bluuebunny/crossref_metadata_2025 huggingface dataset:
HIV-1 Tat Protein Activates both the MyD88 and TRIF Pathways To Induce Tumor Necrosis Factor Alpha and Interleukin-10 in Human Monocytes
Authors: Planès Rémi , Ben Haij Nawal , Leghmari Kaoutar , Serrero Manutea , BenMohamed Lbachir , Bahraoui Elmostafa
Published: April 2016

In this study, we show that the HIV-1 Tat protein interacts with rapid kinetics to engage the Toll-like receptor 4 (TLR4) pathway, leading to the production of proinflammatory and anti-inflammatory cytokines. The pretreatment of human monocytes with Tat protein for 10 to 30 min suffices to irreversibly engage the activation of the TLR4 pathway, leading to the production of tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10), two cytokines strongly implicated in the chronic activation and dysregulation of the immune system during HIV-1 infection. Therefore, this study analyzed whether the HIV-1 Tat protein is able to activate these two pathways separately or simultaneously. Using three complementary approaches, including mice deficient in the MyD88, TIRAP/MAL, or TRIF adaptor, biochemical analysis, and the use of specific small interfering RNAs (siRNAs), we demonstrated (i) that Tat was able to activate both the MyD88 and TRIF pathways, (ii) the capacity of Tat to induce TIRAP/MAL degradation, (iii) the crucial role of the MyD88 pathway in the production of Tat-induced TNF-α and IL-10, (iv) a reduction but not abrogation of IL-10 and TNF-α by Tat-stimulated macrophages from mice deficient in TIRAP/MAL, and (v) the crucial role of the TRIF pathway in Tat-induced IL-10 production. Further, we showed that downstream of the MyD88 and TRIF pathways, the Tat protein activated the protein kinase C (PKC) βII isoform, the mitogen-activated protein (MAP) kinases p38 and extracellular signal-regulated kinase 1/2 (ERK1/2), and NF-κB in a TLR4-dependent manner. Collectively, our data show that by recruiting the TLR4 pathway with rapid kinetics, the HIV-1 Tat protein leads to the engagement of both the MyD88 and TRIF pathways and to the activation of PKC, MAP kinase, and NF-κB signaling to induce the production of TNF-α and IL-10.

IMPORTANCE
In this study, we demonstrate that by recruiting the TLR4 pathway with rapid kinetics, the HIV-1 Tat protein leads to the engagement of both the MyD88 and TRIF pathways and to the activation of PKC-βII, MAP kinase, and NF-κB signaling to induce the production of TNF-α and IL-10, two cytokines strongly implicated in the chronic activation and dysregulation of the immune system during HIV-1 infection. Thus, it may be interesting to target Tat as a pathogenic factor early after HIV-1 infection. This could be achieved either by vaccination approaches including Tat as an immunogen in potential candidate vaccines or by developing molecules capable of neutralizing the effect of the Tat protein.
Contributions of Charged Residues in Structurally Dynamic Capsid Surface Loops to Rous Sarcoma Virus Assembly
Authors: Heyrana Katrina J. , Goh Boon Chong , Perilla Juan R. , Nguyen Tam-Linh N. , England Matthew R. , Bewley Maria C. , Schulten Klaus , Craven Rebecca C.
Published: April 2016

Extensive studies of orthoretroviral capsids have shown that many regions of the CA protein play unique roles at different points in the virus life cycle. The N-terminal domain (NTD) flexible-loop (FL) region is one such example: exposed on the outer capsid surface, it has been implicated in Gag-mediated particle assembly, capsid maturation, and early replication events. We have now defined the contributions of charged residues in the FL region of the Rous sarcoma virus (RSV) CA to particle assembly. Effects of mutations on assembly were assessed
in vivo
and
in vitro
and analyzed in light of new RSV Gag lattice models. Virus replication was strongly dependent on the preservation of charge at a few critical positions in Gag-Gag interfaces. In particular, a cluster of charges at the beginning of FL contributes to an extensive electrostatic network that is important for robust Gag assembly and subsequent capsid maturation. Second-site suppressor analysis suggests that one of these charged residues, D87, has distal influence on interhexamer interactions involving helix α7. Overall, the tolerance of FL to most mutations is consistent with current models of Gag lattice structures. However, the results support the interpretation that virus evolution has achieved a charge distribution across the capsid surface that (i) permits the packing of NTD domains in the outer layer of the Gag shell, (ii) directs the maturational rearrangements of the NTDs that yield a functional core structure, and (iii) supports capsid function during the early stages of virus infection.

IMPORTANCE
The production of infectious retrovirus particles is a complex process, a choreography of protein and nucleic acid that occurs in two distinct stages: formation and release from the cell of an immature particle followed by an extracellular maturation phase during which the virion proteins and nucleic acids undergo major rearrangements that activate the infectious potential of the virion. This study examines the contributions of charged amino acids on the surface of the Rous sarcoma virus capsid protein in the assembly of appropriately formed immature particles and the maturational transitions that create a functional virion. The results provide important biological evidence in support of recent structural models of the RSV immature virions and further suggest that immature particle assembly and virion maturation are controlled by an extensive network of electrostatic interactions and long-range communication across the capsid surface.
Incongruity between Prion Conversion and Incubation Period following Coinfection
Authors: Langenfeld Katie A. , Shikiya Ronald A. , Kincaid Anthony E. , Bartz Jason C.
Published: April 2016

When multiple prion strains are inoculated into the same host, they can interfere with each other. Strains with long incubation periods can suppress conversion of strains with short incubation periods; however, nothing is known about the conversion of the long-incubation-period strain during strain interference. To investigate this, we inoculated hamsters in the sciatic nerve with long-incubation-period strain 139H prior to superinfection with the short-incubation-period hyper (HY) strain of transmissible mink encephalopathy (TME). First, we found that 139H is transported along the same neuroanatomical tracks as HY TME, adding to the growing body of evidence indicating that PrPScfavors retrograde transneuronal transport. In contrast to a previous report, we found that 139H interferes with HY TME infection, which is likely due to both strains targeting the same population of neurons following sciatic nerve inoculation. Under conditions where 139H blocked HY TME from causing disease, the strain-specific properties of PrPSccorresponded with the strain that caused disease, consistent with our previous findings. In the groups of animals where incubation periods were not altered, we found that the animals contained a mixture of 139H and HY TME PrPSc. This finding expands the definition of strain interference to include conditions where PrPScformation is altered yet disease outcome is unaltered. Overall, these results contradict the premise that prion strains are static entities and instead suggest that strain mixtures are dynamic regardless of incubation period or clinical outcome of disease.

IMPORTANCEPrions can exist as a mixture of strains in naturally infected animals, where they are able to interfere with the conversion of each other and to extend incubation periods. Little is known, however, about the dynamics of strain conversion under conditions where incubation periods are not affected. We found that inoculation of the same animal with two strains can result in the alteration of conversion of both strains under conditions where the resulting disease was consistent with infection with only a single strain. These data challenge the idea that prion strains are static and suggests that strain mixtures are more dynamic than previously appreciated. This observation has significant implications for prion adaptation.
Coinfections: Another Variable in the Herpesvirus Latency-Reactivation Dynamic
Authors: Reese Tiffany A.
Published: April 2016

Chronic viruses, such as herpesviruses, shape host physiology. These viruses modulate the inflammatory state of the immune system and have evolved to harness inflammation as a mechanism to regulate viral latency and reactivation. In this review, I examine some of the recent work demonstrating the important role of inflammation in the regulation of the herpesvirus life cycle and discuss recent work that implicates coinfection in the regulation of herpesvirus latency.
IS
26
-Mediated Formation of Transposons Carrying Antibiotic Resistance Genes
Authors: Harmer Christopher J. , Hall Ruth M.
Published: April 2016

In Gram-negative bacteria, IS
26
recruits antibiotic resistance genes into the mobile gene pool by forming transposons carrying many different resistance genes. In addition to replicative transposition, IS
26
was recently shown to use a novel conservative movement mechanism in which an incoming IS
26
targets a preexisting one. Here, we have demonstrated how IS
26
-bounded class I transposons can be produced from translocatable units (TUs) containing only an IS
26
and a resistance gene via the conservative reaction. TUs were incorporated next to an existing IS
26
, creating a class I transposon, and if the targeted IS
26
is in a transposon, the product resembles two transposons sharing a central IS
26
, a configuration observed in some resistance regions and when a transposon is tandemly duplicated. Though homologous recombination could also incorporate a TU, Tnp26 is far more efficient. This provides insight into how IS
26
builds transposons and brings additional transposons into resistance regions.
Complete colonoscopy: impact of patients' demographics and anthropometry on caecal intubation time
Authors: Akere Adegboyega , Otegbayo Jesse Abiodun
Published: April 2016

Background and aim

Factors that affect caecal intubation during colonoscopy include age and sex of the patient, quality of bowel preparation, prior abdominal or pelvic surgery and pelvic inflammatory disease, among others. The aim of this prospective study was to evaluate the effects of patients' demography such as age and sex, as well as anthropometry (height, weight and body mass index (BMI)) on caecal intubation time (CIT).

Patients and methods

All consecutive patients referred for colonoscopy over a period of 6 months were recruited into the study. Prior to the procedure, patients' demographic data as well as history of prior abdominal or pelvic surgery were recorded. The height and weight of each patient were taken, and the BMI calculated. CIT was measured from the time of insertion of the colonoscope into the anal canal to the time when the base of the caecum was intubated.

Results

A total of 167 patients comprising 99 (59.3%) males and 68 (40.7%) females were studied. The mean CIT of the procedures was 912.5±477.1 s with a range of 180–3180 s. It was more prolonged in patients older than 65 years of age, in males and in those with prior abdominal/pelvic surgery, although no significant difference was observed among the groups. Multivariate logistic regression analysis showed that increased BMI and non-usage of additional manoeuvres independently reduced CIT.

Conclusions

Older age, male gender, prior abdominal/pelvic surgery, use of additional manoeuvres and lower BMI were found to prolong CIT.
What drives quality improvement in chronic kidney disease (CKD) in primary care: process evaluation of the Quality Improvement in Chronic Kidney Disease (QICKD) trial
Authors: Nihat Akin , de Lusignan Simon , Thomas Nicola , Tahir Mohammad Aumran , Gallagher Hugh
Published: April 2016

Objectives

This study is a process evaluation of the Quality Improvement in Chronic Kidney Disease (QICKD) study, comparing audit-based education (ABE) and sending clinical guidelines and prompts (G&P) with usual practice, in improving systolic blood pressure control in primary care. This evaluation aimed to explore how far clinical staff in participating practices were aware of the intervention, and why change in practice might have taken place.

Setting

4 primary care practices in England: 2 received ABE, and 2 G&P. We purposively selected 1 northern/southern/city and rural practice from each study arm (from a larger pool of 132 practices as part of the QICKD trial).

Participants

The 4 study practices were purposively sampled, and focus groups conducted with staff from each. All staff members were invited to attend.

Interventions

Focus groups in each of 4 practices, at the mid-study point and at the end. 4 additional trial practices not originally selected for in-depth process evaluation took part in end of trial focus groups, to a total of 12 focus groups. These were recorded, transcribed and analysed using the framework approach.

Results

5 themes emerged: (1) involvement in the study made participants more positive about the CKD register; (2) clinicians did not always explain to patients that they had CKD; (3) while practitioners improved their monitoring of CKD, many were sceptical that it improved care and were more motivated by pay-for-performance measures; (4) the impact of study interventions on practice was generally positive, particularly the interaction with specialists, included in ABE; (5) the study stimulated ideas for future clinical practice.

Conclusions

Improving quality in CKD is complex. Lack of awareness of clinical guidelines and scepticism about their validity are barriers to change. While pay-for-performance incentives are the main driver for change, quality improvement interventions can have a complementary influence.
Barriers and facilitators to staying in work after stroke: insight from an online forum
Authors: Balasooriya-Smeekens Chantal , Bateman Andrew , Mant Jonathan , De Simoni Anna
Published: April 2016

Objective

To explore barriers and facilitators to staying in work following stroke.

Design

Qualitative analysis of posts regarding staying in work following stroke using the archives of an online forum for stroke survivors.

Participants

60 stroke survivors (29 male, 23 female, 8 not stated; mean age at stroke 44 years) who have returned to work, identified using terms ‘return to work’ and ‘back at work’.

Setting

Posts from UK stroke survivors and family members on Talkstroke, the forum of the Stroke Association, between 2004 and 2011.

Results

Stroke and transient ischaemic attack (TIA) survivors reported residual impairments that for many had impact on work. Most impairments were ‘invisible’, including fatigue, problems with concentration, memory and personality changes. Participants described positive (eg, back at work being better than expected) and negative work experiences, including being at risk of losing the job because of stroke-related impairments. Barriers to successfully staying in work included lack of understanding of stroke—in particular invisible impairments—of survivors, employers and general practitioners (GPs), and lack of support in terms of formal adjustments, and ‘feeling supported’. Stroke survivors described how they developed their own coping strategies, and how workplace and employer helped them to stay in work.

Conclusions

Despite having been able to return to work after a stroke, people may still experience difficulties in staying in work and risking losing their job. There is a need to improve awareness, in particular of invisible stroke-related impairments, among stroke survivors, work personnel and clinicians. This might be achieved through improved assessments of residual impairments in the workplace and in general practice. Future studies should investigate the effect of unrecognised fatigue and invisible impairments on staying in work following stroke, and explore the potential role for primary care in supporting stroke survivors who have returned to employment.
Survey of public definitions of the term ‘overdiagnosis’ in the UK
Authors: Ghanouni Alex , Meisel Susanne F , Renzi Cristina , Wardle Jane , Waller Jo
Published: April 2016

Objectives

To determine how ‘overdiagnosis’ is currently conceptualised among adults in the UK in light of previous research, which has found that the term is difficult for the public to understand and awareness is low. This study aimed to add to current debates on healthcare in which overdiagnosis is a prominent issue.

Design

An observational, web-based survey was administered by a survey company.

Setting

Participants completed the survey at a time and location of their choosing.

Participants

390 consenting UK adults aged 50–70 years. Quota sampling was used to achieve approximately equal numbers in three categories of education and equal numbers of men and women.

Primary outcome measures

Participants were asked whether they had seen or heard the term ‘overdiagnosis’. If they had, they were then invited to explain in a free-text field what they understood it to mean. If they had not previously encountered it, they were invited to say what they thought it meant. Responses were coded and interpreted using content analysis and descriptive statistics.

Results

Data from 390 participants were analysed. Almost a third (30.0%) of participants reported having previously encountered the term. However, their responses often indicated that they had no knowledge of its meaning. The most prevalent theme consisted of responses related to the diagnosis itself. Subthemes indicated common misconceptions, including an ‘overly negative or complicated diagnosis’, ‘false-positive diagnosis’ or ‘misdiagnosis’. Other recurring themes consisted of responses related to testing (ie, ‘too many tests’), treatment (eg, ‘overtreatment’) and patient psychology (eg, ‘overthinking’). Responses categorised as consistent with ‘overdiagnosis’ (defined as detection of a disease that would not cause symptoms or death) were notably rare (n=10; 2.6%).

Conclusions

Consistent with previous research, public awareness of ‘overdiagnosis’ in the UK is low and its meaning is often misunderstood or misinterpreted.
Incidence of adverse events in antipsychotic-naïve children and adolescents treated with antipsychotic drugs: a French multicentre naturalistic study protocol (ETAPE)
Authors: Menard Marie-Line , Thümmler Susanne , Giannitelli Marianna , Olliac Bertrand , Bonnot Olivier , Cohen David , Askenazy Florence
Published: April 2016

Introduction

In France, over recent years, the prescription rate of antipsychotic (AP) remained stable in children and adolescents. Prescription of second-generation antipsychotics increased, whereas prescription of first-generation antipsychotics decreased. Off-label prescriptions are very frequent in this population. Adverse events (AEs) in youth treated with AP are common and may be severe. AEs have hitherto been poorly monitored in naturalistic studies independent from industry.

Method and analysis

We describe a French prospective multicentre study in an AP-naïve paediatric population named Etude de la Tolérance des AntiPsychotique chez l'Enfant (ETAPE). The study started in April 2013. So far, 200 patients have been included. The inclusion criteria are: male or female inpatients aged from 6 to 18 years, treated with an AP drug for less than 28 days, never been treated or having received AP for less than 3 months, discontinued at least 6 months prior to inclusion. These assessments of AE are performed at inclusion, as well as at 3, 6, 9 and 12 months after the introduction of the AP. The monitoring period will end in May 2016.

Ethics and dissemination

The study protocol was approved by the Ethics Committee ‘Sud Méditerrané V’ (number 12.082) and by the French National Agency for Medicines and Health Products Safety (number 2012-004546-15). All patients and their parents signed informed consent on enrolment in the study. We will submit the results of the study to relevant journals and offer national and international presentations. This study will enable better characterisation of the prescription of AP drugs. The results will further help to develop quality standards and recommendations for monitoring AE during the prescription of AP.

Trial registration number

NCT02007928.
Managing breathlessness: a palliative care approach
Authors: Chin Chloe , Booth Sara
Published: April 2016

Breathlessness is an important and common symptom globally, affecting patients with a variety of malignant and non-malignant diseases. It causes considerable suffering to patients and also their families, and is a significant cost to healthcare systems. Optimal management of the symptom should therefore be of interest and importance to a wide range of clinicians. Best practice in the management of breathlessness consists of both non-pharmacological and pharmacological interventions as evidenced by recent randomised controlled trials of multidisciplinary breathlessness support services. As well as providing evidence for integration of early palliative care into respiratory services, these revealed that patient distress due to breathlessness can be significantly reduced and better outcomes can be achieved at lower cost than standard care.
Pig surgery: cryptorchidectomy using an inguinal approach
Authors: Scollo A. , Martelli P. , Borri E. , Mazzoni C.
Published: April 2016

The objective of the study was to determine whether a less‐invasive surgical technique used in cryptorchid horses, dogs and cats can be used successfully to remove retained testicles in pigs on farm. In total, 284 monolateral cryptorchid pigs underwent surgery on‐farm condition, during which an incision was made over the inguinal ring and the undescended testicle was located for removal via identification of the vaginal process and the embryonic gubernaculum. A traction of these structures allowed the testis to pass through the deep and the superficial rings up to its exteriorisation outside the abdominal wall through the inguinal canal. The undescended testicle was located in the abdomen in 258 cases (90.8 per cent) and in the inguinal region in the remaining 26 cases (9.1 per cent). In none of the pigs was the abdominal cavity breached or the inguinal rings enlarged. However, in 23 pigs (8.1 per cent) the gubernaculum testis was thin and it frayed and ruptured when traction was applied, requiring a recovering by inserting a finger and Kelly curved forceps into the abdomen through the inguinal ring. In two pigs (0.7 per cent), the undescended testicle was not found. All surgical procedures were completed within 6–12 minutes. Four pigs died within two days after surgery (1.4 per cent). Major intraoperative or long‐term complications did not occur. Results suggested that this surgical method is highly effective and could be used as a primary surgical approach in cryptorchid pigs as it is in cryptorchid dogs, cats and horses.
Nitrous oxide emissions as affected by liquid and solid pig manures applied to annual and perennial forage crops on a sandy loam soil
Authors: Nikièma Paligwendé , Akinremi O.O. , Tenuta M.
Published: April 2016

Emissions of nitrous oxide (N2O-N) from manure applied to annual crop (AC) and perennial forage (PF) are poorly quantified for the Canadian Prairie Region. This study used static chambers over two growing seasons to assess soil N2O-N emissions from solid pig manure (SPM) and liquid pig manure (LPM) in AC and PF systems on a sandy loam soil. In 2011, when manure application coincided with hot and wet soil conditions, both manure treatments in AC induced N2O-N emission episodes a week later. In the PF, however, only LPM resulted in an N2O-N emission peak after 8 d. In 2012, manure application did not coincide with hot and wet soil conditions, and emission rates were smaller. Overall, the effect of manure type was inconsistent. In 2011, cumulative emissions in AC from LPM and SPM were 5.8 and 7.8 kg N2O-N ha−1, respectively, and in PF were 10.7 and 0.6 kg N2O-N ha−1, respectively. In 2012, cumulative emissions were <1 kg N2O-N ha−1, except LPM in PF.  In 2011, LPM had significantly higher emission factor (EF ≍ 7%) than SPM (≤0.2%) in both AC and PF, whereas in 2012 manure type had no effect on EF (≍ 0). Over the two growing seasons and across manure types, EF did not differ between AC and PF. These results suggest that SPM would reduce N2O-N emission relative to LPM when conditions favor intense denitrification.
NES-REBS: A novel nuclear export signal prediction method using regular expressions and biochemical properties
Authors: Wu Tingfang , Wang Xun , Zhang Zheng , Gong Faming , Song Tao , Chen Zhihua , Zhang Pan , Zhao Yang
Published: April 2016

A nuclear export signal (NES) is a protein localization signal, which is involved in binding of cargo proteins to nuclear export receptor, thus contributes to regulate localization of cellular proteins. Consensus sequences of NES have been used to detect NES from protein sequences, but suffer from poor predictive power. Some recent peering works were proposed to use biochemical properties of experimental verified NES to refine NES candidates. Those methods can achieve high prediction rates, but their execution time will become unacceptable for large-scale NES searching if too much properties are involved. In this work, we developed a novel computational approach, named NES-REBS, to search NES from protein sequences, where biochemical properties of experimental verified NES, including secondary structure and surface accessibility, are utilized to refine NES candidates obtained by matching popular consensus sequences. We test our method by searching 262 experimental verified NES from 221 NES-containing protein sequences. It is obtained that NES-REBS runs in 2–3[Formula: see text]mins and performs well by achieving precision rate 47.2% and sensitivity 54.6%.
THE DETERMINANTS OF ORGANISATIONAL CREATIVITY METHODS: AN EMPIRICAL STUDY BASED ON A FRENCH SURVEY
Authors: CHASSAGNON VIRGILE , HANED NACIBA , LE BAS CHRISTIAN
Published: April 2016

This paper analyses the determinants of different organisational techniques dedicated to creativity by stressing the crucial role played by the dynamic innovative capacities of firms in this process. In particular, we show that the impact of creativity methods varies with the type of innovator (product versus process; single versus complex). We use a bivariate probit estimation on a sample of 4,570 manufacturing firms drawn from the 2010 French Community Innovation Surveys (CIS 2010) to study how the innovation profiles of firms impact the propensity to use organisational creativity methods. The estimation results show a strong but differentiated impact of the innovation profiles of firms (products/process, single/complex) on the use of different creativity methods. These empirical results display the accuracy of modern research on the determinants of intra-firm organisation of creativity.
A Day-Ahead Wave Healing in a Power Grid
Authors: Stefanov S. Z. , Wang Paul P.
Published: April 2016

The paper deals with a wind wave, which is a day-ahead wave healing of a power grid with lots of wind farms and a transmission fault. This wave healing restores synchronization and shape of a power grid. The synchronization restoration is achieved by Casimir force, adjusted by an energy spike. The shape restoration is achieved via an energy spike, adjusted by the change of the free energy of the grid.
Vector-valued modular forms and the modular orbifold of elliptic curves
Authors: Candelori Luca , Franc Cameron
Published: April 2016

This paper presents the theory of holomorphic vector-valued modular forms from a geometric perspective. More precisely, we define certain holomorphic vector bundles on the modular orbifold of generalized elliptic curves whose sections are vector-valued modular forms. This perspective simplifies the theory, and it clarifies the role that exponents of representations of [Formula: see text] play in the holomorphic theory of vector-valued modular forms. Further, it allows one to use standard techniques in algebraic geometry to deduce free-module theorems and dimension formulae (deduced previously by other authors using different techniques), by identifying the modular orbifold with the weighted projective line [Formula: see text].
Partitions into a small number of part sizes
Authors: Keith William J.
Published: April 2016

We study [Formula: see text], the number of partitions of [Formula: see text] into [Formula: see text] part sizes, and find numerous arithmetic progressions where [Formula: see text] and [Formula: see text] take on values divisible by 2 and 4. Expanding an earlier work, we show [Formula: see text] for ([Formula: see text]) = (36,30), (72,42), (252,114), (196,70), and likely many other progressions for which our method should easily generalize. Of some independent interest, we prove that the overpartition function [Formula: see text] in the first three progressions (the fourth is known), and thereby show that [Formula: see text] in each of these progressions as well, and discuss the relationship between these congruences in more generality. We end with open questions in this area.
On Effective Location-Aware Music Recommendation
Authors: Cheng Zhiyong , Shen Jialie
Published: April 2016

Rapid advances in mobile devices and cloud-based music service now allow consumers to enjoy music anytime and anywhere. Consequently, there has been an increasing demand in studying intelligent techniques to facilitate context-aware music recommendation. However, one important context that is generally overlooked is user’s venue, which often includes surrounding atmosphere, correlates with activities, and greatly influences the user’s music preferences. In this article, we present a novel venue-aware music recommender system called VenueMusic to effectively identify suitable songs for various types of popular venues in our daily lives. Toward this goal, a Location-aware Topic Model (LTM) is proposed to (i) mine the common features of songs that are suitable for a venue type in a latent semantic space and (ii) represent songs and venue types in the shared latent space, in which songs and venue types can be directly matched. It is worth mentioning that to discover meaningful latent topics with the LTM, a Music Concept Sequence Generation (MCSG) scheme is designed to extract effective semantic representations for songs. An extensive experimental study based on two large music test collections demonstrates the effectiveness of the proposed topic model and MCSG scheme. The comparisons with state-of-the-art music recommender systems demonstrate the superior performance of VenueMusic system on recommendation accuracy by associating venue and music contents using a latent semantic space. This work is a pioneering study on the development of a venue-aware music recommender system. The results show the importance of considering the influence of venue types in the development of context-aware music recommender systems.
Identifying Power-Efficient Multicore Cache Hierarchies via Reuse Distance Analysis
Authors: Badamo Michael , Casarona Jeff , Zhao Minshu , Yeung Donald
Published: April 2016

To enable performance improvements in a power-efficient manner, computer architects have been building CPUs that exploit greater amounts of thread-level parallelism. A key consideration in such CPUs is properly designing the on-chip cache hierarchy. Unfortunately, this can be hard to do, especially for CPUs with high core counts and large amounts of cache. The enormous design space formed by the combinatorial number of ways in which to organize the cache hierarchy makes it difficult to identify power-efficient configurations. Moreover, the problem is exacerbated by the slow speed of architectural simulation, which is the primary means for conducting such design space studies.

A powerful tool that can help architects optimize CPU cache hierarchies is reuse distance (RD) analysis. Recent work has extended uniprocessor RD techniques-i.e., by introducing concurrent RD and private-stack RD profiling—to enable analysis of different types of caches in multicore CPUs. Once acquired, parallel locality profiles can predict the performance of numerous cache configurations, permitting highly efficient design space exploration. To date, existing work on multicore RD analysis has focused on developing the profiling techniques and assessing their accuracy. Unfortunately, there has been no work on using RD analysis to optimize CPU performance or power consumption.

This article investigates applying multicore RD analysis to identify the most power efficient cache configurations for a multicore CPU. First, we develop analytical models that use the cache-miss counts from parallel locality profiles to estimate CPU performance and power consumption. Although future scalable CPUs will likely employ multithreaded (and even out-of-order) cores, our current study assumes single-threaded in-order cores to simplify the models, allowing us to focus on the cache hierarchy and our RD-based techniques. Second, to demonstrate the utility of our techniques, we apply our models to optimize a large-scale tiled CPU architecture with a two-level cache hierarchy. We show that the most power efficient configuration varies considerably across different benchmarks, and that our locality profiles provide deep insights into why certain configurations are power efficient. We also show that picking the best configuration can provide significant gains, as there is a 2.01x power efficiency spread across our tiled CPU design space. Finally, we validate the accuracy of our techniques using detailed simulation. Among several simulated configurations, our techniques can usually pick the most power efficient configuration, or one that is very close to the best. In addition, across all simulated configurations, we can predict power efficiency with 15.2% error.
Designing Future Warehouse-Scale Computers for Sirius, an End-to-End Voice and Vision Personal Assistant
Authors: Hauswald Johann , Laurenzano Michael A. , Zhang Yunqi , Yang Hailong , Kang Yiping , Li Cheng , Rovinski Austin , Khurana Arjun , Dreslinski Ronald G. , Mudge Trevor , Petrucci Vinicius , Tang Lingjia , Mars Jason
Published: April 2016

As user demand scales for intelligent personal assistants (IPAs) such as Apple’s Siri, Google’s Google Now, and Microsoft’s Cortana, we are approaching the computational limits of current datacenter (DC) architectures. It is an open question how future server architectures should evolve to enable this emerging class of applications, and the lack of an open-source IPA workload is an obstacle in addressing this question. In this article, we present the design of Sirius, an open end-to-end IPA Web-service application that accepts queries in the form of voice and images, and responds with natural language. We then use this workload to investigate the implications of four points in the design space of future accelerator-based server architectures spanning traditional CPUs, GPUs, manycore throughput co-processors, and FPGAs. To investigate future server designs for Sirius, we decompose Sirius into a suite of eight benchmarks (Sirius Suite) comprising the computationally intensive bottlenecks of Sirius. We port Sirius Suite to a spectrum of accelerator platforms and use the performance and power trade-offs across these platforms to perform a total cost of ownership (TCO) analysis of various server design points. In our study, we find that accelerators are critical for the future scalability of IPA services. Our results show that GPU- and FPGA-accelerated servers improve the query latency on average by 8.5× and 15×, respectively. For a given throughput, GPU- and FPGA-accelerated servers can reduce the TCO of DCs by 2.3× and 1.3×, respectively.
The Gest-Rest Family
Authors: Carrington Patrick , Chang Jian-Ming , Chang Kevin , Hornback Catherine , Hurst Amy , Kane Shaun K.
Published: April 2016

Interacting with touch screen-based computing devices can be difficult for individuals with mobility impairments that affect their hands, arms, neck, or head. These problems may be especially difficult for power wheelchair users, as the frame of their wheelchair may obstruct the users’ range of motion and reduce their ability to reach objects in the environment. The concept of “chairable” input devices refers to input devices that are designed to fit with the form of an individual's wheelchair, much like wearable technology fits with an individual's clothing. In this paper, we introduce a new family of chairable input devices: Gest-Rests. A Gest-Rest is a gesture based input device that fits over a standard power wheelchair armrest. A Gest-Rest enables users to perform traditional touch screen gestures, such as press and flick, as well as pressure-based gestures such as squeezing and punching. We have developed the Gest-Rest Family, a suite of armrest-based input devices designed for power wheelchair users. In this paper, we present formative evaluations of these prototypes with wheelchair users and therapists and present their opinions of this new integrated input technology. Our results show the benefits of armrest-based input devices as well as a comparison of physical switches, force sensing, and capacitive input for individuals with limited dexterity.
Efficient Fluid Simulation on the Surface of a Sphere
Authors: Hill David J. , Henderson Ronald D.
Published: April 2016

For the purposes of computer graphics, we have developed a simulation tool to model fluid flow on the surface of a sphere with the inclusion of control parameters for the benefit of art directability. Difficulties associated with the use of spherical coordinates were surmounted by the use of locally modified consistent equations that result from an analysis of the singular equations in the neighborhood of the poles. The resulting system was solved efficiently for only a small additional cost when compared to a two-dimensional planar simulation.
Control Explicit--Data Symbolic Model Checking
Authors: Bauch Petr , Havel Vojtěch , Barnat Jiří
Published: April 2016

Automatic verification of programs and computer systems with data nondeterminism (e.g., reading from user input) represents a significant and well-motivated challenge. The case of parallel programs is especially difficult, because then also the control flow nontrivially complicates the verification process. We apply the techniques of explicit-state model checking to account for the control aspects of a program to be verified and use
set-based reduction
of the data flow, thus handling the two sources of nondeterminism separately. We build the theory of set-based reduction using first-order formulae in the bit-vector theory to encode the sets of variable evaluations representing program data. These representations are tested for emptiness and equality (state matching) during the verification, and we harness modern satisfiability modulo theory solvers to implement these tests.

We design two methods of implementing the state matching, one using quantifiers and one that is quantifier-free, and we provide both analytical and experimental comparisons. Further experiments evaluate the efficiency of the set-based reduction method, showing the classical, explicit approach to fail to scale with the size of data domains. Finally, we propose and evaluate two heuristics to decrease the number of expensive satisfiability queries, together yielding a 10-fold speedup.
Less is More
Authors: Pavese Esteban , Braberman Víctor , Uchitel Sebastian
Published: April 2016

Model-based reliability estimation of systems can provide useful insights early in the development process. However, computational complexity of estimating metrics such as mean time to first failure (MTTFF), turnaround time (TAT), or other domain-based quantitative measures can be prohibitive both in time, space, and precision. In this article, we present an alternative to exhaustive model exploration, as in probabilistic model checking, and partial random exploration, as in statistical model checking. Our hypothesis is that a (carefully crafted) partial systematic exploration of a system model can provide better bounds for these quantitative model metrics at lower computation cost. We present a novel automated technique for metric estimation that combines simulation, invariant inference, and probabilistic model checking. Simulation produces a probabilistically relevant set of traces from which a state invariant is inferred. The invariant characterises a partial model, which is then exhaustively explored using probabilistic model checking. We report on experiments that suggest that metric estimation using this technique (for both fully probabilistic models and those exhibiting nondeterminism) can be more effective than (full-model) probabilistic and statistical model checking, especially for system models for which the events of interest are rare.
L4 Microkernels
Authors: Heiser Gernot , Elphinstone Kevin
Published: April 2016

The L4 microkernel has undergone 20 years of use and evolution. It has an active user and developer community, and there are commercial versions that are deployed on a large scale and in safety-critical systems. In this article we examine the lessons learnt in those 20 years about microkernel design and implementation. We revisit the L4 design articles and examine the evolution of design and implementation from the original L4 to the latest generation of L4 kernels. We specifically look at seL4, which has pushed the L4 model furthest and was the first OS kernel to undergo a complete formal verification of its implementation as well as a sound analysis of worst-case execution times. We demonstrate that while much has changed, the fundamental principles of minimality, generality, and high inter-process communication (IPC) performance remain the main drivers of design and implementation decisions.
Molecular Plasmonics
Authors: Wilson Andrew J. , Willets Katherine A.
Published: April 2016

In this review, we survey recent advances in the field of molecular plasmonics beyond the traditional sensing modality. Molecular plasmonics is explored in the context of the complex interaction between plasmon resonances and molecules and the ability of molecules to support plasmons self-consistently. First, spectroscopic changes induced by the interaction between molecular and plasmonic resonances are discussed, followed by examples of how tuning molecular properties leads to active molecular plasmonic systems. Next, the role of the position and polarizability of a molecular adsorbate on surface-enhanced Raman scattering signals is examined experimentally and theoretically. Finally, we introduce recent research focused on using molecules as plasmonic materials. Each of these examples is intended to highlight the role of molecules as integral components in coupled molecule-plasmon systems, as well as to show the diversity of applications in molecular plasmonics.
Applications of Optical Microcavity Resonators in Analytical Chemistry
Authors: Wade James H. , Bailey Ryan C.
Published: April 2016

Optical resonator sensors are an emerging class of analytical technologies that use recirculating light confined within a microcavity to sensitively measure the surrounding environment. Bolstered by advances in microfabrication, these devices can be configured for a wide variety of chemical or biomolecular sensing applications. We begin with a brief description of optical resonator sensor operation, followed by discussions regarding sensor design, including different geometries, choices of material systems, methods of sensor interrogation, and new approaches to sensor operation. Throughout, key developments are highlighted, including advancements in biosensing and other applications of optical sensors. We discuss the potential of alternative sensing mechanisms and hybrid sensing devices for more sensitive and rapid analyses. We conclude with our perspective on the future of optical microcavity sensors and their promise as versatile detection elements within analytical chemistry.
Ant Genetics: Reproductive Physiology, Worker Morphology, and Behavior
Authors: Friedman D.A. , Gordon D.M.
Published: April 2016

Many exciting studies have begun to elucidate the genetics of the morphological and physiological diversity of ants, but as yet few studies have investigated the genetics of ant behavior directly. Ant genomes are marked by extreme rates of gene turnover, especially in gene families related to olfactory communication, such as the synthesis of cuticular hydrocarbons and the perception of environmental semiochemicals. Transcriptomic and epigenetic differences are apparent between reproductive and sterile females, males and females, and workers that differ in body size. Quantitative genetic approaches suggest heritability of task performance, and population genetic studies indicate a genetic association with reproductive status in some species. Gene expression is associated with behavior including foraging, response to queens attempting to join a colony, circadian patterns of task performance, and age-related changes of task. Ant behavioral genetics needs further investigation of the feedback between individual-level physiological changes and socially mediated responses to environmental conditions.
Elevated Gα11expression in osteoblast lineage cells promotes osteoclastogenesis and leads to enhanced trabecular bone accrual in response to pamidronate
Authors: Dela Cruz Ariana , Grynpas Marc D. , Mitchell Jane
Published: April 2016

Osteoblastic cells indirectly induce osteoclastogenesis in the bone microenvironment by expressing paracrine factors such as RANKL and M-CSF, leading to increased bone resorption. These cytokines can be regulated by a variety of intracellular pathways, which include G protein-coupled receptor signaling. To explore how enhanced signaling of the Gαq/11pathway in osteoblast lineage cells may mediate osteoclast formation, we cocultured wild-type (WT) preosteoclasts with BMSCs derived from either WT or transgenic mice with osteoblast-specific overexpression of Gα11(G11-Tg). G11-Tg cocultures had elevated osteoclast numbers with greater resorptive capacity and increased expression of Rankl, Rankl:Opg (osteoprotegerin), and M-csf compared with cocultures with WT BMSCs. As well, cocultures with G11-Tg BMSCs required a higher concentration of OPG to inhibit osteoclast formation and less angiotensin II to increase osteoclast size. These indicate that G11-Tg osteoblasts drive the increased osteoclast formation and osteopenia seen in G11-Tg mice. Pamidronate treatment of G11-Tg mice restored the trabecular bone loss phenotype, as bone mineral density, bone volume, trabecular number, separation, and expressions of osteoblastic and osteoclastic genes were comparable with WT parameters. These changes were characterized by enhanced accumulation of calcified cartilage in trabecular bone, demonstrating that resorption of the cartilaginous intermediate by osteoclasts is more affected by bisphosphonate treatment in G11-Tg mice. In conclusion, overexpression of Gα11in osteoblastic cells promotes osteoclastogenesis by upregulation of Rankl and M-csf and bone loss by increased osteoclast resorption of the trabecular bone and cartilaginous matrix.