data were collected through a nationwide household randomly selected 23 523 children and adolescents aged ≤18 years. Known participants with diabetes were classified according to their diabetes type, while participants without diabetes were subjected to fasting plasma glucose assessment and patients with diabetes were identified using the American Diabetes Association (ADA) criteria. All the studied participants were tested for lipid parameters. Multivariate logistic regression analysis was used to assess different risk factors.

Results

The overall prevalence of diabetes was 10.84%, of which 0.45% were known type 1 and type 2 patients with diabetes and 10.39% were either newly identified cases of diabetes (4.27%) or IFG (6.12%) with more than 90% of the participants with diabetes being unaware of their disease. The prevalence of known type 1 and type 2 diabetes as well as the newly identified cases was higher than what has been reported internationally. Age, male gender, obesity, urban residency, high family income and presence of dyslipidaemia were found to be significant risk factors for diabetes and IFG.

Conclusions

Diabetes and IFG are highly prevalent in this society with the majority of the patients being unaware of their disease, which warrants urgent adoption of early detection, treatment and prevention programmes.
Gravity as the breakdown of conformal invariance
Authors: Amelino-Camelia Giovanni , Arzano Michele , Gubitosi Giulia , Magueijo João
Published: June 2015

In this paper, we propose that at the beginning of the universe gravity existed in a limbo either because it was switched off or because it was only conformally coupled to all particles. This picture can be reverse-engineered from the requirement that the cosmological perturbations be (nearly) scale-invariant without the need for inflation. It also finds support in recent results in quantum gravity suggesting that spacetime becomes two-dimensional at super-Planckian energies. We advocate a novel top-down approach to cosmology based on the idea that gravity and the Big Bang Universe are relics from the mechanism responsible for breaking the fundamental conformal invariance. Such a mechanism should leave clear signatures in departures from scale-invariance in the primordial power spectrum and the level of gravity waves generated.
Nature abhors a horizon
Authors: Kraus Per , Mathur Samir D.
Published: June 2015

The information paradox can be resolved if we recognize that the wave functional in gravity [Formula: see text] should be considered on the whole of superspace, the space of possible [Formula: see text]. The largeness of the Bekenstein entropy implies a vast space of gravitational solutions, which are conjectured to be fuzzball configurations. In the WKB approximation, the wave functional for a collapsing shell is oscillatory in a small region of superspace, and the classical approximation picks out this part. But the wave functional will be damped (“under the barrier”) in the remainder of this vast superspace. We perform a simple computation to show that at the threshold of black hole formation, the barrier is lowered enough to make the latter part oscillatory; this alters the classical evolution and avoids horizon formation.
Post-Newtonian direct and mixed orbital effects due to the oblateness of the central body
Authors: Iorio L.
Published: June 2015

The orbital dynamics of a test particle moving in the nonspherically symmetric field of a rotating oblate primary is impacted also by certain indirect, mixed effects arising from the interplay of the different Newtonian and post-Newtonian accelerations which induce known direct perturbations. We systematically calculate the indirect gravitoelectromagnetic shifts per orbit of the Keplerian orbital elements of the test particle arising from the crossing among the first even zonal harmonic J2 of the central body and the post-Newtonian static and stationary components of its gravitational field. We also work out the Newtonian shifts per orbit of order [Formula: see text], and the direct post-Newtonian gravitoelectric effects of order J2c-2 arising from the equations of motion. In the case of both the indirect and direct gravitoelectric J2c-2 shifts, our calculation holds for an arbitrary orientation of the symmetry axis of the central body. We yield numerical estimates of their relative magnitudes for systems ranging from Earth's artificial satellites to stars orbiting supermassive black holes. As far as their measurability is concerned, highly elliptical orbital configuration are desirable.
An Extended TAM to Explore Behavioural Intention of Consumers to Use M-Commerce
Authors: Chang Shih-Chi , Sun Chia-Chi , Pan Lee-Yuan , Wang Ming-Ying
Published: June 2015

This study proposes a research framework that integrates personal innovativeness, perceived risk, cost and enjoyment with the technology acceptance model (TAM). We used the proposed model to explore the antecedents of consumer behavioural intention (BI) to adopt mobile commerce (m-commerce). Excluding missing answers and invalid questionnaires, 477 valid responses were collected. In addition to confirmatory factor analysis (CFA), we used structural equation modelling (SEM) to examine the relationships among the constructs in the proposed model. Our findings indicated that the younger group (under 30) had lower stickiness to m-commerce. Among the constructs, perceived enjoyment (PE) had the most significant influence on BI, followed by attitude, perceived ease of use (PEOU), perceived usefulness (PU) and perceived risk. Our research results could be used as a guide and reference for m-commerce service providers to improve and operate their services.
Effect of Confining Pressure on Stress Intensity Factors for Cracked Brazilian Disk
Authors: Hua Wen , Xu Jigang , Dong Shiming , Song Jizhou , Wang Qingyuan
Published: June 2015

An analytical model, verified by the finite element method, is developed to study the effect of confining pressure on stress intensity factors for the cracked Brazilian disk. The closed-form expressions for stress intensity factors under both confining pressure and diametric forces are obtained based on the weight function method. The results show that the confining pressure has no effect on the mode II stress intensity factor; however, the mode I stress intensity factor decreases with the increase of confining pressure and the change may be above 100% for a large confining pressure. In addition, the effect of confining pressure on the loading condition of pure mode II crack is also investigated. It is shown that the critical loading angle for pure mode II crack decreases as the confining pressure increases. Depending on the magnitude of confining pressure, the failure problem of a disk may be no longer a pure fracture problem. These results have established the theoretical foundation to measure the fracture toughness of materials under confining pressure.
Integrating Multiple Dependency Corpora for Inducing Wide-Coverage Japanese CCG Resources
Authors: Uematsu Sumire , Matsuzaki Takuya , Hanaoka Hiroki , Miyao Yusuke , Mima Hideki
Published: June 2015

A novel method to induce wide-coverage Combinatory Categorial Grammar (CCG) resources for Japanese is proposed in this article. For some languages including English, the availability of large annotated corpora and the development of data-based induction of lexicalized grammar have enabled deep parsing, i.e., parsing based on lexicalized grammars. However, deep parsing for Japanese has not been widely studied. This is mainly because most Japanese syntactic resources are represented in chunk-based dependency structures, while previous methods for inducing grammars are dependent on tree corpora. To translate syntactic information presented in chunk-based dependencies to phrase structures as accurately as possible, integration of annotation from multiple dependency-based corpora is proposed. Our method first integrates dependency structures and predicate-argument information and converts them into phrase structure trees. The trees are then transformed into CCG derivations in a similar way to previously proposed methods. The quality of the conversion is empirically evaluated in terms of the coverage of the obtained CCG lexicon and the accuracy of the parsing with the grammar. While the transforming process used in this study is specialized for Japanese, the framework of our method would be applicable to other languages for which dependency-based analysis has been regarded as more appropriate than phrase structure-based analysis due to morphosyntactic features.
Keyword Extraction from Arabic Documents using Term Equivalence Classes
Authors: Awajan Arafat
Published: June 2015

The rapid growth of the Internet and other computing facilities in recent years has resulted in the creation of a large amount of text in electronic form, which has increased the interest in and importance of different automatic text processing applications, including keyword extraction and term indexing. Although keywords are very useful for many applications, most documents available online are not provided with keywords. We describe a method for extracting keywords from Arabic documents. This method identifies the keywords by combining linguistics and statistical analysis of the text without using prior knowledge from its domain or information from any related corpus. The text is preprocessed to extract the main linguistic information, such as the roots and morphological patterns of derivative words. A cleaning phase is then applied to eliminate the meaningless words from the text. The most frequent terms are clustered into equivalence classes in which the derivative words generated from the same root and the non-derivative words generated from the same stem are placed together, and their count is accumulated. A vector space model is then used to capture the most frequent N-gram in the text. Experiments carried out using a real-world dataset show that the proposed method achieves good results with an average precision of 31% and average recall of 53% when tested against manually assigned keywords.
Improving Telugu Dependency Parsing using Combinatory Categorial Grammar Supertags
Authors: Kumari B. Venkata Seshu , Rao Ramisetty Rajeshwara
Published: June 2015

We show that Combinatory Categorial Grammar (CCG) supertags can improve Telugu dependency parsing. In this process, we first extract a CCG lexicon from the dependency treebank. Using both the CCG lexicon and the dependency treebank, we create a CCG treebank using a chart parser. Exploring different morphological features of Telugu, we develop a supertagger using maximum entropy models. We provide CCG supertags as features to the Telugu dependency parser (MST parser). We get an improvement of 1.8% in the unlabelled attachment score and 2.2% in the labelled attachment score. Our results show that CCG supertags improve the MST parser, especially on verbal arguments for which it has weak rates of recovery.
Role of neurons and glia in the CNS actions of the renin-angiotensin system in cardiovascular control
Authors: de Kloet Annette D. , Liu Meng , Rodríguez Vermalí , Krause Eric G. , Sumners Colin
Published: June 2015

Despite tremendous research efforts, hypertension remains an epidemic health concern, leading often to the development of cardiovascular disease. It is well established that in many instances, the brain plays an important role in the onset and progression of hypertension via activation of the sympathetic nervous system. Further, the activity of the renin-angiotensin system (RAS) and of glial cell-mediated proinflammatory processes have independently been linked to this neural control and are, as a consequence, both attractive targets for the development of antihypertensive therapeutics. Although it is clear that the predominant effector peptide of the RAS, ANG II, activates its type-1 receptor on neurons to mediate some of its hypertensive actions, additional nuances of this brain RAS control of blood pressure are constantly being uncovered. One of these complexities is that the RAS is now thought to impact cardiovascular control, in part, via facilitating a glial cell-dependent proinflammatory milieu within cardiovascular control centers. Another complexity is that the newly characterized antihypertensive limbs of the RAS are now recognized to, in many cases, antagonize the prohypertensive ANG II type 1 receptor (AT1R)-mediated effects. That being said, the mechanism by which the RAS, glia, and neurons interact to regulate blood pressure is an active area of ongoing research. Here, we review the current understanding of these interactions and present a hypothetical model of how these exchanges may ultimately regulate cardiovascular function.
Single-motor-unit discharge characteristics in human lumbar multifidus muscle
Authors: Lothe Lise R. , Raven Tim J. L. , Eken Torsten
Published: June 2015

The underlying neurophysiology of postural control of the lower back in humans is poorly understood. We have characterized motor unit (MU) discharge activity in the deep lumbar multifidus (LM) muscle in nine healthy subjects (20–40 yr, 3 females). Bilateral fine wire electrodes were implanted at L4 spinal level using ultrasound guidance. EMG was recorded during spontaneous sitting and standing and during voluntary force production. Individual MUs were analyzed with regard to instantaneous discharge rate, interspike interval variability, alternation of activity between MUs, and cross correlation between concurrently active MUs quantified by the common drive coefficient (CDC). Significant effects of sitting vs. standing were seen on median discharge rate and interspike interval variability. Median discharge rate in 71 units was 5.4 and 6.9 pulses/s during spontaneous sitting and standing and 7.4 pulses/s during voluntary force production. Several MUs fired doublets. CDC analysis of 87 MU pairs showed a significantly higher common drive in spontaneous than in voluntary activity and significant differences between unilateral and bilateral pairs, although not when spontaneously active in standing. In spite of common drive, MUs were recruited from inactivity to tonic discharge lasting for several minutes without changes in discharge rate in already active MUs, and several instances were documented where activity was rotated between MUs. We argue that this behavior is indicative of self-sustained discharge in LM motoneurons, establishing intrinsic motoneuron properties as a central mechanism for postural control of deep back muscles.
MATLAB-based automated patch-clamp system for awake behaving mice
Authors: Desai Niraj S. , Siegel Jennifer J. , Taylor William , Chitwood Raymond A. , Johnston Daniel
Published: June 2015

Automation has been an important part of biomedical research for decades, and the use of automated and robotic systems is now standard for such tasks as DNA sequencing, microfluidics, and high-throughput screening. Recently, Kodandaramaiah and colleagues ( Nat Methods 9: 585–587, 2012) demonstrated, using anesthetized animals, the feasibility of automating blind patch-clamp recordings in vivo. Blind patch is a good target for automation because it is a complex yet highly stereotyped process that revolves around analysis of a single signal (electrode impedance) and movement along a single axis. Here, we introduce an automated system for blind patch-clamp recordings from awake, head-fixed mice running on a wheel. In its design, we were guided by 3 requirements: easy-to-use and easy-to-modify software; seamless integration of behavioral equipment; and efficient use of time. The resulting system employs equipment that is standard for patch recording rigs, moderately priced, or simple to make. It is written entirely in MATLAB, a programming environment that has an enormous user base in the neuroscience community and many available resources for analysis and instrument control. Using this system, we obtained 19 whole cell patch recordings from neurons in the prefrontal cortex of awake mice, aged 8–9 wk. Successful recordings had series resistances that averaged 52 ± 4 MΩ and required 5.7 ± 0.6 attempts to obtain. These numbers are comparable with those of experienced electrophysiologists working manually, and this system, written in a simple and familiar language, will be useful to many cellular electrophysiologists who wish to study awake behaving mice.
Resource Allocation Algorithm Based on Profit Maximization for Crowd Sensing
Authors: Gao Kun , Wang Bin , Yu Xinwu
Published: June 2015

The key to realizing the crowd sensing network is to overcome the resource restrictions of energy, bandwidth, computing, and so on. First of all, due to the number of users and sensor availability will be dynamic change over time, crowd sensing system is difficult to accurately predict and allocate resource to accomplish a specific task. Secondly, there is a need to consider how to choose an effective subset from a large number of users with different sensing ability, so as to allocate the sensing devices in communication resources under the constraint conditions. This paper proposes a profit maximization algorithm for resource allocation component in crowd sensing environment. The proposed algorithm not only considers the current profit of crowd sensing service request but also considers the long-term expected profits, so as to ensure long-term maximum profit. The objective function is no longer to minimize the completion time but rather to achieve the target profit maximization. The experimental results show that the new algorithm is feasible and superior to the traditional algorithms.
Response Surface Methodology for the Optimization of Preparation of Biocomposites Based on Poly(lactic acid) and Durian Peel Cellulose
Authors: Penjumras Patpen , Abdul Rahman Russly , Talib Rosnita A. , Abdan Khalina
Published: June 2015

Response surface methodology was used to optimize preparation of biocomposites based on poly(lactic acid) and durian peel cellulose. The effects of cellulose loading, mixing temperature, and mixing time on tensile strength and impact strength were investigated. A central composite design was employed to determine the optimum preparation condition of the biocomposites to obtain the highest tensile strength and impact strength. A second‐order polynomial model was developed for predicting the tensile strength and impact strength based on the composite design. It was found that composites were best fit by a quadratic regression model with high coefficient of determination (R2) value. The selected optimum condition was 35 wt.% cellulose loading at 165°C and 15 min of mixing, leading to a desirability of 94.6%. Under the optimum condition, the tensile strength and impact strength of the biocomposites were 46.207 MPa and 2.931 kJ/m2, respectively.
A Community Finding Method for Weighted Dynamic Online Social Network Based on User Behavior
Authors: Chen Dongming , Dong Yanlin , Huang Xinyu , Chen Haiyan , Wang Dongqi
Published: June 2015

Revealing the structural features of social networks is vitally important to both scientific research and practice, and the explosive growth of online social networks in recent years has brought us dramatic advances to understand social structures. Here we proposed a community detection approach based on user interaction behavior in weighted dynamic online social networks. We researched interaction behaviors in online social networks and built a directed and unweighted network model in terms of the Weibo following relationships between social individuals at the very beginning. In order to refine the interaction behavior, level one fuzzy comprehensive evaluation model was employed to describe how closely individuals are connected to each other. According to this intimate degree description, weights are tagged to the prior unweighted model we built. Secondly, a heuristic community detection algorithm for dynamic network was provided based on the improved version of modularity called module density. As for the heuristic rule, we chose greedy strategy and merely fed the algorithms with the changed parts within neighboring time slice. Experimental results show that the proposed algorithm can obtain high accuracy and simultaneously get comparatively lower time complexity than some typical algorithms. More importantly, our algorithm needs no a priori conditions.
Propranolol for Paroxysmal Sympathetic Hyperactivity with Lateralizing Hyperhidrosis after Stroke
Authors: Siefferman Jason W. , Lai George
Published: June 2015

Brain injury can lead to impaired cortical inhibition of the hypothalamus, resulting in increased sympathetic nervous system activation. Symptoms of paroxysmal sympathetic hyperactivity may include hyperthermia, tachycardia, tachypnea, vasodilation, and hyperhidrosis. We report the case of a 41-year-old man who suffered from a left middle cerebral artery stroke and subsequently developed central fever, contralateral temperature change, and hyperhidrosis. His symptoms abated with low-dose propranolol and then returned upon discontinuation. Restarting propranolol again stopped his symptoms. This represents the first report of propranolol being used for unilateral dysautonomia after stroke. Propranolol is a lipophilic nonselective beta-blocker which easily crosses the blood-brain barrier and may be used to treat paroxysmal sympathetic hyperactivity.
Towards Ordered Silicon Nanostructures through Self‐Assembling Mechanisms and Processes
Authors: Puglisi R. A.
Published: June 2015

The design and development of innovative architectures for memory storage and energy conversion devices are at the forefront of current research efforts driving us towards a sustainable future. However, issues related to the cost, efficiency, and reliability of current technologies are still severely limiting their overtake of the standard designs. The use of ordered nanostructured silicon is expected to overcome these limitations and push the advancement of the alternative technologies. Specifically, self‐assembling of block copolymers has been recognized as a promising and cost‐effective approach to organize silicon nanostructures. This work reviews some of the most important findings on block copolymer self‐assembling and complements those with the results of new experimental studies. First of all, a quantitative analysis is presented on the ordering and fluctuations expected in the synthesis of silicon nanostructures by using standard synthesis methods like chemical vapour deposition. Then the effects of the several parameters guiding the ordering mechanisms in the block copolymer systems, such as film thickness, molecular weight, annealing conditions, solvent, and substrate topography are discussed. Finally, as a proof of concept, an in‐house developed example application to solar cells is presented, based on silicon nanostructures resulting from self‐assembling of block copolymers.
Pervasive Radio Mapping of Industrial Environments Using a Virtual Reality Approach
Authors: Nedelcu Adrian-Valentin , Machedon-Pisu Mihai , Duguleana Mihai , Talaba Doru
Published: June 2015

Wireless communications in industrial environments are seriously affected by reliability and performance issues, due to the multipath nature of obstacles within such environments. Special attention needs to be given to planning a wireless industrial network, so as to find the optimum spatial position for each of the nodes within the network, and especially for key nodes such as gateways or cluster heads. The aim of this paper is to present a pervasive radio mapping system which captures (senses) data regarding the radio spectrum, using low‐cost wireless sensor nodes. This data is the input of radio mapping algorithms that generate electromagnetic propagation profiles. Such profiles are used for identifying obstacles within the environment and optimum propagation pathways. With the purpose of further optimizing the radio planning process, the authors propose a novel human‐network interaction (HNI) paradigm that uses 3D virtual environments in order to display the radio maps in a natural, easy‐to‐perceive manner. The results of this approach illustrate its added value to the field of radio resource planning of industrial communication systems.
Microstructure Modifications and Associated Corrosion Improvements in GH4169 Superalloy Treated by High Current Pulsed Electron Beam
Authors: Su Yichang , Li Guangyu , Niu Liyuan , Yang Shengzhi , Cai Jie , Guan Qingfeng
Published: June 2015

The surface of the nickel‐based superalloy GH4169 was subjected to high‐current pulsed electron beam (HCPEB) treatment. The microstructural morphologies of the material were analysed by means of optical microscope (OP), scanning electron microscope (SEM), and transmission electron microscope (TEM). The results reveal that the irradiated surface was remelted and many craters were formed. The density of craters decreased with the increment of HCPEB pulses. After 20‐pulsed HCPEB irradiation, nanostructures were formed in the melted region of the surface. Furthermore, slipping bands and high density of dislocations were also formed due to the severe plastic deformation. The selective purification effect, homogenized composition, nanostructures, and dislocation slips introduced by HCPEB irradiation bring a significant improvement of corrosion resistance of GH4169 superalloy.
Optimization of Processing Parameters in ECM of Die Tool Steel Using Nanofluid by Multiobjective Genetic Algorithm
Authors: Sathiyamoorthy V. , Sekar T. , Elango N.
Published: June 2015

Formation of spikes prevents achievement of the better material removal rate (MRR) and surface finish while using plain NaNO3 aqueous electrolyte in electrochemical machining (ECM) of die tool steel. Hence this research work attempts to minimize the formation of spikes in the selected workpiece of high carbon high chromium die tool steel using copper nanoparticles suspended in NaNO3 aqueous electrolyte, that is, nanofluid. The selected influencing parameters are applied voltage and electrolyte discharge rate with three levels and tool feed rate with four levels. Thirty‐six experiments were designed using Design Expert 7.0 software and optimization was done using multiobjective genetic algorithm (MOGA). This tool identified the best possible combination for achieving the better MRR and surface roughness. The results reveal that voltage of 18 V, tool feed rate of 0.54 mm/min, and nanofluid discharge rate of 12 lit/min would be the optimum values in ECM of HCHCr die tool steel. For checking the optimality obtained from the MOGA in MATLAB software, the maximum MRR of 375.78277 mm3/min and respective surface roughness Ra of 2.339779 μm were predicted at applied voltage of 17.688986 V, tool feed rate of 0.5399705 mm/min, and nanofluid discharge rate of 11.998816 lit/min. Confirmatory tests showed that the actual performance at the optimum conditions was 361.214 mm3/min and 2.41 μm; the deviation from the predicted performance is less than 4% which proves the composite desirability of the developed models.
Increased Th17/Treg Ratio in Poststroke Fatigue
Authors: Liu Xinjing , Kenkare Komal , Li Shanshan , Desai Varsha , Wong John , Luo Xun , Wood Lisa J. , Xu Yuming , Wang Qing Mei
Published: June 2015

Fatigue is a major debilitating symptom after stroke. The biological mechanisms underlying poststroke fatigue (PFS) are unknown. We hypothesized that PSF is associated with an alteration in the balance between Th17 and Treg cells. To test this hypothesis we assessed fatigue in 30 stroke survivors using the Fatigue Scale for Motor and Cognitive Functions (FSMC). Peripheral blood was collected for assessment of Th17 and Treg cell populations and measurement of interleukin‐10 (IL‐10). Participants were dichotomized into severe fatigue (n = 14) and low‐moderate fatigue (n = 16) groups by K‐mean cluster analysis of FSMC scores. There were no group differences in age, gender, stroke type, stroke severity, or time since stroke. Stroke survivors in the severe fatigue group reported greater anxiety (p = 0.004) and depression (p = 0.001) than in the low‐moderate fatigue group. The ratio of Th17 to Treg cells was significantly increased in the severe fatigue group relative to the mild‐moderate fatigue group (p = 0.035). Serum levels of IL‐10 negatively correlated withTh17/Treg ratio (r = −0.408,  p = 0.025). Our preliminary findings suggest that an imbalance in the Th17/Treg ratio is associated with the severity of PSF.
Evaluating Insects as Bioindicators of Heavy Metal Contamination and Accumulation near Industrial Area of Gujrat, Pakistan
Authors: Azam Iqra , Afsheen Sumera , Zia Ahmed , Javed Muqaddas , Saeed Rashid , Sarwar Muhammad Kaleem , Munir Bushra
Published: June 2015

To study the accumulation and contamination of heavy metals (i.e., Cd, Cr, Cu, Ni, and Zn) in soil, air, and water, few insect species were assayed as ecological indicators. Study area comes under industrial zone of district Gujrat of Punjab, Pakistan. Insects used as bioindicators included a libellulid dragonfly (Crocothemis servilia), an acridid grasshopper (Oxya hyla hyla), and a nymphalid butterfly (Danaus chrysippus) near industrial zone of Gujrat. Accumulation of Cd was highest in insect species followed by Cu, Cr, Zn, and Ni atp<0.05. Hierarchical cluster analysis (HACA) was carried out to study metal accumulation level in all insects. Correlation and regression analysis confirmed HACA observations and declared concentration of heavy metals above permissible limits. Metal concentrations in insects were significantly higher near industries and nallahs in Gujrat and relatively higher concentrations of metals were found in Orthoptera than Odonata and Lepidoptera. The total metal concentrations in insects were pointed significantly higher at sites S3 (Mid of HalsiNala), S9 (End of HalsiNala), and S1 (Start of HalsiNala), whereas lowest value was detected at site S6 (Kalra Khasa) located far from industrial area. HACA indicates that these insect groups are potential indicators of metal contamination and can be used in biomonitoring.
The Key Role of Calmodulin in KRAS-Driven Adenocarcinomas
Authors: Nussinov Ruth , Muratcioglu Serena , Tsai Chung-Jung , Jang Hyunbum , Gursoy Attila , Keskin Ozlem
Published: June 2015

KRAS4B is a highly oncogenic splice variant of the KRAS isoform. It is the only isoform associated with initiation of adenocarcinomas. Insight into why and how KRAS4B can mediate ductal adenocarcinomas, particularly of the pancreas, is vastly important for its therapeutics. Here we point out the overlooked critical role of calmodulin (CaM). Calmodulin selectively binds to GTP-bound K-Ras4B; but not to other Ras isoforms. Cell proliferation and growth require the MAPK (Raf/MEK/ERK) and PI3K/Akt pathways. We propose that Ca2+/calmodulin promote PI3Kα/Akt signaling, and suggest how. The elevated calcium levels clinically observed in adenocarcinomas may explain calmodulin's involvement in recruiting and stimulating PI3Kα through interaction with its n/cSH2 domains as well as K-Ras4B; importantly, it also explains why K-Ras4B specifically is a key player in ductal carcinomas, such as pancreatic (PDAC), colorectal (CRC), and lung cancers. We hypothesize that calmodulin recruits and helps activate PI3Kα at the membrane, and that this is the likely reason for Ca2+/calmodulin dependence in adenocarcinomas. Calmodulin can contribute to initiation/progression of ductal cancers via both PI3Kα/Akt and Raf/MEK/ERK pathways. Blocking the K-Ras4B/MAPK pathway and calmodulin/PI3Kα binding in a K-Ras4B/calmodulin/PI3Kα trimer could be a promising adenocarcinoma-specific therapeutic strategy. Mol Cancer Res; 13(9); 1265–73. ©2015 AACR.
A Genome-Wide Scan Identifies Variants in NFIB Associated with Metastasis in Patients with Osteosarcoma
Authors: Mirabello Lisa , Koster Roelof , Moriarity Branden S. , Spector Logan G. , Meltzer Paul S. , Gary Joy , Machiela Mitchell J. , Pankratz Nathan , Panagiotou Orestis A. , Largaespada David , Wang Zhaoming , Gastier-Foster Julie M. , Gorlick Richard , Khanna Chand , de Toledo Silvia Regina Caminada , Petrilli Antonio S. , Patiño-Garcia Ana , Sierrasesúmaga Luis , Lecanda Fernando , Andrulis Irene L. , Wunder Jay S. , Gokgoz Nalan , Serra Massimo , Hattinger Claudia , Picci Piero , Scotlandi Katia , Flanagan Adrienne M. , Tirabosco Roberto , Amary Maria Fernanda , Halai Dina , Ballinger Mandy L. , Thomas David M. , Davis Sean , Barkauskas Donald A. , Marina Neyssa , Helman Lee , Otto George M. , Becklin Kelsie L. , Wolf Natalie K. , Weg Madison T. , Tucker Margaret , Wacholder Sholom , Fraumeni Joseph F. , Caporaso Neil E. , Boland Joseph F. , Hicks Belynda D. , Vogt Aurelie , Burdett Laurie , Yeager Meredith , Hoover Robert N. , Chanock Stephen J. , Savage Sharon A.
Published: June 2015

Metastasis is the leading cause of death in patients with osteosarcoma, the most common pediatric bone malignancy. We conducted a multistage genome-wide association study of osteosarcoma metastasis at diagnosis in 935 osteosarcoma patients to determine whether germline genetic variation contributes to risk of metastasis. We identified an SNP, rs7034162, in NFIB significantly associated with metastasis in European osteosarcoma cases, as well as in cases of African and Brazilian ancestry (meta-analysis of all cases: P = 1.2 × 10−9; OR, 2.43; 95% confidence interval, 1.83–3.24). The risk allele was significantly associated with lowered NFIB expression, which led to increased osteosarcoma cell migration, proliferation, and colony formation. In addition, a transposon screen in mice identified a significant proportion of osteosarcomas harboring inactivating insertions in Nfib and with lowered NFIB expression. These data suggest that germline genetic variation at rs7034162 is important in osteosarcoma metastasis and that NFIB is an osteosarcoma metastasis susceptibility gene.

Significance: Metastasis at diagnosis in osteosarcoma is the leading cause of death in these patients. Here we show data that are supportive for the NFIB locus as associated with metastatic potential in osteosarcoma. Cancer Discov; 5(9); 920–31. ©2015 AACR.

This article is highlighted in the In This Issue feature, p. 893
Recessive
MYH6
Mutations in Hypoplastic Left Heart With Reduced Ejection Fraction
Authors: Theis Jeanne L. , Zimmermann Michael T. , Evans Jared M. , Eckloff Bruce W. , Wieben Eric D. , Qureshi Muhammad Y. , O’Leary Patrick W. , Olson Timothy M.
Published: June 2015

Background—

The molecular underpinnings of hypoplastic left heart are poorly understood. Staged surgical palliation has dramatically improved survival, yet eventual failure of the systemic right ventricle necessitates cardiac transplantation in a subset of patients. We sought to identify genetic determinants of hypoplastic left heart with latent right ventricular dysfunction in individuals with a Fontan circulation.

Methods and Results—

Evaluation of cardiac structure and function by echocardiography in patients with hypoplastic left heart and their first-degree relatives identified 5 individuals with right ventricular ejection fraction ≤40% after Fontan operation. Whole genome sequencing was performed on DNA from 21 family members, filtering for genetic variants with allele frequency <1% predicted to alter protein structure or expression. Secondary family-based filtering for de novo and recessive variants revealed rare inherited missense mutations on both paternal and maternal alleles of
MYH6
, encoding myosin heavy chain 6, in 2 patients who developed right ventricular dysfunction 3 to 11 years postoperatively. Parents and siblings who were heterozygous carriers had normal echocardiograms. Protein modeling of the 4 highly conserved amino acid substitutions, residing in both head and tail domains, predicted perturbation of protein structure and function.

Conclusions—

In contrast to dominant
MYH6
mutations with variable penetrance identified in other congenital heart defects and dilated cardiomyopathy, this study reveals compound heterozygosity for recessive
MYH6
mutations in patients with hypoplastic left heart and reduced systemic right ventricular ejection fraction. These findings implicate a shared molecular basis for the developmental arrest and latent myopathy of left and right ventricles, respectively.
HIF Hydroxylase Pathways in Cardiovascular Physiology and Medicine
Authors: Bishop Tammie , Ratcliffe Peter J.
Published: June 2015

Hypoxia inducible factors (HIFs) are α/β heterodimeric transcription factors that direct multiple cellular and systemic responses in response to changes in oxygen availability. The oxygen sensitive signal is generated by a series of iron and 2-oxoglutarate–dependent dioxygenases that catalyze post-translational hydroxylation of specific prolyl and asparaginyl residues in HIFα subunits and thereby promote their destruction and inactivation in the presence of oxygen. In hypoxia, these processes are suppressed allowing HIF to activate a massive transcriptional cascade. Elucidation of these pathways has opened several new fields of cardiovascular research. Here, we review the role of HIF hydroxylase pathways in cardiac development and in cardiovascular control. We also consider the current status, opportunities, and challenges of therapeutic modulation of HIF hydroxylases in the therapy of cardiovascular disease.