bluuebunny/crossref_metadata_2025 huggingface dataset:
Forwardflow
Authors: Gibson Dan , Wood David A.
Published: October 2012

Chip Multiprocessors (CMPs) are now commodity hardware, but commoditization of parallel software remains elusive. In the near term, the current trend of increased core-per-socket count will continue, despite a lack of parallel software to exercise the hardware. Future CMPs must deliver thread-level parallelism when software provides threads to run, but must also continue to deliver performance gains for single threads by exploiting instruction-level parallelism and memory-level parallelism. However, power limitations will prevent conventional cores from exploiting both simultaneously.

This work presents the Forwardflow Architecture, which can scale its execution logic up to run single threads, or down to run multiple threads in a CMP. Forwardflow dynamically builds an explicit internal dataflow representation from a conventional instruction set architecture, using forward dependence pointers to guide instruction wakeup, selection, and issue. Forwardflow's backend is organized into discrete units that can be individually (de-)activated, allowing each core's performance to be scaled by system software at the architectural level.

On single threads, Forwardflow core scaling yields a mean runtime reduction of 21% for a 37% increase in power consumption. For multithreaded workloads, a Forwardflow-based CMP allows system software to select the performance point that best matches available power.
Energy-performance tradeoffs in processor architecture and circuit design
Authors: Azizi Omid , Mahesri Aqeel , Lee Benjamin C. , Patel Sanjay J. , Horowitz Mark
Published: October 2012

Power consumption has become a major constraint in the design of processors today. To optimize a processor for energy-efficiency requires an examination of energy-performance trade-offs in all aspects of the processor design space, including both architectural and circuit design choices. In this paper, we apply an integrated architecture-circuit optimization framework to map out energy-performance trade-offs of several different high-level processor architectures. We show how the joint architecture-circuit space provides a trade-off range of approximately 6.5x in performance for 4x energy, and we identify the optimal architectures for different design objectives. We then show that many of the designs in this space come at very high marginal costs. Our results show that, for a large range of design objectives, voltage scaling is effective in efficiently trading off performance and energy, and that the choice of optimal architecture and circuits does not change much during voltage scaling. Finally, we show that with only two designs--a dual-issue in-order design and a dual-issue out-of-order design, both properly optimized-a large part of the energy-performance trade-off space can be covered within 3% of the optimal energy-efficiency.
Web search using mobile cores
Authors: Janapa Reddi Vijay , Lee Benjamin C. , Chilimbi Trishul , Vaid Kushagra
Published: October 2012

The commoditization of hardware, data center economies of scale, and Internet-scale workload growth all demand greater power efficiency to sustain scalability. Traditional enterprise workloads, which are typically memory and I/O bound, have been well served by chip multiprocessors com- prising of small, power-efficient cores. Recent advances in mobile computing have led to modern small cores capable of delivering even better power efficiency. While these cores can deliver performance-per-Watt efficiency for data center workloads, small cores impact application quality-of-service robustness, and flexibility, as these workloads increasingly invoke computationally intensive kernels. These challenges constitute the price of efficiency. We quantify efficiency for an industry-strength online web search engine in production at both the microarchitecture- and system-level, evaluating search on server and mobile-class architectures using Xeon and Atom processors.
The impact of management operations on the virtualized datacenter
Authors: Soundararajan Vijayaraghavan , Anderson Jennifer M.
Published: October 2012

Virtualization has the potential to dramatically reduce the total cost of ownership of datacenters and increase the flexibility of deployments for general-purpose workloads. If present trends continue, the datacenter of the future will be largely virtualized. The base platform in such a datacenter will consist of physical hosts that run hypervisors, and workloads will run within virtual machines on these platforms. From a system management perspective, the virtualized environment enables a number of new workflows in the datacenter. These workflows involve operations on the physical hosts themselves, such as upgrading the hypervisor, as well as operations on the virtual machines, such as reconfiguration or reverting from snapshots. While traditional datacenter design has focused on the cost vs. capability tradeoffs for the end-user applications running in the datacenter, we argue that the management workload from these workflows must be factored into the design of the virtualized datacenter.

In this paper, we examine data from real-world virtualized deployments to characterize common management workflows and assess their impact on resource usage in the datacenter. We show that while many end-user applications are fairly light on I/O requirements, the management workload has considerable network and disk I/O requirements. We show that the management workload scales with the increasing compute power in the datacenter. Finally, we discuss the implications of this management workload for the datacenter.
The rebirth of neural networks
Authors: Temam Olivier
Published: October 2012

After the hype of the 1990s, where companies like Intel or Philips built commercial hardware systems based on neural networks, the approach quickly lost ground for multiple reasons: hardware neural networks were no match for software neural networks run on rapidly progressing general-purpose processors, their application scope was considered too limited, and even progress in machine-learning theory overshadowed neural networks.

However, in the past few years, a remarkable convergence of trends and innovations is casting a new light on neural networks and could make them valuable components of future computing systems. Trends in technology call for architectures which can sustain a large number of defects, something neural networks are intrinsically capable of. Tends in applications, summarized in the recent RMS categorization, highlight a number of key algorithms which are eligible to neural networks implementations. At the same time, innovations in technology, such as the recent realization of a memristor, are creating the conditions for the efficient hardware implementation of neural networks. Innovations in machine learning, with the recent advent of Deep Networks, have revived interest in neural networks. Finally, recent findings in neurobiology carry even greater prospects, where detailed explanations of how complex functions, such as vision, can be implemented further open up the defect-tolerance and application potential of neural network architectures.
Necromancer
Authors: Ansari Amin , Feng Shuguang , Gupta Shantanu , Mahlke Scott
Published: October 2012

Aggressive technology scaling into the nanometer regime has led to a host of reliability challenges in the last several years. Unlike on-chip caches, which can be efficiently protected using conventional schemes, the general core area is less homogeneous and structured, making tolerating defects a much more challenging problem. Due to the lack of effective solutions, disabling non-functional cores is a common practice in industry to enhance manufacturing yield, which results in a significant reduction in system throughput. Although a faulty core cannot be trusted to correctly execute programs, we observe in this work that for most defects, when starting from a valid architectural state, execution traces on a defective core actually coarsely resemble those of fault-free executions. In light of this insight, we propose a robust and heterogeneous core coupling execution scheme, Necromancer, that exploits a functionally dead core to improve system throughput by supplying hints regarding high-level program behavior. We partition the cores in a conventional CMP system into multiple groups in which each group shares a lightweight core that can be substantially accelerated using these execution hints from a potentially dead core. To prevent this
undead
core from wandering too far from the correct path of execution, we dynamically resynchronize architectural state with the lightweight core. For a 4-core CMP system, on average, our approach enables the coupled core to achieve 78.5% of the performance of a fully functioning core. This defect tolerance and throughput enhancement comes at modest area and power overheads of 5.3% and 8.5%, respectively.
Comparison of search engines non-neutral and neutral behaviors
Authors: Coucheney Pierre , Maillé Patrick , Tuffin Bruno
Published: October 2012

Network neutrality has recently attracted a lot of attention but search neutrality is also becoming a vivid subject of discussion because a non-neutral search may prevent some relevant content from being accessed by users. We propose in this paper to model two situations of a non-neutral search engine behavior, which can rank the link propositions according to the profit a search can generate for it instead of just relevance: the case when the search engine owns some content, and the case when it imposes a tax on organic links, a bit similarly to what it does for commercial links. We analyze the particular (and deterministic) situation of a single keyword, and describe the problem for the whole potential set of keywords.
Guaranteeing user welfare in network service
Authors: Yu Seung Min , Kim Seong-Lyun
Published: October 2012

Due to the emergence of smart devices, mobile data traffic grows exponentially. A Cisco report predicts that global mobile data traffic will increase 26-fold between 2010 and 2015. Therefore, the spectrum shortage continues and the spectrum price increases, which will eventually lead to decrease of user welfare. Another side effect of the data traffic growth is the polarization of data traffic among users. To resolve these problems, we introduce two subsidy schemes (i.e., price and quality of service (QoS) subsidy schemes) and mathematically analyze the effect of each scheme. We identify that if the regulator has sufficient spectrum amount for the network service, then the QoS subsidy scheme will be a good choice for all players in the network service market. Otherwise, the price subsidy scheme can be better from user welfare perspective. Even though our analytic results are derived under some assumptions for mathematical tractability, it will provide good intuitions for spectrum regulation.
Pricing of insurance policies against cloud storage price rises
Authors: Mastroeni Loretta , Naldi Maurizio
Published: October 2012

When a company migrates to cloud storage, the way back is neither fast nor cheap. The company is then locked up in the storage contract and exposed to upward market prices, which reduce the company's profit and may even bring it below zero. We propose a protection means based on an insurance contract, by which the cloud purchaser is indemnified when the current storage price exceeds a pre-defined threshold. By applying the financial options theory, we provide a formula for the insurance price (the premium). By using historical data on market prices for disks, we apply the formula in realistic scenarios. We show that the premium grows nearly quadratically with the duration of the coverage period as long as this is below one year, but grows more slowly, though faster than linearly, over longer coverage periods.
ISP vs. ISP+CDN
Authors: Lee Dongmyung , Mo Jeonghoon , Park Jinwoo
Published: October 2012

This paper provides an economic analysis of the ISP-operated CDN under a duopolistic competition. The two ISPs are modeled as a platform in a two-sided market providing Internet access to both content providers and consumers. By formulating a 4-level Stackelberg game, we have found that the equilibrium strategy of an ISP in determining whether to launch CDN service depends on the marginal cost of cache server deployment and the two contrary effects: "Competition Effect" and "Delay Reduction Effect."
Predictive modeling and analysis of OP2 on distributed memory GPU clusters
Authors: Mudalige G. R. , Giles M. B. , Bertolli C. , Kelly P. H.J.
Published: October 2012

OP2 is an "active" library framework for the development and solution of unstructured mesh based applications. It aims to decouple the scientific specification of an application from its parallel implementation to achieve code longevity and near-optimal performance through re-targeting the backend to different multi-core/many-core hardware. This paper presents a predictive performance analysis and benchmarking study of OP2 on heterogeneous cluster systems. We first present the design of a new OP2 back-end that enables the execution of applications on distributed memory clusters, and benchmark its performance during the solution of a 1.5M and 26M edge-based CFD application written using OP2. Benchmark systems include a large-scale CrayXE6 system and an Intel Westmere/InfiniBand cluster. We then apply performance modeling to predict the application's performance on an NVIDIA Tesla C2070 based GPU cluster, enabling us to compare OP2's performance capabilities on emerging distributed memory heterogeneous systems. Results illustrate the performance benefits that can be gained through many-core solutions both on single-node and heterogeneous configurations in comparison to traditional homogeneous cluster systems for this class of applications.
Sender-side Buffers and the Case for Multimedia Adaptation
Authors: Erbad Aiman , Krasic Charles
Published: October 2012

The Internet/Web architecture has developed to the point where it is common for the most popular sites to operate at a virtually unlimited scale, and many sites now cater to hundreds of millions of unique users. Performance and availability are generally essential to attract and sustain such user bases. As such, the network and server infrastructure plays a critical role in the fierce competition for users. Web pages should load in tens to a few hundred milliseconds at most. Similarly, sites strive to maintain *multiple nines* availability targets--for example, a site should be available to users 99.999 percent of the time over a one-year period.
The Membrane Fusion Enigma: SNAREs, Sec1/Munc18 Proteins, and Their Accomplices—Guilty as Charged?
Authors: Rizo Josep , Südhof Thomas C.
Published: October 2012

Neurotransmitter release is governed by proteins that have homo-logs in most types of intracellular membrane fusion, including the Sec1/Munc18 protein Munc18-1 and the SNARE proteins syntaxin-1, synaptobrevin/VAMP, and SNAP-25. The SNAREs initiate fusion by forming tight SNARE complexes that bring the vesicle and plasma membranes together. SNARE maintenance in a functional state depends on two chaperone systems (Hsc70/αCSP/SGT and synuclein); defects in these systems lead to neurodegeneration. Munc18-1 binds to an autoinhibitory closed conformation of syntaxin-1, gating formation of SNARE complexes, and also binds to SNARE complexes, which likely underlies the crucial function of Munc18-1 in membrane fusion by an as-yet unclear mechanism. Syntaxin-1 opening is mediated by Munc13s through their MUN domain, which is homologous to diverse tethering factors and may also have a general role in fusion. MUN domain activity is likely modulated in diverse presynaptic plasticity processes that depend on Ca2+ and RIM proteins, among others.
Feedback-dependent generalization
Authors: Taylor Jordan A. , Hieber Laura L. , Ivry Richard B.
Published: October 2012

Generalization provides a window into the representational changes that occur during motor learning. Neural network models have been integral in revealing how the neural representation constrains the extent of generalization. Specifically, two key features are thought to define the pattern of generalization. First, generalization is constrained by the properties of the underlying neural units; with directionally tuned units, the extent of generalization is limited by the width of the tuning functions. Second, error signals are used to update a sensorimotor map to align the desired and actual output, with a gradient-descent learning rule ensuring that the error produces changes in those units responsible for the error. In prior studies, task-specific effects in generalization have been attributed to differences in neural tuning functions. Here we ask whether differences in generalization functions may arise from task-specific error signals. We systematically varied visual error information in a visuomotor adaptation task and found that this manipulation led to qualitative differences in generalization. A neural network model suggests that these differences are the result of error feedback processing operating on a homogeneous and invariant set of tuning functions. Consistent with novel predictions derived from the model, increasing the number of training directions led to specific distortions of the generalization function. Taken together, the behavioral and modeling results offer a parsimonious account of generalization that is based on the utilization of feedback information to update a sensorimotor map with stable tuning functions.
Novel two-alternative forced choice paradigm for bilateral vibrotactile whisker frequency discrimination in head-fixed mice and rats
Authors: Mayrhofer Johannes M. , Skreb Vida , von der Behrens Wolfger , Musall Simon , Weber Bruno , Haiss Florent
Published: October 2012

Rats and mice receive a constant bilateral stream of tactile information with their large mystacial vibrissae when navigating in their environment. In a two-alternative forced choice paradigm (2-AFC), head-fixed rats and mice learned to discriminate vibrotactile frequencies applied simultaneously to individual whiskers on the left and right sides of the snout. Mice and rats discriminated 90-Hz pulsatile stimuli from pulsatile stimuli with lower repetition frequencies (10–80 Hz) but with identical kinematic properties in each pulse. Psychometric curves displayed an average perceptual threshold of 50.6-Hz and 53.0-Hz frequency difference corresponding to Weber fractions of 0.56 and 0.58 in mice and rats, respectively. Both species performed >400 trials a day (>200 trials per session, 2 sessions/day), with a peak performance of >90% correct responses. In general, rats and mice trained in the identical task showed comparable psychometric curves. Behavioral readouts, such as reaction times, learning rates, trial omissions, and impulsivity, were also very similar in the two species. Furthermore, whisking of the animals before stimulus presentation reduced task performance. This behavioral paradigm, combined with whisker position tracking, allows precise stimulus control in the 2-AFC task for head-fixed rodents. It is compatible with state-of-the-art neurophysiological recording techniques, such as electrophysiology and two-photon imaging, and therefore represents a valuable framework for neurophysiological investigations of perceptual decision-making.
Mathematical model of dopamine autoreceptors and uptake inhibitors and their influence on tonic and phasic dopamine signaling
Authors: Dreyer Jakob Kisbye , Hounsgaard Jørn
Published: October 2012

Dopamine (DA) D2-like autoreceptors are an important component of the DA system, but their influence on postsynaptic DA signaling is not well understood. They are, directly or indirectly, involved in drug abuse and in treatment of schizophrenia and attention deficit hyperactive disorder: DA autoreceptors influence the behavioral effect of cocaine and methylphenidate and may be the target of antipsychotic medications such as haloperidol. DA autoreceptors are active at two levels: Somatodendritic autoreceptors mainly influence firing rate of DA neurons, and presynaptic autoreceptors control release of neurotransmitter at axonal terminals. Here we develop a mathematical model that captures the dynamics of this dual autoregulation system. Our model predicts a biphasic autoreceptor response between DA terminals and somatodendritic regions that influences the postsynaptic integration of DAergic firing patterns. We applied our model to study how DA uptake inhibition affects the translation of DA cell firing into activation of postsynaptic DA receptors. While uptake inhibition increased tonic activation of low-affinity postsynaptic receptors, high-affinity state receptors saturated and thus became insensitive to phasic DA signaling. This effect had remarkable regional specificity: While high-affinity DA receptors saturated at low levels of uptake inhibition in nucleus accumbens, they only saturated at higher levels of uptake inhibition in dorsal striatum. Based on high-affinity receptor saturation, the model predicted that removal of autoreceptor control would lead to cocaine hypersensitivity.
Helmholtz Bright Spatial Solitons and Surface Waves at Power-Law Optical Interfaces
Authors: Christian J. M. , McCoy E. A. , McDonald G. S. , Sánchez-Curto J. , Chamorro-Posada P.
Published: October 2012

We consider arbitrary angle interactions between spatial solitons and the planar boundary between two optical materials with a single power-law nonlinear refractive index. Extensive analysis has uncovered a wide range of new qualitative phenomena in non-Kerr regimes. A universal Helmholtz-Snell law describing soliton refraction is derived using exact solutions to the governing equation as a nonlinear basis. New predictions are tested through exhaustive computations, which have uncovered substantially enhanced Goos-Hänchen shifts at some non-Kerr interfaces. Helmholtz nonlinear surface waves are analyzed theoretically, and their stability properties are investigated numerically for the first time. Interactions between surface waves and obliquely incident solitons are also considered. Novel solution behaviours have been uncovered, which depend upon a complex interplay between incidence angle, medium mismatch parameters, and the power-law nonlinearity exponent.
Steroid Cell Ovarian Neoplasm, Not Otherwise Specified: A Case Report and Review of the Literature
Authors: Singh Paul , Deleon Frank , Anderson Ralph
Published: October 2012

Background. Steroid cell ovarian tumors, not otherwise specified, represent a unique cause of female virilization. Most commonly encountered in premenopausal women, these tumors can exist throughout a women’s lifetime, from before puberty until after menopause.Case. Steroid cell, not otherwise specified, was diagnosed in a 70-year-old female significant for hirsutism. The patient demonstrated elevated total testosterone levels with normal gonadotropins, DHEA, and DHEA-S levels. CT imaging revealed a right ovarian mass and subsequent laparoscopic right oophorectomy yielded clinical improvement promptly.Conclusion. Virilization in females can occur based on ovarian or adrenal pathology. In terms of ovarian-based female virilization, many tumors exist that may induce women to demonstrate masculine features, such as pure Sertoli, pure Leydig, Sertoli-Leydig combinations, and gynandroblastomas. Each of these tumor types possesses a unique histologic pattern that allows for pathologic identification after removal. A rare source of ovarian-based female virilization is steroid cell neoplasms, not otherwise specified, that do not demonstrate these specific histologic characteristics and thus represent a diagnosis of exclusion after other causes of ovarian-based female virilization have been ruled out.
Internal Jugular Vein Entrapment in a Multiple Sclerosis Patient
Authors: Simka Marian , Majewski Eugeniusz , Fortuna Marek , Zaniewski Maciej
Published: October 2012

We describe a multiple sclerosis patient presenting with compression of the internal jugular vein caused by aberrant omohyoid muscle. Previously this patient underwent balloon angioplasty of the same internal jugular vein. Ten months after this endovascular procedure, Doppler sonography revealed totally collapsed middle part of the treated vein with no outflow detected. Still, the vein widened and the flow was restored when the patient’s mouth opened. Thus, the abnormality was likely to be caused by muscular compression. Surgical exploration confirmed that an atypical omohyoid muscle was squeezing the vein. Consequently, pathological muscle was transected. Sonographic control three weeks after surgical procedure revealed a decompressed vein with fully restored venous outflow. Although such a muscular compression can be successfully managed surgically, future research has to establish its clinical relevance.
Remission Achieved in Refractory Advanced Takayasu Arteritis Using Rituximab
Authors: Ernst D. , Greer M. , Stoll M. , Meyer-Olson D. , Schmidt R. E. , Witte T.
Published: October 2012

A 25-year-old patient was referred due to subclavian stenosis, identified on echocardiography. She presented with exertional dizziness and dyspnoea. Questioning revealed bilateral arm claudication. Examination demonstrated an absent right ulnar pulse and asymmetrical brachial blood pressure. Bruits were evident over both common carotid arteries. Doppler ultrasound and MRI angiograms revealed occlusion or stenosis in multiple large arteries. Takayasu arteritis (TA) was diagnosed and induction therapy commenced: 1 mg/kg oral prednisolone and 500 mg/m2intravenous cyclophosphamide (CYC). Attempts to reduce prednisolone below 15 mg/d proved impossible due to recurring disease activity. Adjuvant azathioprine 100 mg/d was subsequently added. Several weeks later, the patient was admitted with a left homonymous hemianopia. The culprit lesion in the right carotid artery was surgically managed and the patient discharged on azathioprine 150 mg/d and prednisolone 30 mg/d. Despite this, deteriorating exertional dyspnoea and angina pectoris were reported. Reimaging confirmed new stenosis in the right pulmonary artery. Surgical treatment proved infeasible. Given evidence of refractory disease activity on maximal standard therapy, we initiated rituximab, based on recently reported B-cell activity in TA.
Parkinsonism following Bee Sting: A Case Report
Authors: Mittal Ruchika , Munjal Sanjay , Khurana Dheeraj , Gupta Ashok
Published: October 2012

We are reporting here a rare case of Parkinsonism (Hypokinetic dysarthria) caused after a bee stung, a member of the hymenoptera order. The main aim of this report is to orient the clinicians with the possibility of extrapyramidal syndromes because of hymenoptera stings.
Structure and Abrasive Wear of Composite HSS M2/WC Coating
Authors: Gnyusov S. F. , Durakov V. G. , Tarasov S. Yu.
Published: October 2012

Features of phase-structure formation and abrasive wear resistance of composite coatings “WC-M2 steel” worn against tungsten monocarbide have been investigated. It was established that adding 20 wt.% WC to the deposited powder mixture leads to the increase in M6C carbide content. These carbides show a multimodal size distribution consisting of~5.9 μm eutectic carbides along the grain boundaries,~0.25 μm carbides dispersed inside the grains. Also a greater amount of metastable austenite (~88 vol.%) is found. The high abrasive wear resistance of these coatings is provided byγ→α′-martensitic transformation and multimodal size distribution of reinforcing particles.
Renal Function in Patients with Hypertension Associated Congestive Cardiac Failure Seen in a Tertiary Hospital
Authors: Osuji C. U. , Nwaneli C. U. , Onwubere B. J. , Onwubuya E. I. , Ahaneku G. I.
Published: October 2012

Background. Chronic kidney disease is frequently seen in patients with congestive cardiac failure and is an independent risk factor for morbidity and mortality. The aim of this study was to determine the prevalence of chronic kidney disease in patients with hypertension associated congestive cardiac failure.Method. One hundred and fifty patients with hypertension associated congestive cardiac failure were recruited consecutively from the medical outpatient department and the medical wards of the Nnamdi Azikiwe University Teaching Hospital Nnewi over a one year period, January to December 2010. Patients’ biodata and medical history were obtained, detailed physical examination done and each patient had a chest X-ray, 12 lead ECG, urinalysis, serum urea and creatinine assay done. Ethical clearance was obtained from the Ethical Review Board of our institution and data analysed using SPSS-version 16.Results. There were 86 males and 64 females with mean age62.7±12.5years. The mean blood pressures were systolic152.8±28.5 mmHg and diastolic94.3±18 mmHg. 84.7% had blood pressure ≥140/90 mmHg on presentation. The mean GFR was70.1±31.3 mls/min. 76% of subjects had GFR <90 mls/min and no statistical significant difference between males and females,P=0.344. The mean serum urea was7.2±51 mmol/L while the mean serum creatinine was194±416.2 mmol/L.Conclusions. This study has demonstrated that majority of patients presenting with hypertension associated congestive cardiac failure have some degree of chronic kidney disease.
Value Distribution and Uniqueness Results of Zero‐Order Meromorphic Functions to Their q‐Shift
Authors: Guan Haiwa , Wang Gang , Luo Qiuqin
Published: October 2012

We investigate value distribution and uniqueness problems of meromorphic functions with their q‐shift. We obtain that if f is a transcendental meromorphic (or entire) function of zero order, and Q(z) is a polynomial, then afn(qz) + f(z) − Q(z) has infinitely many zeros, where q ∈ ℂ∖{0}, a is nonzero constant, and n ≥ 5 (or n ≥ 3). We also obtain that zero‐order meromorphic function share is three distinct values IM with its q‐difference polynomial P(f), and if limsup r→∞(N(r, f)/T(r, f)) < 1, then f ≡ P(f).
CMD: A Database to Store the Bonding States of Cysteine Motifs with Secondary Structures
Authors: Bostan Hamed , Salim Naomie , Hussein Zeti Azura , Klappa Peter , Shamsir Mohd Shahir
Published: October 2012

Computational approaches to the disulphide bonding state and its connectivity pattern prediction are based on various descriptors. One descriptor is the amino acid sequence motifs flanking the cysteine residue motifs. Despite the existence of disulphide bonding information in many databases and applications, there is no complete reference and motif query available at the moment. Cysteine motif database (CMD) is the first online resource that stores all cysteine residues, their flanking motifs with their secondary structure, and propensity values assignment derived from the laboratory data. We extracted more than 3 million cysteine motifs from PDB and UniProt data, annotated with secondary structure assignment, propensity value assignment, and frequency of occurrence and coefficiency of their bonding status. Removal of redundancies generated 15875 unique flanking motifs that are always bonded and 41577 unique patterns that are always nonbonded. Queries are based on the protein ID, FASTA sequence, sequence motif, and secondary structure individually or in batch format using the provided APIs that allow remote users to query our database via third party software and/or high throughput screening/querying. The CMD offers extensive information about the bonded, free cysteine residues, and their motifs that allows in-depth characterization of the sequence motif composition.
Ipsilateral Rotational Autokeratoplasty for the Management of Traumatic Corneal Scar
Authors: Günes Alime , Kansu Bozkurt Tahir , Unlu Cihan , Sezgin Akcay Betül Ilkay , Bayramlar Hüseyin
Published: October 2012

A 40-years-old male patient with a corneal scar secondary to perforating eye injury had undergone ipsilateral rotational autokeratoplasty in our clinics. The corneal scar involved the pupillary area. The patient had a preoperative visual acuity of counting fingers. The patient’s cornea was trephined with a 0.5 mm temporal decentration. The 8.0 mm autograft was rotated approximately 180° to relocate the scar to the temporal aspect of the cornea. The final position of the corneal scar was temporal of the visual axis and central area was clear. The visual acuity at 1-, 3-, and 6-months followups was better than the first visual acuity in the patient. Ipsilateral rotational autokeratoplasty has many advantages over conventional keratoplasty. There is no risk of immunological rejection of the graft, postoperative corticosteroids are not needed as frequently, and donor cornea is not required. A rotational autograft can be a powerful alternative to conventional keratoplasty for some patients with traumatic corneal scars.
Endometriosis in Adolescence
Authors: Dessole Margherita , Melis Gian Benedetto , Angioni Stefano
Published: October 2012

Endometriosis is a common cause of pelvic pain and infertility. The majority of women report symptoms since adolescence, and there are rare cases of endometriosis in premenarchal age patients. Symptoms in adolescence are similar to those in adulthood. Treatment usually consists of oral contraceptives and nonsteroidal anti-inflammatory drugs. In cases where this treatment is not successful, laparoscopy and biopsy of the lesions are necessary for diagnosis. However, emerging new technologies provide new options, in particular the use of serological markers.
Novel Therapeutic/Integrative Approaches for Celiac Disease and Dermatitis Herpetiformis
Authors: Fasano Alessio
Published: October 2012

Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. Gluten is a protein component in wheat and other cereals like rye and barley. At present, the only available treatment is a strict gluten-free diet. Recent advances have increased our understanding of the molecular basis for this disorder. Last decade has seen new scientific developments in this disease and led to the formulation of new concepts of pathophysiology that offer possible targets for new treatments or interventions integrative to the gluten-free diet.
Intrapleural Bortezomib for the Therapy of Myelomatous Pleural Effusion: A Case Report
Authors: Klanova Magdalena , Klener Pavel , Trneny Marek , Straub Jan , Spicka Ivan
Published: October 2012

Myelomatous pleural effusion (MPE) is an extremely rare manifestation of multiple myeloma (MM). We present a case of MPE in a patient with IgG-κMM treated with intrapleural bortezomib with systemic bortezomib-based therapy. Although we observed good local response, the patient succumbed due to systemic myeloma progression.
Sensitization of TRAIL-Induced Cell Death by 20(S)-Ginsenoside Rg3 via CHOP-Mediated DR5 Upregulation in Human Hepatocellular Carcinoma Cells
Authors: Lee Ju-Yeon , Jung Kyung Hee , Morgan Michael J. , Kang Yi-Rae , Lee Hee-Seung , Koo Gi-Bang , Hong Soon-Sun , Kwon Sung Won , Kim You-Sun
Published: October 2012

The TRAIL pathway is a potential therapeutic target for anticancer drugs due to selective cytotoxicity in cancer cells. Despite considerable promise, TRAIL or TRAIL receptor agonists have been used thus far with limited success in multiple clinical trials, in part due to acquired TRAIL resistance during chemotherapeutic treatment. Hepatocellular carcinoma (HCC) is a common solid tumor and the third leading cause of cancer-related death worldwide. Classical chemotherapy is not effective for HCC treatment and targeted therapy is limited to sorafenib. Isolated from Panax ginseng CA Meyer, 20(S)-ginsenoside Rg3 is a steroidal saponin with high pharmacologic activity that has been shown to sensitize cells to some chemotherapeutic agents. We investigated the sensitizing effect of Rg3 on TRAIL-induced cell death in HCC cells. We show Rg3 is capable of promoting TRAIL-induced apoptosis in a number of HCC cell lines, including HepG2, SK-Hep1, Huh-7, and Hep3B, but not in normal HL-7702 hepatocytes, indicating that Rg3 sensitization to TRAIL may be specific to cancer cells. Mechanistically, we found that Rg3 upregulates DR5 expression at the transcriptional level. DR5 upregulation in this case is mediated by C/EBP homology protein (CHOP), an important endoplasmic reticulum stress responsive protein. Furthermore, Rg3 is well tolerated and enhances the therapeutic efficacy of TRAIL in mouse xenograft models, suggesting that chemosensitization also occurs in vivo. Taken together, our study identifies Rg3 as a novel anticancer therapeutic agent and supports the further development of Rg3 as a chemosensitizer in combined therapy with TRAIL. Mol Cancer Ther; 12(3); 274–85. ©2012 AACR.
Non-invasive algorithms for the diagnosis of pulmonary hypertension
Authors: Wexberg Paul , Heinzl Harald , Lang Irene , Bonderman Diana
Published: October 2012

Precapillary pulmonary hypertension (PH) is diagnosed when mean pulmonary arterial pressure (mPAP) equals or exceeds 25 mmHg and the pulmonary capillary wedge pressure (PCWP) is equal or lower than 15 mmHg. Because both parameters can only be derived from invasive hemodynamic assessment, right heart catheter (RHC) is still a gold standard for the diagnosis of PH. Severe precapillary PH corresponds to pulmonary vascular disease and carries a poor prognosis. Unfortunately, due to a generally low specificity of non-invasive estimates of systolic pulmonary pressure, at least 50% of patients with suspicion of PH need to undergo invasive RHC for exclusion of precapillary PH. Therefore, and also in order to manage the growing number of postcapillary PH due to heart and lung disease in the general population, pulmonary and cardiologic diagnostic algorithms combining multiple parameters have been developed. Recent disease scores are reviewed, and an outlook is given on emerging evidence from the DETECT clinical study holding the promise to non-invasively predict precapillary PH in vulnerable patients. These diagnostic trees help limit unnecessary procedures and help differentiate the current categories of PH. However, one has to keep in mind that the diagnosis of PH is still made by hemodynamic assessment.
Plasma proteomics of patients with non-valvular atrial fibrillation on chronic anti-coagulation with warfarin or a direct factor Xa inhibitor
Authors: Chan Mark , Lin Min , Lucas Joseph , Moseley Arthur , Will Thompson J , Cyr Derek , Ueda Hitoshi , Kajikawa Mariko , Ortel Thomas , Becker Richard
Published: October 2012

Plasma proteins mediate thrombogenesis, inflammation, endocardial injury and structural remodelling in atrial fibrillation (AF). We hypothesised that anti-coagulation with rivaroxaban, a direct factor Xa inhibitor, would differentially modulate biologically-relevant plasma proteins, compared with warfarin, a multi-coagulation protein antagonist. We performed unbiased liquid chromatography/tandem mass spectroscopy and candidate multiplexed protein immunoassays among Japanese subjects with non-valvular chronic AF who were randomly assigned to treatment with 24 weeks of rivaroxaban (n=93) or warfarin (n=94). Nine metaproteins, including fibulin-1 (p=0.0033), vitronectin (p=0.0010), haemoglobin α(p=0.0012), apolipoproteins C-II (p=0.0017) and H (p=0.0023), complement C5 precursor (p=0.0026), coagulation factor XIIIA (p=0.0026) and XIIIB (p=0.0032) subunits, and 10 candidate proteins, including thrombomodulin (p=0.0004), intercellular adhesion molecule-3 (p=0.0064), interleukin-8 (p=0.0007) and matrix metalloproteinase-3 (p=0.0003), were differentially expressed among patients with and without known clinical risk factors for stroke and bleeding in AF. Compared with warfarin, rivaroxaban treatment was associated with a greater increase in thrombomodulin (Δ0.1 vs. 0.3 pg/ml, p=0.0026) and a trend towards a reduction in matrix metalloproteinase-9 (Δ2.2 vs. –4.9 pg/ml, p=0.0757) over 24 weeks. Only modest correlations were observed between protein levels and prothrombin time, factor Xa activity and prothrombinase-induced clotting time. Plasma proteomics can identify distinct functional patterns of protein expression that report on known stroke and bleeding risk phenotypes in an ethnically-homogeneous AF population. The greater upregulation of thrombomodulin among patients randomised to rivaroxaban represents a proof-of-principle that pharmacoproteomics can be employed to discern novel effects of factor Xa inhibition beyond standard pharmacodynamic measures.
Mitochondria and Mitophagy
Authors: Kubli Dieter A. , Gustafsson Åsa B.
Published: October 2012

Mitochondria are primarily responsible for providing the contracting cardiac myocyte with a continuous supply of ATP. However, mitochondria can rapidly change into death-promoting organelles. In response to changes in the intracellular environment, mitochondria become producers of excessive reactive oxygen species and release prodeath proteins, resulting in disrupted ATP synthesis and activation of cell death pathways. Interestingly, cells have developed a defense mechanism against aberrant mitochondria that can cause harm to the cell. This mechanism involves selective sequestration and subsequent degradation of the dysfunctional mitochondrion before it causes activation of cell death. Induction of mitochondrial autophagy, or mitophagy, results in selective clearance of damaged mitochondria in cells. In response to stress such as ischemia/reperfusion, prosurvival and prodeath pathways are concomitantly activated in cardiac myocytes. Thus, there is a delicate balance between life and death in the myocytes during stress, and the final outcome depends on the complex cross-talk between these pathways. Mitophagy functions as an early cardioprotective response, favoring adaptation to stress by removing damaged mitochondria. In contrast, increased oxidative stress and apoptotic proteases can inactivate mitophagy, allowing for the execution of cell death. Herein, we discuss the importance of mitochondria and mitophagy in cardiovascular health and disease and provide a review of our current understanding of how these processes are regulated.
The Roles of Asymmetric Inflow Forcing Induced by Outer Rainbands in Tropical Cyclone Secondary Eyewall Formation
Authors: Qiu Xin , Tan Zhe-Min
Published: October 2012

This study analyzes the secondary eyewall formation (SEF) process in an idealized cloud-resolving simulation of a tropical cyclone. In particular, the unbalanced boundary layer response to asymmetric inflow forcing induced by outer rainbands (ORBs) is examined in order to understand the mechanisms driving the sustained convection outside the primary eyewall during the early phase of SEF.

The enhancement of convection in the SEF region follows the formation and inward contraction of an ORB. The azimuthal distribution of the enhanced convection is highly asymmetric but regular, generally along a half circle starting from the downwind portion of the ORB. It turns out that the descending radial inflow in the middle and downwind portions of the ORB initiates/maintains a strong inflow in the boundary layer. The latter is able to penetrate into the inner-core region, sharpens the gradient of radial velocity, and reinforces convergence. Consequently, warm and moist air is continuously lifted up at the leading edge of the strong inflow to support deep convection. Moreover, the inflow from the ORB creates strong supergradient winds that are ejected outward downwind, thereby enhancing convergence and convection on the other side of the storm. The results provide new insight into the key processes responsible for convection enhancement during the early phase of SEF in three dimensions and suggest the limitations of axisymmetric studies. There are also implications regarding the impact of the asymmetric boundary layer flow under a translating storm on SEF.
Race and Gender Equity in Sports
Authors: Pickett Moneque Walker , Dawkins Marvin P. , Braddock Jomills Henry
Published: October 2012

Males have been the dominant focus of sports participation in America since the 19th century. Serious examination of women’s participation in sports did not begin to receive substantial treatment until the early 1970s, when social and legal forces led to the enactment of Title IX of the 1972 Education Amendments to the Civil Rights Act of 1964. The purpose of the present study is to address the question of whether Black and White women have benefited equally from Title IX by (a) examining Post–Title IX trends in Black and White females’ sport participation in high school and college, using data from national longitudinal surveys; (b) assessing the effect of race on sport participation opportunities for high school girls based on these data:, and (c) examining legal cases involving Title IX to assess the extent to which legal challenges have improved access to and participation of Black women in sports relative to their White female counterparts. The findings of the current study reveal that this benefit has not been shared equally by White and African American females. High schools attended by African American females do not offer the same range of sports as those available in schools attended by White females.
Flood in Thailand: Assessing Institutionalised Capacities to Reduce Vulnerability
Authors: Mishra Sujit Kumar
Published: October 2012

During the monsoons in Thailand, floods pose significant risks to the country’s population. Yet, despite its regular occurrence, the magnitude of economic losses arising from the consequences is poorly understood. This article focuses on the policy framework and institutional capacity of Thailand for handling the disaster effectively. Evidences based on review of documents and reports, interviews with government department officials and field observations have hinted at improved institutional performances, such as early warning mechanism at grassroots level and emergency relief services, besides the formation of an emergency committee at the outset of the monsoon season in flood-prone areas. The analysis and findings of this article identify several institutional incapacities in terms of weak extension services, poor coordination across administrative bodies and line agencies, dysfunctional relationship between the planner and the affected groups, poor implementation and skewed government intervention which lead to suboptimal output. Hence, it is suggested that in order to minimise losses in such a situation, it is necessary that a system be created for increasing preparedness at all levels, that is, government, civil society and community, to effectively reactivate these institutions in performing the roles they are intended for.
Blind Side
Authors: Cochran Evan , Dhillon Manpreet , Rabow Jerome , Vega Yvette Meza , Yeghnazar Pauline
Published: October 2012

In this article, newspaper reviews of the film, “The Blind Side,” are examined in the mainstream, African American, and alternative press. We select and code all comments in those reviews about the two protagonists, one white and one black. Our analysis revealed different degrees of favorableness and negativity about the protagonists, in the three types of American newspaper media. Our findings reveal that all three types of newspapers favor classifying the white heroine in greater positive terms than the African American character.
Managing Impressions
Authors: Greenebaum Jessica B.
Published: October 2012

Goffman’s concept of impression management, front stage/backstage, and face work are used to explain how the participants in this qualitative study engage in promoting veganism and vegetarianism to omnivores in daily interactions. The participants often feel silenced by stereotypes, misinformation, and conflict. They believe that this persistence of stereotypes is a psychological defense mechanism by omnivores to mask feelings of guilt. To manage this tension and present this cause in a positive light, vegetarians and vegans engage in “face-saving” techniques to protect both parties from attack and alienation. These include rejecting “in-your-face” confrontations and adopting preventative “face-saving” strategies such as avoiding confrontation, waiting for an appropriate time, focusing on health benefits, and leading by example.