A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2004; you can also visit the original URL.
The file type is
Lecture Notes in Computer Science
PRCS is an attempt to provide a version-control system for collections of les with a simple operational model, a clean user interface, and high performance. PRCS is characterized by the use of project description les to input most commands, instead of a point-and-click or a line-oriented interface. It employs optimistic concurrency control and encourages operations on the entire project rather than individual les. Although its current implementation uses RCS in the back-end, the interfacedoi:10.1007/bfb0053876 fatcat:wc4wgpy4wnhlvkcvhspl6cii6e
more »... tely hides its presence. PRCS is free. This paper describes the advantages and disadvantages of our approach, and discusses implementation issues.
We describe an approach for using Java as a basis for a design and specification language for embedded systems and use our JavaTime system to illustrate many of the aspects of the approach. Java is a pragmatic choice for several reasons. Since it is a member of the C "family" of languages, it is familiar to designers. Unlike C and C++, it has standard support for concurrency. Its treatment of arrays permits better static and dynamic error checking than is conveniently feasible in C and C++.doi:10.1007/978-94-011-4698-2_11 fatcat:czxjdsuimjduvaaxfn2o5ro5ou
more »... lly, while Java's expressive power is comparable to C++, it is a much simpler language, which greatly eases the task of introducing additional analysis into compilers. Successive, formal refinement is an approach we have developed for specification of embedded systems using a general-purpose programming language. Systems are formally modeled as Abstractable Reactive systems, and Java is used as the design input language. A policy-of-use is applied to Java, in the form of language usage restrictions and class-library extensions, to ensure consistency with the formal model. A process of incremental, userguided program transformation is used to refine a Java program until it is consistent with the policy-of-use. This approach allows systems design to begin with the flexibility of a general-purpose language, followed by gradual refinement into a more restricted form necessary for specification.
Alchemical free energy methods with molecular mechanics (MM) force fields are now widely used in the prioritization of small molecules for synthesis in structure-enabled drug discovery projects because of their ability to deliver 1-2 kcal/mol accuracy in well-behaved protein-ligand systems. Surpassing this accuracy limit would significantly reduce the number of compounds that must be synthesized to achieve desired potencies and selectivities in drug design campaigns. However, MM force fieldsdoi:10.1101/2020.07.29.227959 fatcat:c26oln3hj5ba3huc5gpjf2vqve
more »... e a challenge to achieving higher accuracy due to their inability to capture the intricate atomic interactions of the physical systems they model. A major limitation is the accuracy with which ligand intramolecular energetics---especially torsions---can be modeled, as poor modeling of torsional profiles and coupling with other valence degrees of freedom can have a significant impact on binding free energies. Here, we demonstrate how a new generation of hybrid machine learning / molecular mechanics (ML/MM) potentials can deliver significant accuracy improvements in modeling protein-ligand binding affinities. Using a nonequilibrium perturbation approach, we can correct a standard, GPU-accelerated MM alchemical free energy calculation in a simple post-processing step to efficiently recover ML/MM free energies and deliver a significant accuracy improvement with small additional computational effort. To demonstrate the utility of ML/MM free energy calculations, we apply this approach to a benchmark system for predicting kinase:inhibitor binding affinities---a congeneric ligand series for non-receptor tyrosine kinase TYK2 (Tyk2)---wherein state-of-the-art MM free energy calculations (with OPLS2.1) achieve inaccuracies of 0.93±0.12 kcal/mol in predicting absolute binding free energies. Applying an ML/MM hybrid potential based on the ANI2x ML model and AMBER14SB/TIP3P with the OpenFF 1.0.0 ("Parsley") small molecule force field as an MM model, we show that it is possible to significantly reduce the error in absolute binding free energies from 0.97 [95% CI: 0.68, 1.21] kcal/mol (MM) to 0.47 [95% CI: 0.31, 0.63] kcal/mol (ML/MM).
25 We hypothesized that acute dietary nitrate (NO3 -) provided as concentrated beetroot juice 26 supplement would improve endurance running performance of well-trained runners in 27 normobaric hypoxia. Ten male runners (mean (SD): sea level V O2max 66 (7) mL . kg -1. min -1 , 10 28 km personal best 36 (2) min) completed incremental exercise to exhaustion at 4000 m and a 10 29 km treadmill time trial at 2500 m simulated altitude on separate days, after supplementation 30 with ~7 mmol NO3and adoi:10.1139/apnm-2014-0470 pmid:25942474 fatcat:l35ntipt7bbe5gkhjar45ngjga
more »... cebo, 2.5 h before exercise. Oxygen cost, arterial oxygen 31 saturation, heart rate and ratings of perceived exertion (RPE) were determined during the 32 incremental exercise test. Differences between treatments were determined using means [95% 33 confidence intervals], paired sample t-tests and a probability of individual response analysis. 34 NO3supplementation increased plasma [nitrite] (NO3 -, 473 (226) nM vs. placebo, 61 (37) nM, 35 P < 0.001) but did not alter time to exhaustion during the incremental test (NO3 -, 402 (80) s vs. 36 placebo 393 (62) s, P = 0.5) or time to complete the 10 km time trial (NO3 -, 2862 (233) s vs. 37 placebo, 2874 (265) s, P = 0.6). Further, no practically meaningful beneficial effect on time 38 trial performance was observed as the 11 [-60 to 38] s improvement was less than the a priori 39 determined minimum important difference (51 s), and only three runners experienced a 'likely, 40 probable' performance improvement. NO3also did not alter oxygen cost, arterial oxygen 41 saturation, heart rate or RPE. Acute dietary NO3supplementation did not consistently enhance 42 running performance of well-trained athletes in normobaric hypoxia. 43 44 KEY WORDS: 45 Nitrate, nitrite, nitric oxide, exercise, hypoxia. 46
Successive, formal refinement is a new approach for specification of embedded systems using a general-purpose programming language. Systems are formally modeled as Abstractable Synchronous Reactive systems, and Java is used as the design input language. A policy of use is applied to Java, in the form of language usage restrictions and class-library extensions, to ensure consistency with the formal model. A process of incremental, user-guided program transformation is used to refine a Javadoi:10.1145/277044.277058 dblp:conf/dac/YoungMSTHN98 fatcat:gtciq6vy2rbkfkfnaheunp5npu
more »... m until it is consistent with the policy of use. The final product is a system specification possessing the properties of the formal model, including deterministic behavior, bounded memory usage, and bounded execution time. This approach allows systems design to begin with the flexibility of a general-purpose language, followed by gradual refinement into a more restricted form necessary for specification.
Objective-The presence of psychosis in Alzheimer disease denotes an Alzheimer disease phenotype with more rapid cognitive deterioration than that which is present in Alzheimer disease without psychosis. Discovery of novel pharmacotherapies which engage therapeutic targets for prevention or treatment of Alzheimer disease with psychosis would benefit from identifying the neurobiology of resilience to psychosis in Alzheimer disease. Method-Quantitative immunohistochemistry was used to measuredoi:10.1176/appi.ajp.2018.17080858 pmid:30021459 pmcid:PMC6167138 fatcat:lyy7qt2iozb3toz4qrshrhhuje
more »... ple neuropathologies in dorsolateral prefrontal cortex from early and middle-stage Alzheimer disease subjects who differed based on psychosis status. Synaptic proteins were quantified by liquid-chromatography/ mass spectrometry in gray matter homogenates from these subjects and from neuropathologically unaffected subjects. The synaptic proteome was similarly evaluated in cortical gray matter homogenate and postsynaptic density fractions from an APPswe/PSEN1dE9 mouse model of For questions and correspondence please contact: Robert A. Sweet, M.D.; Mail: Biomedical Science Tower,
Site description The field experiment was conducted in 2013 on a Rhodic Ferralsol (described in detail in Macdonald et al. 2014 ) at the Wollongbar Primary Industries Institute, NSW, Australia (28.49.34 ...doi:10.1007/s42773-019-00005-6 fatcat:qv34e2osvzcidp7s3pea62iv3y
Two studies determined the interactions of urea inclusion to a dried distillers grains plus solubles (DDGS; 29.4% CP, 5.48% ether extract) supplement fed at 2 amounts and 2 frequencies to steers consuming ad libitum Smooth Bromegrass hay (6.8% CP). In Exp. 1, 120 (247 kg; SD = 20) steers were fed individually for 84 d with treatments arranged in a 2 x 2 x 2 factorial. Supplement was fed every day (D) or 3x/week (ALT), amount of supplement fed was 6.36 kg/week (LO) or 12.73 kg/week (HI) anddoi:10.1093/jas/skac064.153 fatcat:d3a34fxsljdrvnqgum5sjxhgea
more »... ined either no urea (-U) or 1.3% urea (+U). In Exp. 2, 8 ruminally cannulated steers (310 kg; SD = 25) were used in an 8 x 6 row-column design with 8 steers and 6, 14-d periods. Treatment design was the same as Exp. 1, except that supplement was fed at a rate of 0.4% (LO) or 0.8% of BW (HI) and supplement was fed either daily (D) or every other day (ALT). In Exp. 1, ADG was 0.30 kg/d greater, and hay DMI was reduced by 0.39 kg/d for HI vs. LO (P < 0.01). Hay DMI was reduced by 0.54 kg/d for ALT vs. D (P < 0.01). In Exp. 2, hay DMI was also reduced HI vs. LO (P < 0.01). Rumen pH was decreased on the day of feeding for steers on ALT (P < 0.01) and was reduced for steers fed HI vs. LO. A reduction in in situ NDF disappearance was observed on the day ALT received supplement between HI and LO (P < 0.01). However, there was no difference between NDF digestibility between D and ALT (P > 0.05). Urea had no effect on digestion or ADG, suggesting RDP was not deficient. Dried distillers grains can be supplemented infrequently without reducing animal performance.
Both allergic and non-allergic asthma phenotypes are thought to vary by specific housing and other indoor environmental conditions. This study evaluated risk factors for allergic asthma phenotypes in First Nation children, an understudied Canadian population with recognized increased respiratory morbidity. We conducted a cross-sectional survey with a clinical component to assess the respiratory health of 351 school-age children living on two rural reserve communities. Asthma was defined asdoi:10.3390/children7050038 pmid:32349273 pmcid:PMC7278566 fatcat:gkqibbg4xbdazowfhs52vmdtku
more »... tal report of physician diagnosed asthma or a report of wheeze in the past 12 months. Atopy was determined by a ≥ 3-mm wheal response to any of six respiratory allergens upon skin prick testing (SPT). Important domestic and personal characteristics evaluated included damp housing conditions, household heating, respiratory infections and passive smoking exposure. Asthma and atopy prevalence were 17.4% and 17.1%, respectively. Of those with asthma, 21.1% were atopic. We performed multivariate multinomial logistic regression modelling with three outcomes: non-atopic asthma, atopic asthma and no asthma for 280 children who underwent SPT. After adjusting for potential confounders, children with atopic asthma were more likely to be obese and to live in homes with either damage due to dampness (p < 0.05) or signs of mildew/mold (p = 0.06). Both natural gas home heating and a history of respiratory related infections were associated with non-atopic asthma (p < 0.01). Domestic risk factors for asthma appear to vary by atopic status in First Nations children. Determining asthma phenotypes could be useful in environmental management of asthma in this population.
Despite expanding interest in ecosystem service research over the past three decades, in-depth understanding of the contribution of forests and trees to food production and livelihoods remains limited. This review synthesizes the current evidence base examining the contribution of forest and trees to agricultural production and livelihoods in the tropics, where production often occurs within complex land use mosaics that are increasingly subjected to concomitant climatic and anthropogenicdoi:10.1016/j.forpol.2017.01.012 fatcat:7dvfdycc4rfu3mkkjmhkiaw7nu
more »... res. Using systematic review methodology we found 74 studies investigating the effect of forest or tree-based ecosystem service provision on a range of outcomes such as crop yield, biomass, soil fertility, and income. Our findings suggest that when incorporating forests and trees within an appropriate and contextualized natural resource management strategy, there is potential to maintain, and in some cases, enhance yields comparable to solely monoculture systems. Furthermore, this review has illustrated the potential of achieving net livelihood gains through integrating trees on farms, providing rural farmers with additional income sources, and greater resilience strategies to adapt to market or climatic shocks. However, we also identify significant gaps in the current knowledge that demonstrate a need for larger-scale, longer term research to better understand the contribution of forest and trees within the broader landscape and their associated impacts on livelihoods and food production systems.
doi:10.1083/jcb.201004104 pmid:20513764 pmcid:PMC2878938 fatcat:ixmveesicvc6bfolxuwf32eftu
Due to the recent domestication of peanut from a single tetraploidization event, relatively little genetic diversity underlies the extensive morphological and agronomic diversity in peanut cultivars today. To broaden the genetic variation in future breeding programs, it is necessary to characterize germplasm accessions for new sources of variation and to leverage the power of genome-wide association studies (GWAS) to discover markers associated with traits of interest. We report an analysis ofdoi:10.1186/s12864-019-5824-9 fatcat:f5ri425ry5aztbs7i5lx7nhm6u
more »... inkage disequilibrium (LD), population structure, and genetic diversity, and examine the ability of GWA to infer marker-trait associations in the U.S. peanut mini core collection genotyped with a 58 K SNP array. Results: LD persists over long distances in the collection, decaying to r 2 = half decay distance at 3.78 Mb. Structure within the collection is best explained when separated into four or five groups (K = 4 and K = 5). At K = 4 and 5, accessions loosely clustered according to market type and subspecies, though with numerous exceptions. Out of 107 accessions, 43 clustered in correspondence to the main market type subgroup whereas 34 did not. The remaining 30 accessions had either missing taxonomic classification or were classified as mixed. Phylogenetic network analysis also clustered accessions into approximately five groups based on their genotypes, with loose correspondence to subspecies and market type. Genome wide association analysis was performed on these lines for 12 seed composition and quality traits. Significant marker associations were identified for arachidic and behenic fatty acid compositions, which despite having low bioavailability in peanut, have been reported to raise cholesterol levels in humans. Other traits such as blanchability showed consistent associations in multiple tests, with plausible candidate genes. Conclusions: Based on GWA, population structure as well as additional simulation results, we find that the primary limitations of this collection for GWAS are a small collection size, significant remaining structure/genetic similarity and long LD blocks that limit the resolution of association mapping. These results can be used to improve GWAS in peanut in future studiesfor example, by increasing the size and reducing structure in the collections used for GWAS.
& Aims-Clostridium difficile (C.difficile) is the leading cause of nosocomial infectious diarrhea. Increasing incidence, antibiotic resistance and more virulent strains have dramatically increased the number of C.difficile-related deaths worldwide. The innate host response mechanisms to C.difficile are not resolved; however, we hypothesize that hypoxiainducible factor (HIF-1) plays an innate protective role in C.difficile colitis. Thus, we assessed the impact of C.difficile toxins on thedoi:10.1053/j.gastro.2010.03.045 pmid:20347817 pmcid:PMC3063899 fatcat:aotj3mobynd6xg35maywxde2x4
more »... ion of HIF-1 and evaluated the role of HIF-1α in C.difficile-mediated injury/inflammation. Methods- In vitro studies assessed HIF-1α mRNA, protein levels and DNA binding events in human mucosal biopsies and Caco-2 cells exposed to C.difficile toxins. In vivo studies employed the murine ileal loop model of C.difficile toxin-induced intestinal injury. Mice with targeted deletion of HIF-1α in the intestinal epithelium were used to assess the impact of HIF-1α signaling in response to C.difficile toxin.
In situ voltammetry used for chemical analysis of a variety of freshwater and marine habitats for Fe(ii) oxidizing bacteria.doi:10.1039/c4em00073k pmid:24924809 fatcat:m36gsrge2nfgtj2h53xry3tvlm
« Previous Showing results 1 — 15 out of 1,135 results