An Instruction to Accelerate Software Caches

In this paper we propose an instruction to accelerate software caches. While DMAs are very efficient for predictable data sets that can be fetched before they are needed, they introduce a large latency overhead for computations with unpredictable access behavior. Software caches are advantageous when the data set is not predictable but exhibits locality. However, software caches also incur a large overhead. Because the main overhead is in the access function, we propose an instruction that replaces the look-up function of the software cache. This instruction is evaluated using the Multidimensional Software Cache and two multimedia kernels, GLCM and H.264 Motion Compensation. The results show that the proposed instruction accelerates the software cache access time by a factor of 2.6. This improvement translates to a 2.1 speedup for GLCM and 1.28 for MC, when compared with the IBM software cache

Identification and removal of low-complexity sites in allele-specific analysis of ChIP-seq data

Motivation: High-throughput sequencing technologies enable the genome-wide analysis of the impact of genetic variation on molecular phenotypes at unprecedented resolution. However, although powerful, these technologies can also introduce unexpected artifacts. Results: We investigated the impact of library amplification bias on the identification of allele-specific (AS) molecular events from high-throughput sequencing data derived from chromatin immunoprecipitation assays (ChIP-seq). Putative AS DNA binding activity for RNA polymerase II was determined using ChIP-seq data derived from lymphoblastoid cell lines of two parent-daughter trios. We found that, at high-sequencing depth, many significant AS binding sites suffered from an amplification bias, as evidenced by a larger number of clonal reads representing one of the two alleles. To alleviate this bias, we devised an amplification bias detection strategy, which filters out sites with low read complexity and sites featuring a significant excess of clonal reads. This method will be useful for AS analyses involving ChIP-seq and other functional sequencing assays. Availability: The R package absfilter for library clonality simulations and detection of amplification-biased sites is available from http://updepla1srv1.epfl.ch/waszaks/absfilter Contact: [email protected] or [email protected] Supplementary information: Supplementary data are available at Bioinformatics onlin

A Morphing Technique Applied to Lung Motions in Radiotherapy: Preliminary Results

Organ motion leads to dosimetric uncertainties during a patient’s treatment. Much work has been done to quantify the dosimetric effects of lung movement during radiation treatment. There is a particular need for a good description and prediction of organ motion. To describe lung motion more precisely, we have examined the possibility of using a computer technique: a morphing algorithm. Morphing is an iterative method which consists of blending one image into another image. To evaluate the use of morphing, Four Dimensions Computed Tomography (4DCT) acquisition of a patient was performed. The lungs were automatically segmented for different phases, and morphing was performed using the end-inspiration and the end-expiration phase scans only. Intermediate morphing files were compared with 4DCT intermediate images. The results showed good agreement between morphing images and 4DCT images: fewer than 2 % of the 512 by 256 voxels were wrongly classified as belonging/not belonging to a lung section. This paper presents preliminary results, and our morphing algorithm needs improvement. We can infer that morphing offers considerable advantages in terms of radiation protection of the patient during the diagnosis phase, handling of artifacts, definition of organ contours and description of organ motion

HER2 testing in breast cancer: Opportunities and challenges

Human epidermal growth factor receptor 2 (HER2) is overexpressed in 15-25% of breast cancers, usually as a result of HER2 gene amplification. Positive HER2 status is considered to be an adverse prognostic factor. Recognition of the role of HER2 in breast cancer growth has led to the development of anti-HER2 directed therapy, with the humanized monoclonal antibody trastuzumab (Herceptin (R)) having been approved for the therapy of HER2-positive metastatic breast cancer. Clinical studies have further suggested that HER2 status can provide important information regarding success or failure of certain hormonal therapies or chemotherapies. As a result of these developments, there has been increasing demand to perform HER2 testing on current and archived breast cancer specimens. This article reviews the molecular background of HER2 function, activation and inhibition as well as current opinions concerning its role in chemosensitivity and interaction with estrogen receptor biology. The different tissue-based assays used to detect HER2 amplification and overexpression are discussed with respect to their advantages and disadvantages, when to test (at initial diagnosis or pre-treatment), where to test (locally or centralized) and the need for quality assurance to ensure accurate and valid testing results

In situ Überwachung photokatalytischer Prozesse mit polymeren Kohlenstoffnitrid-Dünnschichtfilmen

Polymeric carbon nitride has attracted significant interest in heterogeneous photocatalysis due to its activity under visible-light irradiation. Herein, we report on using carbon nitride-coated NMR tubes for in-situ studies of photocatalytic reaction mechanisms. In a first step, we exploited carbon nitride-coated crimp vials as batch photoreactors for visible photocatalytic fluorinations of unactivated C(sp3)-H bonds, with moderate to excellent yields and reusability over multiple cycles. Eventually, carbon nitride-coated NMR tubes were used as a photoreactor by coupling them with optical fiber irradiation directly inside the spectrometer. This enabled us to follow the reaction with in-situ NMR spectroscopy identifying reactive intermediates otherwise elusive in conventional analyses. The method provides advantages for the study of photocatalytic mechanisms of complex reactions and substantially reduces the need of comparative tests for depicting reaction intermediates and conversion pathways

Dancing in time: feasibility and acceptability of a contemporary dance programme to modify risk factors for falling in community dwelling older adults

Background: Falls are a common cause of injury in older adults, with the prevention of falls being a priority for public health departments around the world. This study investigated the feasibility, and impact of an 8 week contemporary dance programme on modifiable physical (physical activity status, mobility, sedentary behaviour patterns) and psychosocial (depressive state, fear of falling) risk factors for falls. Methods: An uncontrolled ‘pre-post’ intervention design was used. Three groups of older (60 yrs.+) adults were recruited from local community groups to participate in a 3 separate, 8 week dance programmes. Each programme comprised two, 90 min dance classes per week. Quantitative measures of physical activity, sedentary behaviour, depression, mobility and fear of falling were measured at baseline (T1) and after 8 weeks of dance (T2). Weekly attendance was noted, and post-study qualitative work was conducted with participants in 3 separate focus groups. A combined thematic analysis of these data was conducted. Results: Of the 38 (Mean Age = 77.3 ± 8.4 yrs., 37 females) who attended the dance sessions, 22 (21 females; 1 male; mean age = 74.8, ±8.44) consented to be part of the study. Mean attendance was 14.6 (±2.6) sessions, and mean adherence was 84.3% (±17). Significant increases in moderate and vigorous physical activity were noted, with a significant decrease in sitting time over the weekdays (p < 0.05). Statistically significant decreases in the mean Geriatric Depression Scale (p < 0.05) and fear of falling (p < 0.005) score were noted, and the time taken to complete the TUG test decreased significantly from 10.1 s to 7.7 s over the 8 weeks (p < 0.005). Themes from the focus groups included the dance programme as a means of being active, health Benefits, and dance-related barriers and facilitators. Conclusions: The recruitment of older adults, good adherence and favourability across all three sites indicate that a dance programme is feasible as an intervention, but this may be limited to females only. Contemporary dance has the potential to positively affect the physical activity, sitting behaviour, falls related efficacy, mobility and incidence of depression in older females which could reduce their incidence of falls. An adequately powered study with control groups are required to test this intervention further

ERBB2 in Cat Mammary Neoplasias Disclosed a Positive Correlation between RNA and Protein Low Expression Levels: A Model for erbB-2 Negative Human Breast Cancer

Human ERBB2 is a proto-oncogene that codes for the erbB-2 epithelial growth factor receptor. In human breast cancer (HBC), erbB-2 protein overexpression has been repeatedly correlated with poor prognosis. In more recent works, underexpression of this gene has been described in HBC. Moreover, it is also recognised that oncogenes that are commonly amplified or deleted encompass point mutations, and some of these are associated with HBC. In cat mammary lesions (CMLs), the overexpression of ERBB2 (27%–59.6%) has also been described, mostly at the protein level and although cat mammary neoplasias are considered to be a natural model of HBC, molecular information is still scarce. In the present work, a cat ERBB2 fragment, comprising exons 10 to 15 (ERBB2_10–15) was achieved for the first time. Allelic variants and genomic haplotype analyses were also performed, and differences between normal and CML populations were observed. Three amino acid changes, corresponding to 3 non-synonymous genomic sequence variants that were only detected in CMLs, were proposed to damage the 3D structure of the protein. We analysed the cat ERBB2 gene at the DNA (copy number determination), mRNA (expression levels assessment) and protein levels (in extra- and intra protein domains) in CML samples and correlated the last two evaluations with clinicopathological features. We found a positive correlation between the expression levels of the ERBB2 RNA and erbB-2 protein, corresponding to the intracellular region. Additionally, we detected a positive correlation between higher mRNA expression and better clinical outcome. Our results suggest that the ERBB2 gene is post-transcriptionally regulated and that proteins with truncations and single point mutations are present in cat mammary neoplastic lesions. We would like to emphasise that the recurrent occurrence of low erbB-2 expression levels in cat mammary tumours, suggests the cat mammary neoplasias as a valuable model for erbB-2 negative HBC.POCI/CVT/62940/2004 and by the PhD grants (SFRH/BD/23406/2005 and SFRH/BD/31754/2006, of the Science and Technology Foundation (FCT) from Portugal

Inter-phylum circulation of a beta-lactamase-encoding gene: a rare but observable event.

Beta-lactamase-mediated degradation of beta-lactams is the most common mechanism of beta-lactam resistance in Gram-negative bacteria. Beta-lactamase-encoding genes can be transferred between closely related bacteria, but spontaneous inter-phylum transfers (between distantly related bacteria) have never been reported. Here, we describe an extended-spectrum beta-lactamase (ESBL)-encoding gene (bla &lt;sub&gt;MUN-1&lt;/sub&gt; ) shared between the Pseudomonadota and Bacteroidota phyla. An Escherichia coli strain was isolated from a patient in Münster (Germany). Its genome was sequenced. The ESBL-encoding gene (named bla &lt;sub&gt;MUN-1&lt;/sub&gt; ) was cloned, and the corresponding enzyme was characterized. The distribution of the gene among bacteria was investigated using the RefSeq Genomes database. The frequency and relative abundance of its closest homolog in the global microbial gene catalog (GMGC) were analyzed. The E. coli strain exhibited two distinct morphotypes. Each morphotype possessed two chromosomal copies of the bla &lt;sub&gt;MUN-1&lt;/sub&gt; gene, with one morphotype having two additional copies located on a phage-plasmid p0111. Each copy was located within a 7.6-kb genomic island associated with mobility. bla &lt;sub&gt;MUN-1&lt;/sub&gt; encoded for an extended-spectrum Ambler subclass A2 beta-lactamase with 43.0% amino acid identity to TLA-1. bla &lt;sub&gt;MUN-1&lt;/sub&gt; was found in species among the Bacteroidales order and in Sutterella wadsworthensis (Pseudomonadota). Its closest homolog in GMGC was detected frequently in human fecal samples. This is, to our knowledge, the first reported instance of inter-phylum transfer of an ESBL-encoding gene, between the Bacteroidota and Pseudomonadota phyla. Although the gene was frequently detected in the human gut, inter-phylum transfer was rare, indicating that inter-phylum barriers are effective in impeding the spread of ESBL-encoding genes, but not entirely impenetrable

Technology use, adoption and behaviour in older adults: results from the iStoppFalls Project

Technology use is a common constituent of modern life. However, little is known about older adults’ use of technology. This article presents a subset of data collected via the technology deployed in the iStoppFalls randomized control trial. The primary focus lies on questions about digital device/Internet use, ownership, length, and frequency as well as social networking. Data was collected from participants aged 65 years or older. Seventy-eight participants completed a specifically developed technology survey as part of the baseline assessment. Results showed that the majority of subjects owned a computer with men being its main user. Participants used technological devices on a daily basis for more than 1 year. The main reason for using technology was e-mail communication, search engines, text processing, and online shopping. Only a few participants used social network applications, with Google+ and Facebook being the most popular ones. Future work should consider an in-depth qualitative approach to further increase understanding of technology use in older adults

Brønsted Acid Catalysis—Structural Preferences and Mobility in Imine/Phosphoric Acid Complexes

Despite the huge success of enantioselective Bronsted acid catalysis, experimental data about structures and activation modes of substrate/catalyst complexes in solution are very rare. Here, for the first time, detailed insights into the structures of imine/Bronsted acid catalyst complexes are presented on the basis of NMR data and underpinned by theoretical calculations. The chiral Bronsted acid catalyst R-TRIP (3,3'-bis(2,4,6-triisopropylphenyl)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate) was investigated together with six aromatic imines. For each investigated system, an E-imine/R-TRIP complex and a Z-imine/R-TRIP complex were observed. Each of these complexes consists of two structures, which are in fast exchange on the NMR time scale; i.e., overall four structures were found. Both identified E-imine/R-TRIP structures feature a strong hydrogen bond but differ in the orientation of the imine relative to the catalyst. The exchange occurs by tilting the imine inside the complex and thereby switching the oxygen that constitutes the hydrogen bond. A similar situation is observed for all investigated Z-imine/R-TRIP complexes. Here, an additional exchange pathway is opened via rotation of the imine. For all investigated imine/R-TRIP complexes, the four core structures are highly preserved. Thus, these core structures are independent of electron density and substituent modulations of the aromatic imines. Overall, this study reveals that the absolute structural space of binary imine/TRIP complexes is large and the variations of the four core structures are small. The high mobility is supposed to promote reactivity, while the preservation of the core structures in conjunction with extensive pi-pi and CH-pi interactions leads to high enantioselectivities and tolerance of different substrates