Abstract
The Deep Underground Neutrino Experiment (DUNE) is a dual-site experiment for long-baseline neutrino oscillation studies, able to resolve the neutrino mass hierarchy and measure
δ
CP
. DUNE ...will also have sensitivity to supernova neutrinos and to processes beyond the Standard Model, such as nucleon decay searches. The Far Detector (FD) will consist of four liquid argon TPC (17.5 kt total mass) with systems for the detection of charge and scintillation light produced by an ionization event. The charge detection system permits both calorimetry and position determination. In addition, the photon-detection system (PDS) enhances the detector capabilities for all DUNE physics drivers. The PDS of the first FD module consists of light collector modules placed in the inactive space between the innermost wire planes of the TPC anode. The light collectors, the so-called X-ARAPUCAS, are functionally a light trap that captures wavelength-shifted photons inside boxes with highly reflective internal surfaces where they are guided to Silicon Photo-multipliers (SiPM) by wavelength-shifting (WLS) bars. Functionality and operational tests of the X-ARAPUCAS to be installed in ProtoDUNE-SP phase II (FD DUNE prototype at the scale 1:20), as well as the measurement of their absolute detection efficiency is reported in this publication.
Background. Variation in the IL28B gene is associated with sustained virologic response (SVR) to pegylated interferon plus ribavirin in hepatitis C virus (HCV)—monoinfected patients with genotype 1. ...Data on other genotypes and on patients coinfected with human immunodeficiency virus (HIV) and HCV are more limited. We aimed to assess the predictive ability of variations in the single-nucleotide polymorphism rs12979860 for SVR in HIV/HCV-coinfected patients, regardless of HCV genotype. Methods. The rs12979860 genotype was determined by polymerase chain reaction in 154 patients who had received therapy against HCV with pegylated interferon plus ribavirin. Results. rs12979860 genotype was TT in 20 patients (13%), TC in 66 patients (43%), and CC in 68 patients (44%). Rates of SVR in patients with genotype CC and in those with genotype TC or TT, according to HCV genotype, were, respectively, 50% and 17% (P < .001) in patients with genotype 1, 80% and 25% (P=.027) in patients with genotype 4, and 93% and 77% (P=.115) in patients with genotype 3. The median (interquartile range) low-density lipoprotein cholesterol level in patients with rs12979860 CC was 89 mg/dL (73–120 mg/dL) versus 75 mg/dL (55–91 mg/dL) (P=.001) in those with TC or TT. Independent predictors of SVR were HCV genotype 2–3 (odds ratio OR, 13.98; 95% confidence interval CI, 4.87–40.1; P < .001), rs12979860 CC (OR, 5.05; 95% CI, 2.04–12.5; P < .001), baseline plasma HCV RNA load of ⩽600,000 IU/mL (OR, 1.99; 95% CI, 1.18–3.34; P=.009), and female sex (OR, 4.28; 95% CI, 1.08–16.96; P=.039). Conclusions. IL28B gene variations independently predict SVR in HIV/HCV-coinfected patients with HCV genotype 1 and non—genotype 1 HCV infection. The association between rs12979860 and plasma low-density lipoprotein cholesterol suggests that the system low-density lipoprotein ligand/receptor might be involved in the effect of this genotype.
Abstract
Materials with strongly correlated electrons often exhibit interesting physical properties. An example of these materials is the layered oxide perovskite Sr
2
RuO
4
, which has been ...intensively investigated due to its unusual properties. Whilst the debate on the symmetry of the superconducting state in Sr
2
RuO
4
is still ongoing, a deeper understanding of the Sr
2
RuO
4
normal state appears crucial as this is the background in which electron pairing occurs. Here, by using low-energy muon spin spectroscopy we discover the existence of surface magnetism in Sr
2
RuO
4
in its normal state. We detect static weak dipolar fields yet manifesting at an onset temperature higher than 50 K. We ascribe this unconventional magnetism to orbital loop currents forming at the reconstructed Sr
2
RuO
4
surface. Our observations set a reference for the discovery of the same magnetic phase in other materials and unveil an electronic ordering mechanism that can influence electron pairing with broken time reversal symmetry.
In this study, a series of novel 3-
-A derivatives of the natural triterpenes α-amyrin (
) and 3-epilupeol (
) were synthesized by a one-pot radical scission-oxidation procedure and evaluated
and
for ...their capacity to inhibit the inflammatory process. For the
studies, the
-4-hydroxy-l-proline methyl ester derivatives (
and
) were consistently effective in inhibiting NO, IL-6, and TNF-α secretion, as well as inhibition of NF-κB activation, in RAW cells stimulated by LPS. The further
anti-inflammatory study revealed that the
-4-hydroxy-l-proline methyl ester derivatives (
and
), together with
, were the most effective in inhibiting TPA-induced edema. Interestingly, the α-amyrin derivatives were the most potent inhibitors of COX-2, but inhibited COX-1 only to some extent. The hydroxyl derivative (
) was selective for COX-2 inhibition (66.3 ± 1.1% at 17.5 μM) without affecting the COX-1 isoform and did not present toxicity. Molecular docking studies revealed that these compounds bind with their polar region in the cavity over Arg-120, and their lipophilic part is orientated to the HEM cofactor similarly to the natural substrate arachidonic acid in the catalytic site of COX-2. These results indicated that
-A ursane derivatives could be considered promising candidates for the future development of selective NF-κB and COX-2 inhibitors.
Interest in the development of new sources of transplantable materials for the treatment of injury or disease has led to the convergence of tissue engineering with stem cell technology. Bone and ...joint disorders are expected to benefit from this new technology because of the low self-regenerating capacity of bone matrix secreting cells. Herein, the differentiation of stem cells to bone cells using active multilayered capsules is presented. The capsules are composed of poly-L-glutamic acid and poly-L-lysine with active growth factors embedded into the multilayered film. The bone induction from these active capsules incubated with embryonic stem cells was demonstrated in vitro. Herein, we report the unique demonstration of a multilayered capsule-based delivery system for inducing bone formation in vivo. This strategy is an alternative approach for in vivo bone formation. Strategies using simple chemistry to control complex biological processes would be particularly powerful, as they make production of therapeutic materials simpler and more easily controlled.
•Routine strategies for hepatitis C virus (HCV) genotyping have several limitations. Deep sequencing methods can solve this problem.•Accurate determination of viral genotypes and subtypes would allow ...optimal patient management and the most effective therapy.•Mixed infections may represent a key factor for efficient therapy. Patients infected with more than one HCV genotype (mixed infection) can be detected only by deep sequencing methods.•These patients can fail treatment with direct-acting antiviral agents, hence next-generation sequencing methods are highly recommended in clinical practice.
The effectiveness of the new generation of hepatitis C treatments named direct-acting antiviral agents (DAAs) depends on the genotype, subtype, and resistance-associated substitutions present in individual patients. The aim of this study was to evaluate a massive sequencing platform for the analysis of genotypes and subtypes of hepatitis C virus (HCV) in order to optimize therapy.
A total of 84 patients with hepatitis C were analyzed. The routine genotyping methodology for HCV used at the study institution (Versant HCV Assay, LiPA) was compared with a deep sequencing platform (454/GS-Junior and Illumina MiSeq).
The mean viral load in these HCV patients was 6.89×106±7.02×105. Viral genotypes analyzed by LiPA were distributed as follows: 26% genotype 1a (22/84), 55% genotype 1b (46/84), 1% genotype 1 (1/84), 2.5% genotype 3 (2/84), 6% genotype 3a (5/84), 6% genotype 4a/c/d (5/84). When analyzed by deep sequencing, the samples were distributed as follows: 27% genotype 1a (23/84), 56% genotype 1b (47/84), 8% genotype 3a (7/84), 5% genotype 4d (4/84), 2.5% genotype 4f (2/84). Six of the 84 patients (7%) were infected with more than one subtype. Among these, 33% (2/6) failed DAA-based triple therapy.
The detection of mixed infection could explain some treatment failures. Accurate determination of viral genotypes and subtypes would allow optimal patient management and improve the effectiveness of DAA therapy.
•Farm sustainability efficiency is measured accounting for technology heterogeneity.•Technical, environmental, and social dimensions of production are considered.•Farm contribution to employment ...opportunities for women is used as a social output.•Technology heterogeneity exists across farms operating in different natural regions.•Sierra farms outperformed Selva farms in all three dimensions of sustainability efficiency.
This article uses a non-parametric non-convex metafrontier approach to estimate farm sustainability efficiency while considering heterogeneity in production technologies stemming from differences in the production environment under which farming takes place. Sustainability efficiency measures reflect farmers’ ability to increase production of desirable agricultural outputs, reduce fertilizer-induced nitrous oxide emissions, and create employment opportunities for women. This is the first attempt to measure efficiency in terms of firms’ contribution to employment opportunities for women, a social and developmental issue gaining much public attention. The empirical application uses data on 1109 Peruvian coffee farms over the period 2017–2019. Sample farms operate in two natural regions of Peru – namely Sierra, and Selva – where farming systems differ because of variations in resource endowments and socioeconomic conditions. Results indicate the presence of interregional heterogeneity in production technologies of sample farms. Sierra coffee farms outperformed coffee farms located in the Selva region in all three dimensions of sustainability efficiency, suggesting that it is the latter that are in greater need of efficiency improvement interventions. Results further show that both Sierra and Selva coffee farms performed worst with respect to environmental efficiency, implying a greater scope for reducing nitrous oxide emissions with existing production technology and resources.
The Deep Underground Neutrino Experiment (DUNE) is a dual-site experiment for long-baseline neutrino oscillation studies, and for neutrino astrophysics and nucleon decay searches. The far detector is ...a 40-kton underground liquid argon time-projection-chamber (LAr TPC), in which the photon detector system adds precise timing capabilities. The ProtoDUNE Dual-Phase detector will consist of a 6×6×6 m3 LAr TPC to be operated at the CERN Neutrino Platform and the photon detection system will be formed by 8-inch cryogenic photomultipliers from Hamamatsu. The PMT model (R5912-20Mod) performance at cryogenic temperature is studied including dark current, gain, and linearity with the light intensity and pulse rate. In addition, the PMT base design is validated. At cold, a decrease of the PMT amplification, or fatigue effect, is measured as the PMT output current increases, either, due to high gain, light intensity or rate. Also, the characterization results of the 40 photomultipliers to be used in ProtoDUNE Dual-Phase are presented.
As shared mobility burst in different cities as one of the most innovative transport solutions, few efforts are found related to the exploration of dockless services and more specifically, to ...analysing opinions from those users that are subscribed to both, docked and dockless services simultaneously. Therefore, our study explores station-based bike-sharing users’ preferences for other dockless services. To that end, we firstly divide the sample into two groups: Group 1 being users that only use Bicimad (Madrid's station-based bike-sharing) and Group 2 being Bicimad users that are also subscribed to other dockless services. Results show that both groups have similar users’ profiles according to their socio-demographic characteristics (male, 35–49 years old, well-educated, medium income and employee), although Group 2 shows a slightly higher rate of under-26-year-olds, which could be supporting the idea that these services are more attractive for the youngest. Moreover, our findings show that approximately 12% of station-based bike-sharing users are also subscribed to dockless services. At a higher rate, those subscribed to dockless services live outside the city centre, where the bike-sharing system is not available, showing that the two models may essentially have a complemental relationship, especially in the peripheries. Finally, results point at the importance of bike-sharing systems having a positive impact on its users, as they are keener to try new dockless options and a reduced willingness to use private cars. Insights may help to better inform public policy and promote the use of shared micromobility.
ProtoDUNE-DP is a <inline-formula> <tex-math notation="LaTeX">6\times 6\times 6\,\,\text{m}^{3} </tex-math></inline-formula> liquid argon time-projection-chamber operated at the CERN Neutrino ...Platform in 2019-2020 as a prototype of the dual phase concept for the Deep Underground Neutrino Experiment (DUNE) far detector. The photon detection system (PDS) is based on 36 8-in photomultiplier tubes (PMTs) and allows triggering on the scintillation light signals produced by cosmic rays and other charged particles traversing the detector. The acquisition and calibration software specifically developed for the ProtoDUNE-DP PDS is described in this article. This software controls the high-voltage power supplies, the calibration system, and the PDS DAQ. It has been developed with Qt Creator and features different operation modes and a graphical user interface. This software has already been validated and used during the ProtoDUNE-DP operation.
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