Whey and casein proteins differentially affect postprandial blood glucose and satiety mechanisms, with relevance for type 2 diabetes and obesity. Therefore, the purpose of this work was to ...investigate the effect of the casein-to-whey protein ratio and total protein concentration of milks consumed with cereal on postprandial blood glucose, appetite ratings, and subsequent food intake in a randomized, controlled, double-blinded study with healthy young adults (n = 32, 23.4 ± 3.1 yr, body mass index = 22.2 ± 2.5 kg/m2). Fasted participants consumed milk (250 mL) with either 80:20 or 40:60 (modified) casein-to-whey protein ratios at commercially normal (3.1%, wt) or high protein (9.3%, wt) concentration, or control (water with whey permeate), each along with 2 servings of oat-based breakfast cereal. Blood glucose concentrations were determined from finger prick blood samples and appetite was assessed using visual analog scales. Participants consumed a measured ad libitum pizza lunch at 120 min and blood glucose determination and appetite assessment continued following the lunch meal (140–200 min) to observe the second meal effect. Pre-lunch (0–120 min) incremental area under the curve (iAUC) and mean change from baseline blood glucose were reduced with consumption of all milk treatments relative to control. However, we found no differences between all treatments on pre-lunch appetite change from baseline and total area under the curve (tAUC) or lunch meal food intake. In terms of protein concentration results, high protein (9.3%, wt) treatments contrasted to normal protein (3.1%, wt) treatments lowered blood glucose change from baseline and iAUC, and post-lunch appetite change from baseline and tAUC. Protein ratio showed a modest effect in that modified (40:60) protein ratio lowered pre-lunch blood glucose change from baseline but not iAUC, and normal (80:20) protein ratio lowered pre-lunch appetite change from baseline but not tAUC. Therefore, high-carbohydrate breakfast meals with increased protein concentration (9.3%, wt) could be a dietary strategy for the attenuation of blood glucose and improved satiety ratings after the second meal.
In this proof-of-concept study, we aim to produce a polyurethane (PU)-based composite that can reduce the amount of viable SARS-CoV-2 virus in contact with the surface of the polymeric film without ...further interventions such as manual cleaning. Current protocols for maintaining the hygiene of commonly used touchpoints (door handles, light switches, shop counters) typically rely on repeated washing with antimicrobial products. Since the start of the SARS-CoV-2 pandemic, frequent and costly surface sanitization by workers has become standard procedure in many public areas. Therefore, materials that can be retrofitted to touchpoints, yet inhibit pathogen growth for extended time periods are an important target. Herein, we design and synthesise the PU using a one-pot synthetic procedure on a multigram scale from commercial starting materials. The PU forms a robust composite thin film when loaded with 10 wt% silver nanoparticles (AgNPs). The addition of AgNPs increases the ultimate tensile strength, modules of toughness and modulus of elasticity at the cost of a reduced elongation at break when compared to the pristine PU. Comparative biological testing was carried out by the addition of pseudotyped virus (PV) bearing the SARS-CoV-2 beta (B.1.351) VOC spike protein onto the film surfaces of either the pristine PU or the PU nanocomposite. After 24 h without further human intervention the nanocomposite reduced the amount of viable virus by 67% (p = 0.0012) compared to the pristine PU treated under the same conditions. The significance of this reduction in viable virus load caused by our nanocomposite is that PUs form the basis of many commercial paints and coatings. Therefore, we envisage that this work will provide the basis for further progress towards producing a retrofittable surface that can be applied to a wide variety of common touchpoints.
A model for the simulation of orientational effects in straight and bent periodic atomic structures is presented. The continuum potential approximation has been adopted. The model allows the ...manipulation of particle trajectories by means of straight and bent crystals and the scaling of the cross sections of hadronic and electromagnetic processes for channeled particles. Based on such a model, an extension of the Geant4 toolkit has been developed. The code has been validated against data from channeling experiments carried out at CERN.
Genetic and environmental factors that might affect gestation length (GL) were investigated. Data included information from >11million parturitions from 1999 through 2006 for 7 US dairy breeds. ...Effects examined were year, herd-year, month, and age within parity of conception; parturition code (sex and multiple-birth status); lactation length and standardized milk yield of cow; service sire; cow sire; and cow. All effects were fixed except for service sire, cow sire, and cow. Mean GL for heifers and cows, respectively, were 277.8 and 279.4 d for Holsteins, 278.4 and 280.0 d for Jerseys, 279.3 and 281.1 d for Milking Shorthorns, 281.6 and 281.7 d for Ayrshires, 284.8 and 285.7 d for Guernseys, and 287.2 and 287.5 d for Brown Swiss. Estimated standard deviations of GL were greatly affected by data restrictions but generally were approximately 5 to 6 d. Year effects on GL were extremely small, but month effects were moderate. For Holstein cows, GL was 2.0 d shorter for October conceptions than for January and February conceptions; 4.7 and 5.6 d shorter for multiple births of the same sex than for single-birth females and males, respectively; 0.8 d longer for lactations of ≤250 d than for lactations of ≥501 d; and 0.6 d shorter for standardized yield of ≤8,000kg than for yield of ≥14,001kg. Estimates for GL heritability from parities 2 to 5 were 33 to 36% for service sire and 7 to 12% for cow sire; corresponding estimates from parity 1 were 46 to 47% and 10 to 12%. Estimates of genetic correlations between effects of service sire and cow sire on GL were 0.70 to 0.85 for Brown Swiss, Holsteins, and Jerseys, which indicates that those traits likely are controlled by many of the same genes and can be used to evaluate each other. More accurate prediction of calving dates can help dairy producers to meet management requirements of pregnant animals and to administer better health care during high-risk phases of animals’ lives. However, intentional selection for either shorter or longer GL is not recommended without consideration of its possible effect on other dependent traits (e.g., calving ease and stillbirth).
Efforts to develop new antiviral chemotherapeutic approaches are focusing on compounds that target either influenza virus replication itself or host factor(s) that are critical to influenza ...replication. Host protease mediated influenza hemagglutinin (HA) cleavage is critical for activation of virus infectivity and as such is a chemotherapeutic target. Influenza pathogenesis involves a “vicious cycle” in which host proteases activate progeny virus which in turn amplifies replication and stimulates further protease activities which may be detrimental to the infected host. Aprotinin, a 58 amino acid polypeptide purified from bovine lung that is one of a family of host-targeted antivirals that inhibit serine proteases responsible for influenza virus activation. This drug and similar agents, such as leupeptin and camostat, suppress virus HA cleavage and limit reproduction of human and avian influenza viruses with a single arginine in the HA cleavage site. Site-directed structural modifications of aprotinin are possible to increase its intracellular targeting of cleavage of highly virulent H5 and H7 hemagglutinins possessing multi-arginine/lysine cleavage site. An additional mechanism of action for serine protease inhibitors is to target a number of host mediators of inflammation and down regulate their levels in virus-infected hosts. Aprotinin is a generic drug approved for intravenous use in humans to treat pancreatitis and limit post-operative bleeding. As an antiinfluenzal compound, aprotinin might be delivered by two routes: (i) a small-particle aerosol has been approved in Russia for local respiratory application in mild-to-moderate influenza and (ii) a proposed intravenous administration for severe influenza to provide both an antiviral effect and a decrease in systemic pathology and inflammation.
•The High Temperature Gas-Cooled Reactor is a relatively mature technology; deployable within a decade.•US Department of Energy sponsorship of HTGR technology research and development is resulting in ...the retirement of significant risks confronting deployment.•Extensive testing confirms that modern TRISO and graphite grades meet designer requirements.•Alloy 617 has been approved by the ASME for nuclear construction up to 425 °C.•Design and high fidelity fuel core analysis tools are being developed and benchmarked.•Significant gains have been made in the advanced reactor regulatory framework.
The modular high temperature reactor is a leading candidate for near-term deployment of an advanced reactor concept. The US Department of Energy supports the development of high temperature reactors through qualification of fuels, materials, and analysis methods that exploit the capabilities of the national laboratories (mainly Idaho, Oak Ridge, and Argonne) to generate the fundamental fuel, material, and core behavior data needed to support design and licensing efforts by vendors. Industrial vendors of high temperature reactor concepts provide input to the R&D program and engage in the design of the systems, structures, and components that are unique to their designs. Although there is considerable variation in the plant designs being developed, they all exploit the properties and behavior of the TRISO fuel, material, and analysis methods being tested in the DOE qualification programs. This paper summarizes the goals and recent progress of the Department of Energy’s Gas-Cooled Reactor research and development campaign and how it supports a wide variety of industrial efforts to deploy high temperature reactors to serve modern energy markets.
Classical nucleation theory teaches the idea that molecular clusters form and grow in solution and that depending on prevailing conditions there is a chance for some to grow large enough to overcome ...the interfacial energy penalty and become mature crystals. However, from such a kinetic analysis, nothing is learnt of the nature of the composition or the molecular packing in such clusters. As a means of addressing this shortcoming consideration has, in the past, been given to the idea that in certain systems crystallography may offer additional, structural, insights. From this approach the notions of ‘nucleation pathway’ or ‘nucleation transition state’ have become useful concepts around which to formulate hypotheses as to how clusters may yield specific molecular packing, resulting for example, in the observation of crystal polymorphs. Here we offer an in-depth crystallographic analysis related to the nucleation of the α and β polymorphs of para-aminobenzoic acid in an attempt to reveal the pathways leading to the two forms. Using a combination of CSD analyses, crystal structure prediction and targeted crystallizations we explore plausible solution pathways to these polymorphs and discuss our results in the light of known kinetic data for the nucleation and growth of this material.
Survival rates and productive herd life were examined for 13.8million US dairy cows that calved from January 1, 1980, through March 2, 2005. Cows that left the herd for dairy purposes or were from ...herds that discontinued Dairy Herd Improvement testing were excluded from any calculations to prevent underestimation of population longevity. Mean lactation length for cows without subsequently recorded lactations ranged from 205 to 235 d across breed–parity subsets and were 4 to 29 d longer for parities 2 through 7 than for parity 1. Mean survival rates were 73% to parity 2; 50% to parity 3; 32% to parity 4; and 19, 10, 5, and 2% to parities 5 through 8, respectively. The mean number of parities for Holsteins declined from 3.2 for those first calving in 1980 to 2.8 for those first calving in 1994. Mean numbers of parities for other breeds first calving in 1994 were 2.9 for Ayrshires and Brown Swiss, 2.4 for Guernseys, and 3.2 for Jerseys. Breed means for productive herd life (through parity 8) ranged from 28 to 36 mo. All regressions of mean number of parities or mean productive herd life on year were negative. The trend for decline of many of those indicators of longevity slowed or ended after the early 1990s. Between 31 (Jersey) and 39% (Guernsey) of herds were made up of first-calf heifers.
We present a broad comparative assessment of nested subsets in species composition among ecological communities. We assembled presence-absence data from a broad range of taxa, geographic regions, and ...spatial scales; and subjected this collection of datasets to common analyses, including a variety of metrics for measuring nestedness and null hypotheses against which to evaluate them. Here we identify ecological patterns in the prevalence and strength of nested subset structure, and assess differences and biases among the available methodologies. In all, we compiled 279 presence-absence matrices, of which 163 do not overlap in their coverage of species and sites. The survey includes studies on vertebrates, arthropods, mollusks, plants, and other taxa; from north temperate, tropical, and south temperate latitudes. Our results were as follows. Statistically significant nestedness was common. Assemblages from landbridge archipelagos were strongly nested, and immigration experiments were least nested. This adds further empirical support to the hypothesis that extinction plays a major role in producing nested structure. Nestedness was positively correlated with the ratio of the areas of the largest and smallest sites, suggesting that the range in area of sites affects nestedness. Taxonomic differences in nestedness were weak. Higher taxonomic levels showed stronger nesting than their constituent lower taxa. We observed no effect of distance of isolation on nestedness; nor any effects of latitude. With regard to methodology, the metrics Nc and Ut yielded similar results, although Nc proved slightly more flexible in use, and deals differently with tied sites. Similarities also exist in the behavior of N0 ("N") and Up, and between N1 and Ua. Standardized nestedness metrics were mostly insensitive to matrix size, and were useful in comparative analyses among presence-absence matrices. Most metrics were affected by the proportion of presences in the matrix. All analyses of nestedness, therefore, should test for bias due to matrix fill. We suggest that the factors controlling nested subset structure can be thought of as four filters that species pass to occur at a site: a sampling filter, a distance filter, a habitat filter, and an area filter -- and three constraints on community homogeneity: evolutionary history, recent history, and spatial variation in the environment. The scale of examination can also have important effects on the degree of nestedness observed.
Abiraterone acetate and Enzalutamide are novel anti-androgens that are key treatments to improve both progression-free survival and overall survival in patients with metastatic castration-resistant ...prostate cancer. In this study, we aimed to determine whether combinations of AR inhibitors with radiation are additive or synergistic, and investigated the underlying mechanisms governing this. This study also aimed to compare and investigate a biological rationale for the selection of Abiraterone versus Enzalutamide in combination with radiotherapy as currently selection is based on consideration of side effect profiles and clinical experience. We report that AR suppression with Enzalutamide produces a synergistic effect only in AR-sensitive prostate models. In contrast, Abiraterone displays synergistic effects in combination with radiation regardless of AR status, alluding to potential alternative mechanisms of action. The underlying mechanisms governing this AR-based synergy are based on the reduction of key AR linked DNA repair pathways such as NHEJ and HR, with changes in HR potentially the result of changes in cell cycle distribution, with these reductions ultimately resulting in increased cell death. These changes were also shown to be conserved in combination with radiation, with AR suppression 24 hours before radiation leading to the most significant differences. Comparison between Abiraterone and Enzalutamide highlighted Abiraterone from a mechanistic standpoint as being superior to Abiraterone for all endpoints measured. Therefore, this provides a potential rationale for the selection of Abiraterone over Enzalutamide.
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