A legacy slope failure in Penlee Quarry - a warning to others

PublishedArticlePenlee Quarry is a large quarry in West Cornwall that has been in operation since the late 1880s. It was a major producer of aggregate, but since 2003 under new ownership, quarry operations have concentrated on maintenance and preparatory works for the recovery of armourstone and the eventual construction of a marina. The western face of this quarry was excavated between the 1950s and 1970s and is akin to other legacy slopes found at several older British quarries. The slope is up to 90m in height, has little benching and has shown increasing signs of instability since 2005. Initially instability was evidenced by rockfall and more recently by serious collapses that have indicated the need for appropriate geotechnical design of a new replacement slope. This paper sets out background and historical data and then considers investigations into the underlying mechanisms and rock structures that have contributed to instability and are relevant to the design of measures to overcome the potential for future significant ground movements. Methods to remotely assess the controlling joint sets are discussed and the rationale behind the excavated solution to facilitate future workings is outlined. High, over-steep rock faces with limited, ineffective benching and excessive bench heights that may be found in some older quarries, as at Penlee, are likely to become a matter of increasing concern. In addition the potential for major air blast or flow slide phenomena needs further investigation in these legacy slopes some of which are present in Southwest England

DIFFERENTIAL EFFECTS OF VARYING DOSES OF DIETARY NITRATE ON MUSCLE FUNCTION AND BLOOD PRESSURE IN OLDER SUBJECTS

We have recently demonstrated that dietary nitrate, a source of nitric oxide via the enterosalivary pathway, can improve muscle contractile function in healthy older men and women. Nitrate ingestion has also been shown to reduce blood pressure in older individuals. However, the optimal dose for eliciting these beneficial effects is unknown. We therefore performed a randomized, double-blind, crossover study to determine the effects of ingesting 3.3 mL/kg of beetroot juice (BRJ) containing 0, 212, or 425 µmol/kg of nitrate in six healthy older (age 69±3 y) subjects. Maximal knee extensor speed (Vmax) and power (Pmax) were measured 2 h after BRJ ingestion using isokinetic dynamometry; blood pressure was monitored periodically throughout each study. Mean arterial pressure (in mmHg) was lower (P<0.05) after the high (80±4) vs. the low (84±3) or placebo (88±2) doses. Vmax (in rad/s), however, was higher (P<0.05) after the low dose (11.7±0.8), but not the high dose (10.8±1.0), compared to the placebo (10.5±1.0). Pmax (in W/kg) also tended to be higher (P=0.11) in the low (3.9±0.5) compared to the placebo (3.7±0.5) or high (3.7±0.5) trials. Five out of six subjects achieved a higher Vmax and Pmax after the low vs. the high dose. We conclude that dietary nitrate has differential effects on muscle function and blood pressure in older individuals. A high dose of nitrate intake further lowers blood pressure but does not enhance muscle contractility as much as a lower dose. Supported by Indiana University Purdue University Indianapolis and by the NIA (R21 AG053606)

Crystal structure analysis reveals Pseudomonas PilY1 as an essential calcium-dependent regulator of bacterial surface motility

Several bacterial pathogens require the “twitching” motility produced by filamentous type IV pili (T4P) to establish and maintain human infections. Two cytoplasmic ATPases function as an oscillatory motor that powers twitching motility via cycles of pilus extension and retraction. The regulation of this motor, however, has remained a mystery. We present the 2.1 Å resolution crystal structure of the Pseudomonas aeruginosa pilus-biogenesis factor PilY1, and identify a single site on this protein required for bacterial translocation. The structure reveals a modified β-propeller fold and a distinct EF-hand-like calcium-binding site conserved in pathogens with retractile T4P. We show that preventing calcium binding by PilY1 using either an exogenous calcium chelator or mutation of a single residue disrupts Pseudomonas twitching motility by eliminating surface pili. In contrast, placing a lysine in this site to mimic the charge of a bound calcium interferes with motility in the opposite manner—by producing an abundance of nonfunctional surface pili. Our data indicate that calcium binding and release by the unique loop identified in the PilY1 crystal structure controls the opposing forces of pilus extension and retraction. Thus, PilY1 is an essential, calcium-dependent regulator of bacterial twitching motility

Initiation of Dialysis Is Associated With Impaired Cardiovascular Functional Capacity

Background The transition to dialysis period carries a substantial increased cardiovascular risk in patients with chronic kidney disease. Despite this, alterations in cardiovascular functional capacity during this transition are largely unknown. The present study therefore sought to assess ventilatory exercise response measures in patients within 1 year of initiating dialysis. Methods and Results We conducted a cross‐sectional study of 241 patients with chronic kidney disease stage 5 from the CAPER (Cardiopulmonary Exercise Testing in Renal Failure) study and from the intradialytic low‐frequency electrical muscle stimulation pilot randomized controlled trial cohorts. Patients underwent cardiopulmonary exercise testing and echocardiography. Of the 241 patients (age, 48.9 [15.0] years; 154 [63.9%] men), 42 were predialytic (mean estimated glomerular filtration rate, 14 mL·min −1 ·1.73 m −2 ), 54 had a dialysis vintage ≤12 months, and 145 had a dialysis vintage &gt;12 months. Dialysis vintage ≤12 months exhibited a significantly impaired cardiovascular functional capacity, as assessed by oxygen uptake at peak exercise (18.7 [5.8] mL·min −1 ·kg −1 ) compared with predialysis (22.7 [5.2] mL·min −1 ·kg −1 ; P &lt;0.001). Dialysis vintage ≤12 months also exhibited reduced peak workload, impaired peak heart rate, reduced circulatory power, and increased left ventricular mass index ( P &lt;0.05 for all) compared with predialysis. After excluding those with prior kidney transplant, dialysis vintage &gt;12 months exhibited a lower oxygen uptake at peak exercise (17.0 [4.9] mL·min −1 ·kg −1 ) compared with dialysis vintage ≤12 months (18.9 [5.9] mL·min −1 ·kg −1 ; P =0.033). Conclusions Initiating dialysis is associated with a significant impairment in oxygen uptake at peak exercise and overall decrements in ventilatory and hemodynamic exercise responses that predispose patients to functional dependence. The magnitude of these changes is comparable to the differences between low‐risk New York Heart Association class I and higher‐risk New York Heart Association class II to IV heart failure

Beetroot supplementation in women enjoying exercise together (BEE SWEET): Rationale, design and methods

Background: Postmenopausal women exhibit higher rates of disability and cardiovascular disease (CVD) with aging compared to men. Whereas habitual exercise training is a known strategy to enhance physiologic function in men and premenopausal women, exercise-related adaptations are often modest in postmenopausal women. We propose dietary nitrate (beetroot juice) administered prior to exercise training may be a feasible approach to improve mobility and cardio-metabolic health outcomes in postmenopausal women. Methods: Our randomized, placebo-controlled study aims to determine preliminary effects sizes for changes in functional mobility and endothelium-dependent vasodilation across three study arms: exercise only (EX), exercise + placebo (EX + PL), and exercise + beetroot (EX + BR). Thirty-six postmenopausal women are recruited in small cohorts wherein group exercise is implemented to facilitate social support and adherence to an 8-week training progression. Participants are randomized to one of three study arms (n = 12 per group) following baseline assessments. Post-intervention assessments are used to determine pre-post changes in outcome measures including distance covered during a 6 min walk test, walking economy, muscle speed and power, and endothelial-dependent vasodilation as determined by flow-mediated dilation. Measures of feasibility include recruitment, retention, adherence to exercise prescription, perceived exercise session difficulty, and adverse event rates. Discussion: Evidence-based, translational strategies are needed to optimize exercise training-related adaptations in postmenopausal women. Findings will inform larger randomized clinical trials to determine if pre-exercise consumption of beetroot juice is an efficacious strategy to promote mobility and attenuate CVD disease risk

The long journey to a Systems Biology of neuronal function

Computational neurobiology was born over half a century ago, and has since been consistently at the forefront of modelling in biology. The recent progress of computing power and distributed computing allows the building of models spanning several scales, from the synapse to the brain. Initially focused on electrical processes, the simulation of neuronal function now encompasses signalling pathways and ion diffusion. The flow of quantitative data generated by the "omics" approaches, alongside the progress of live imaging, allows the development of models that will also include gene regulatory networks, protein movements and cellular remodelling. A systems biology of brain functions and disorders can now be envisioned. As it did for the last half century, neuroscience can drive forward the field of systems biology

Expedition 390 Preliminary Report. South Atlantic Transect 1

The South Atlantic Transect (SAT) is a multidisciplinary scientific ocean drilling project that comprises four International Ocean Discovery Program (IODP) expeditions: engineering Expeditions 390C and 395E as well as Expeditions 390 and 393. Altogether, the expeditions aim to recover complete sedimentary sections and the upper 100–350 m of the underlying oceanic crust along a slow/intermediate spreading rate Mid-Atlantic Ridge crustal flow line at ~31°S. The sediments along this transect were originally spot cored more than 50 y ago during Deep Sea Drilling Project Leg 3 (December 1968–January 1969) to help verify the theories of seafloor spreading and plate tectonics. Given dramatic advances in drilling technology and analytical capabilities since Leg 3, many high-priority scientific objectives can be addressed by revisiting the transect. The SAT expeditions target six primary sites on 7, 15, 31, 49, and 61 Ma ocean crust, which fill critical gaps in our sampling of intact in situ ocean crust with regards to crustal age, spreading rate, and sediment thickness. Drilling these sites is required to investigate the history of the low-temperature hydrothermal interactions between the aging ocean crust and the evolving South Atlantic Ocean and quantify past hydrothermal contributions to global biogeochemical cycles. Samples from the transect of the previously unexplored sediment- and basalt-hosted deep biosphere beneath the South Atlantic Gyre are essential to refining global biomass estimates and examining microbial ecosystems’ responses to variable conditions in a low-energy gyre and aging ocean crust. The transect is located near World Ocean Circulation Experiment Line A10, providing access to records of carbonate chemistry and deepwater mass properties across the western South Atlantic through key Cenozoic intervals of elevated atmospheric CO2 and rapid climate change. Reconstruction of the history of the deep western boundary current and deepwater formation in the Atlantic basins will yield crucial data to test hypotheses regarding the role of evolving thermohaline circulation patterns in climate change and the effects of tectonic gateways and climate on ocean acidification. Engineering Expeditions 390C and 395E cored a single hole through the sediment/basement interface with the advanced piston corer/extended core barrel system at five of the six primary proposed SAT sites and installed a reentry system with casing either into basement or within 10 m of basement at each of those five sites. Expedition 390 (7 April–7 June 2022) conducted operations at three of the SAT sites, recovering 700 m of core (77% recovery) over 30.3 days of on-site operations. Sediment coring, basement drilling, and logging were conducted at two sites on 61 Ma crust, and sediment coring was completed at the 7 Ma crust site. At Site U1557 on 61 Ma crust, the drill bit was deposited on the seafloor prior to downhole logging, leaving Hole U1557D available for future deepening and to establish a legacy borehole for basement hydrothermal and microbiological experiments. Expedition 390 scientists additionally described, and analyzed data from, 792 m of core collected during Expeditions 390C and 395E. Expedition 393 plans to operate at four sites, conducting basement drilling and downhole logging at the 7 Ma site, in addition to sediment coring, basement drilling, and logging at the sites intermediate in age

Differences in selectivity to natural images in early visual areas (V1–V3)

High-level regions of the ventral visual pathway respond more to intact objects compared to scrambled objects. The aim of this study was to determine if this selectivity for objects emerges at an earlier stage of processing. Visual areas (V1–V3) were defined for each participant using retinotopic mapping. Participants then viewed intact and scrambled images from different object categories (bottle, chair, face, house, shoe) while neural responses were measured using fMRI. Our rationale for using scrambled images is that they contain the same low-level properties as the intact objects, but lack the higher-order combinations of features that are characteristic of natural images. Neural responses were higher for scrambled than intact images in all regions. However, the difference between intact and scrambled images was smaller in V3 compared to V1 and V2. Next, we measured the spatial patterns of response to intact and scrambled images from different object categories. We found higher within-category compared to between category correlations for both intact and scrambled images demonstrating distinct patterns of response. Spatial patterns of response were more distinct for intact compared to scrambled images in V3, but not in V1 or V2. These findings demonstrate the emergence of selectivity to natural images in V3

Short-Term Exercise Training Does Not Stimulate Skeletal Muscle ATP Synthesis in Relatives of Humans With Type 2 Diabetes

OBJECTIVE-We tested the hypothesis that short-term exercise training improves hereditary insulin resistance by stimulating ATP synthesis and investigated associations With gene polymorphisms. RESEARCH DESIGN AND METHODS-We studied 24 nono-bese first-degree relatives of type 2 diabetic patients and 12 control subjects at rest, and 48 h after three bouts of exercise. In addition to measurements of oxygen uptake and insulin sensitivity (oral glucose tolerance test), ectopic lipids and mitochondrial ATP synthesis were assessed using H-1 and P-31 magnetic resonance spectroscopy, respectively. They were genotyped for polymorphisms in genes regulating mitochondrial function, PPARGC1A (rs8192678) and NDUFB6 (rs540467). RESULTS-Relatives had slightly lower (P = 0.012) insulin sensitivity than control subjects. In control subjects, ATP synthase flux rose by 18% (P = 0.0001), being 23% higher (P = 0.002) than that in relatives after exercise training. Relatives responding to exercise training with increased ATP synthesis (+19%, P = 0.009) showed improved insulin sensitivity (P = 0.009) compared with those whose insulin sensitivity did not improve. A polymorphism in the NDUFB6 gene from respiratory chain complex I related to ATP synthesis (P = 0.02) and insulin Sensitivity response to exercise training (P = 0.05). ATP synthase flux correlated with O-2 uptake and insulin sensitivity. CONCLUSIONS-The ability of short-term exercise to stimulate ATP production distinguished individuals with improved insulin sensitivity from those whose insulin sensitivity did not improve. lit addition, the NDUFB6 gene polymorphism appeared to modulate this adaptation. This finding suggests that genes involved in mitochondrial function contribute to the response of ATP synthesis to exercise training. Diabetes 58:1333-1341, 200

Severe loss of mechanical efficiency in COVID‐19 patients

Background: There is limited information about the impact of coronavirus disease (COVID-19) on the muscular dysfunction, despite the generalized weakness and fatigue that patients report after overcoming the acute phase of the infection. This study aimed to detect impaired muscle efficiency by evaluating delta efficiency (DE) in patients with COVID-19 compared with subjects with chronic obstructive pulmonary disease (COPD), ischaemic heart disease (IHD), and control group (CG). Methods: A total of 60 participants were assigned to four experimental groups: COVID-19, COPD, IHD, and CG (n = 15 each group). Incremental exercise tests in a cycle ergometer were performed to obtain peak oxygen uptake (VO2 peak). DE was obtained from the end of the first workload to the power output where the respiratory exchange ratio was 1. Results: A lower DE was detected in patients with COVID-19 and COPD compared with those in CG (P ≤ 0.033). However, no significant differences were observed among the experimental groups with diseases (P > 0.05). Lower VO2 peak, peak ventilation, peak power output, and total exercise time were observed in the groups with diseases than in the CG (P < 0.05). A higher VO2 , ventilation, and power output were detected in the CG compared with those in the groups with diseases at the first and second ventilatory threshold (P < 0.05). A higher power output was detected in the IHD group compared with those in the COVID-19 and COPD groups (P < 0.05) at the first and second ventilatory thresholds and when the respiratory exchange ratio was 1. A significant correlation (P < 0.001) was found between the VO2 peak and DE and between the peak power output and DE (P < 0.001). Conclusions: Patients with COVID-19 showed marked mechanical inefficiency similar to that observed in COPD and IHD patients. Patients with COVID-19 and COPD showed a significant decrease in power output compared to IHD during pedalling despite having similar response in VO2 at each intensity. Resistance training should be considered during the early phase of rehabilitation