137 research outputs found
Opportunities for human factors in machine learning
IntroductionThe field of machine learning and its subfield of deep learning have grown rapidly in recent years. With the speed of advancement, it is nearly impossible for data scientists to maintain expert knowledge of cutting-edge techniques. This study applies human factors methods to the field of machine learning to address these difficulties.MethodsUsing semi-structured interviews with data scientists at a National Laboratory, we sought to understand the process used when working with machine learning models, the challenges encountered, and the ways that human factors might contribute to addressing those challenges.ResultsResults of the interviews were analyzed to create a generalization of the process of working with machine learning models. Issues encountered during each process step are described.DiscussionRecommendations and areas for collaboration between data scientists and human factors experts are provided, with the goal of creating better tools, knowledge, and guidance for machine learning scientists
Isolation of Bacillus producing Chitinase from Soil: Production and Purification of Chito-oligosaccharides from Chitin Extracted from Fresh Water Crustaceans and Antimicrobial Activity of Chitinase
In the present investigation Bacillus sp. strain was isolated and screened from the red soil collected from Doiwala region of Dehradun (U.K), India. Serial dilution technique was adopted to isolate the organism and was screened for its chitinolytic activity. The biochemical tests were performed to prove its validity. The microorganism was also screened by inoculating a loop full of the isolated strain in basic cresol red dye and incubated for about 18- 24 h. The conversion of colour of the red dye into purple (pH, 6.5- 8.8) was taken as an indication for the presence of Bacillus sp. Amylase production by the organism was also screened by introduction of iodine in the broth/agar culture having starch. The broth/agar medium having starch but no bacterial strain was used as the control. The disappearance of color confirmed the presence of Bacillus strain producing amylase which degrades the starch. The chitinous wastes were collected from fresh water crustaceans viz. fresh water crab (Potamon sp.) and fresh water prawn (Palaemon sp.) and the chitin extracted was used as the substrate for chitinase. The yield of chitin extracted from fresh water prawn (Palaemon sp.) was found to be comparatively higher than that of chitin extracted from fresh water crab (Potamon sp.). Standard colloidal chitin was used as the reference control. The enzyme activity of chitinase for degradation of chitin extracted from crab and prawn was compared. The results confirmed that chitinase activity for degradation of crab chitin was comparatively higher than that of degradation of prawn chitin. The enzyme activities were found to be 0.11 µg/ml/minute and 0.09 µg/ml/minute for degradation of crab and prawn chitin respectively. The antimicrobial activity of chitinase extracted was determined against the bacterial and fungal cultures. Potent antibacterial activity of chitinase was observed against the bacterial cultures but no antifungal activity was observed. The chitinase produced by the species was able to degrade the chitin and chito-oligosaccharides produced was separated by TLC and purified by HPLC
Circulating extracellular vesicles induce monocyte dysfunction and are associated with sepsis and high mortality in cirrhosis
BACKGROUND: Sepsis is common in cirrhosis and is often a result of immune dysregulation. Specific stimuli and pathways of inter-cellular communications between immune cells in cirrhosis and sepsis are incompletely understood. Immune cell-derived Extracellular Vesicles (EV) were studied to understand mechanisms of sepsis in cirrhosis. METHODS: Immune-cell derived EV were measured in cirrhosis patients [Child-Turcotte-Pugh (Child) score A, n=15; B n=16; C n=43 and Child-C with sepsis (n=38)], and healthy controls (HC, n=11). In-vitro and in-vivo functional relevance of EV in cirrhosis and associated sepsis was investigated. RESULTS: Monocyte, neutrophil and hematopoietic stem cells associated EV progressively increased with higher Child score (p0.3, p<0.001), which further increased in Child C sepsis than without sepsis(p<0.001); monocyte EV showing the highest association with disease stage [p=0.013; Odds ratio-4.14(1.34-12.42)]. A threshold level of monocyte EV of 53/µl predicted mortality in patients of Child C with sepsis [Odds ratio-6.2 (2.4-15.9), AUROC=0.76, p<0.01]. In vitro EV from cirrhotic with sepsis compared without sepsis, induced mobilization arrest in healthy monocytes within 4 hours (p=0.004), reduced basal oxygen consumption rate (p<0.001) and induced pro-inflammatory genes (p<0.05). The septic-EV on adoptive transfer to C57/BL6J mice, induced sepsis like condition within 24h with leukocytopenia (p=0.005), intrahepatic inflammation with increased CD11b+ cells (p=0.03) and bone marrow hyperplasia (p<0.01). CONCLUSION: Extracellular vesicles induce functional impairment in circulating monocytes and contribute to the development and perpetuation of sepsis. High levels of monocyte EV correlate with mortality and can help early stratification of sicker patients
Crystal engineering of HIV-1 reverse transcriptase for structure-based drug design
HIV-1 reverse transcriptase (RT) is a primary target for anti-AIDS drugs. Structures of HIV-1 RT, usually determined at ∼2.5–3.0 Å resolution, are important for understanding enzyme function and mechanisms of drug resistance in addition to being helpful in the design of RT inhibitors. Despite hundreds of attempts, it was not possible to obtain the structure of a complex of HIV-1 RT with TMC278, a nonnucleoside RT inhibitor (NNRTI) in advanced clinical trials. A systematic and iterative protein crystal engineering approach was developed to optimize RT for obtaining crystals in complexes with TMC278 and other NNRTIs that diffract X-rays to 1.8 Å resolution. Another form of engineered RT was optimized to produce a high-resolution apo-RT crystal form, reported here at 1.85 Å resolution, with a distinct RT conformation. Engineered RTs were mutagenized using a new, flexible and cost effective method called methylated overlap-extension ligation independent cloning. Our analysis suggests that reducing the solvent content, increasing lattice contacts, and stabilizing the internal low-energy conformations of RT are critical for the growth of crystals that diffract to high resolution. The new RTs enable rapid crystallization and yield high-resolution structures that are useful in designing/developing new anti-AIDS drugs
Mortality in dialysis patients may not be associated with ESA dose: a 2-year prospective observational study
Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials
Aims:
The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials.
Methods and Results:
Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594).
Conclusions:
GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation
Mineralogy and Cation Exchange Properties of Libby Vermiculite Separates as Affected by Particle-Size Reduction*
Preferential binding of fullerene and fullerenol with the N-terminal and middle regions of amyloid beta peptide: an in silico investigation
Vishal Pandya,1 Lokesh Baweja,1,2 Alok Dhawan1,2 1Division of Biological & Life Sciences, School of Arts & Sciences, (Formerly, Institute of Life Sciences), Ahmedabad University, Ahmedabad, Gujarat, 2Nanotherapeutics & Nanomaterial Toxicology Group, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow, Uttar Pradesh, India Abstract: Amyloid beta (Aβ) deposits are implicated in the pathogenesis of debilitating neurodegenerative disorders such as Alzheimer’s disease. In the present study, the interactions of carbon-based nanoparticles (NPs) such as fullerene and fullerenol having different surface chemistry with Aβ were investigated using molecular dynamics simulations and docking studies. A detailed analysis of docking results showed that in 68% of the Aβ conformations, fullerene and fullerenol showed interactions with the N-terminal region of the peptide. However, the high-affinity binding site (E=−48.31 kJ/mol) of fullerene resides in the hydrophobic middle region of the peptide, whereas fullerenol interacts favorably with the charged N-terminal region with a binding energy of −50.42 kJ/mol. The above differences in binding could be attributed to the surface chemistry of fullerene and fullerenol. Moreover, the N-terminal and middle regions of Aβ play an important role in Aβ aggregation. Therefore, the binding of fullerene and fullerenol could inhibit amyloid aggregation. This information will be helpful in designing NPs for targeting amyloid-related disorders. Keywords: fullerene, fullereno
Response of Corn to Small Amounts of Fertilizer Placed with the Seed: IV. Comparison of Dry and Liquid Forms 1
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