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Objective To evaluate the impact of hepatitis C virus (HCV) elimination via interferon (IFN)-based therapy on gene expression profiles related to the immune system in HIV/HCV-coinfected patients. Methods We conducted a prospective study in 28 HIV/HCV-coinfected patients receiving IFN-based therapy at baseline (HIV/HCV-b) and week 24 after sustained virological response (HIV/HCV-f). Twenty-seven HIV-monoinfected patients (HIV-mono) were included as a control. RNA-seq analysis was performed on peripheral blood mononuclear cells (PBMCs). Genes with a fold-change (FC) >= 1.5 (in either direction) and false discovery rate (FDR)

During the filling of the Large Hadron Collider (LHC), it is desirable to keep the RF cavity voltage constant both in amplitude and phase to minimize the emittance blow-up and injection losses. To have a constant voltage and to minimize power consumption, a special beam-loading compensation scheme called half-detuning is used in the LHC, for which the cavity fundamental resonant frequency needs to be de-tuned from the RF frequency by an appropriate value. This, however, can result in fast coupled-bunch instabilities caused by the asymmetry of the fundamental cavity impedance. To mitigate them, a fast direct RF feedback and a one-turn delay feedback are presently used in the LHC. The semi-analytical model that describes the dynamics of the Low-Level RF system in the LHC shows that, depending on the mitigation scenario, the required transient RF power during injection could significantly exceed the steady-state value. This means that for High-Luminosity LHC (HL-LHC) beam intensities, one can potentially reach the limit of available RF power. In this paper, the model is described, and benchmarks with LHC measurements are presented. We also shortly revisit the damping requirements for the longitudinal coupled-bunch instability at injection energy, to find a compromise between longitudinal stability and RF power requirements for the HL-LHC beam., CERN Yellow Reports: Conference Proceedings, Vol. 9 (2020): Proceedings of the ICFA mini-Workshop on Mitigation of Coherent Beam Instabilities in Particle Accelerators, Zermatt, Switzerland, 23–27 September 2019

Background: To assess the effects of eradication of hepatitis C virus (HCV) on cardiovascular risk (CVR) and preclinical atherosclerosis in HIV/HCV-coinfected patients. Setting: Prospective cohort study. Methods: We assessed serum lipids, 10-year Framingham CVR scores, pulse wave velocity, carotid intima-media thickness, and biomarkers of inflammation and endothelial dysfunction (BMKs) at baseline and 96 weeks (wk) after initiation of anti-HCV therapy (Rx) in HIV/HCV-coinfected patients. Results: A total of 237 patients were included. Anti-HCV therapy comprised pegylated interferon and ribavirin plus 1 direct-acting antiviral in 55.2%, pegylated interferon and ribavirin in 33.8%, and all-oral direct-acting antiviral in 11.0%. A total of 147 (62.0%) patients achieved sustained viral response (SVR). Median increases in low-density lipoprotein cholesterol in patients with and without SVR were 14 mg/dL and 0 mg/dL (P = 0.024), respectively. Increases in CVR categories were found in 26.9% of patients with SVR (P = 0.005 vs. baseline) and 8.1% of patients without SVR (P = 0.433). This resulted in a significant interaction between SVR and CVR over time (P < 0.001). No significant effect of SVR was observed for pulse wave velocity (P = 0.446), carotid intima-media thickness (P = 0.320), and BMKs of inflammation and endothelial dysfunction. Conclusions: In coinfected patients, eradication of HCV had no effect on markers of preclinical atherosclerosis and BMKs of inflammation and endothelial dysfunction but was associated with a clinically relevant rise in serum low-density lipoprotein cholesterol. Evaluation of CVR should be an integral part of care after the cure of chronic hepatitis C in patients with HIV.

The Large Hadron Collider (LHC) is one of the largest scientific instruments ever built. Since opening up anew energy frontier for exploration in 2010, it has gathered a global user community of about 9000 scientists working in fundamental particle physics and the physics of hadronic matter at extreme temperature and density. To sustain and extend its discovery potential, the LHC will need a major upgrade in the 2020s. This will increase its instantaneous luminosity (rate of collisions) by a factor of five beyond the original design valueand the integrated luminosity (totalnumber of collisions) by a factor ten. The LHC is already a highly complexand exquisitely optimised machine so this upgrade must be carefully conceived and will require new infrastructures(underground and on surface)and over a decade to implement. The new configuration, known as High Luminosity LHC (HL-LHC), relies on a number of key innovations that push accelerator technology beyond its present limits. Among these are cutting-edge 11–12Tesla superconducting magnets, compact superconducting cavities for beam rotation with ultra-precise phase control, new technology and physical processes for beam collimation and 100 metre-long high-power superconducting links with negligible energy dissipation, all of which required several years of dedicated R&D; effort on a global international level. The present document describes the technologies and components that will be used to realise the projectand is intended to serve as the basis for the detailed engineering design of the HL-LHC.

During the LHC Run 2, many advances have been made on the beam dynamics in the longitudinal plane. The controlled longitudinal emittance blow-up used in the acceleration ramp was improved and bunch flattening was implemented for bunch length control during collisions. In order to minimise RF power consumption, the capture voltage was optimised and the full-detuning beam-loading compensation scheme was made operational for the ramp and at top energy. Various experimental and simulation studies have helped to improve operation and prepare for the future runs at increased intensities.

In this paper we study the influence of cooling rate on the structural properties of silver nanowires with 1.6 nm of diameter. This study is done employing molecular dynamics methods with a tight-binding potential. The cooling rates used are in the range of 0.25-25 K/ps. The structural analysis of these systems is performed studying the pair correlation function and the pair analysis technique. The results indicate that the cooling rate affects significantly the structural properties of silver nanowires finding two representative rates, the rupture rate of 2.55 K/ps, where the nanowire is broken into two nanoparticles, and the collapse rate of 1.73 K/ps, where the two nanoparticles collapse to one spherical nanoparticle., En el presente trabajo se estudia la influencia de la velocidad de enfriamiento sobre las propiedades estructurales de nanohilos de plata de 1.6 nm de diámetro. Este estudio se realiza con el método de Dinámica Molecular empleando un potencial de interacción tipo tight-binding. Las velocidades de enfriamiento que se usan están dentro del rango de 0.25-25 K/ps. El análisis estructural de estos sistemas se realiza mediante la función de correlación de pares y la técnica de análisis de pares. Los resultados indican que la velocidad de enfriamiento afecta considerablemente las propiedades estructurales de los nanohilos de plata y que se presentan dos velocidades representativas, la velocidad de ruptura de 2.55 K/ps, donde el nanohilo se rompe en dos nanopartículas, y la velocidad de colapso de 1.73 K/ps, donde las dos nanopartículas colapsan a una nano-partícula esférica.

In the present work we study the influence of the unfolding procedure on the electronic level spacing statistics of silver nanoparticles (in their most stable configuration) with 923 and 2057 atoms, which were obtained employing molecular dynamics simulation with a tighet-binding potential. The results indicate that there is a strong dependence of the Brody parameter with the degree "n" of the polynomial used to make the unfolding procedure, especially for small n. For n=>6 the Brody parameter, independently of the nanoparticle sizes, remains almost constant. Thus, it was determined that the Brody parameter is close to the value corresponding to the Wiguer distribution, which is expected for systems in the metallic regime., En el presente trabajo se estudia la influencia del procedimiento de re-escalado sobre la estadística de separación de niveles electrónicos de nanonpartículas de plata (en su configuración mas estable) con 923 y 2057 átomos, las cuales fueron obtenidas mediante simulación de dinámica molecular empleando un potencial tipo light-binding. Los resultados indican que existe una fuerte dependencia del parámetro de Brody con el grado "n" del polinomio usado para realizar el método de re-escalado, sobre todo para n pequeño. Para n>=6 el parámetro de Brody, independientemente del tamaño de las nanopartículas, permanece casi constante. Así, se determino que el parámetro de Brody está cercano al valor correspondiente a la distribución de Wigner, lo cual es esperado para sistemas en el régimen metálico.

In the present work we study the influence of disorder on the electronic level statistics of a copper nanoparticle with 3568 atoms (Cu3568). The most stable configuration was obtained from molecular dynamic simulations employing a Johnson’s potential for copper. The results indicate that for weak disorder on the on-site energy of the tight-binding Hamiltonian, the nearest-neighbors level spacing distribution is similar to the Wigner distribution. Howerver, for strong disorder the distribution changes to a Poisson-like distribution which is expected for strongly disordered systems., En el presente trabajo se estudia la influencia del desorden en la estadística de separación de niveles electrónicos de una nanopartícula de cobre con 3568 átomos (Cu3568). La configuración más estable de dicha partícula fue obtenida de la simulación de dinámica molecular empleando el potencial de Johnson para cobre. Los resultados indican que al incluir poco desorden en la energía de sitio del hamiltoniano tipo tight-binding, la distribución de separación de niveles más cercanos se asemeja a la distribución de Wigner. Sin embargo, al incrementar el desorden, la distribución se aproxima más a una de tipo Poisson, lo cual es esperado para sistemas fuertemente desordenados.

To develop an assay for the early detection and quantification of minor human immunodeficiency virus-1 populations bearing multiple drug resistance (MDR) mutations.The oligonucleotide ligation assay (OLA) is based on ligation of probe and detector oligonucleotides annealed to a polymerase chain reaction amplicon strand with detection by an enzyme immunoassay. In OLA-MDR, oligonucleotides were designed to detect MDR mutations. The method was validated with wild-type and MDR mutant clones mixed at different proportions.K103N mutants were detected as minor populations (5%-30%) by OLA in 6 of 18 samples from patients treated with nonnucleoside reverse transcription inhibitors and classified as wild type by sequencing. In one patient, the kinetics of the increase of MDR mutants could be followed in sequential samples, with K103N being detected earlier by OLA than by sequencing. Q151M mutants were detected as minor populations (13%-24%) by OLA but not by sequencing in 4 samples.Oligonucleotide ligation assay MDR exhibits higher sensitivity than sequencing for detection of minor MDR mutant populations.

We analyze the effects of strategic behavior by a large informed trader in a price discovery process used in opening auctions in continuous trading systems. It is found that the large informed trader manipulates the market using a contrarian strategy to neutralize the effect of the trades of competitive informed agents. Furthermore, consistent with the empirical evidence available, we find that information revelation accelerates close to the opening, that the market price approaches but does not converge to the fundamental value, and that the expected trading volume displays a U-shaped pattern. Copyright © 2001, RAND., Partial support from DGICYT projects 93-0679 and PB98-0696 is gratefully acknowledged.

Polymerase chain reaction (PCR) is a new diagnostic procedure which has been used to recognise HIV-infected individuals who remain seronegatives.Genomic DNA isolated from the peripheral blood mononuclear cells of 90 high-risk individuals were analyzed by PCR using gag primers SK 38/39. Subjects were classified in four groups: 42 drug abusers, 35 heterosexual partners of HIV-infected individuals, 9 homosexual men, and 4 health care workers accidentally exposed to HIV. Liquid hybridization using radiolabelled probes was done to confirm the results. All samples were also tested for HIV antigen and antibodies (Ab) using EIA and Western blot (WB).Two out of 11 (18%) drug abusers and 5 out of 34 (14%) couples were PCR positive in absence of HIV antibodies. This silent HIV infections were not recognized in homosexuals and health care workers. All 38 seropositive samples were PCR positive. None of the samples PCR+/Ab- was positive for HIV antigenemia or showed indeterminate results in the WB assay.Silent HIV infections were recognized in drug abusers (18%) and couples of HIV-infected individuals (14%). Mechanisms involved in the production of this "occult" HIV infections are reviewed.