Bubble Measurements Downstream of Hydraulic Jumps

A phase Doppler anemometer (PDA) system was used to measure the velocity profiles and air bubble size distributions downstream of two-dimensional hydraulic jumps for different upstream flow conditions in a 1.92m long laboratory flume. The PDA detected bubbles from 1 to 500 [microns] in diameter, and more were found at the bottom of the downstream flow near the elevation of the upstream free surface. This distribution was more marked for smaller bubbles, those with diameters less that 100 [microns]. The migration of the bubbles is controlled by the effects of buoyancy and by turbulent mixing; the relative magnitude of their effects on bubble distribution depends strongly on bubble size, and also on the energy of the upstream flow

Rates of Performance Loss and Neuromuscular Activity in Men and Women During Cycling: Evidence for A Common Metabolic Basis of Muscle Fatigue

The durations that muscular force and power outputs can be sustained until failure fall predictably on an exponential decline between an individual’s 3-s burst maximum to the maximum performance they can sustain aerobically. The exponential time constants describing these rates of performance loss are similar across individuals, suggesting that a common metabolically based mechanism governs muscle fatigue; however, these conclusions come from studies mainly on men. To test whether the same physiological understanding can be applied to women, we compared the performance-duration relationships and neuromuscular activity between seven men [23.3 ± 1.9 (SD) yr] and seven women (21.7 ± 1.8 yr) from multiple exhaustive bouts of cycle ergometry. Each subject performed trials to obtain the peak 3-s power output (Pmax), the mechanical power at the aerobic maximum (Paer), and 11–14 constant-load bouts eliciting failure between 3 and 300 s. Collectively, men and women performed 180 exhaustive bouts spanning an ~6-fold range of power outputs (118–1116 W) and an ~35-fold range of trial durations (8–283 s). Men generated 66% greater Pmax (956 ± 109 W vs. 632 ± 74 W) and 68% greater Paer (310 ± 47 W vs. 212 ± 15 W) than women. However, the metabolically based time constants describing the time course of performance loss were similar between men (0.020 ± 0.003/s) and women (0.021 ± 0.003/s). Additionally, the fatigue-induced increases in neuromuscular activity did not differ between the sexes when compared relative to the pedal forces at Paer. These data suggest that muscle fatigue during short-duration dynamic exercise has a common metabolically based mechanism determined by the extent that ATP is resynthesized by anaerobic metabolism

Mechanisms for the Age-related Increase in Fatigability of the Knee Extensors in Old and Very Old Adults

The mechanisms for the age-related increase in fatigability during high-velocity contractions in old and very old adults ({greater than or equal to}80 yrs) are unresolved. Moreover, whether the increased fatigability with advancing age and the underlying mechanisms differ between men and women are not known. The purpose of this study was to quantify the fatigability of knee extensor muscles and identify the mechanisms of fatigue in 30 young (22.6 {plus minus} 0.4 yrs; 15 men), 62 old (70.5 {plus minus} 0.7 yrs; 33 men), and 12 very old (86.0 {plus minus} 1.3 yrs; 6 men) men and women elicited by high-velocity concentric contractions. Participants performed 80 maximal velocity contractions (1 contraction per 3 s) with a load equivalent to 20% of the maximum voluntary isometric contraction. Voluntary activation and contractile properties were quantified before and immediately following exercise (\u3c10 \u3es) using transcranial magnetic stimulation and electrical stimulation. Absolute mechanical power output was 97% and 217% higher in the young compared to old and very old adults, respectively. Fatigability (reductions in power) progressively increased across age groups, with a power loss of 17% in young, 31% in old, and 44% in very old adults. There were no sex differences in fatigability among any of the age groups. The age-related increase in power loss was strongly associated with changes in the involuntary twitch amplitude (r=0.75,

Physical Activity Modulates Corticospinal Excitability of the Lower Limb in Young and Old Adults

Aging is associated with reduced neuromuscular function, which may be due in part to altered corticospinal excitability. Regular physical activity (PA) may ameliorate these age-related declines, but the influence of PA on corticospinal excitability is unknown. The purpose of this study was to determine the influence of age, sex, and PA on corticospinal excitability by comparing the stimulus-response curves of motor evoked potentials (MEP) in 28 young (22.4 ± 2.2 yr; 14 women and 14 men) and 50 old adults (70.2 ± 6.1 yr; 22 women and 28 men) who varied in activity levels. Transcranial magnetic stimulation was used to elicit MEPs in the active vastus lateralis muscle (10% maximal voluntary contraction) with 5% increments in stimulator intensity until the maximum MEP amplitude. Stimulus-response curves of MEP amplitudes were fit with a four-parameter sigmoidal curve and the maximal slope calculated (slopemax). Habitual PA was assessed with tri-axial accelerometry and participants categorized into either those meeting the recommended PA guidelines for optimal health benefits (\u3e10,000 steps/day, high-PA; n = 21) or those not meeting the guidelines (n = 41). The MEP amplitudes and slopemax were greater in the low-PA compared with the high-PA group (P \u3c 0.05). Neither age nor sex influenced the stimulus-response curve parameters (P \u3e 0.05), suggesting that habitual PA influenced the excitability of the corticospinal tract projecting to the lower limb similarly in both young and old adults. These findings provide evidence that achieving the recommended PA guidelines for optimal health may mediate its effects on the nervous system by decreasing corticospinal excitability

The DAXX co-repressor is directly recruited to active regulatory elements genome-wide to regulate autophagy programs in a model of human prostate cancer.

While carcinoma of the prostate is the second most common cause of cancer death in the US, current methods and markers used to predict prostate cancer (PCa) outcome are inadequate. This study was aimed at understanding the genome-wide binding and regulatory role of the DAXX transcriptional repressor, recently implicated in PCa. ChIP-Seq analysis of genome-wide distribution of DAXX in PC3 cells revealed over 59,000 DAXX binding sites, found at regulatory enhancers and promoters. ChIP-Seq analysis of DNA methyltransferase 1 (DNMT1), which is a key epigenetic partner for DAXX repression, revealed that DNMT1 binding was restricted to a small number of DAXX sites. DNMT1 and DAXX bound close to transcriptional activator motifs. DNMT1 sites were found to be dependent on DAXX for recruitment by analyzing DNMT1 ChIP-Seq following DAXX knockdown (K/D), corroborating previous findings that DAXX recruits DNMT1 to repress its target genes. Massively parallel RNA sequencing (RNA-Seq) was used to compare the transcriptomes of WT and DAXX K/D PC3 cells. Genes induced by DAXX K/D included those involved in autophagy, and DAXX ChIP-Seq peaks were found close to the transcription start sites (TSS) of autophagy genes, implying they are more likely to be regulated by DAXX. In conclusion, DAXX binds active regulatory elements and co-localizes with DNMT1 in the prostate cancer genome. Given DAXX's putative regulatory role in autophagy, future studies may consider DAXX as a candidate marker and therapeutic target for prostate cancer

Physical Activity Modulates Corticospinal Excitability of the Lower Limb in Young and Old Adults

Aging is associated with reduced neuromuscular function, which may be due in part to altered corticospinal excitability. Regular physical activity (PA) may ameliorate these age-related declines, but the influence of PA on corticospinal excitability is unknown. The purpose of this study was to determine the influence of age, sex, and PA on corticospinal excitability by comparing the stimulus-response curves of motor evoked potentials (MEP) in 28 young (22.4 ± 2.2 yr; 14 women and 14 men) and 50 old adults (70.2 ± 6.1 yr; 22 women and 28 men) who varied in activity levels. Transcranial magnetic stimulation was used to elicit MEPs in the active vastus lateralis muscle (10% maximal voluntary contraction) with 5% increments in stimulator intensity until the maximum MEP amplitude. Stimulus-response curves of MEP amplitudes were fit with a four-parameter sigmoidal curve and the maximal slope calculated (slopemax). Habitual PA was assessed with tri-axial accelerometry and participants categorized into either those meeting the recommended PA guidelines for optimal health benefits (\u3e10,000 steps/day, high-PA; n = 21) or those not meeting the guidelines (n = 41). The MEP amplitudes and slopemax were greater in the low-PA compared with the high-PA group (P \u3c 0.05). Neither age nor sex influenced the stimulus-response curve parameters (P \u3e 0.05), suggesting that habitual PA influenced the excitability of the corticospinal tract projecting to the lower limb similarly in both young and old adults. These findings provide evidence that achieving the recommended PA guidelines for optimal health may mediate its effects on the nervous system by decreasing corticospinal excitability

Influence of non-covalent preorganization on supramolecular effective molarities.

A family of closely related zinc porphyrin-pyridine complexes were used to examine the influence of linker preorganization on supramolecular effective molarities for formation of intramolecular H-bonds. Each pyridine ligand was equipped with a side-chain containing two H-bond acceptors, one on the end of the chain (terminal) and one in the middle of the chain (linker). These H-bond acceptors make intramolecular interactions with phenol H-bond donors on the porphyrin periphery. Two different H-bonding acceptors were used as linker groups in order to construct frameworks with significantly different degrees of preorganization: ester linkers populate the H-bonded state 60-70% of the time, whereas amide linkers populate the H-bonded state 90-100% of the time. Thus the amide linkers provide a significantly more preorganised ligand framework than the ester linkers. Effective molarities (EM) for intramolecular H-bonds between the terminal H-bond acceptor groups on the ligands (esters and amides) and the porphyrin phenol groups were quantified using 32 chemical double mutant cycles. The values of EM for interactions with the terminal H-bond acceptors are independent of the nature of the linker H-bond acceptor (weakly bonded ester or strongly bonded amide), which indicates that preorganization of the linker has no effect on chelate cooperativity in these systems.We thank the EPSRC, the China Scholarship Council, and the University of Sheffield for funding.This is the final version of the article. It first appeared from the Royal Society of Chemistry via http://dx.doi.org/10.1039/C5OB00231

M–M Bond-Stretching Energy Landscapes for M_2(dimen)_(4)^(2+) (M = Rh, Ir; dimen = 1,8-Diisocyanomenthane) Complexes

Isomers of Ir_2(dimen)_(4)^(2+) (dimen = 1,8-diisocyanomenthane) exhibit different Ir–Ir bond distances in a 2:1 MTHF/EtCN solution (MTHF = 2-methyltetrahydrofuran). Variable-temperature absorption data suggest that the isomer with the shorter Ir–Ir distance is favored at room temperature [K = ~8; ΔH° = −0.8 kcal/mol; ΔS° = 1.44 cal mol^(–1) K^(–1)]. We report calculations that shed light on M_2(dimen)_(4)^(2+) (M = Rh, Ir) structural differences: (1) metal–metal interaction favors short distances; (2) ligand deformational-strain energy favors long distances; (3) out-of-plane (A_(2u)) distortion promotes twisting of the ligand backbone at short metal–metal separations. Calculated potential-energy surfaces reveal a double minimum for Ir_2(dimen)_(4)^(2+) (4.1 Å Ir–Ir with 0° twist angle and ~3.6 Å Ir–Ir with ±12° twist angle) but not for the rhodium analogue (4.5 Å Rh–Rh with no twisting). Because both the ligand strain and A_(2u) distortional energy are virtually identical for the two complexes, the strength of the metal–metal interaction is the determining factor. On the basis of the magnitude of this interaction, we obtain the following results: (1) a single-minimum (along the Ir–Ir coordinate), harmonic potential-energy surface for the triplet electronic excited state of Ir_2(dimen)_(4)^(2+) (R_(e,Ir–Ir) = 2.87 Å; F_(Ir–Ir) = 0.99 mdyn Å^(–1)); (2) a single-minimum, anharmonic surface for the ground state of Rh_2(dimen)_(4)^(2+) (R_(e,Rh–Rh) = 3.23 Å; F_(Rh–Rh) = 0.09 mdyn Å^(–1)); (3) a double-minimum (along the Ir–Ir coordinate) surface for the ground state of Ir_2(dimen)_(4)^(2+) (R_(e,Ir–Ir) = 3.23 Å; F_(Ir–Ir) = 0.16 mdyn Å^(–1))