Towards high performance computing for molecular structure prediction using IBM Cell Broadband Engine--an implementation perspective.

BACKGROUND: RNA structure prediction problem is a computationally complex task, especially with pseudo-knots. The problem is well-studied in existing literature and predominantly uses highly coupled Dynamic Programming (DP) solutions. The problem scale and complexity become embarrassingly humungous to handle as sequence size increases. This makes the case for parallelization. Parallelization can be achieved by way of networked platforms (clusters, grids, etc) as well as using modern day multi-core chips. METHODS: In this paper, we exploit the parallelism capabilities of the IBM Cell Broadband Engine to parallelize an existing Dynamic Programming (DP) algorithm for RNA secondary structure prediction. We design three different implementation strategies that exploit the inherent data, code and/or hybrid parallelism, referred to as C-Par, D-Par and H-Par, and analyze their performances. Our approach attempts to introduce parallelism in critical sections of the algorithm. We ran our experiments on SONY Play Station 3 (PS3), which is based on the IBM Cell chip. RESULTS: Our results suggest that introducing parallelism in DP algorithm allows it to easily handle longer sequences which otherwise would consume a large amount of time in single core computers. The results further demonstrate the speed-up gain achieved in exploiting the inherent parallelism in the problem and also elicits the advantages of using multi-core platforms towards designing more sophisticated methodologies for handling a fairly long sequence of RNA. CONCLUSION: The speed-up performance reported here is promising, especially when sequence length is long. To the best of our literature survey, the work reported in this paper is probably the first-of-its-kind to utilize the IBM Cell Broadband Engine (a heterogeneous multi-core chip) to implement a DP. The results also encourage using multi-core platforms towards designing more sophisticated methodologies for handling a fairly long sequence of RNA to predict its secondary structure.

Computational promoter analysis of mouse, rat and human antimicrobial peptide-coding genes.

BACKGROUND: Mammalian antimicrobial peptides (AMPs) are effectors of the innate immune response. A multitude of signals coming from pathways of mammalian pathogen/pattern recognition receptors and other proteins affect the expression of AMP-coding genes (AMPcgs). For many AMPcgs the promoter elements and transcription factors that control their tissue cell-specific expression have yet to be fully identified and characterized. RESULTS: Based upon the RIKEN full-length cDNA and public sequence data derived from human, mouse and rat, we identified 178 candidate AMP transcripts derived from 61 genes belonging to 29 AMP families. However, only for 31 mouse genes belonging to 22 AMP families we were able to determine true orthologous relationships with 30 human and 15 rat sequences. We screened the promoter regions of AMPcgs in the three species for motifs by an ab initio motif finding method and analyzed the derived promoter characteristics. Promoter models were developed for alpha-defensins, penk and zap AMP families. The results suggest a core set of transcription factors (TFs) that regulate the transcription of AMPcg families in mouse, rat and human. The three most frequent core TFs groups include liver-, nervous system-specific and nuclear hormone receptors (NHRs). Out of 440 motifs analyzed, we found that three represent potentially novel TF-binding motifs enriched in promoters of AMPcgs, while the other four motifs appear to be species-specific. CONCLUSION: Our large-scale computational analysis of promoters of 22 families of AMPcgs across three mammalian species suggests that their key transcriptional regulators are likely to be TFs of the liver-, nervous system-specific and NHR groups. The computationally inferred promoter elements and potential TF binding motifs provide a rich resource for targeted experimental validation of TF binding and signaling studies that aim at the regulation of mouse, rat or human AMPcgs.

Neuronal nitric oxide synthase gene transfer promotes cardiac vagal gain of function.

Nitric oxide (NO) generated from neuronal nitric oxide synthase (NOS-1) in intrinsic cardiac ganglia has been implicated in parasympathetic-induced bradycardia. We provide direct evidence that NOS-1 acts in a site-specific manner to promote cardiac vagal neurotransmission and bradycardia. NOS-1 gene transfer to the guinea pig right atrium increased protein expression and NOS-1 immunolocalization in cholinergic ganglia. It also increased the release of acetylcholine and enhanced the heart rate (HR) response to vagal nerve stimulation (VNS) in vitro and in vivo. NOS inhibition normalized the HR response to VNS in the NOS-1-treated group compared with the control groups (enhanced green fluorescent protein and sham) in vitro. In contrast, an acetylcholine analogue reduced HR to the same extent in all groups before and during NOS inhibition. These results demonstrate that NOS-1-derived NO acts presynaptically to facilitate vagally induced bradycardia and that upregulation of NOS-1 via gene transfer may provide a novel method for increasing cardiac vagal function.

Who is the ideal candidate for autologous chondrocyte implantation?

We investigated the prognostic indicators for collagen-covered autologous chondrocyte implantation (ACI-C) performed for symptomatic osteochondral defects of the knee. We analysed prospectively 199 patients for up to four years after surgery using the modified Cincinnati score. Arthroscopic assessment and biopsy of the neocartilage was also performed whenever possible. The favourable factors for ACI-C include younger patients with higher pre-operative modified Cincinnati scores, a less than two-year history of symptoms, a single defect, a defect on the trochlea or lateral femoral condyle and patients with fewer than two previous procedures on the index knee. Revision ACI-C in patients with previous ACI and mosaicplasties which had failed produced significantly inferior clinical results. Gender (p = 0.20) and the size of the defect (p = 0.97) did not significantly influence the outcome.

Collagen-covered autologous chondrocyte implantation for osteochondritis dissecans of the knee: two- to seven-year results.

We prospectively studied the clinical, arthroscopic and histological results of collagen-covered autologous chondrocyte implantation (ACI-C) in patients with symptomatic osteochondritis dissecans of the knee. The study included 37 patients who were evaluated at a mean follow-up of 4.08 years. Clinical results showed a mean improvement in the modified Cincinnati score from 46.1 to 68.4. Excellent and good clinical results were seen in 82.1% of those with juvenile-onset osteochondritis dissecans but in only 44.4% of those with adult-onset disease. Arthroscopy at one year revealed International Cartilage Repair Society grades of 1 or 2 in 21 of 24 patients (87.5%). Of 23 biopsies, 11 (47.8%) showed either a hyaline-like or a mixture of hyaline-like and fibrocartilage, 12 (52.2%) showed fibrocartilage. The age at the time of ACI-C determined the clinical outcome for juvenile-onset disease (p = 0.05), whereas the size of the defect was the major determinant of outcome in adult-onset disease (p = 0.01).

ANTIMIC: a database of antimicrobial sequences.

Antimicrobial peptides (AMPs) are important components of the innate immune system of many species. These peptides are found in eukaryotes, including mammals, amphibians, insects and plants, as well as in prokaryotes. Other than having pathogen-lytic properties, these peptides have other activities like antitumor activity, mitogen activity, or they may act as signaling molecules. Their short length, fast and efficient action against microbes and low toxicity to mammals have made them potential candidates as peptide drugs. In many cases they are effective against pathogens that are resistant to conventional antibiotics. They can serve as natural templates for the design of novel antimicrobial drugs. Although there are vast amounts of data on natural AMPs, they are not available through one central resource. We have developed a comprehensive database (ANTIMIC, http://research.i2r. a-star.edu.sg/Templar/DB/ANTIMIC/) of known and putative AMPs, which contains approximately 1700 of these peptides. The database is integrated with tools to facilitate efficient extraction of data and their analysis at molecular level, as well as search for new AMPs. These tools include BLAST, PDB structure viewer and the Antimic profile module.

Dragon TF Association Miner: a system for exploring transcription factor associations through text-mining.

We present Dragon TF Association Miner (DTFAM), a system for text-mining of PubMed documents for potential functional association of transcription factors (TFs) with terms from Gene Ontology (GO) and with diseases. DTFAM has been trained and tested in the selection of relevant documents on a manually curated dataset containing >3000 PubMed abstracts relevant to transcription control. On our test data the system achieves sensitivity of 80% with specificity of 82%. DTFAM provides comprehensive tabular and graphical reports linking terms to relevant sets of documents. These documents are color-coded for easier inspection. DTFAM complements the existing biological resources by collecting, assessing, extracting and presenting associations that can reveal some of the not so easily observable connections among the entities found which could explain the functions of TFs and help decipher parts of gene transcriptional regulatory networks. DTFAM summarizes information from a large volume of documents saving time and making analysis simpler for individual users. DTFAM is freely available for academic and non-profit users at http://research.i2r.a-star.edu.sg/DRAGON/TFAM/.

Computer model for recognition of functional transcription start sites in RNA polymerase II promoters of vertebrates.

This paper introduces a new computer system for recognition of functional transcription start sites (TSSs) in RNA polymerase II promoter regions of vertebrates. This system allows scanning complete vertebrate genomes for promoters with significantly reduced number of false positive predictions. It can be used in the context of gene finding through its recognition of the 5' end of genes. The implemented recognition model uses a composite-hierarchical approach, artificial intelligence, statistics, and signal processing techniques. It also exploits the separation of promoter sequences into those that are C+G-rich or C+G-poor. The system was evaluated on a large and diverse human sequence-set and exhibited several times higher accuracy than several publicly available TSS-finding programs. Results obtained using human chromosome 22 data showed even greater specificity than the evaluation set results. The system has been implemented in the Dragon Promoter Finder package, which can be accessed at http://sdmc.krdl.org.sg:8080/promoter/.

Barriers to condom use: results from a study in Mumbai (Bombay), India.

The consistent and correct use of condoms coupled with risk reduction education strategies, continue to play an important role in the reduction and prevention of HIV/AIDS transmission. Therefore understanding and incorporating strategies to overcome barriers to condom use in such education and prevention efforts are critical. This is particularly necessary in countries such as India, where HIV/AIDS has become a serious public health crisis. The current study documents and provides preliminary data on the use of condoms, reasons for and barriers to condom use, and sources of information about safer sex practices among a sexually active adult sample of 49 women and 203 men in Mumbai, India. Despite limitations such as the use of a nonrandom sample of participants composed predominantly of young, English-speaking males, the study findings provide some insights into the importance of and the need to address issues of privacy regarding condom purchase and use in India. Most notably, the lack of privacy in stores and the social stigma associated with condom use were indicated as the most significant barriers. These and other study findings suggest the need to ease the social costs and constraints to safe behaviors through increased acceptance of condoms and promotion of their consistent use. This could serve as an important means to curb the epidemic of HIV/AIDS in India.

Acceptability of the female condom among STD clinic patients.

This study examines the acceptability of the female condom among African American and Latino patients from two inner-city sexually transmitted disease (STD) clinics through focus group discussions. Prior to the initial focus group sessions, 90% (n = 90) had heard about the female condom, 8% (n = 8) had seen it, and 2% (n = 2) had used it. Among the 41 participants (22 males and 19 females) attending a second focus group session, 85.4% (n = 35) had used the female condom at least once. Female study participants who had previous experience inserting a barrier contraceptive device, such as a diaphragm, indicated that they felt more comfortable inserting the female condom than those who had never used such a device. Male participants indicated that they were more comfortable using the female condom with their steady partners than with casual partners, whereas female participants indicated no such distinctions. These and other study findings suggest that need to promote and expand the use of the female condom as a device that protects women from STD transmissions including HIV and AIDS.

PIP: The acceptability of the female condom was explored through mixed-gender focus group discussions involving 100 Black and Hispanic men and women recruited from two US inner-city sexually transmitted disease clinics. Before the initial group sessions, 90 participants (90%) had heard about the female condom, 8 (8%) had seen it, and 2 (2%) had used the device. Female participants initially reacted negatively to the condom's appearance, size, and obtrusiveness and expressed uncertainty about how it could be inserted. Male participants, on the other hand, focused on utilitarian rather than aesthetic issues. After handling the device, more than half of female and male participants endorsed a more positive attitude. Women with previous experience with a barrier contraceptive device such as the vaginal diaphragm were more likely to feel comfortable about female condom use. Among the 22 males and 19 females who returned for a second group session after having been given a supply of female condoms to try, 35 (85.4%) had used the device at least once. 10 participants noted that bringing up the topic of female condom use enabled them to discuss safer sex practices with their steady partners for the first time. Women who, in the initial discussions, viewed the female condom as a means of gaining control over their sexuality, gained awareness of the need for substantial male support and cooperation. Men were more comfortable using the device with regular than casual partners, but women made no such distinction. Although it is acknowledged that participants who returned for the second discussion may have had more favorable experiences than those who did not, the preliminary data suggest that the female condom is acceptable to men and women at risk of HIV. HIV/AIDS prevention campaigns aimed at promoting female condom use should address the technical skills and knowledge of female anatomy needed for method use, empowerment and negotiation skills, and ways to eroticize female condom use.

Correlates of intention to use the female condom among women taking methadone.

PIP: The correlates of high-risk women's intentions to use the female condom were investigated in a descriptive study involving 148 sexually active women from 3 US methadone clinics. 51% of women were Latina and 38% were African-American; the mean age was 39 years. Male condoms, douching, sterilization, and withdrawal were the most frequently used contraceptive methods in the 90 days preceding the study. 56% had heard of the female condom, but only 6% had used it. Of the 139 women who had never used the female condom, 32% indicated they intended to use it in the future. Such intention was significantly, positively correlated with age under 39 years, African-American ethnicity, and the belief the female condom offers users a sense of personal control over their sexuality. Those who intended to use the female condom were more likely to have previously used male condoms, believe their partners would be supportive of the device, think female condom use could be erotic and fun, feel confident in their ability to negotiate safer sex, and to welcome an additional option for practicing safer sex. They were also less likely than their counterparts, who did not intend to use a female condom, to believe use of this method would imply they had a sexually transmitted disease or were too eager to have sex. Compared with women who did not intend to use the female condom, those who did were more likely to discuss the device with at least 1 member of their social network. These findings confirm the necessity of considering gender relations and social networks in the design of female condom promotion strategies.^ieng

Modular neck femoral stems.

Following the recall of modular neck hip stems in July 2012, research into femoral modularity will intensify over the next few years. This review aims to provide surgeons with an up-to-date summary of the clinically relevant evidence. The development of femoral modularity, and a classification system, is described. The theoretical rationale for modularity is summarised and the clinical outcomes are explored. The review also examines the clinically relevant problems reported following the use of femoral stems with a modular neck. Joint replacement registries in the United Kingdom and Australia have provided data on the failure rates of modular devices but cannot identify the mechanism of failure. This information is needed to determine whether modular neck femoral stems will be used in the future, and how we should monitor patients who already have them implanted.

A review of rapid prototyped surgical guides for patient-specific total knee replacement.

Improvements in the surgical technique of total knee replacement (TKR) are continually being sought. There has recently been interest in three-dimensional (3D) pre-operative planning using magnetic resonance imaging (MRI) and CT. The 3D images are increasingly used for the production of patient-specific models, surgical guides and custom-made implants for TKR. The users of patient-specific instrumentation (PSI) claim that they allow the optimum balance of technology and conventional surgery by reducing the complexity of conventional alignment and sizing tools. In this way the advantages of accuracy and precision claimed by computer navigation techniques are achieved without the disadvantages of additional intra-operative inventory, new skills or surgical time. This review describes the terminology used in this area and debates the advantages and disadvantages of PSI.

Detection and preliminary analysis of motifs in promoters of anaerobically induced genes of different plant species.

BACKGROUND AND AIMS: Plants can suffer from oxygen limitation during flooding or more complete submergence and may therefore switch from Kreb's cycle respiration to fermentation in association with the expression of anaerobically inducible genes coding for enzymes involved in glycolysis and fermentation. The aim of this study was to clarify mechanisms of transcriptional regulation of these anaerobic genes by identifying motifs shared by their promoter regions. METHODS: Statistically significant motifs were detected by an in silico method from 13 promoters of anaerobic genes. The selected motifs were common for the majority of analysed promoters. Their significance was evaluated by searching for their presence in transcription factor-binding site databases (TRANSFAC, PlantCARE and PLACE). Using several negative control data sets, it was tested whether the motifs found were specific to the anaerobic group. KEY RESULTS: Previously, anaerobic response elements have been identified in maize (Zea mays) and arabidopsis (Arabidopsis thaliana) genes. Known functional motifs were detected, such as GT and GC motifs, but also other motifs shared by most of the genes examined. Five motifs detected have not been found in plants hitherto but are present in the promoters of animal genes with various functions. The consensus sequences of these novel motifs are 5'-AAACAAA-3', 5'-AGCAGC-3', 5'-TCATCAC-3', 5'-GTTT(A/C/T)GCAA-3' and 5'-TTCCCTGTT-3'. CONCLUSIONS: It is believed that the promoter motifs identified could be functional by conferring anaerobic sensitivity to the genes that possess them. This proposal now requires experimental verification.

Prediction Models for DNA Transcription Termination Based on SOM Networks.

This paper presents two efficient models for predicting transcription termination (TT) in human DNA. A neural network, self-organizing map, was used for finding features from a human polyadenylation (polyA) sites dataset. We derived prediction models related to different polyA signals. A program, "Dragon PolyAtt", for predicting TT regions was designed for the two most frequent polyA sites "AAUAAA" and "AUUAAA". In our tests, Dragon PolyAtt predicts TT regions with a sensitivity of 48.4% (13.6%) and specificity of 74% (79.1%) when searching for polyA signal "AAUAAA" ("AUUAAA"). Both tests were done on human chromosome 21. Results of Dragon PolyAtt system are substantially better than those obtained by the well-known "polyadq" program.

Addressing barriers to community care of battered women in rural environments: creating a policy of social inclusion.

Given domestic violence continues to be a serious social problem, recently acknowledged as a national public health epidemic as well, the need to examine existing formal helping services and address the barriers to service utilization among battered women is warranted. Social exclusion is the process by which multi-dimensionally disadvantaged individuals are prohibited from obtaining formal helping services. Although not a policy per se, many community helpers and organizations inadvertently contribute to erecting barriers which exclude battered women from using such services, particularly in rural environments. Suggestions to transform a process of social exclusion to social inclusion for battered women is offered.

An examination of intimate partner violence in rural communities: results from a hospital emergency department study from Southwest United States.

Intimate partner violence (IPV) affects women disproportionately, women being 5-8 times more likely than men to be victimized by their intimates. Women in abusive relationships use a disproportionate share of health care services, including more visits to the emergency departments. Female clients from two hospital emergency departments in the rural Southwest were recruited and administered semistructured interviews. Study findings indicate the prevalence and pervasiveness of IPV among study participants and illustrate the significant effects of and predictive nature of three factors associated with abuse in the past to current IPV.

Domestic violence and help-seeking behaviors among rural women: results from a shelter-based study.

Research on domestic violence and help-seeking behaviors of women living in rural communities has been limited. This study adds to existing knowledge by examining this type of violence along with mental health characteristics and related help-seeking behaviors of a sample of predominantly Hispanic women seeking shelter at a rural domestic violence shelter. Study participants experienced physical, verbal, emotional, and sexual abuse, harassment, stalking, and abuse with a weapon in their current intimate relationship. Twenty-four percent of study participants of Hispanic backgrounds and 10% of participants from all other racial/ethnic groups reported experiencing all types of abuse listed above. When compared with other study participants, a greater percentage of Hispanic participants indicated that they had thought of and/or attempted suicide. Participants' help-seeking behaviors from formal support systems suggest a mismatch between the types of abuse experienced and the resultant help-seeking behaviors they used. These help-seeking behaviors also indicate the relevance of mental health characteristics (e.g., suicide ideation) in these behaviors. These and findings from other studies may provide the impetus for a systematic documentation of domestic violence and help-seeking behaviors of women living in rural communities.