277 research outputs found

    Production Management Model Based on Lean Manufacturing and Change Management Aimed at Reducing Order Fulfillment Times in Micro and Small Wooden Furniture Companies in Peru

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    This research study seeks to identify and prioritize the causes of order fulfillment delays in a small wooden furniture manufacturing company. The authors propose a 5-phase Lean Optimization model to address and reduce this problem. Post-implementation results yielded a 54.87% reduction in material search and transportation times, a 32.86% reduction in travel times between stations, and a 19.81% increase in line efficiency. In addition, order fulfillment percentages increased from 12.5% to 60%

    Anti-CRISPR-mediated control of gene editing and synthetic circuits in eukaryotic cells.

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    Repurposed CRISPR-Cas molecules provide a useful tool set for broad applications of genomic editing and regulation of gene expression in prokaryotes and eukaryotes. Recent discovery of phage-derived proteins, anti-CRISPRs, which serve to abrogate natural CRISPR anti-phage activity, potentially expands the ability to build synthetic CRISPR-mediated circuits. Here, we characterize a panel of anti-CRISPR molecules for expanded applications to counteract CRISPR-mediated gene activation and repression of reporter and endogenous genes in various cell types. We demonstrate that cells pre-engineered with anti-CRISPR molecules become resistant to gene editing, thus providing a means to generate "write-protected" cells that prevent future gene editing. We further show that anti-CRISPRs can be used to control CRISPR-based gene regulation circuits, including implementation of a pulse generator circuit in mammalian cells. Our work suggests that anti-CRISPR proteins should serve as widely applicable tools for synthetic systems regulating the behavior of eukaryotic cells

    DNA Methylation-Independent Reversion of Gemcitabine Resistance by Hydralazine in Cervical Cancer Cells

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    BACKGROUND: Down regulation of genes coding for nucleoside transporters and drug metabolism responsible for uptake and metabolic activation of the nucleoside gemcitabine is related with acquired tumor resistance against this agent. Hydralazine has been shown to reverse doxorubicin resistance in a model of breast cancer. Here we wanted to investigate whether epigenetic mechanisms are responsible for acquiring resistance to gemcitabine and if hydralazine could restore gemcitabine sensitivity in cervical cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: The cervical cancer cell line CaLo cell line was cultured in the presence of increasing concentrations of gemcitabine. Down-regulation of hENT1 & dCK genes was observed in the resistant cells (CaLoGR) which was not associated with promoter methylation. Treatment with hydralazine reversed gemcitabine resistance and led to hENT1 and dCK gene reactivation in a DNA promoter methylation-independent manner. No changes in HDAC total activity nor in H3 and H4 acetylation at these promoters were observed. ChIP analysis showed H3K9m2 at hENT1 and dCK gene promoters which correlated with hyper-expression of G9A histone methyltransferase at RNA and protein level in the resistant cells. Hydralazine inhibited G9A methyltransferase activity in vitro and depletion of the G9A gene by iRNA restored gemcitabine sensitivity. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that acquired gemcitabine resistance is associated with DNA promoter methylation-independent hENT1 and dCK gene down-regulation and hyper-expression of G9A methyltransferase. Hydralazine reverts gemcitabine resistance in cervical cancer cells via inhibition of G9A histone methyltransferase

    Utilization of mechanical power and associations with clinical outcomes in brain injured patients. a secondary analysis of the extubation strategies in neuro-intensive care unit patients and associations with outcome (ENIO) trial

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    BackgroundThere is insufficient evidence to guide ventilatory targets in acute brain injury (ABI). Recent studies have shown associations between mechanical power (MP) and mortality in critical care populations. We aimed to describe MP in ventilated patients with ABI, and evaluate associations between MP and clinical outcomes.MethodsIn this preplanned, secondary analysis of a prospective, multi-center, observational cohort study (ENIO, NCT03400904), we included adult patients with ABI (Glasgow Coma Scale <= 12 before intubation) who required mechanical ventilation (MV) >= 24 h. Using multivariable log binomial regressions, we separately assessed associations between MP on hospital day (HD)1, HD3, HD7 and clinical outcomes: hospital mortality, need for reintubation, tracheostomy placement, and development of acute respiratory distress syndrome (ARDS).ResultsWe included 1217 patients (mean age 51.2 years [SD 18.1], 66% male, mean body mass index [BMI] 26.3 [SD 5.18]) hospitalized at 62 intensive care units in 18 countries. Hospital mortality was 11% (n = 139), 44% (n = 536) were extubated by HD7 of which 20% (107/536) required reintubation, 28% (n = 340) underwent tracheostomy placement, and 9% (n = 114) developed ARDS. The median MP on HD1, HD3, and HD7 was 11.9 J/min [IQR 9.2-15.1], 13 J/min [IQR 10-17], and 14 J/min [IQR 11-20], respectively. MP was overall higher in patients with ARDS, especially those with higher ARDS severity. After controlling for same-day pressure of arterial oxygen/fraction of inspired oxygen (P/F ratio), BMI, and neurological severity, MP at HD1, HD3, and HD7 was independently associated with hospital mortality, reintubation and tracheostomy placement. The adjusted relative risk (aRR) was greater at higher MP, and strongest for: mortality on HD1 (compared to the HD1 median MP 11.9 J/min, aRR at 17 J/min was 1.22, 95% CI 1.14-1.30) and HD3 (1.38, 95% CI 1.23-1.53), reintubation on HD1 (1.64; 95% CI 1.57-1.72), and tracheostomy on HD7 (1.53; 95%CI 1.18-1.99). MP was associated with the development of moderate-severe ARDS on HD1 (2.07; 95% CI 1.56-2.78) and HD3 (1.76; 95% CI 1.41-2.22).ConclusionsExposure to high MP during the first week of MV is associated with poor clinical outcomes in ABI, independent of P/F ratio and neurological severity. Potential benefits of optimizing ventilator settings to limit MP warrant further investigation

    Fungal planet description sheets: 951–1041

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    Novel species of fungi described in this study include those from various countries as follows: Antarctica , Apenidiella antarctica from permafrost, Cladosporium fildesense fromanunidentifiedmarinesponge. Argentina , Geastrum wrightii onhumusinmixedforest. Australia , Golovinomyces glandulariae on Glandularia aristigera, Neoanungitea eucalyptorum on leaves of Eucalyptus grandis, Teratosphaeria corymbiicola on leaves of Corymbia ficifolia, Xylaria eucalypti on leaves of Eucalyptus radiata. Brazil, Bovista psammophila on soil, Fusarium awaxy on rotten stalks of Zea mays, Geastrum lanuginosum on leaf litter covered soil, Hermetothecium mikaniae-micranthae (incl. Hermetothecium gen. nov.)on Mikania micrantha, Penicillium reconvexovelosoi in soil, Stagonosporopsis vannaccii from pod of Glycine max. British Virgin Isles , Lactifluus guanensis onsoil. Canada , Sorocybe oblongispora on resin of Picea rubens. Chile, Colletotrichum roseum on leaves of Lapageria rosea. China, Setophoma caverna fromcarbonatiteinKarstcave. Colombia , Lareunionomyces eucalypticola on leaves of Eucalyptus grandis. Costa Rica, Psathyrella pivae onwood. Cyprus , Clavulina iris oncalcareoussubstrate. France , Chromosera ambigua and Clavulina iris var. occidentalis onsoil. French West Indies , Helminthosphaeria hispidissima ondeadwood. Guatemala , Talaromyces guatemalensis insoil. Malaysia , Neotracylla pini (incl. Tracyllales ord. nov. and Neotra- cylla gen. nov.)and Vermiculariopsiella pini on needles of Pinus tecunumanii. New Zealand, Neoconiothyrium viticola on stems of Vitis vinifera, Parafenestella pittospori on Pittosporum tenuifolium, Pilidium novae-zelandiae on Phoenix sp. Pakistan , Russula quercus-floribundae onforestfloor. Portugal , Trichoderma aestuarinum from salinewater. Russia , Pluteus liliputianus on fallen branch of deciduous tree, Pluteus spurius on decaying deciduouswoodorsoil. South Africa , Alloconiothyrium encephalarti, Phyllosticta encephalarticola and Neothyrostroma encephalarti (incl. Neothyrostroma gen. nov.)onleavesof Encephalartos sp., Chalara eucalypticola on leaf spots of Eucalyptus grandis × urophylla, Clypeosphaeria oleae on leaves of Olea capensis, Cylindrocladiella postalofficium on leaf litter of Sideroxylon inerme , Cylindromonium eugeniicola (incl. Cylindromonium gen. nov.)onleaflitterof Eugenia capensis , Cyphellophora goniomatis on leaves of Gonioma kamassi , Nothodactylaria nephrolepidis (incl. Nothodactylaria gen. nov. and Nothodactylariaceae fam. nov.)onleavesof Nephrolepis exaltata , Falcocladium eucalypti and Gyrothrix eucalypti on leaves of Eucalyptus sp., Gyrothrix oleae on leaves of Olea capensis subsp. macrocarpa , Harzia metro sideri on leaf litter of Metrosideros sp., Hippopotamyces phragmitis (incl. Hippopota- myces gen. nov.)onleavesof Phragmites australis , Lectera philenopterae on Philenoptera violacea , Leptosillia mayteni on leaves of Maytenus heterophylla , Lithohypha aloicola and Neoplatysporoides aloes on leaves of Aloe sp., Millesimomyces rhoicissi (incl. Millesimomyces gen. nov.) on leaves of Rhoicissus digitata , Neodevriesia strelitziicola on leaf litter of Strelitzia nicolai , Neokirramyces syzygii (incl. Neokirramyces gen. nov.)onleafspots o

    B0 meson decays to rho0 K*0, f0 K*0, and rho-K*+, including higher K* resonances

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    We present branching fraction measurements for the decays B0 -> rho0 K*0, B0 -> f0 K*0, and B0 -> rho- K*+, where K* is an S-wave (K pi)_0* or a K*(892) meson; we also measure B0 -> f0 K_2*(1430)^0. For the K*(892) channels, we report measurements of longitudinal polarization fractions (for rho final states) and direct CP-violation asymmetries. These results are obtained from a sample of (471.0 +/- 2.8) x 10^6 BBbar pairs collected with the BaBar detector at the PEP-II asymmetric-energy e+ e- collider at the SLAC National Accelerator Laboratory. We observe rho0 K*(892)^0, rho0 (K pi)_0^{*0}, f0 K*(892)^0, and rho- K*(892)+ with greater than 5 sigma significance, including systematics. We report first evidence for f0 (K pi)_0^{*0} and f0 K_2*(1430)^0, and place an upper limit on rho- (K pi)_0^{*+}. Our results in the K*(892) channels are consistent with no direct CP-violation.Comment: 17 pages, 6 postscript figures, submitted to Phys. Rev.

    Description and performance of track and primary-vertex reconstruction with the CMS tracker

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    A description is provided of the software algorithms developed for the CMS tracker both for reconstructing charged-particle trajectories in proton-proton interactions and for using the resulting tracks to estimate the positions of the LHC luminous region and individual primary-interaction vertices. Despite the very hostile environment at the LHC, the performance obtained with these algorithms is found to be excellent. For tbar t events under typical 2011 pileup conditions, the average track-reconstruction efficiency for promptly-produced charged particles with transverse momenta of pT > 0.9GeV is 94% for pseudorapidities of |η| < 0.9 and 85% for 0.9 < |η| < 2.5. The inefficiency is caused mainly by hadrons that undergo nuclear interactions in the tracker material. For isolated muons, the corresponding efficiencies are essentially 100%. For isolated muons of pT = 100GeV emitted at |η| < 1.4, the resolutions are approximately 2.8% in pT, and respectively, 10μm and 30μm in the transverse and longitudinal impact parameters. The position resolution achieved for reconstructed primary vertices that correspond to interesting pp collisions is 10–12μm in each of the three spatial dimensions. The tracking and vertexing software is fast and flexible, and easily adaptable to other functions, such as fast tracking for the trigger, or dedicated tracking for electrons that takes into account bremsstrahlung

    Alignment of the CMS tracker with LHC and cosmic ray data

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    © CERN 2014 for the benefit of the CMS collaboration, published under the terms of the Creative Commons Attribution 3.0 License by IOP Publishing Ltd and Sissa Medialab srl. Any further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation and DOI.The central component of the CMS detector is the largest silicon tracker ever built. The precise alignment of this complex device is a formidable challenge, and only achievable with a significant extension of the technologies routinely used for tracking detectors in the past. This article describes the full-scale alignment procedure as it is used during LHC operations. Among the specific features of the method are the simultaneous determination of up to 200 000 alignment parameters with tracks, the measurement of individual sensor curvature parameters, the control of systematic misalignment effects, and the implementation of the whole procedure in a multi-processor environment for high execution speed. Overall, the achieved statistical accuracy on the module alignment is found to be significantly better than 10μm

    Multi-messenger observations of a binary neutron star merger

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    On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta
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