The Vector Processor

The Vector Processor is a device designed for the purpose of economically achieving maximum speed in the computer execution of a group of common scientific and engineering calculations. Each element of the vector, the individual data item, may be a number, a logical value, or a character. A vector\u27s elements must be all of the same type. A vector may have meaning in its own right, or it may be part of an array, a row or a column of elements. Manipulations and operations with vectors have been used by mathematicians, scientists and engineers for centuries in procedures for analysis and design. The IBM PC is chosen as the General Purpose Processor and the Vector Controller is designed to coordinate the activities of a group of components called Math Coprocessors with that of the IBM PC. The two processors cooperate by sharing the buses and ignoring each other’s instructions. The bus sharing is managed by the interface signals. The vector operations are done in the Math Coprocessors, by loading the data elements sequentially into the Math Coprocessors and executing an instruction in parallel. The sequential and the parallel operations are controlled by the Vector Controller which recognizes the vector instructions. In the absence of instructions involving vector quantities, the Vector Controller has one of the Math Coprocessors connected to the General Purpose Processor as in the conventional architecture. This allows for maximum speed in executing ordinary arithmetic operations. When a vector instruction appears, it is decoded by the Vector Controller and appropriate action taken. The effect of these actions is to load the elements of the required vectors sequentially from Memory into the Math Coprocessors, do the required operations simultaneously, and then write the results out sequentially to Memory. This simultaneous operation on a number of data elements is the key to the speed of this processor. The ensuing chapters describe the hardware and software requirements for the design. Understanding of the hardware design requires the knowledge of the architecture of the 8088 and the 8087 processors. The next two chapters, Chapter II and Chapter III, explain the architecture of the 8088 CPU and the 8087 Math Coprocessor, in brief. Chapter IV describes System Clock and Bus Cycles giving an idea system. Chapter V and detail the hardware Controller. Finally, about timing requirements of the subsequent Chapters explain in implementation of the Vector the software requirements are described in Chapter IX, with Conclusions in Chapter X

Detection of very long antisense transcripts by whole transcriptome RNA-Seq analysis of Listeria monocytogenes by semiconductor sequencing technology

The Gram-positive bacterium Listeria monocytogenes is the causative agent of listeriosis, a severe food-borne infection characterised by abortion, septicaemia, or meningoencephalitis. L. monocytogenes causes outbreaks of febrile gastroenteritis and accounts for community-acquired bacterial meningitis in humans. Listeriosis has one of the highest mortality rates (up to 30%) of all food-borne infections. This human pathogenic bacterium is an important model organism for biomedical research to investigate cell-mediated immunity. L. monocytogenes is also one of the best characterised bacterial systems for the molecular analysis of intracellular parasitism. Recently several transcriptomic studies have also made the ubiquitous distributed bacterium as a model to understand mechanisms of gene regulation from the environment to the infected host on the level of mRNA and non-coding RNAs (ncRNAs). We have used semiconductor sequencing technology for RNA-seq to investigate the repertoire of listerial ncRNAs under extra- and intracellular growth conditions. Furthermore, we applied a new bioinformatic analysis pipeline for detection, comparative genomics and structural conservation to identify ncRNAs. With this work, in total, 741 ncRNA locations of potential ncRNA candidates are now known for L. monocytogenes, of which 611 ncRNA candidates were identified by RNA-seq. 441 transcribed ncRNAs have never been described before. Among these, we identified novel long non-coding antisense RNAs with a length of up to 5,400 nt e.g. opposite to genes coding for internalins, methylases or a high-affinity potassium uptake system, namely the kdpABC operon, which were confirmed by qRT-PCR analysis. RNA-seq, comparative genomics and structural conservation of L. monocytogenes ncRNAs illustrate that this human pathogen uses a large number and repertoire of ncRNA including novel long antisense RNAs, which could be important for intracellular survival within the infected eukaryotic host

Genomewide comparison and novel ncRNAs of Aquificales

Background  The Aquificales are a diverse group of thermophilic bacteria that thrive in terrestrial and marine hydrothermal environments. They can be divided into the families Aquificaceae, Desulfurobacteriaceae and Hydrogenothermaceae. Although eleven fully sequenced and assembled genomes are available, only little is known about this taxonomic order in terms of RNA metabolism.  Results  In this work, we compare the available genomes, extend their protein annotation, identify regulatory sequences, annotate non-coding RNAs (ncRNAs) of known function, predict novel ncRNA candidates, show idiosyncrasies of the genetic decoding machinery, present two different types of transfer-messenger RNAs and variations of the CRISPR systems. Furthermore, we performed a phylogenetic analysis of the Aquificales based on entire genome sequences, and extended this by a classification among all bacteria using 16S rRNA sequences and a set of orthologous proteins.  Combining severalin silicofeatures (e.g. conserved and stable secondary structures, GC-content, comparison based on multiple genome alignments) with an in vivo dRNA-seq transcriptome analysis of Aquifex aeolicus, we predict roughly 100 novel ncRNA candidates in this bacterium.  Conclusions  We have here re-analyzed the Aquificales, a group of bacteria thriving in extreme environments, sharing the feature of a small, compact genome with a reduced number of protein and ncRNA genes. We present several classical ncRNAs and riboswitch candidates. By combining in silico analysis with dRNA-seq data of A. aeolicus we predict nearly 100 novel ncRNA candidates

Enhanced early visual processing in response to snake and trypophobic stimuli

Background: Trypophobia refers to aversion to clusters of holes. We investigated whether trypophobic stimuli evoke augmented early posterior negativity (EPN). Methods: Twenty-four participants filled out a trypophobia questionnaire and watched the random rapid serial presentation of 450 trypophobic pictures, 450 pictures of poisonous animals, 450 pictures of snakes, and 450 pictures of small birds (1800 pictures in total, at a rate of 3 pictures/s). The EPN was scored as the mean activity at occipital electrodes (PO3, O1, Oz, PO4, O2) in the 225-300 ms time window after picture onset. Results: The EPN was significantly larger for snake pictures than for the other categories, and significantly larger for trypophobic pictures and poisonous animal pictures than for bird pictures. Remarkably, the scores on the trypophobia questionnaire were correlated with the EPN amplitudes for trypophobic pictures at the occipital cluster (r = -.46, p = .025). Conclusions: The outcome for the EPN indicates that snakes, and to a somewhat lesser extent trypophobic stimuli and poisonous animals, trigger early automatic visual attention. This supports the notion that the aversion that is induced by trypophobic stimuli reflects ancestral threat and has survival value. The possible influence of the spectral composition of snake and trypophobic stimuli on the EPN is discussed

Intake of dairy products and associations with major atherosclerotic cardiovascular diseases:a systematic review and meta-analysis of cohort studies

Abstract Specific types of dairy products may be differentially associated with atherosclerotic cardiovascular disease (CVD). We conducted a systematic review and meta-analysis of cohort studies to summarize findings on the associations between total dairy product intake and intake of dairy product subgroups and the risk of major atherosclerotic CVDs in the general adult population. Our protocol was registered in PROSPERO (CRD42019125455). PubMed and Embase were systematically searched through 15 August 2019. For high versus low intake and dose–response meta-analysis, random-effects modelling was used to calculate summary risk ratios (RR). There were 13 cohort studies included for coronary heart disease (CHD), 7 for ischemic stroke and none for peripheral artery disease. High-fat milk was positively associated with CHD (RR 1.08 (95% confidence interval 1.00–1.16) per 200 g higher intake/day) and cheese was inversely associated with CHD (RR 0.96 (95% confidence interval 0.93–0.98) per 20 g higher intake/day). Heterogeneity, however, was observed in high versus low meta-analyses. Milk was inversely associated with ischemic stroke in high versus low meta-analysis only. In conclusion, this systematic review indicates a positive association of high-fat milk and an inverse association of cheese with CHD risk. The findings should be interpreted in the context of the observed heterogeneity

The role of the gut microbiome in the association between habitual anthocyanin intake and visceral abdominal fat in population-level analysis

BACKGROUND: Flavonoid intake modifies the composition of the gut microbiome, which contributes to the metabolism of flavonoids. Few studies have examined the contribution of the gut microbiome to the health benefits associated with flavonoid intake. OBJECTIVES: We aimed to examine associations between habitual intakes of flavonoid subclasses and MRI-determined visceral (VAT) and subcutaneous (SAT) adipose tissue. Uniquely, we also identified associations between the aforementioned measurements and gut microbiome composition sequenced from 16S ribosomal RNA genes. METHODS: We undertook cross-sectional analyses of 618 men and women (n = 368 male), aged 25-83 y, from the PopGen cohort. RESULTS: Higher intake of anthocyanins was associated with lower amounts of VAT [tertile (T)3-T1: -0.49 dm3; β: -8.9%; 95% CI: -16.2%, -1.1%; P = 0.03] and VAT:SAT ratio (T3-T1: -0.04; β: -7.1%; 95% CI: -13.5%, -0.3%; P = 0.03). Higher intakes of anthocyanin-rich foods were also inversely associated with VAT [quantile (Q)4-Q1: -0.39 dm3; β: -9.9%; 95% CI: -17.4%, -1.6%; P = 0.02] and VAT:SAT ratio (Q4-Q1: -0.04; β: -6.5%; 95% CI: -13.3%, -0.9%; P = 0.03). Participants with the highest intakes of anthocyanin-rich foods also had higher microbial diversity (Q4-Q1: β: 0.18; 95% CI: 0.06, 0.31; P < 0.01), higher abundances of Clostridiales (Q4-Q1: β: 449; 95% CI: 96.3, 801; P = 0.04) and Ruminococcaceae (Q4-Q1: β: 313; 95% CI: 33.6, 591; P = 0.04), and lower abundance of Clostridium XIVa (Q4-Q1: β: -41.1; 95% CI: -72.4, -9.8; P = 0.04). Participants with the highest microbial diversity, abundances of Clostridiales and Ruminococcaceae, and lower abundance of Clostridium XIVa had lower amounts of VAT. Up to 18.5% of the association between intake of anthocyanin-rich foods and VAT could be explained by the gut microbiome. CONCLUSIONS: These novel data suggest that higher microbial diversity and abundance of specific taxa in the Clostridiales order may contribute to the association between higher intake of anthocyanins and lower abdominal adipose tissue

Illness perceptions and quality of life in patients with non-small-cell lung cancer

__Purpose:__ Examine illness perceptions, functional health and quality of life of lung cancer patients throughout chemotherapy treatment. __Patients and Methods:__ Longitudinal design with baseline measure 12 days after the first chemotherapy and follow-up measure 3 months later, where illness perceptions (BIPQ), functional health, and quality of life (EORTC QLQ-C-30) were measured. A total of 21 patients with non-small-cell lung cancer took part. Non-parametric testing was performed given the pilot nature of the study and the associated relatively small sample size. __Results:__ Small to medium changes in illness perceptions and functional health between the two measurement points were detected, with both becoming more positive. More negative illness perceptions at the beginning of the treatment were associated with less functioning and lower quality of life at both beginning and end of treatment. __Conclusion:__ Addressing illness perceptions seems a clinically relevant approach in improving functioning and quality of life of patients with non-small-cell lung cancer

Cellular gene expression during Hepatitis C virus replication as revealed by Ribosome Profiling

Background: Hepatitis C virus (HCV) infects human liver hepatocytes, often leading to liver cirrhosis and hepatocellular carcinoma (HCC). It is believed that chronic infection alters host gene expression and favors HCC development. In particular, HCV replication in Endoplasmic Reticulum (ER) derived membranes induces chronic ER stress. How HCV replication affects host mRNA translation and transcription at a genome wide level is not yet known. Methods: We used Riboseq (Ribosome Profiling) to analyze transcriptome and translatome changes in the Huh-7.5 hepatocarcinoma cell line replicating HCV for 6 days. Results: Established viral replication does not cause global changes in host gene expression—only around 30 genes are significantly differentially expressed. Upregulated genes are related to ER stress and HCV replication, and several regulated genes are known to be involved in HCC development. Some mRNAs (PPP1R15A/GADD34, DDIT3/CHOP, and TRIB3) may be subject to upstream open reading frame (uORF) mediated translation control. Transcriptional downregulation mainly affects mitochondrial respiratory chain complex core subunit genes. Conclusion: After establishing HCV replication, the lack of global changes in cellular gene expression indicates an adaptation to chronic infection, while the downregulation of mitochondrial respiratory chain genes indicates how a virus may further contribute to cancer cell-like metabolic reprogramming (“Warburg effect”) even in the hepatocellular carcinoma cells used here

Proteome profiling in cerebrospinal fluid reveals novel biomarkers of Alzheimer's disease

Neurodegenerative diseases are a growing burden, and there is an urgent need for better biomarkers for diagnosis, prognosis, and treatment efficacy. Structural and functional brain alterations are reflected in the protein composition of cerebrospinal fluid (CSF). Alzheimer's disease (AD) patients have higher CSF levels of tau, but we lack knowledge of systems-wide changes of CSF protein levels that accompany AD. Here, we present a highly reproducible mass spectrometry (MS)-based proteomics workflow for the in-depth analysis of CSF from minimal sample amounts. From three independent studies (197 individuals), we characterize differences in proteins by AD status (> 1,000 proteins, CV < 20%). Proteins with previous links to neurodegeneration such as tau, SOD1, and PARK7 differed most strongly by AD status, providing strong positive controls for our approach. CSF proteome changes in Alzheimer's disease prove to be widespread and often correlated with tau concentrations. Our unbiased screen also reveals a consistent glycolytic signature across our cohorts and a recent study. Machine learning suggests clinical utility of this proteomic signature