A road map for applied data sciences supporting sustainability in advanced manufacturing: the information quality dimensions

Abstract Data science is a multidisciplinary blend of data inference, algorithm development, and technology in order to solve analytically complex problems. Sustainability is a critical asset of a manufacturing enterprise. It enables a business to differentiate itself from competitors and to compete efficiently and effectively to the best of its ability. This paper is a review of data analytics, and how it supports advanced manufacturing with an emphasis on sustainability. The objective is to present a context for a roadmap for applied data science addressing such analytic challenges. We start with a general introduction to advanced manufacturing and trends in modern analytics tools and technology. We then list challenges of analytics supporting advanced manufacturing and sustainability aspects. The information quality (InfoQ) framework is proposed as a backbone to evaluate the analytics needed in advanced manufacturing. The eight InfoQ dimensions are: 1) Data Resolution, 2) Data Structure, 3) Data Integration, 4) Temporal Relevance, 5) Chronology of Data and Goal, 6) Generalizability, 7) Operationalization and 8) Communication. These dimensions provide a classification of advanced manufacturing analytics domains. The paper provides a roadmap for the development of applied analytic techniques supporting advanced manufacturing and sustainability. The objective is to motivate researchers, practitioners and industrialists to support such a roadmap

Quiescience as a mechanism for cyclical hypoxia and acidosis

Tumour tissue characteristically experiences fluctuations in substrate supply. This unstable microenvironment drives constitutive metabolic changes within cellular populations and, ultimately, leads to a more aggressive phenotype. Previously, variations in substrate levels were assumed to occur through oscillations in the hæmodynamics of nearby and distant blood vessels. In this paper we examine an alternative hypothesis, that cycles of metabolite concentrations are also driven by cycles of cellular quiescence and proliferation. Using a mathematical modelling approach, we show that the interdependence between cell cycle and the microenvironment will induce typical cycles with the period of order hours in tumour acidity and oxygenation. As a corollary, this means that the standard assumption of metabolites entering diffusive equilibrium around the tumour is not valid; instead temporal dynamics must be considered

Single-dose liposomal amphotericin B (AmBisome®) for the treatment of Visceral Leishmaniasis in East Africa: study protocol for a randomized controlled trial

BACKGROUND: AmBisome® is an efficacious, safe anti-leishmanial treatment. There is growing interest in its use, either as a single dose or in combination treatments. In East Africa, the minimum optimal single-dosage has not been identified. METHODS/DESIGN: An open-label, 2-arm, non-inferiority, multi-centre randomised controlled trial is being conducted to determine the optimal single-dose treatment with AmBisome®.Patients in the single-dose arm will receive one infusion on day 1, at a dose depending on body weight. For the first group of patients entered to the trial, the dose will be 7.5 mg/kg, but if this dose is found to be ineffective then in subsequent patient series the dose will be escalated progressively to 10, 12.5 and 15 mg/kg. Patients in the reference arm will receive a multi-dose regimen of AmBisome® (3 mg/kg/day on days 1-5, 14 and 21: total dose 21 mg/kg). Patients will be hospitalised for approximately one month after the start of treatment and then followed up at three and six months. The primary endpoint is the status of patients six months after treatment. A secondary endpoint is assessment at day 30. Treatment success is determined as the absence of parasites on microscopy samples taken from bone marrow, lymph node or splenic aspirates. Interim analyses to assess the comparative efficacy of the single dose are planned after recruitment of 20 and 40 patients per arm. The final non-inferiority analysis will include 120 patients per arm, to determine if the single-dose efficacy 6 months after treatment is not more than 10% inferior to the multi-dose. DISCUSSION: An effective, safe single-dose treatment would reduce hospitalization and treatment costs. Results will inform the design of combination treatment studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT00832208

NPT088 reduces both amyloid-b and tau pathologies in transgenic mice

Introduction: Alzheimer’s disease (AD) is characterized by appearance of both extracellular senile plaques and intracellular neurofibrillary tangles, comprised of aggregates of misfolded amyloid-b (Ab) and hyper-phosphorylated tau, respectively. In a previous study, we demonstrated that g3p, a capsid protein from bacteriophage M13, binds to and remodels misfolded aggregates of proteins that assume an amyloid conformation. We engineered a fusion protein (“NPT088”) consisting of the active fragment of g3p and human-IgG1-Fc. Methods: Aged Tg2576 mice or rTg4510 mice received NPT088 weekly via IP injection. Cognitive and/or functional motor endpoints were monitored during dosing. Pathology was quantified biochemically and immunohistochemically. Results: NPT088-lowered Ab plaque and improved cognitive performance of aged Tg2576 mice. Moreover, NPT088 reduced phospho-tau pathology, reduced brain atrophy, and improved cognition in rTg4510 mice. Discussion: These observations establish NPT088 as a novel therapeutic approach and potential drug class that targets both Ab and tau, the hallmark pathologies of AD

A novel a-L-Arabinofuranosidase of Family 43 Glycoside Hydrolase (Ct43Araf ) from Clostridium thermocellum

Articles in International JournalsThe study describes a comparative analysis of biochemical, structural and functional properties of two recombinant derivatives from Clostridium thermocellum ATCC 27405 belonging to family 43 glycoside hydrolase. The family 43 glycoside hydrolase encoding a-L-arabinofuranosidase (Ct43Araf) displayed an N-terminal catalytic module CtGH43 (903 bp) followed by two carbohydrate binding modules CtCBM6A (405 bp) and CtCBM6B (402 bp) towards the C-terminal. Ct43Araf and its truncated derivative CtGH43 were cloned in pET-vectors, expressed in Escherichia coli and functionally characterized. The recombinant proteins displayed molecular sizes of 63 kDa (Ct43Araf) and 34 kDa (CtGH43) on SDS-PAGE analysis. Ct43Araf and CtGH43 showed optimal enzyme activities at pH 5.7 and 5.4 and the optimal temperature for both was 50uC. Ct43Araf and CtGH43 showed maximum activity with rye arabinoxylan 4.7 Umg21 and 5.0 Umg21, respectively, which increased by more than 2-fold in presence of Ca2+ and Mg2+ salts. This indicated that the presence of CBMs (CtCBM6A and CtCBM6B) did not have any effect on the enzyme activity. The thin layer chromatography and high pressure anion exchange chromatography analysis of Ct43Araf hydrolysed arabinoxylans (rye and wheat) and oat spelt xylan confirmed the release of L-arabinose. This is the first report of a-L-arabinofuranosidase from C. thermocellum having the capacity to degrade both pnitrophenol- a-L-arabinofuranoside and p-nitrophenol-a-L-arabinopyranoside. The protein melting curves of Ct43Araf and CtGH43 demonstrated that CtGH43 and CBMs melt independently. The presence of Ca2+ ions imparted thermal stability to both the enzymes. The circular dichroism analysis of CtGH43 showed 48% b-sheets, 49% random coils but only 3% a-helices

Nucleoside Analogue Reverse Transcriptase Inhibitors Differentially Inhibit Human LINE-1 Retrotransposition

Intact LINE-1 elements are the only retrotransposons encoded by the human genome known to be capable of autonomous replication. Numerous cases of genetic disease have been traced to gene disruptions caused by LINE-1 retrotransposition events in germ-line cells. In addition, genomic instability resulting from LINE-1 retrotransposition in somatic cells has been proposed as a contributing factor to oncogenesis and to cancer progression. LINE-1 element activity may also play a role in normal physiology. LINE-1 retrotransposition reporter assay, we evaluated the abilities of several antiretroviral compounds to inhibit LINE-1 retrotransposition. The nucleoside analogue reverse transcriptase inhibitors (nRTIs): stavudine, zidovudine, tenofovir disoproxil fumarate, and lamivudine all inhibited LINE-1 retrotransposition with varying degrees of potencies, while the non-nucleoside HIV-1 reverse transcriptase inhibitor nevirapine showed no effect.Our data demonstrates the ability for nRTIs to suppress LINE-1 retrotransposition. This is immediately applicable to studies aimed at examining potential roles for LINE-1 retrotransposition in physiological processes. In addition, our data raises novel safety considerations for nRTIs based on their potential to disrupt physiological processes involving LINE-1 retrotransposition

Effectiveness of All-Oral Antiviral Regimens in 996 Human Immunodeficiency Virus/Hepatitis C Virus Genotype 1–Coinfected Patients Treated in Routine Practice

Background.Large cohorts are needed to assess human immunodeficiency virus (HIV)/hepatitis C virus (HCV) real-world treatment outcomes. We examined the effectiveness of ledipasvir/sofosbuvir with or without ribavirin (LDV/SOF ± RBV) and ombitasvir/ paritaprevir/ritonavir plus dasabuvir (OPrD) ± RBV in HIV/HCV genotype 1 (GT1)-coinfected patients initiating HCV therapy in clinical practice.Methods.Observational intent-to-treat cohort analysis using the Veterans Affairs Clinical Case Registry to identify HIV/HCV GT1-coinfected veterans initiating 12 weeks of LDV/SOF ± RBV or OPrD ± RBV. Multivariate models of sustained virologic response (SVR) included age, race, cirrhosis, proton pump inhibitor (PPI) prescription, prior HCV treatment, body mass index, genotype subtype, and HCV treatment regimen.Results.Nine hundred ninety-six HIV/HCV GT1-coinfected veterans initiated therapy: 757 LDV/SOF, 138 LDV/SOF + RBV, 28 OPrD, and 73 OPrD + RBV. Overall SVR was 90.9% (823/905); LDV/SOF 92.1% (631/685), LDV/SOF + RBV 86.3% (113/131), OPrD 88.9% (24/27), and OPrD + RBV 88.7% (55/62). SVR was 85.9% (176/205) and 92.4% (647/700) in those with and without cirrhosis (P = .006). SVR was similar between African Americans (90.5% [546/603]) and all others (91.7% [277/302]). PPI use with LDV/SOF ± RBV did not affect SVR (89.7% [131/146] with PPI and 91.5% [613/670] without PPI). Cirrhosis was predictive of reduced SVR (0.51 [95% confidence interval {CI}, .31-.87]; P = .01). Median creatinine change did not differ among patients receiving LDV/SOF and tenofovir disoproxil fumarate (TDF) without a protease inhibitor (PI) (0.18 [interquartile range {IQR}, 0.08-0.30]; n = 372), LDV/SOF and TDF/PI (0.17 [IQR, 0.04-0.30]; n = 100), and LDV/SOF without TDF (0.15 [IQR, 0.00-0.30]; n = 423).Conclusions.SVR rates in HIV/HCV GT1-coinfected patients were high. African American race or PPI use with LDV/SOF ± RBV was not associated with lower SVR rates, but cirrhosis was. Renal function did not worsen on LDV/SOF regimens with TDF

A Spatial Distribution Study of Faunal Remains from Two Lower Magdalenian Occupation Levels in El Mirón Cave, Cantabria, Spain

Abstract: Human behaviour can be reconstructed by analysing specific activities and campsite organization using spatial analysis. The dense occupation layers of the Lower Cantabrian Magdalenian in the Northern Spain reveal varied aspects of Upper Palaeolithic lifeways, including evidence of specific localized activities. The outer vestibule of El Mirón cave has a particularly rich and intact Lower Magdalenian occupation horizon, Levels 15–17. The excavations in the outer vestibule “Cabin” area of the site revealed excellent bone preservation. Artefacts and faunal remains were individually recorded and sediments water-screened to yield a large sample of archaeological finds and spatial data. Zooarchaeological analysis provided the taxonomic, anatomic and taphonomic determination of the faunal individual finds. Smaller animal remains were categorized and counted; special attention was given to the identification of anthropogenic modifications such as burnt bones or bone flakes. These small refuse items are considered to be useful, in situ indicators of localized activities. The spatial distribution analysis of this dense and complex palimpsest of El Mirón Lower Cantabrian Magdalenian layers required GIS based methods including density analysis, heatmaps and cluster analysis. Based on the spatial distribution of Level 15 and 16 faunal remains, different activity areas were identified comprising hearth, working and dropping zones. These results imply the deliberately segregated use of space within the Lower Cantabrian Magdalenian site area, in which bone-processing activities played a central rol

Adherence in the CAPRISA 004 tenofovir gel microbicide trial.

CAPRISA, 2014.High adherence is key to microbicide effectiveness. Here we provide a description of adherence interventions and the adherence rates achieved in the CAPRISA 004 Tenofovir Gel Trial. Adherence support for the before-and-after dosing strategy (BAT 24) was provided at enrolment and at each monthly study visit. This initially comprised individual counselling and was replaced midway by a structured theory-based adherence support program (ASP) based on motivational interviewing. The 889 women were followed for an average of 18 months and attended a total of 17031 monthly visits. On average women reported 5 sex acts and returned 5.9 empty applicators per month. The adherence rate based on applicator count in relation to all reported sex acts was 72.2% compared to the 82.0% self-reported adherence during the last sex act. Adherence support activities, which achieve levels of adherence similar to or better than those achieved by the CAPRISA 004 ASP, will be critical to the success of future microbicide trials