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The aerosol composition of electronic cigarettes (ECs) suggests that exposure to toxicants during use is greatly reduced compared to exposure from combustible cigarettes (CCs). This randomized, parallel-group, clinical study enrolled smokers to switch to Vuse Solo (VS) Digital Vapor Cigarettes (Original or Menthol) or Nicorette 4 mg nicotine gum (NG) in a controlled setting. Subjects who smoked CCs ad libitum for 2 days during a baseline period were then randomized to ad libitum use of either VS or NG for 5 days. Biomarkers of 23 toxicants were measured in 24-hour urine samples and blood collected at baseline and following product switch. A total of 153 subjects completed the study. Total nicotine equivalents decreased in all groups, but higher levels were observed in the VS groups compared to the NG groups, with decreases of 38% and 60%-67%, respectively. All other biomarkers were significantly decreased in subjects switched to VS, and the magnitude of biomarker decreases was similar to subjects switched to NG. Decreases ranged from 30% to greater than 85% for constituents such as benzene and acrylonitrile. These results indicate that exposure to toxicants when using VS is significantly reduced compared to CC smoking, and these reductions are similar to those observed with use of NG. Although statistically significantly decreased, nicotine exposure is maintained closer to CC smoking with VS use compared to NG use. This research suggests that use of VS exposes consumers to fewer and lower levels of smoke toxicants than CCs while still providing nicotine to the consumer. This is the first study to report changes in nicotine delivery and biomarkers of tobacco exposure following a short-term product switch from CCs to either an EC or NG in a controlled environment. The study shows that nicotine exposure decreased in both groups but was maintained closer to CC smoking with the EC groups. Biomarkers of tobacco combustion decreased to similar levels in both EC and gum groups.

Purpose - The objective of this article is to investigate the binding of several lactones to soya protein isolate and soya protein under different conditions and, particularly, the extent of binding of the lactones γ-9, γ-10, δ-10 and δ-11, in different concentrations as well as the effect of various parameters on their binding ability.Design methodology approach - Capillary column gas chromatography was used for the determination of lactones and the manual system was used for taking samples and for headspace analysis. Infrared spectroscopy was used for confirmation and investigation.Findings - The percentage of binding of lactones γ-9, γ-10, δ-10, δ-11 on the soya protein is almost the same (about 33-34 per cent). According to the Klotz equation, the bound ligand concentration was calculating as the number of moles of ligand bound per mole of protein. The results varied, but were similar. Specific experiments in water system with soya protein isolate (1 per cent) showed that the time taken for lactones γ-10 and δ-11 to reach equilibrium, the factors of temperature and pH affected the percentage of lactone bound.Research limitations implications - The amount of added lactone in products containing soya protein isolate should be investigated by using panel tests to confirm the improvement of flavour.Practical implications - Flavour binding of lactones can be used to provide some foods with the required flavour impression by adding lactones to a bland soy protein base.Originality value - The flavour binding of lactones, which was investigated in the present paper, has not been adequately investigated in previous scientific research and the effects of the factors that influence their binding are very important.

Dietary factors affecting zinc bioavailability were evaluated according to their relative distribution in the individual daily meals making up the basic diet of 17 institutionalized, mentally handicapped adult women. Mean intake values of zinc, phytate, nonstarch polysaccharides (NSP), calcium, protein, and energy were calculated from a dietary survey of 7 consecutive days, which also served to obtain values for the two zinc bioavailability predictor formulas, phytate/Zn millimolar ratio and [Ca] [phytate]/[Zn][energy] ratio. Mean daily zinc intake was 8.5 ±1.8 mg, with noon and evening meals accounting for the highest contribution to this value (45% and 35%, respectively), whereas breakfast meals' contribution was 16%. The mean protein intake was 55 ±13 g, with noon and evening meals being the major contributors to total daily intake (42% and 38%, respectively). Breakfast meals accounted for 77% of daily phytate intake, giving a respective phytate/Zn millimolar ratio of 20.4 ±7.6 and a [Ca][phytate]/[Zn][energy] ratio of 336 ±127 mmol/Mcal. Values for both ratios based on noon and evening meals were negligible in comparison. The mean daily NSP intake was 9.8 ±4.2 g, with 53% of total daily intake supplied from breakfast meals, whereas noon and evening meals accounted for 30% and 14%, respectively. The results, while suggesting that zinc bioavailability is unlikely to be adversely affected, indicated that dietary fiber intake levels are probably inadequate, particularly in view of the nonambulant condition and low physical activity prevalent in such individuals, who may, as a consequence, be susceptible to health disorders associated with impaired bowel function and constipation.[PUBLICATION ABSTRACT]

In this paper, we demonstrate an application of the Transformer self-attention mechanism in the context of materials science. Our network, the Compositionally Restricted Attention-Based network (CrabNet), explores the area of structure-agnostic materials property predictions when only a chemical formula is provided. Our results show that CrabNet’s performance matches or exceeds current best-practice methods on nearly all of 28 total benchmark datasets. We also demonstrate how CrabNet’s architecture lends itself towards model interpretability by showing different visualization approaches that are made possible by its design. We feel confident that CrabNet and its attention-based framework will be of keen interest to future materials informatics researchers.

During the Early Bronze Age, populations of the western Eurasian steppe expanded across an immense area of northern Eurasia. Combined archaeological and genetic evidence supports widespread Early Bronze Age population movements out of the Pontic–Caspian steppe that resulted in gene flow across vast distances, linking populations of Yamnaya pastoralists in Scandinavia with pastoral populations (known as the Afanasievo) far to the east in the Altai Mountains 1 , 2 and Mongolia 3 . Although some models hold that this expansion was the outcome of a newly mobile pastoral economy characterized by horse traction, bulk wagon transport 4 – 6 and regular dietary dependence on meat and milk 5 , hard evidence for these economic features has not been found. Here we draw on proteomic analysis of dental calculus from individuals from the western Eurasian steppe to demonstrate a major transition in dairying at the start of the Bronze Age. The rapid onset of ubiquitous dairying at a point in time when steppe populations are known to have begun dispersing offers critical insight into a key catalyst of steppe mobility. The identification of horse milk proteins also indicates horse domestication by the Early Bronze Age, which provides support for its role in steppe dispersals. Our results point to a potential epicentre for horse domestication in the Pontic–Caspian steppe by the third millennium bc , and offer strong support for the notion that the novel exploitation of secondary animal products was a key driver of the expansions of Eurasian steppe pastoralists by the Early Bronze Age. Analysis of ancient proteins suggests that Early Bronze Age dairying and horse domestication catalysed eastern Yamnaya migrations.

Research and practice in critical care medicine have long been defined by syndromes, which, despite being clinically recognizable entities, are, in fact, loose amalgams of heterogeneous states that may respond differently to therapy. Mounting translational evidence—supported by research on respiratory failure due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection—suggests that the current syndrome-based framework of critical illness should be reconsidered. Here we discuss recent findings from basic science and clinical research in critical care and explore how these might inform a new conceptual model of critical illness. De-emphasizing syndromes, we focus on the underlying biological changes that underpin critical illness states and that may be amenable to treatment. We hypothesize that such an approach will accelerate critical care research, leading to a richer understanding of the pathobiology of critical illness and of the key determinants of patient outcomes. This, in turn, will support the design of more effective clinical trials and inform a more precise and more effective practice at the bedside.The authors propose a new conceptual model of critical illness that moves away from the current syndrome-based framework in favor of more precise biological descriptors—spurred by mounting translational evidence and insights from Coronavirus Disease 2019 (COVID-19) research.

Interferon-inducible GTPases of the Immunity Related GTPase (IRG) and Guanylate Binding Protein (GBP) families provide resistance to intracellular pathogenic microbes. IRGs and GBPs stably associate with pathogen-containing vacuoles (PVs) and elicit immune pathways directed at the targeted vacuoles. Targeting of Interferon-inducible GTPases to PVs requires the formation of higher-order protein oligomers, a process negatively regulated by a subclass of IRG proteins called IRGMs. We found that the paralogous IRGM proteins Irgm1 and Irgm3 fail to robustly associate with \"non-self\" PVs containing either the bacterial pathogen Chlamydia trachomatis or the protozoan pathogen Toxoplasma gondii. Instead, Irgm1 and Irgm3 reside on \"self\" organelles including lipid droplets (LDs). Whereas IRGM-positive LDs are guarded against the stable association with other IRGs and GBPs, we demonstrate that IRGM-stripped LDs become high affinity binding substrates for IRG and GBP proteins. These data reveal that intracellular immune recognition of organelle-like structures by IRG and GBP proteins is partly dictated by the missing of \"self\" IRGM proteins from these structures.

Cassava ( Manihot esculenta ) is a starchy root crop that supports over a billion people in tropical and subtropical regions of the world. This staple, however, produces the neurotoxin cyanide and requires processing for safe consumption. Excessive consumption of insufficiently processed cassava, in combination with protein-poor diets, can have neurodegenerative impacts. This problem is further exacerbated by drought conditions which increase this toxin in the plant. To reduce cyanide levels in cassava, we used CRISPR-mediated mutagenesis to disrupt the cytochrome P450 genes CYP79D1 and CYP79D2 whose protein products catalyze the first step in cyanogenic glucoside biosynthesis. Knockout of both genes eliminated cyanide in leaves and storage roots of cassava accession 60444; the West African, farmer-preferred cultivar TME 419; and the improved variety TMS 91/02324. Although knockout of CYP79D2 alone resulted in significant reduction of cyanide, mutagenesis of CYP79D1 did not, indicating these paralogs have diverged in their function. The congruence of results across accessions indicates that our approach could readily be extended to other preferred or improved cultivars. This work demonstrates cassava genome editing for enhanced food safety and reduced processing burden, against the backdrop of a changing climate.