bluuebunny/crossref_metadata_2025 huggingface dataset:
Do crystal structures obviate the need for theoretical models of GPCRs for structure‐based virtual screening?
Authors: Tang Hao , Wang Xiang Simon , Hsieh Jui‐Hua , Tropsha Alexander
Published: January 2012

Recent highly expected structural characterizations of agonist‐bound and antagonist‐bound beta‐2 adrenoreceptor (β2AR) by X‐ray crystallography have been widely regarded as critical advances to enable more effective structure‐based discovery of GPCRs ligands. It appears that this very important development may have undermined many previous efforts to develop 3D theoretical models of GPCRs. To address this question directly, we have compared several historical β2AR models versus the inactive state and nanobody‐stabilized active state of β2AR crystal structures in terms of their structural similarity and effectiveness of use in virtual screening for β2AR specific agonists and antagonists. Theoretical models, incluing both homology and de novo types, were collected from five different groups who have published extensively in the field of GPCRs modeling. All models were built before X‐ray structures became available. In general, β2AR theoretical models differ significantly from the crystal structure in terms of TMH definition and the global packing. Nevertheless, surprisingly, several models afforded hit rates resulting from virtual screening of large chemical library enriched by known β2AR ligands that exceeded those using X‐ray structures. The hit rates were particularly higher for agonists. Furthemore, the screening performance of models is associated with local structural quality, such as the RMSDs for binding pocket residues and the ability to capture accurately, most if not all critical protein/ligand interactions. These results suggest that carefully built models of GPCRs could capture critical chemical and structural features of the binding pocket, and thus may be even more useful for practical structure‐based drug discovery than X‐ray structures. Proteins 2012. © 2012 Wiley Periodicals, Inc.
Upper mantle P velocity structure beneath the Midwestern United States derived from triplicated waveforms
Authors: Chu Risheng , Schmandt Brandon , Helmberger Don V.
Published: January 2012

Upper mantle seismic velocity structures in both vertical and horizontal directions are key to understanding the structure and mechanics of tectonic plates. Recent deployment of the USArray Transportable Array (TA) in the Midwestern United States provides an extraordinary regional earthquake data set to investigate such velocity structure beneath the stable North American craton. In this paper, we choose an Mw5.1 Canadian earthquake in the Quebec area, which is recorded by about 400 TA stations, to examine the P wave structures between the depths of 150 km to 800 km. Three smaller Midwestern earthquakes at closer distance to the TA are used to investigate vertical and horizontal variations in Pvelocity between depths of 40 km to 150 km. We use a grid‐search approach to find the best 1‐D model, starting with the previously developed S25 regional model. The results support the existence of an 8° discontinuity inP arrivals caused by a negative velocity gradient in the lithosphere between depths of 40 km to 120 km followed by a small (∼1%) jump and then a positive gradient down to 165 km. The Pvelocity then decreases by 2% from 165 km to 200 km, and we define this zone as the regional lithosphere‐asthenosphere boundary (LAB). Beneath northern profiles, waves reflected from the 410 discontinuity (410) are delayed by up to 1 s relative to those turning just below the 410, which we explain by an anomaly just above the discontinuity withPvelocity reduced by ∼3%. The 660 discontinuity (660) appears to be composed of two smaller velocity steps with a separation of 16 km. The inferred low‐velocity anomaly above 410 may indicate high water concentrations in the transition zone, and the complexity of the 660 may be related to Farallon slab segments that have yet to sink into the deep mantle.
Graphene thickness-graded transistors with reduced electronic noise
Authors: Liu Guanxiong , Rumyantsev Sergey , Shur Michael , Balandin Alexander A.
Published: January 2012

The authors demonstrate graphene thickness-graded transistors with high electron mobility and low 1/f noise (f is a frequency). The device channel is implemented with few-layer graphene with the thickness varied from a single layer in the middle to few-layers at the source and drain contacts. It was found that such devices have electron mobility comparable to the reference single-layer graphene devices while producing lower noise levels. The metal doping of graphene and difference in the electron density of states between the single-layer and few-layer graphene cause the observed noise reduction. The results shed light on the noise origin in graphene.
Investigating Phenotypic Variability inColletotrichum lindemuthianumPopulations
Authors: Pinto J. M. A. , Pereira R. , Mota S. F. , Ishikawa F. H. , Souza E. A.
Published: January 2012

Colletotrichum lindemuthianum, causal agent of anthracnose in the common bean, has wide genetic variability. Differential bean cultivars and morphological and physiological characteristics were used to analyze 74 isolates of C. lindemuthianum collected in two counties in the state of Minas Gerais, Brazil. Six different races were found, with a predominance of race 65 at both locations. Isolates were classified according to their sensitivities to the fungicide thiophanate-methyl, normally used in the control of common bean anthracnose. In all, ≈10% of isolates were resistant to the fungicide in vitro. Characteristics such as indexes of mycelia growth rate, colony diameter, sporulation capacity, and percentage of germination demonstrated the high genetic variability of C. lindemuthianum. We also observed variation in conidial cytology. The conidia of most isolates showed septa formation after germination, in contrast to septa absence, previously reported in the literature. Sexual and asexual reproduction were evaluated for mechanisms that may contribute in the generation of variability in C. lindemuthianum. Conidial anastomosis tubes were commonly found, indicating that asexual reproduction can help increase variability in this species. Information from this study confirmed high variability in C. lindemuthianum and will guide future studies in basic knowledge and applied technologies.
The data acquisition and reduction challenge at the Large Hadron Collider
Authors: Cittolin Sergio
Published: January 2012

The Large Hadron Collider detectors are technological marvels—which resemble, in functionality, three-dimensional digital cameras with 100 Mpixels—capable of observing proton–proton (pp) collisions at the crossing rate of 40 MHz. Data handling limitations at the recording end imply the selection of only one pp event out of each 10
5
. The readout and processing of this huge amount of information, along with the selection of the best approximately 200 events every second, is carried out by a trigger and data acquisition system, supplemented by a sophisticated control and monitor system. This paper presents an overview of the challenges that the development of these systems has presented over the past 15 years. It concludes with a short historical perspective, some lessons learnt and a few thoughts on the future.
Psychosocial therapeutic interventions for volatile substance use: a systematic review
Authors: MacLean Sarah , Cameron Jacqui , Harney Angela , Lee Nicole K.
Published: January 2012

Aims  Volatile substance use (VSU) is associated with a range of adverse outcomes, including cognitive impairment and death. It occurs disproportionately within young and marginalized populations. A previous international systematic review of VSU treatment identified no relevant studies. This paper reports on a systematic review of a range of study types concerning psychosocial interventions for VSU.

Methods  Search parameters were developed using the Population, Intervention, Professionals, Outcomes, Health care setting and Contexts (PIPOH) tool with input from an expert committee. Included were randomized controlled trials (RCTs), comparative studies with or without concurrent controls, case series studies and grey literature, published in English during 1980–2010.

Results  The initial search identified 2344 references. After two screening phases, 23 studies of VSU therapeutic interventions remained. Of these, 19 concerned psychosocial interventions, which we discuss as: case management; counselling; recreation and engagement programmes; and residential treatment. Studies were conducted in Australia, Canada, the United States, United Kingdom and Brazil. No RCTs were identified and studies were generally of low evidentiary levels.

Conclusions  Even when a range of study types are included, clear conclusions for volatile substance use psychological treatment are not supported, but three intervention types merit further examination: family therapy, activity‐based programmes and Indigenous‐led residential approaches. Future volatile substance use research could be enhanced by developing and validating outcome measurement tools. Robust multi‐site studies are also required.
Technical aspects of clinical high‐resolution manometry studies
Authors: Bredenoord A. J. , Hebbard G. S
Published: January 2012

Background  A number of commercial and research systems are available for making high‐resolution manometry recordings.

Purpose  In this document, we review the standard equipment, patient preparation and routine protocol for high‐resolution manometry. The major differences between HRM systems lie in the method of signal transduction, with solid‐state catheter systems recording form intraluminal transducers and water perfusion systems recording pressures from external transducers via a perfused silicone catheter. The variations in recording systems result in different mechanical and electrical characteristics which dictate different techniques for setting up and using equipment. These issues are relevant in terms of costs and day to day management, but have little clinical significance. After the equipment is prepared for a manometric study, the esophagus is intubated transnasally with the manometric catheter and the catheter is positioned so that the UES and LES/diaphragm are visualized on the recording screen. The subject then undergoes 10 5ml water swallows in the supine position. Manometric data may be integrated with other data streams such as multichannel impedance or images from fluoroscopy to increase the power of the technique in difficult cases.
Skin infections and infestations in prison inmates
Authors: Oninla Olumayowa A. , Onayemi Olaniyi
Published: January 2012

Background  Skin infections and infestations are common in a prison environment. The prison is in dynamic equilibrium with the larger society. Hence, it serves as a reservoir of infections which can spread to the larger society. The study sets out to find out how rampant these infections might be in the prison and the factors responsible.

Materials and methods  Inmates at a Nigerian prison in Ilesha, Osun State, were examined for skin infections. Personal hygiene and living conditions were critically examined.

Results  The overall prevalent rate of infectious dermatoses was 49.2% (150/305). There were 178 infections. Dermatophytes accounted for 64%, pityriasis versicolor 27%, bacterial infections 3.4%, and others 5.6%. Only frequency of soap use and accommodation arrangement significantly contributed to the overall prevalence. However, infectious dermatoses were significantly affected by prison status (PP = 0.04), frequency of bath (PP = 0.025), changing of clothing (PP = 0.05), accommodation arrangement (P = 0.0001), frequency of soap usage (P = 0.005), and toilet facility (P = 0.001). The HIV status of the inmates was unknown. Hence, effect of HIV infection cannot be ascertained.

Conclusion  Skin infections and infestations are common in prison. A change in living conditions and personal hygiene will definitely help in reducing these infections.
Who should receive recruitment and retention incentives? Improved targeting of rural doctors using medical workforce data
Authors: Humphreys John S. , McGrail Matthew R. , Joyce Catherine M. , Scott Anthony , Kalb Guyonne
Published: January 2012

Objective:  The objective of this study was to define an improved classification for allocating incentives to support the recruitment and retention of doctors in rural Australia.

Design and setting:  Geo‐coded data (n = 3636 general practitioners (GPs)) from the national Medicine in Australia: Balancing Employment and Life study were used to examine statistical variation in four professional indicators (total hours worked, public hospital work, on call after‐hours and difficulty taking time off) and two non‐professional indicators (partner employment and schooling opportunities) which are all known to be related to difficulties with recruitment and retention.

Main outcome measures:  The main outcome measure used for the study was an association of six sentinel indicators for GPs with practice location and population size of community.

Results:  Four distinct homogeneous population size groups were identified (0–5000, 5001‐15 000, 15 001–50 000 and >50 000). Although geographical remoteness (measured using the Australian Standard Geographical Classification – Remoteness Areas (ASGC‐RA)) was statistically associated with all six indicators (P < 0.001), population size provided a more sensitive measure in directing where recruitment and retention incentives should be provided. A new six‐level rurality classification is proposed, based on a combination of four population size groups and the five ASGC‐RA levels. A significant increase in statistical association is measured in four of six indicators (and a slight increase in one indicator) using the new six‐level classification versus the existing ASGC‐RA classification.

Conclusions:  This new six‐level geographical classification provides a better basis for equitable resource allocation of recruitment and retention incentives to doctors based on the attractiveness of non‐metropolitan communities, both professionally and non‐professionally, as places to work and live.
Surgical excision of intraductal breast papilloma diagnosed on core biopsy
Authors: Lu Qinghui , Tan Ern Yu , Ho Bernard , Chen Juliana J. C. , Chan Patrick M. Y.
Published: January 2012

Background:  The need for surgical excision of benign papillary lesions diagnosed on core biopsy remains debatable. This lack of consensus arises because although there is a possibility of histological underestimation, there are as yet no reliable predictors of malignancy. We therefore aimed to evaluate the incidence of histological underestimation in our practice, and to identify factors that predict for this, in order to reduce unnecessary surgery without missing out on possible malignancy.

Methods:  Retrospective review of 106 patients diagnosed with a papillary lesion on percutaneous image‐guided core biopsy was performed between 1 January 2005 and 31 December 2008. The presence of atypia on core biopsy and the presence of malignancy in the surgical specimen were correlated with standard clinical, radiological and pathological features.

Results:  Histological underestimation occurred in 15 of 81 patients (19%). Malignancy was more likely when atypia was present in the core biopsy (P= 0.04, OR 5.17). Otherwise, a final diagnosis of malignancy was not correlated with any clinical or radiological features (P > 0.05). The presence of atypia was also not correlated with any clinical or radiological features.

Conclusion:  In our study, 19% of patients with a benign papillary lesion diagnosed on core biopsy were found to have atypical ductal hyperplasia or malignancy following surgery. In view of this, together with the absence of reliable predictive factors for malignancy, we recommend surgical excision of all papillary lesions diagnosed on core biopsy.
‘Trainee’ evaluation of the English National Training Programme for laparoscopic colorectal surgery
Authors: Wyles S. M. , Miskovic D. , Ni M. , Kennedy R. H. , Hanna G. B. , Coleman M. G.
Published: January 2012

Aim  The aim of this study was to review trainees’ opinions of the training they had received through the National Training Programme (NTP).

Method  An online questionnaire was distributed to NTP trainees who had completed five or more training episodes within the programme. Demographic data were collected. Opinion was given using a five‐point Likert scale (1 = strongly disagree, 2 = disagree, 3 = undecided, 4 = agree, 5 = strongly agree). Percentages, mean values and SD were presented. ANOVA and Mann–Whitney U‐tests were used to examine the impact of different factors on ratings and the difference between ratings, respectively.

Results  Fifty‐four registered trainees fulfilled the inclusion criteria, and 37 (69% response rate) completed the questionnaire. Teaching sessions were organized using an inreach (11%), in‐house (11%), outreach (27%) or combination (51%) system of training. Trainees felt that their trainers seldom cancelled sessions (93%), that it was easy to organize (92%) and consent (100%) the patient, and that their hospital was supportive of training (97%). Trainees stated that overall their trainers were excellent at training (Likert scale = 4.71 ± 0.46) and that they received regular feedback (87%). The only variable to have a significant impact on the level of NTP approval was whether the trainee was able to choose his or her trainer (supportive of NTP, chose trainer P = 0.050; critical of NTP, chose trainer P = 0.020).

Conclusion  The large majority of trainees was highly satisfied with the training received in this innovative programme, irrespective of region or training structure used, thus demonstrating acceptability of the programme in its current form.
Surgical therapy for multiple sclerosis tremor: a 12‐year follow‐up study
Authors: Hassan A. , Ahlskog J. E. , Rodriguez M. , Matsumoto J. Y.
Published: January 2012

Background and purpose:  Severe multiple sclerosis (MS) tremor causes disability poorly responsive to medication. Deep brain stimulation (DBS) or thalamotomy can suppress tremor, but long‐term outcomes are unclear.

Methods:  Nine patients with MS tremor underwent disability measures at baseline and 12 months post‐surgery (six thalamotomy, three DBS) in 1997–1998 (previously reported, Matsumoto et al., Neurology 2001;57:1876–82). We report the prospective 12‐year follow‐up of this cohort for tremor, disability, and death.

Results:  Surgery was initially successful in all. Tremor recurred in all patients within median 3 months, although two DBS patients were tremor‐free for 5 years. Median tremor‐free survival (tremor‐free time/survival time) was 4.3%. At 12‐year follow‐up, four survivors (two thalamotomy, two DBS) (Expanded Disability Status Scale scores 8–8.5) were severely disabled. Five patients were dead (four thalamotomy, one DBS) median 5.8 years post‐operative.

Conclusions:  Surgery benefit for severe tremor was overall short‐lived (median 3 months), with long‐term poor prognosis. Although two DBS patients had sustained 5‐year tremor‐suppression, the observed progressive disability and death in this cohort bear importance for long‐term success in future MS tremor surgery trials.
Treatment for Helicobacter pylori infection and risk of parkinson’s disease in Denmark
Authors: Nielsen H. H. , Qiu J. , Friis S. , Wermuth L. , Ritz B.
Published: January 2012

Background and purpose:  It has been speculated that gastrointestinal infection with Helicobacter pylori (HP) contributes to the development of Parkinson’s disease (PD). We used nationwide Danish registers to investigate this hypothesis.

Methods:  We identified 4484 patients with a first time PD diagnosis between 2001 and 2008 from the Danish National Patient Register (DNPR) and 22 416 population controls from the Danish Civil Registration System (CRS). Information on drug use was obtained from the National Prescription Registry (NPR). We used logistic regression to compute odds ratios (OR) for the association between treatment for HP and risk of PD.

Results:  Prescriptions for HP‐eradication drugs and proton pump inhibitors (PPI) 5 or more years prior to the diagnosis of PD were associated with a 45% and 23% increase in PD risk, respectively. Hospitalizations and outpatient visits for gastritis and peptic/duodenal ulcers, however, were not associated with PD.

Conclusions:  Our population‐based study suggests that chronic HP infections and/or gastritis contribute to PD or that these are PD‐related pathologies that precede motor symptoms.
Medial temporal lobe is vulnerable to vascular risk factors in men: a population‐based study
Authors: Qiu C. , Zhang Y. , Bronge L. , Herlitz A. , Aspelin P. , Bäckman L. , Fratiglioni L. , Wahlund L. ‐O.
Published: January 2012

Background and purpose:  Vascular risk factors (VRFs) are known to cause cerebral microvascular disease, but evidence supporting an effect of VRFs on regional brain atrophy is mixed. We investigate whether an aggregation of VRFs is associated with volume of hippocampus and entorhinal cortex in elderly people living in the community.

Methods:  This cross‐sectional study consists of 523 participants (age ≥60 years, 59.3% women) of the SNAC‐K Study in central Stockholm, Sweden, who were free of clinical stroke and cognitive impairment. We collected data on VRFs through interviews, clinical examination and inpatient register system. Hippocampal and entorhinal cortex volume was manually measured on magnetic resonance images. Data were analysed with general linear regression models controlling for demographics and total intracranial volume.

Results:  In men, high total cholesterol and diabetes were significantly or marginally associated with smaller hippocampus and entorhinal cortex; when current smoking, binge alcohol drinking, high cholesterol and diabetes were aggregated, an increasing number of VRFs were significantly associated with decreasing volume of hippocampus and entorhinal cortex (P for linear trend <0.01). In women, none of individual VRFs or their aggregation was significantly associated with the volume of these brain regions, except former smoking that was significantly associated with a larger volume of these regions.

Conclusions:  Aggregation of VRFs is associated with reduced hippocampal and entorhinal cortex volume in apparently healthy elderly men, but not in women. This implies that in men, the medial temporal lobe is vulnerable to cardiovascular risk factors.
Developing Interfacial Phase Diagrams for Applications in Activated Sintering and Beyond: Current Status and Future Directions
Authors: Luo Jian
Published: January 2012

This article critically assesses the current status and future directions for the development of interfacial phase diagrams for applications in activated sintering and other fields. The origin of solid‐state activated sintering is attributed to the enhanced mass transport in sintering‐aid‐based, nanoscale, quasi‐liquid, interfacial films that are stabilized below the bulk solidus line. Interfacial thermodynamic models have been developed via extending a phenomenological premelting theory and incorporating the computational thermodynamic (CalPhaD) methods. A primitive type of interfacial phase diagrams, λ‐diagrams, have been computed, and these diagrams have been validated by experiments and proven useful. More rigorous interfacial phase diagrams with well‐defined transition lines and critical points may also be constructed. A long‐range scientific goal is proposed to develop interfacial phase diagrams as a new materials science tool. Future studies should be conducted in several areas to achieve this goal, and special efforts should be made to predict the complex interfacial phase behaviors in multicomponent ceramic materials. Potential broad applications are envisaged.
In vivo quantification of epidermis pigmentation and dermis papilla density with reflectance confocal microscopy: variations with age and skin phototype
Authors: Lagarrigue Sophie Garrido , George Jerome , Questel Emmanuel , Lauze Christophe , Meyer Nicolas , Lagarde Jean‐Michel , Simon Michel , Schmitt Anne‐Marie , Serre Guy , Paul Carle
Published: January 2012

Abstract:  Reflectance confocal microscopy (RCM) may help to quantify variations of skin pigmentation induced by different stimuli such as UV radiation or therapeutic intervention. The objective of our work was to identify RCM parameters able to quantify in vivo dermis papilla density and epidermis pigmentation potentially applicable in clinical studies. The study included 111 healthy female volunteers with phototypes I–VI. Photo‐exposed and photo‐protected anatomical sites were imaged. The effect of age was also assessed. Four epidermis components were specifically investigated: stratum corneum, stratum spinosum, basal epidermal layer and dermo‐epidermal junction. Laser power, diameter of corneocytes and upper spinous keratinocytes, brightness of upper spinous and interpapillary spinous keratinocytes, number of dermal papillae and papillary contrast were systematically assessed. Papillary contrast measured at the dermo‐epidermal junction appeared to be a reliable marker of epidermis pigmentation and showed a strong correlation with skin pigmentation assessed clinically using the Fitzpatrick’s classification. Brightness of upper spinous and interpapillary spinous keratinocytes was not influenced by the skin phototype. The number of dermal papillae was significantly lower in subjects with phototypes I–II as compared with darker skin subjects. A dramatic reduction in the number of dermal papillae was noticed with age, particularly in subjects with fair skin. The method presented here provides a new in vivo investigation tool for quantification of dermis papilla density and epidermal pigmentation. Papillary contrast measured at the dermo‐epidermal junction may be selected as a marker of skin pigmentation for evaluation in clinical studies.
The efficacy of maggot debridement therapy – a review of comparative clinical trials
Authors: Zarchi Kian , Jemec Gregor BE
Published: January 2012

Over the last decade, maggot debridement therapy (MDT) has been recognized by many clinicians as a potential adjunct to conventional therapy, and many patients with non healing, chronic ulcers have been treated. Numerous case reports and case series have described the successful use of MDT in a variety of ulcers. However, comparative clinical trials and in particular randomized controlled trials investigating the efficacy of MDT are sparse.

A systematic search in the literature showed three randomized clinical trials and five non randomized studies evaluating the efficacy of sterile Lucilia sericata applied on ulcers with various aetiologies. Of these, seven studies had debridement and/or healing as an outcome variable.

When evaluating maggots as debriding agents, the studies report MDT as being significantly more effective than hydrogel or a mixture of conventional therapy modalities, including hydrocolloid, hydrogel and saline moistened gauze. However, the design of the studies was suboptimal, with important differences in the use of other therapies, such as compression, that may influence both debridement and healing between the compared groups, as well as inappropriately short follow‐up times. The quality of the studies therefore makes it difficult to conclude that MDT shortens healing time. The poor quality of the data used for evaluating the efficacy of MDT highlights the need for more and better designed investigations.
Cultivars, Culture Conditions, and Harvest Time Influence Phenolic and Ascorbic Acid Contents and Antioxidant Capacity of Strawberry (Fragaria x ananassa)
Authors: Pincemail Joël , Kevers Claire , Tabart Jessica , Defraigne Jean‐Olivier , Dommes Jacques
Published: January 2012

Abstract:  Strawberries are a good source of micronutrients, especially antioxidant phenolics. More information is needed to better exploit the health‐promoting effect of such fruits. Several studies focused on the effects of genotype, cultural practices, and seasonal variation on the antioxidant potential of strawberries, but often yielding contradictory results and/or focusing on only 1 source of variability. In the present study, we showed that total phenolic compounds, ascorbic acid, and antioxidant capacity strongly differed between genotypes of strawberry. The precise results revealed the importance of genetic background for the antioxidant capacity and for the content of total phenolics (with up to 3.3‐fold variations). Other parameters may also influence the antioxidant capacity in strawberry such as harvest time, culture conditions, and environmental factors. Moreover, in this study, the harvesting time (at the same ripening stage) appeared to be very important, more important than genotype. Variations of the antioxidant capacity of up to 4.1‐folds were observed following the harvesting time of “Elsanta” cultivar.

Practical Application:  This article compares the antioxidant capacity and the content in ascorbic acid and phenolic compounds of strawberries of different varieties and of fruits harvested from April to December at the same ripening stage. The importance of strawberry antioxidant capacity resides in its benefits for human health.
Exploring violin sound quality: Investigating English timbre descriptors and correlating resynthesized acoustical modifications with perceptual properties
Authors: Fritz Claudia , Blackwell Alan F. , Cross Ian , Woodhouse Jim , Moore Brian C. J.
Published: January 2012

Performers often discuss the sound quality of a violin or the sound obtained by particular playing techniques, calling upon a diverse vocabulary. This study explores the verbal descriptions, made by performers, of the distinctive timbres of different violins. Sixty-one common descriptors were collected and then arranged by violinists on a map, so that words with similar meanings lay close together, and those with different meanings lay far apart. The results of multidimensional scaling demonstrated consistent use among violinists of many words, and highlighted which words are used for similar purposes. These terms and their relations were then used to investigate the perceptual effect of acoustical modifications of violin sounds produced by roving of the levels in five one-octave wide bands, 190–380, 380–760, 760–1520, 1520–3040, and 3040–6080 Hz. Pairs of sounds were presented, and each participant was asked to indicate which of the sounds was more bright, clear, harsh, nasal, or good (in separate runs for each descriptor). Increased brightness and clarity were associated with moderately increased levels in bands 4 and 5, whereas increased harshness was associated with a strongly increased level in band 4. Judgments differed across participants for the qualities nasal and good.
Transmission loss of periodically stiffened laminate composite panels: Shear deformation and in-plane interaction effects
Authors: Mejdi Abderrazak , Legault Julien , Atalla Noureddine
Published: January 2012

This paper investigates the transmission loss of symmetric and asymmetric laminate composite panels periodically reinforced by composite stiffeners. A comprehensive model based on periodic structure theory is developed. First order shear deformation theory is used and the coupling of the in-plane motion of the panel with its out-of-plane motion is taken into account. Stiffeners interact with the panel through three forces (two in-plane, one out-of-plane) and a torsion moment. Three types of cross sections are investigated for the composite stiffeners: I-shaped, C-shaped, and omega-shaped cross-sections. The model is validated numerically by comparison with the finite element/boundary element method. Experimental validations are also conducted. In both cases, excellent agreement is obtained. Numerical results show that the in-plane coupling effect is increased by increasing the panel thickness and the stiffener’s eccentricity. The in-plane coupling effect is also found to increase with frequency.
Comparing vowel perception and production in Spanish and Portuguese: European versus Latin American dialects
Authors: Chládková Kateřina , Escudero Paola
Published: January 2012

Recent acoustic descriptions have shown that Spanish and Portuguese vowels are produced differently in Europe and Latin America. The present study investigates whether comparable between-variety differences exist in vowel perception. Spanish, Peruvian, Portuguese, and Brazilian listeners were tested in a vowel identification task with stimuli sampled from the whole vowel space. The mean perceived first (F1) and second formant (F2) of every vowel category were compared across varieties. For both languages, perception exhibited the same between-variety differences as production for F1 but not F2, which suggests correspondence between produced F1 and perceived vowel height but not between F2 and frontness.
Predicting handoffs in 3G networks
Authors: Javed Umar , Han Dongsu , Caceres Ramon , Pang Jeffrey , Seshan Srinivasan , Varshavsky Alexander
Published: January 2012

Consumers all over the world are increasingly using their smartphones on the go and expect consistent, high quality connectivity at all times. A key network primitive that enables continuous connectivity in cellular networks is
handoff
. Although handoffs are necessary for mobile devices to maintain connectivity, they can also cause short-term disruptions in application performance. Thus, applications could benefit from the ability to predict impending handoffs with reasonable accuracy, and modify their behavior to counter the performance degradation that accompanies handoffs. In this paper, we study whether attributes relating to the cellular network conditions measured at handsets can accurately predict handoffs. In particular, we develop a machine learning framework to predict handoffs in the near future. An evaluation on handoff traces from a large US cellular carrier shows that our approach can achieve 80% accuracy - 27% better than a naive predictor.
Traffic backfilling
Authors: Lagar-Cavilla H. Andrés , Joshi Kaustubh , Varshavsky Alexander , Bickford Jeffrey , Parra Darwin
Published: January 2012

Mobile application developers pay little attention to the interactions between applications and the cellular network carrying their traffic. This results in waste of device energy and network signaling resources. We place part of the blame on mobile OSes: they do not expose adequate interfaces through which applications can interact with the network. We propose traffic backfilling, a technique in which delay-tolerant traffic is opportunistically transmitted by the OS using resources left over by the naturally occurring bursts caused by interactive traffic. Backfilling presents a simple interface with two classes of traffic, and grants the OS and network large flexibility to maximize the use of network resources and reduce device energy consumption. Using device traces and network data from a major US carrier, we demonstrate a large opportunity for traffic backfilling.
ROSY
Authors: Raghavan Karthik , Kamakoti V.
Published: January 2012

In the nanometer era, there has been a steady decline in the semiconductor chip manufacturing yield due to various contributing factors, such as wearout and defects due to complex processes. One of the strategies to alleviate this issue is to recover and use faulty hardware at gracefully degraded performance. A common, though naive, recovery strategy followed in the context of general purpose multicore systems is to disable the cores with faults and use only the fully functional cores. Such a coarse-granular solution is suboptimal, as the disabled cores would have many working modules which go un-utilized. The Resurrecting Operating SYstem (ROSY) presented in this paper is a step towards the development of an operating system that can work on faulty cores by adapting itself to hardware faults using software workarounds, and and utilize their working components. We consider many realistic fault models and present software workarounds for them. We have developed a framework which can be trivially plugged into a fullyfeatured x86 based OS kernel to demonstrate the feasibility of the proposed ideas. Performance evaluation using SPEC benchmarks and real-world applications show that the performance degradation of the depleted cores executing ROSY is on an average between 1.6x to 4x, depending on the fault type.
Existing offset assignments are near optimal for an industrial AFDX network
Authors: Li Xiaoting , Scharbarg Jean-Luc , Ridouard Frédéric , Fraboul Christian
Published: January 2012

Avionics Full DupleX Switched Ethernet (AFDX) has been developed for modern aircraft such as Airbus 380. Due to the non-determinism of switching mechanism, a worst-case delay analysis of the flows entering the network is a key issue for certification reasons. Up to now most existing approaches (such as Network Calculus) consider that all the flows are asynchronous and they do not take into account the scheduling of flows generated by the same end system. It is then pessimistic to take into account such a synchronous scenario. Each end system can be considered as an offset free system, thus the main objective of this paper is to evaluate existing offset assignments in the context of an industrial AFDX network. Existing offset assignments are adapted to take into account specific characteristics of an AFDX network. Worst-case delay results are obtained according to these offset heuristics. It is shown that some existing heuristics are not efficient while some are near optimal for the studied industrial AFDX network.
What FarmVille can teach us about cooperative workflows and architectures
Authors: Cikic Sabine , Kücklich Julian R.
Published: January 2012

An earlier version of this paper was presented at the 2011 IEEE International Symposium on Technology and Society (ISTAS) at Saint Xavier University in Chicago, Illinois (and printed in the 2011 ISTAS proceedings)
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Perhaps the most remarkable characteristic of digital social games such as Zynga's FarmVille is that they are designed in such a way that any user, regardless of their skills and experience, can familiarise themselves in a matter of moments with the object of the game, the interface, and the tools and options involved in playing them. In contrast, developers of collaborative platforms for teaching and research have been struggling for the last 15 to 20 years to gain a wide acceptance among users, and with very limited success. Although simple and intuitive usability has long been recognised as a key design goal, no-one has, apparently, yet succeeded in integrating all the tools and functions required for academic work into a platform with an intuitive interface that target groups make enthusiastic use of. This paper investigates which principles and features may be adopted to make the use of these platforms easier and more intuitive. This electronic document is a "live" template. The various components of your paper [title, text, heads, etc.] are already defined on the style sheet, as illustrated by the portions given in this document.
Report on the SIGCOMM 2011 conference
Authors: Byers John W. , Mogul Jeffrey C. , Adib Fadel , Aikat Jay , Chasaki Danai , Chen Ming-Hung , Chetty Marshini , Fontugne Romain , Gabale Vijay , Gyarmati László , LaCurts Katrina , Liao Qi , Mendonca Marc , Minh Trang Cao , Newaz S.H. Shah , Prakash Pawan , Shvartzshnaider Yan , Yalagandula Praveen , Yang Chun-Yu
Published: January 2012

This document provides reports on the presentations at the SIGCOMM 2011 Conference, the annual conference of the ACM Special Interest Group on Data Communication (SIGCOMM).
The Relationship of Thioredoxin-1 and Cisplatin Resistance: Its Impact on ROS and Oxidative Metabolism in Lung Cancer Cells
Authors: Wangpaichitr Medhi , Sullivan Elizabeth J. , Theodoropoulos George , Wu Chunjing , You Min , Feun Lynn G. , Lampidis Theodore J. , Kuo Macus T. , Savaraj Niramol
Published: January 2012

Elimination of cisplatin-resistant lung cancer cells remains a major obstacle. We have shown that cisplatin-resistant tumors have higher reactive oxygen species (ROS) levels and can be exploited for targeted therapy. Here, we show that increased secretion of the antioxidant thioredoxin-1 (TRX1) resulted in lowered intracellular TRX1 and contributed to higher ROS in cisplatin-resistant tumors in vivo and in vitro. By reconstituting TRX1 protein in cisplatin-resistant cells, we increased sensitivity to cisplatin but decreased sensitivity to elesclomol (ROS inducer). Conversely, decreased TRX1 protein in parental cells reduced the sensitivity to cisplatin but increased sensitivity to elesclomol. Cisplatin-resistant cells had increased endogenous oxygen consumption and mitochondrial activity but decreased lactic acid production. They also exhibited higher levels of argininosuccinate synthetase (ASS) and fumarase mRNA, which contributed to oxidative metabolism (OXMET) when compared with parental cells. Restoring intracellular TRX1 protein in cisplatin-resistant cells resulted in lowering ASS and fumarase mRNAs, which in turn sensitized them to arginine deprivation. Interestingly, cisplatin-resistant cells also had significantly higher basal levels of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). Overexpressing TRX1 lowered ACC and FAS proteins expressions in cisplatin-resistant cells. Chemical inhibition and short interfering RNA of ACC resulted in significant cell death in cisplatin-resistant compared with parental cells. Conversely, TRX1 overexpressed cisplatin-resistant cells resisted 5-(tetradecyloxy)-2-furoic acid (TOFA)-induced death. Collectively, lowering TRX1 expression through increased secretion leads cisplatin-resistant cells to higher ROS production and increased dependency on OXMET. These changes raise an intriguing therapeutic potential for future therapy in cisplatin-resistant lung cancer. Mol Cancer Ther; 11(3); 604–15. ©2012 AACR.
Antitumor Activity of a Novel Bispecific Antibody That Targets the ErbB2/ErbB3 Oncogenic Unit and Inhibits Heregulin-Induced Activation of ErbB3
Authors: McDonagh Charlotte F. , Huhalov Alexandra , Harms Brian D. , Adams Sharlene , Paragas Violette , Oyama Shinji , Zhang Bo , Luus Lia , Overland Ryan , Nguyen Stephanie , Gu Jinming , Kohli Neeraj , Wallace Matt , Feldhaus Michael J. , Kudla Arthur J. , Schoeberl Birgit , Nielsen Ulrik B.
Published: January 2012

The prevalence of ErbB2 amplification in breast cancer has resulted in the heavy pursuit of ErbB2 as a therapeutic target. Although both the ErbB2 monoclonal antibody trastuzumab and ErbB1/ErbB2 dual kinase inhibitor lapatinib have met with success in the clinic, many patients fail to benefit. In addition, the majority of patients who initially respond will unfortunately ultimately progress on these therapies. Activation of ErbB3, the preferred dimerization partner of ErbB2, plays a key role in driving ErbB2-amplified tumor growth, but we have found that current ErbB2-directed therapies are poor inhibitors of ligand-induced activation. By simulating ErbB3 inhibition in a computational model of ErbB2/ErbB3 receptor signaling, we predicted that a bispecific antibody that docks onto ErbB2 and subsequently binds to ErbB3 and blocks ligand-induced receptor activation would be highly effective in ErbB2-amplified tumors, with superior activity to a monospecific ErbB3 inhibitor. We have developed a bispecific antibody suitable for both large scale production and systemic therapy by generating a single polypeptide fusion protein of two human scFv antibodies linked to modified human serum albumin. The resulting molecule, MM-111, forms a trimeric complex with ErbB2 and ErbB3, effectively inhibiting ErbB3 signaling and showing antitumor activity in preclinical models that is dependent on ErbB2 overexpression. MM-111 can be rationally combined with trastuzumab or lapatinib for increased antitumor activity and may in the future complement existing ErbB2-directed therapies to treat resistant tumors or deter relapse. Mol Cancer Ther; 11(3); 582–93. ©2012 AACR.
Dilemmas in the reliable estimation of the in-vitro cell viability in magnetic nanoparticle engineering: which tests and what protocols?
Authors: Hoskins Clare , Wang Lijun , Cheng Woei Ping , Cuschieri Alfred
Published: January 2012

Magnetic nanoparticles [MNPs] made from iron oxides have many applications in biomedicine. Full understanding of the interactions between MNPs and mammalian cells is a critical issue for their applications. In this study, MNPs were coated with poly(ethylenimine) [MNP-PEI] and poly(ethylene glycol) [MNP-PEI-PEG] to provide a subtle difference in their surface charge and their cytotoxicity which were analysed by three standard cell viability assays: 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium [MTS], CellTiter-Blue and CellTiter-Glo (Promega, Southampton, UK) in SH-SY5Y and RAW 264.7 cells The data were validated by traditional trypan blue exclusion. In comparison to trypan blue manual counting, the MTS and Titer-Blue assays appeared to have consistently overestimated the viability. The Titer-Glo also experienced a small overestimation. We hypothesise that interactions were occurring between the assay systems and the nanoparticles, resulting in incorrect cell viability evaluation. To further understand the cytotoxic effect of the nanoparticles on these cells, reactive oxygen species production, lipid peroxidation and cell membrane integrity were investigated. After pegylation, the MNP-PEI-PEG possessed a lower positive surface charge and exhibited much improved biocompatibility compared to MNP-PEI, as demonstrated not only by a higher cell viability, but also by a markedly reduced oxidative stress and cell membrane damage. These findings highlight the importance of assay selection and of dissection of different cellular responses in in-vitro characterisation of nanostructures.
Models and maps: predicting the distribution of corals and other benthic macro‐invertebrates in shelf habitats
Authors: Krigsman Lisa M. , Yoklavich Mary M. , Dick E. J. , Cochrane Guy R.
Published: January 2012

Presence‐absence data of benthic macro‐invertebrates and associated habitat (i.e., sediment type and depth) were collected using a towed camera sled in selected areas along the coast off southern California. Using this information, we developed generalized linear models (GLMs) to predict the probability of occurrence of five commonly observed taxa (cup corals, hydroids, short and tall sea pens, and brittle stars in the sediment) within the Santa Barbara Channel (SBC). We employed a utility‐based approach to validate the models and to identify optimal cutoff thresholds for the GLM predictions, given a relative cost of false negatives and false positives. We present optimal cutoff values under a range of cost ratios. Out‐of‐sample predictive accuracy, assuming equal costs of false negatives and false positives, ranged from 75% to 89%. Estimated area under the characteristic curve (AUC) in our models ranged from 0.76 for brittle stars in sediment to 0.91 for cup corals. An AUC value above 0.7 is an acceptable level of performance, between 0.8 and 0.9 is excellent, and above 0.9 is outstanding. We developed predictive maps of probability of occurrence using our validated models and a seafloor character map based on fine‐scale (2–5 m) data. Cup corals and hydroids had high predicted probabilities of occurrence in areas of hard substrata, while short and tall sea pens were predicted to occur in parts of the SBC that had unconsolidated and mixed sediment. Our model predicted that brittle stars would occur throughout the entire channel on various bottom types. The combination of high‐resolution seafloor character maps and predictive models of invertebrate distributions will aid managers in identifying habitats of particular concern and areas with vulnerable, deep‐sea corals. Our models will be useful for marine spatial planning and ecosystem‐based management, as well as for assessing the effectiveness of essential fish habitat closures and other marine protected areas.