Tumor Suppressor Role of hsa-miR-193a-3p and -5p in Cutaneous Melanoma

Background: Remarkable deregulation of several microRNAs (miRNAs) is demonstrated in cutaneous melanoma. hsa-miR-193a-3p is reported to be under-expressed in tissues and in plasma of melanoma patients, but the role of both miR-193a arms in melanoma is not known yet. Methods: After observing the reduced levels of miR-193a arms in plasma exosomes of melanoma patients, the effects of hsa-miR-193a-3p and –5p transfection in cutaneous melanoma cell lines are investigated. Results: In melanoma cell lines A375, 501Mel, and MeWo, the ectopic over-expression of miR-193a arms significantly reduced cell viability as well as the expression of genes involved in proliferation (ERBB2, KRAS, PIK3R3, and MTOR) and apoptosis (MCL1 and NUSAP1). These functional features were accompanied by a significant downregulation of Akt and Erk pathways and a strong increase in the apoptotic process. Since in silico databases revealed TROY, an orphan member of the tumor necrosis receptor family, as a potential direct target of miR-193a-5p, this possibility was investigated using the luciferase assay and excluded by our results. Conclusions: Our results underline a relevant role of miR-193a, both -3p and -5p, as tumor suppressors clarifying the intracellular mechanisms involved and suggesting that their ectopic over-expression could represent a novel treatment for cutaneous melanoma patients

Phase I/II trial of gemcitabine plus cisplatin and etoposide in patients with small-cell lung cancer

Objective: The objectives of this phase 1/11 study were to define the maximum tolerated dose (MTD), safety, and activity of cisplatin, etoposide, and gemcitabine (PEG) in the treatment of previously untreated patients with small-cell lung cancer (SCLC). Patients and Methods: Chemonaive patients received fixed doses of gemcitabine (1000 mg/m(2) on days I and 8) and cisplatin (70 mg/m(2) on day 2) and escalating doses of etoposide (starting dose of 50 mg/m(2) on days 3,4, and 5) every 3 weeks. No prophylactic granulocyte colony-stimulating factors were used. Results: From September 1998 to April 2000, 56 patients with limited- or extensive-stage SCLC were enrolled and received a total of 235 cycles. Two different etoposide doses were tested in eight patients. At the second level (75 mg/m(2)), two out of two patients experienced dose-limiting toxicities (neutropenia and thrombocytopenia) and no further dose-escalation was attempted, thus an etoposide dose of 50 mg/m 2 was defined as the MTD. In the subsequent phase 11 evaluation, 48 additional patients were enrolled, for a total of 54 patients treated at the MTD. Grade 3/4 neutropenia and thrombocytopenia occurred in 66.7 and 53.7%,, of patients, respectively. Non-hematologic toxicity was mild, with grade 3 diarrhea and fatigue as the main side effects. Two patients died of neutropenic sepsis (one at 75 mg/m(2) and the other at So I n g/In 2 etoposide). Ten complete and 29 partial responses were reported, for an overall response rate of 72.2% (95% confidence interval, 56.6-85.0%). The median duration of response and median survival were 8.0 and 10 months, respectively, with a 1-year survival probability of 37.5%. Conclusions: he combination of PEG is feasible and well tolerated as front-line chemotherapy in SCLC. A randomized comparison of this triplet is underway. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved

Cauliflower Mosaic Virus TAV, a Plant Virus Protein That Functions like Ribonuclease H1 and is Cytotoxic to Glioma Cells

Recent comparisons between plant and animal viruses reveal many common principles that underlie how all viruses express their genetic material, amplify their genomes, and link virion assembly with replication. Cauliflower mosaic virus (CaMV) is not infectious for human beings. Here, we show that CaMV transactivator/viroplasmin protein (TAV) shares sequence similarity with and behaves like the human ribonuclease H1 (RNase H1) in reducing DNA/RNA hybrids detected with S9.6 antibody in HEK293T cells. We showed that TAV is clearly expressed in the cytosol and in the nuclei of transiently transfected human cells, similar to its distribution in plants. TAV also showed remarkable cytotoxic effects in U251 human glioma cells in vitro. *ese characteristics pave the way for future analysis on the use of the plant virus protein TAV, as an alternative to human RNAse H1 during gene therapy in human cells

Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study

Several small studies on patients with COVID-19 and haematological malignancies are available showing a high mortality in this population. The Italian Hematology Alliance on COVID-19 aimed to collect data from adult patients with haematological malignancies who required hospitalisation for COVID-19

Virgo gravitational wave detector: Results and perspectives

The Virgo detector reached during the past science run a sensitivity very close to the design one. During the last year the detector has been improved by suspending the main interferometer mirrors with monolithic fibers, with the goal of reducing the thermal noise contribution and testing the new technology. At the same time the design of the next detector improvements are on-going and they will be implemented during the construction of Advanced Virgo

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| < 0.03 at 95% confidence level. [Figure not available: see fulltext.

Measurement of the W gamma Production Cross Section in Proton-Proton Collisions at root s=13 TeV and Constraints on Effective Field Theory Coefficients

A fiducial cross section for W gamma production in proton-proton collisions is measured at a center-of-mass energy of 13 TeV in 137 fb(-1) of data collected using the CMS detector at the LHC. The W -> e nu and mu nu decay modes are used in a maximum-likelihood fit to the lepton-photon invariant mass distribution to extract the combined cross section. The measured cross section is compared with theoretical expectations at next-to-leading order in quantum chromodynamics. In addition, 95% confidence level intervals are reported for anomalous triple-gauge couplings within the framework of effective field theory.Peer reviewe

Supplement: "Localization and broadband follow-up of the gravitational-wave transient GW150914" (2016, ApJL, 826, L13)

This Supplement provides supporting material for Abbott et al. (2016a). We briefly summarize past electromagnetic (EM) follow-up efforts as well as the organization and policy of the current EM follow-up program. We compare the four probability sky maps produced for the gravitational-wave transient GW150914, and provide additional details of the EM follow-up observations that were performed in the different bands

Performance of the CMS muon trigger system in proton-proton collisions at √s = 13 TeV

The muon trigger system of the CMS experiment uses a combination of hardware and software to identify events containing a muon. During Run 2 (covering 2015-2018) the LHC achieved instantaneous luminosities as high as 2 × 10 cm s while delivering proton-proton collisions at √s = 13 TeV. The challenge for the trigger system of the CMS experiment is to reduce the registered event rate from about 40 MHz to about 1 kHz. Significant improvements important for the success of the CMS physics program have been made to the muon trigger system via improved muon reconstruction and identification algorithms since the end of Run 1 and throughout the Run 2 data-taking period. The new algorithms maintain the acceptance of the muon triggers at the same or even lower rate throughout the data-taking period despite the increasing number of additional proton-proton interactions in each LHC bunch crossing. In this paper, the algorithms used in 2015 and 2016 and their improvements throughout 2017 and 2018 are described. Measurements of the CMS muon trigger performance for this data-taking period are presented, including efficiencies, transverse momentum resolution, trigger rates, and the purity of the selected muon sample. This paper focuses on the single- and double-muon triggers with the lowest sustainable transverse momentum thresholds used by CMS. The efficiency is measured in a transverse momentum range from 8 to several hundred GeV

Search for long-lived particles decaying to jets with displaced vertices in proton-proton collisions at root s=13 Te V

A search is presented for long-lived particles produced in pairs in proton-proton collisions at the LHC operating at a center-of-mass energy of 13 TeV. The data were collected with the CMS detector during the period from 2015 through 2018, and correspond to a total integrated luminosity of 140 fb(-1). This search targets pairs of long-lived particles with mean proper decay lengths between 0.1 and 100 mm, each of which decays into at least two quarks that hadronize to jets, resulting in a final state with two displaced vertices. No significant excess of events with two displaced vertices is observed. In the context of R-parity violating supersymmetry models, the pair production of long-lived neutralinos, gluinos, and top squarks is excluded at 95% confidence level for cross sections larger than 0.08 fb, masses between 800 and 3000 GeV, and mean proper decay lengths between 1 and 25 mm.Peer reviewe