The ENCODE Imputation Challenge: a critical assessment of methods for cross-cell type imputation of epigenomic profiles

A promising alternative to comprehensively performing genomics experiments is to, instead, perform a subset of experiments and use computational methods to impute the remainder. However, identifying the best imputation methods and what measures meaningfully evaluate performance are open questions. We address these questions by comprehensively analyzing 23 methods from the ENCODE Imputation Challenge. We find that imputation evaluations are challenging and confounded by distributional shifts from differences in data collection and processing over time, the amount of available data, and redundancy among performance measures. Our analyses suggest simple steps for overcoming these issues and promising directions for more robust research

The ENCODE Imputation Challenge: a critical assessment of methods for cross-cell type imputation of epigenomic profiles

A promising alternative to comprehensively performing genomics experiments is to, instead, perform a subset of experiments and use computational methods to impute the remainder. However, identifying the best imputation methods and what measures meaningfully evaluate performance are open questions. We address these questions by comprehensively analyzing 23 methods from the ENCODE Imputation Challenge. We find that imputation evaluations are challenging and confounded by distributional shifts from differences in data collection and processing over time, the amount of available data, and redundancy among performance measures. Our analyses suggest simple steps for overcoming these issues and promising directions for more robust research

Single Wire Power Monitoring Utilizing Non- Intrusive Current Measurement

In order to determine the power consumption of an unknown load circuit both its current and voltage must be determined, as well as any phase difference between them. The current measurement is made non-intrusively by using a Rogowski coil, which picks up the magnetic field created by the current through either the supply or the return wire. The coil outputs a voltage which is proportional to the rate of change of current through the wire. This voltage is integrated and sent to a PIC18 microcontroller for further processing and storage. The PIC also implements a voltmeter via the onboard A-D converter to determine the voltage dropped across the load. The current and voltage signals are analyzed to determine the phase difference, and the actual rms current, rms voltage, power factor, and average power are computed. These values are displayed in real-time on an LCD screen, and all data can be uploaded to a computer for graphical analysis

Single Wire Power Monitoring Utilizing Non- Intrusive Current Measurement

In order to determine the power consumption of an unknown load circuit both its current and voltage must be determined, as well as any phase difference between them. The current measurement is made non-intrusively by using a Rogowski coil, which picks up the magnetic field created by the current through either the supply or the return wire. The coil outputs a voltage which is proportional to the rate of change of current through the wire. This voltage is integrated and sent to a PIC18 microcontroller for further processing and storage. The PIC also implements a voltmeter via the onboard A-D converter to determine the voltage dropped across the load. The current and voltage signals are analyzed to determine the phase difference, and the actual rms current, rms voltage, power factor, and average power are computed. These values are displayed in real-time on an LCD screen, and all data can be uploaded to a computer for graphical analysis

Phylogeographic Assessment Reveals Geographic Sources of HIV-1 Dissemination Among Men Who Have Sex With Men in Kenya

HIV-1 transmission dynamics involving men who have sex with men (MSM) in Africa are not well understood. We investigated the rates of HIV-1 transmission between MSM across three regions in Kenya: Coast, Nairobi, and Nyanza. We analyzed 372 HIV-1 partial pol sequences sampled during 2006–2019 from MSM in Coast (N = 178, 47.9%), Nairobi (N = 137, 36.8%), and Nyanza (N = 57, 15.3%) provinces in Kenya. Maximum-likelihood (ML) phylogenetics and Bayesian inference were used to determine HIV-1 clusters, evolutionary dynamics, and virus migration rates between geographic regions. HIV-1 sub-subtype A1 (72.0%) was most common followed by subtype D (11.0%), unique recombinant forms (8.9%), subtype C (5.9%), CRF 21A2D (0.8%), subtype G (0.8%), CRF 16A2D (0.3%), and subtype B (0.3%). Forty-six clusters (size range 2–20 sequences) were found—half (50.0%) of which had evidence of extensive HIV-1 mixing among different provinces. Data revealed an exponential increase in infections among MSM during the early-to-mid 2000s and stable or decreasing transmission dynamics in recent years (2017–2019). Phylogeographic inference showed significant (Bayes factor, BF > 3) HIV-1 dissemination from Coast to Nairobi and Nyanza provinces, and from Nairobi to Nyanza province. Strengthening HIV-1 prevention programs to MSM in geographic locations with higher HIV-1 prevalence among MSM (such as Coast and Nairobi) may reduce HIV-1 incidence among MSM in Kenya

The effect of acute hypoxia on heat shock protein 72 expression and oxidative stress in vivo

The inducible human stress protein HSP72 performs vital roles within the body at rest and during periods of stress. Recently, a previously disclosed quadratic trend in basal HSP72 expression was shown to be reliable and repeatable. The notion of a physiological stressor such as hypoxia disrupting this basal quadratic trend is an interesting one. Monocyte-expressed HSP72 and TBARS were determined every 3 h, over a 12-h period in 12 healthy male subjects on two separate days, with trial day one ascertaining control values. A hypoxic intervention consisting of 75 min at a simulated altitude of 2,980 m, commencing and ceasing at 0930 and 1045, respectively, was incorporated on trail day 2. The hypoxic condition induced significantly (elevated) HSP72 values at 1100 (P = 0.002), 1400 (P < 0.001), 1700 (P = 0.034) and 2000 (P = 0.041) compared to control. Significant increases in plasma TBARS were seen in the hypoxic condition compared to control at 1100 (P = 0.006) and 1400 (P = 0.032). The results demonstrate that a 75-min bout of normobaric hypoxia is sufficient to induce significant increases in HSP72 expression, which disrupts the basal quadratic trend shown by others and here in the control condition. This increase may be linked to the observed changes in oxidative stress. These results may provide a tool for manipulating basal monocyte HSP72 expression within human heat acclimation exercise protocols

The effect of hyperbaric oxygen preconditioning on heat shock protein 72 expression following in vitro stress in human monocytes

Hyperbaric oxygen (HBO) is thought to confer protection to cells via a cellular response to free radicals. This process may involve increased expression of heat shock proteins, in particular the highly inducible heat shock protein 72 (Hsp72). Healthy male volunteers (n = 16) were subjected to HBO for 1 h at 2.8 ATA. Inducible Hsp72 expression was measured by flow cytometry pre-, post- and 4 h-post HBO. Peripheral blood mononuclear cells (PBMC) were isolated from whole blood via density centrifugation pre-, post- and 4 h post-HBO. PBMC were then subjected to an in vitro heat shock at 40°C or hypoxia at 37°C (5% O2) with a control at 37°C. Cells were then analysed for Hsp72 expression by flow cytometry. Monocytes showed no significant changes in Hsp72 expression following HBO. No detectable Hsp72 was seen in lymphocytes or neutrophils. Following in vitro hypoxic exposure, a significant increase in Hsp72 expression was observed in monocytes isolated immediately post- (p = 0.006) and 4 h post-HBO (p = 0.010) in comparison to control values. HBO does not induce Hsp72 expression in PBMC. The reported benefits of HBO in terms of pre-conditioning are not due to inducement of Hsp72 expression in circulating blood cells, but may involve an enhancement of the stress response

Daily quadratic trend in basal monocyte expressed HSP72 in healthy human subjects

The inducible human stress protein heat shock protein 72 (HSP72) performs vital roles within the body at rest and during periods of stress. Recently it was shown over a 24 hour period that basal HSP72 followed a diurnal variation. However, these results and previous literature demonstrate noticeable inter-subject variation in basal HSP72 expression. The notion of intra/inter-day variation in basal HSP72 expression has not been explored in detail. Basal monocyte expressed HSP72 was determined every 3 hours, over a 9 hour period in 12 healthy male subjects (20.2 +/- 1.9 years, 178.7 +/- 5.6 cm, 75.1 +/- 6.0 kg) within a temperature controlled laboratory. A significant quadratic trend was observed for time (F = 26.0, P = 0.001, partial eta(2) = 0.74), where HSP72 decreased between 0800 and 1100 hours (P < 0.001) and then increased between 1100 and 1400 hours (P = 0.015). The main effect for day (F = 2.6, P = 0.14) and the day x time interaction effect (F = 3.9, P = 0.08) were not significant. There was no correlation between serum and monocyte expressed HSP72, with no significant effect for time (F = 2.0, P = 0.21) in serum HSP72 expression. The results support findings by others that basal monocyte expressed HSP72 follows a diurnal variation which incorporates a quadratic trend, which is not compromised by any significant daily variation and that serum HSP72 expression has no endogenous circadian rhythm. The significant quadratic trend in basal monocyte HSP72 expression shown here highlights the need to tightly control variables, such as timing of sample collection, as it is known basal values influence the magnitude of HSP72 expression post-stressor/intervention