Search results for " response"
showing 10 items of 2127 documents
Safety and efficacy of anti-PD-1 inhibitor ABBV-181 in lung and head and neck carcinoma
2019
Abstract Background ABBV-181 is a humanized anti-PD1 monoclonal antibody; dose finding and early safety, PK and pharmacodynamic data have been reported (ESMO18). This report summarizes data from the head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC) expansion cohorts in the Ph1 FIH study (NCT03000257). Methods Patients (pts) with previously treated, advanced HNSCC and NSCLC received ABBV-181 IV, 250 mg Q2W or 500 mg Q4W to progression. Response was assessed by RECIST v1.1 and iRECIST. Results As of April 2019, 81 pts were dosed. Table . 1288P n (%) HNSCC n = 41 NSCLC n = 40 Median days on treatment, range 72, 1–407 71, 1–421 Dose: 250 mg/500 mg 31/10 19/21 …
Insulin Dissociates the Effects of Liver X Receptor on Lipogenesis, Endoplasmic Reticulum Stress, and Inflammation
2016
IF 4.258; International audience; Diabetes is characterized by increased lipogenesis as well as increased endoplasmic reticulum (ER) stress and inflammation. The nuclear hormone receptor liver X receptor (LXR) is induced by insulin and is a key regulator of lipid metabolism. It promotes lipogenesis and cholesterol efflux, but suppresses endoplasmic reticulum stress and inflammation. The goal of these studies was to dissect the effects of insulin on LXR action. We used antisense oligonucleotides to knock down Lxr alpha in mice with hepatocytespecific deletion of the insulin receptor and their controls. We found, surprisingly, that knock-out of the insulin receptor and knockdown of Lxr alpha …
Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins
2017
Viral diseases remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral diseases, new treatments are urgently needed. Here we show that small-molecules, which inhibit cellular anti-apoptotic Bcl-2 proteins (Bcl-2i), induced the premature death of cells infected with different RNA or DNA viruses, whereas, at the same concentrations, no toxicity was observed in mock-infected cells. Moreover, these compounds limited viral replication and spread. Surprisingly, Bcl-2i also induced the premature apoptosis of cells transfected with viral RNA or plasmid DNA but not of mock-transfected cells. These results suggest that Bcl-2i sensiti…
HIV infection with viro-immunological dissociation in a patient with polycystic kidney disease: Candidate for transplantation?
2016
Highlights • Autosomal dominant polycystic kidney disease is the most common among inherited cystic kidney diseases. • Patients with HIV infection are at risk of developing acute kidney injury and chronic kidney disease. • We provide the first report of HIV infection in a patient with polycystic kidney disease. • Lymphopenia should not contraindicate kidney transplantation in patients with HIV infection.
The Yeast eIF2 Kinase Gcn2 Facilitates H 2 O 2 -Mediated Feedback Inhibition of Both Protein Synthesis and Endoplasmic Reticulum Oxidative Folding du…
2021
Recombinant protein production is a known source of oxidative stress. However, knowledge of which reactive oxygen species are involved or the specific growth phase in which stress occurs remains lacking. Using modern, hypersensitive genetic H2O2-specific probes, microcultivation, and continuous measurements in batch culture, we observed H2O2 accumulation during and following the diauxic shift in engineered Saccharomyces cerevisiae, correlating with peak α-amylase production. In agreement with previous studies supporting a role of the translation initiation factor kinase Gcn2 in the response to H2O2, we find that Gcn2-dependent phosphorylation of eIF2α increases alongside translational atten…
Interactive effects of increased temperature and gadolinium pollution in Paracentrotus lividus sea urchin embryos: a climate change perspective
2021
Gradual ocean warming and marine heatwaves represent major threats for marine organisms already facing other anthropogenic-derived hazards, such as chemical contamination in coastal areas. In this study, the combined effects of thermal stress and exposure to gadolinium (Gd), a metal used as a contrasting agent in medical imaging which enters the aquatic environment, were investigated in the embryos and larvae of the sea urchin Paracentrotus lividus. Embryos were exposed to six treatments of three temperatures (18 °C, 21 °C, 24 °C) and two Gd concentrations (control: 0 μM; treated: 20 μM). With respect to developmental progression, increased temperature accelerated development and achievemen…
Balance Perturbations as a Measurement Tool for Trunk Impairment in Cross-Country Sit Skiing
2018
In cross-country sit-skiing, the trunk plays a crucial role in propulsion generation and balance maintenance. Trunk stability is evaluated by automatic responses to unpredictable perturbations; however, electromyography is challenging. The aim of this study was to identify a measure to group sit-skiers according to their ability to control the trunk. Seated in their competitive sit-ski, 10 male and 5 female Paralympic sit-skiers received 6 forward and 6 backward unpredictable perturbations in random order. k-means clustered trunk position at rest, delay to invert the trunk motion, and trunk range of motion significantly into 2 groups. In conclusion, unpredictable perturbations might quantif…
Housing market shocks in italy: A GVAR approach
2020
Abstract In this paper, we use a Global Vector Autoregression (GVAR) model to assess the spatio-temporal mechanism of house price spillovers, also known as “ripple effect”, among 93 Italian provincial housing markets, over the period 2004 − 2016 . In order to better capture the local housing market dynamics, we use data not only on house prices but also on transaction volumes. In particular, we focus on estimating, to what extent, exogenous shocks, interpreted as negative housing demand shocks, arising from 10 Italian regional capitals, impact on their house prices and sales and how these shocks spill over to neighbours housing markets. The negative housing market demand shock hitting the G…
The measurement of populist attitudes: Testing cross-national scales using item response theory
2019
Recent research in the populism literature has devoted considerable efforts to the conceptualisation and examination of populism on the individual level, that is, populist attitudes. Despite rapid progress in the field, questions of adequate measurement and empirical evaluation of measures of populist attitudes remain scarce. Seeking to remedy these shortcomings, we apply a cross-national measurement model, using item response theory, to six established and two new populist indicators. Drawing on a cross-national survey (nine European countries, n = 18,368), we engage in a four-folded analysis. First, we examine the commonly used 6-item populism scale. Second, we expand the measurement wit…
Respuesta sexual en el varón adulto: estudio preliminar
2016
Las personas mayores cada vez otorgan más importancia a la vivencia activa de su sexualidad, lo que choque con algunas de las limitaciones físicas que impone la vejez. El objetivo de este trabajo es acercarnos a la vivencia de la sexualidad en hombres mayores a través de uno de los principales cuestionarios empleados en el estudio de la respuesta sexual masculina: el Índice Internacional de la Función Eréctil. Para ello, 38 hombres de entre 53 y 81 años completaron este y otros instrumentos a través de los cuales se encontró que si bien algunos aspectos de la respuesta sexual (como la función eréctil o el deseo sexual) efectivamente se veían afectados negativamente en hombres mayores, el im…