A Uniform Analysis of the Ly-alpha forest at z = 0 - 5: I. The sample and distribution of clouds at z > 1.7

We present moderate resolution data for 39 QSOs at z $\approx$ 2 obtained at the Multiple Mirror Telescope. These data are combined with spectra of comparable resolution of 60 QSOs with redshifts greater than 1.7 found in the literature to investigate the distribution of Ly-alpha forest lines in redshift and equivalent width. We find a value for $\gamma$, the parameter describing the number distribution of Ly-alpha forest lines in redshift, of $1.88\pm0.22$ for lines stronger than a rest equivalent width of 0.32 $\AA$, in good agreement with some previous studies. The Kolmogorov-Smirnov test was applied to the data and it is found that this single power law is a good fit over the relevant redshift ranges. Simulations of the Lyman alpha forest were performed to determine the completeness of the line lists and to test how well the analysis the underlying line statistics, given this level of completeness.Comment: minor corrections to text, 37 Latex pages, 11 encapsulated Postscript figures, uses emulateapj.sty, To appear in the Sept. 2000 ApJS, line lists and spectra available at http://qso.as.arizona.edu/~jscott/Spectra/index.htm

Comprehensive identification of host modulators of HIV-1 replication using multiple orthologous RNAi reagents

RNAi screens have implicated hundreds of host proteins as HIV-1 dependency factors (HDFs). While informative, these early studies overlap poorly due to false positives and false negatives. To ameliorate these issues, we combined information from the existing HDF screens together with new screens performed with multiple orthologous RNAi reagents (MORR). In addition to being traditionally validated, the MORR screens and the historical HDF screens were quantitatively integrated by the adaptation of an established analysis program, RIGER, for the collective interpretation of each gene\u27s phenotypic significance. False positives were addressed by the removal of poorly expressed candidates through gene expression filtering, as well as with GESS, which identifies off-target effects. This workflow produced a quantitatively integrated network of genes that modulate HIV-1 replication. We further investigated the roles of GOLGI49, SEC13, and COG in HIV-1 replication. Collectively, the MORR-RIGER method minimized the caveats of RNAi screening and improved our understanding of HIV-1-host cell interactions

No Change in Perceptual or Chronotropic Outcome When Altering Preferred Step Frequency for a Short Duration

IIntroduction: Millions of individuals incorporate jogging into their physical activity routines as a leisurely pursuit and as a way to achieve positive health outcomes. People appear to choose jogging speed and the associated step frequency on pure, natural preference. Understandably, kinesthetics are important, but another important underlying factor is metabolic cost. The purpose of this work was to investigate if preferred step frequency (at a preferred jogging pace) also minimizes perceived effort (Borg Rating of Perceived Exertion, 6-20; RPE) and chronotropic stress (heart rate; HR) during a ten-minute activity bout when compared with step frequencies altered by 5%. Methods: Recreationally-trained male subjects underwent two testing visits. The first visit was used to establish RPE and HR responses during a 10-minute jogging activity at preferred speed and step frequency. On a subsequent visit, between two and four days later, with preferred speed maintained, subjects were guided by metronome to strike at either 95% or 105% of their preferred step frequency. The 10-minute runs were randomized, crossed-over, and separated by 20 minutes. RPE and HR were analyzed by repeated measures ANOVA. Results: Fourteen subjects (age: 21.1 ± 0.95; body mass index: 23.2 ± 2.5) enrolled. Preferred jogging speed (speed. 6.4 ± 1.0 miles per hour; 10.2 ± 1.6 kilometers per hour) and step frequency (steps. 161.2 ± 10.3 steps/minute) were determined at the first visit, along with RPE (11.3 ± 1.7) and HR (166.4 ± 12.7). At the second visit, preferred speed was maintained while the frequency of foot-strike was altered. Neither differences in RPE (p = 0.252; 11.3 ± 1.7, 11.6 ± 1.9, 11.8 ± 1.5) nor HR (p = 0.547; 166.4 ± 12.7, 164.7 ± 14.9, 165.2 ± 15.3) were different when comparing the preferred, 95%, and 105% step frequency trials, respectively. Although anecdotal, some subjects verbalized displeasure with the change in pace and most all appeared to markedly alter the initial foot strike phase of the gait to meet the directed foot strike tempo. Discussion: Our data must be interpreted cautiously. While altering step frequency by 5% for a short duration does not appear to alter an individual’s RPE or HR appreciably, the result during longer duration activity may not be the same. In addition, the implications for biomechanical loading and metabolic cost were not presently investigated

A Uniform Analysis of the Ly-alpha forest at z = 0 - 5: II. Measuring the mean intensity of the extragalactic ionizing background using the proximity effect

A homogeneous sample of 99 moderate resolution QSO spectra at z > 1.7 were presented in Paper I, including 39 previously unpublished spectra from the Multiple Mirror Telescope. The statistics of the Lyman alpha forest were discussed. In this analysis, we demonstrate that a proximity effect is present in the data, ie. there exists a significant (5.5$\sigma$) deficit of lines at $z_{abs} \approx z_{em}$. Within 1.5 $h^{-1}$ Mpc of the QSO emission redshift, the significance does depend on QSO luminosity, in accordance with the theory that this effect is caused by enhanced ionization of hydrogen in the vicinity of the QSO from UV photons from the QSO itself. The photoionization model of Bajtlik, Duncan, and Ostriker (1988) permits an estimate of the mean intensity of the extragalactic background radiation at the Lyman limit. We compare the results of this standard analysis with those obtained using a maximum likelihood technique. The best fit value for $J(\nu_{0})$ is 7.0$^{+3.4}_{-4.4}$ x 10$^{-22}$ ergs/s/cm$^{2}$/Hz/sr, over the redshift range 1.7 < z < 3.8, using QSO redshifts based on narrow emission lines. The best fit value for the HI ionization rate is 1.9$^{+1.2}_{-1.0}$ x 10$^{-12}$ s$^{-1}$, in good agreement with models of the background which incorporate QSOs only. This large absorption line sample and these techniques for measuring the background and understanding the systematics involved allow us to place what we believe are are the firmest limits on the background at these redshifts.Comment: revised figures 13 and 14, and other minor corrections, 42 Latex pages, 23 encapsulated Postscript figures, uses emulateapj.sty, To appear in the Sept. 2000 ApJ

Age-Associated mRNA and miRNA Expression Changes in the Blood-Brain Barrier

Functional and structural age-associated changes in the blood-brain barrier (BBB) may affect the neurovascular unit and contribute to the onset and progression of age-associated neurodegenerative pathologies, including Alzheimer’s disease. The current study interrogated the RNA profile of the BBB in an ageing human autopsy brain cohort and an ageing mouse model using combined laser capture microdissection and expression profiling. Only 12 overlapping genes were altered in the same direction in the BBB of both ageing human and mouse cohorts. These included genes with roles in regulating vascular tone, tight junction protein expression and cell adhesion, all processes prone to dysregulation with advancing age. Integrated mRNA and miRNA network and pathway enrichment analysis of the datasets identified 15 overlapping miRNAs that showed altered expression. In addition to targeting genes related to DNA binding and/or autophagy, many of the miRNAs identified play a role in age-relevant processes, including BBB dysfunction and regulating the neuroinflammatory response. Future studies have the potential to develop targeted therapeutic approaches against these candidates to prevent vascular dysfunction in the ageing brain

Genetic variation in TLR genes in Ugandan and South African populations and comparison with HapMap data

Genetic epidemiological studies of complex diseases often rely on data from the International HapMap Consortium for identification of single nucleotide polymorphisms (SNPs), particularly those that tag haplotypes. However, little is known about the relevance of the African populations used to collect HapMap data for study populations conducted elsewhere in Africa. Toll-like receptor (TLR) genes play a key role in susceptibility to various infectious diseases, including tuberculosis. We conducted full-exon sequencing in samples obtained from Uganda (n = 48) and South Africa (n = 48), in four genes in the TLR pathway: TLR2, TLR4, TLR6, and TIRAP. We identified one novel TIRAP SNP (with minor allele frequency [MAF] 3.2%) and a novel TLR6 SNP (MAF 8%) in the Ugandan population, and a TLR6 SNP that is unique to the South African population (MAF 14%). These SNPs were also not present in the 1000 Genomes data. Genotype and haplotype frequencies and linkage disequilibrium patterns in Uganda and South Africa were similar to African populations in the HapMap datasets. Multidimensional scaling analysis of polymorphisms in all four genes suggested broad overlap of all of the examined African populations. Based on these data, we propose that there is enough similarity among African populations represented in the HapMap database to justify initial SNP selection for genetic epidemiological studies in Uganda and South Africa. We also discovered three novel polymorphisms that appear to be population-specific and would only be detected by sequencing efforts

Identifying factors likely to influence compliance with diagnostic imaging guideline recommendations for spine disorders among chiropractors in North America: a focus group study using the Theoretical Domains Framework

Background: The Theoretical Domains Framework (TDF) was developed to investigate determinants of specific clinical behaviors and inform the design of interventions to change professional behavior. This framework was used to explore the beliefs of chiropractors in an American Provider Network and two Canadian provinces about their adherence to evidence-based recommendations for spine radiography for uncomplicated back pain. The primary objective of the study was to identify chiropractors’ beliefs about managing uncomplicated back pain without xrays and to explore barriers and facilitators to implementing evidence-based recommendations on lumbar spine xrays. A secondary objective was to compare chiropractors in the United States and Canada on their beliefs regarding the use of spine x-rays. Methods: Six focus groups exploring beliefs about managing back pain without x-rays were conducted with a purposive sample. The interview guide was based upon the TDF. Focus groups were digitally recorded, transcribed verbatim, and analyzed by two independent assessors using thematic content analysis based on the TDF. Results: Five domains were identified as likely relevant. Key beliefs within these domains included the following: conflicting comments about the potential consequences of not ordering x-rays (risk of missing a pathology, avoiding adverse treatment effects, risks of litigation, determining the treatment plan, and using x-ray-driven techniques contrasted with perceived benefits of minimizing patient radiation exposure and reducing costs; beliefs about consequences); beliefs regarding professional autonomy, professional credibility, lack of standardization, and agreement with guidelines widely varied (social/professional role & identity); the influence of formal training, colleagues, and patients also appeared to be important factors (social influences); conflicting comments regarding levels of confidence and comfort in managing patients without x-rays (belief about capabilities); and guideline awareness and agreements (knowledge). Conclusions: Chiropractors’ use of diagnostic imaging appears to be influenced by a number of factors. Five key domains may be important considering the presence of conflicting beliefs, evidence of strong beliefs likely to impact the behavior of interest, and high frequency of beliefs. The results will inform the development of a theorybased survey to help identify potential targets for behavioral-change strategies

Development and optimisation of a multi-component workplace intervention to increase cycling for the Cycle Nation Project

The Cycle Nation Project (CNP) aimed to develop, test the feasibility of and optimize a multi-component individual-/social-level workplace-based intervention to increase cycling among office staff at a multinational bank (HSBC UK). To do this, we first explored barriers to cycling in a nationally-representative survey of UK adults, then undertook focus groups with bank employees to understand any context-specific barriers and ways in which these might be overcome. These activities led to identification of 10 individual-level, two social-level, and five organizational-level modifiable factors, which were mapped to candidate intervention components previously identified in a scoping review of cycling initiatives. Interviews with HSBC UK managers then explored the practicality of implementing the candidate intervention components in bank offices. The resultant pilot CNP intervention included 32 core components across six intervention functions (education, persuasion, incentivisation, training, environmental restructuring, enablement). Participants received a loan bike for 12-weeks (or their own bike serviced), and a 9-week cycle training course (condensed to 6 weeks for those already confident in basic cycling skills), including interactive information sharing activities, behavior change techniques (e.g., weekly goal setting), bike maintenance training, practical off-road cycling skill games and on-road group rides. Sessions were delivered by trained bank staff members who were experienced cyclists. The CNP pilot intervention was delivered across three sites with 68 participants. It was completed in two sites (the third site was stopped due to COVID-19) and was feasible and acceptable to both women and men and across different ethnicities. In addition, the CNP intervention was successful (at least in the short term) in increasing cycling by 3 rides/week on average, and improving perceptions of safety, vitality, confidence, and motivation to cycle. Following minor modifications, the long-term effectiveness and cost-effectiveness of the CNP intervention should be tested in a full-scale randomized controlled trial

Comprehensive Identification of Host Modulators of HIV-1 Replication using Multiple Orthologous RNAi Reagents

SummaryRNAi screens have implicated hundreds of host proteins as HIV-1 dependency factors (HDFs). While informative, these early studies overlap poorly due to false positives and false negatives. To ameliorate these issues, we combined information from the existing HDF screens together with new screens performed with multiple orthologous RNAi reagents (MORR). In addition to being traditionally validated, the MORR screens and the historical HDF screens were quantitatively integrated by the adaptation of an established analysis program, RIGER, for the collective interpretation of each gene’s phenotypic significance. False positives were addressed by the removal of poorly expressed candidates through gene expression filtering, as well as with GESS, which identifies off-target effects. This workflow produced a quantitatively integrated network of genes that modulate HIV-1 replication. We further investigated the roles of GOLGI49, SEC13, and COG in HIV-1 replication. Collectively, the MORR-RIGER method minimized the caveats of RNAi screening and improved our understanding of HIV-1–host cell interactions