Abstract
We present a framework for characterizing the spatiotemporal power spectrum of the variability expected from the horizon-scale emission structure around supermassive black holes, and we ...apply this framework to a library of general relativistic magnetohydrodynamic (GRMHD) simulations and associated general relativistic ray-traced images relevant for Event Horizon Telescope (EHT) observations of Sgr A*. We find that the variability power spectrum is generically a red-noise process in both the temporal and spatial dimensions, with the peak in power occurring on the longest timescales and largest spatial scales. When both the time-averaged source structure and the spatially integrated light-curve variability are removed, the residual power spectrum exhibits a universal broken power-law behavior. On small spatial frequencies, the residual power spectrum rises as the square of the spatial frequency and is proportional to the variance in the centroid of emission. Beyond some peak in variability power, the residual power spectrum falls as that of the time-averaged source structure, which is similar across simulations; this behavior can be naturally explained if the variability arises from a multiplicative random field that has a steeper high-frequency power-law index than that of the time-averaged source structure. We briefly explore the ability of power spectral variability studies to constrain physical parameters relevant for the GRMHD simulations, which can be scaled to provide predictions for black holes in a range of systems in the optically thin regime. We present specific expectations for the behavior of the M87* and Sgr A* accretion flows as observed by the EHT.
IntroductionRepetitive transcranial magnetic stimulation (rTMS) with theta burst stimulation (i.e. TBS) of the dorsolateral prefrontal cortex (DLPFC) is an innovative treatment for major depressive ...disorder (MDD). However, fewer than 50% of patients show sufficient response to this treatment; markers for response prediction are urgently needed. Research shows considerable individual variability in the brain responses to rTMS. However, whether differences in individual DLPFC modulation by rTMS can be used as a predictive marker for treatment response remains to be investigated. Here, we present a research programme that will exploit the combination of functional near-infrared spectroscopy (fNIRS) with brain stimulation. Concurrent TBS/fNIRS will allow us to systematically investigate TBS-induced modulation of blood oxygenation as a proxy for induced brain activity changes. The findings from this study will (1) elucidate the immediate effects of excitatory and inhibitory TBS on prefrontal activity in TBS treatment-naïve patients with MDD and (2) validate the potential utility of TBS-induced brain modulation at baseline for the prediction of antidepressant response to 4 weeks of daily TBS treatment.Methods and analysisOpen-label, parallel-group experiment consisting of two parts. In part 1, 70 patients and 37 healthy controls will be subjected to concurrent TBS/fNIRS. Intermittent TBS (iTBS) and continuous TBS (cTBS) will be applied on the left and right DLPFC, respectively. fNIRS data will be acquired before, during and several minutes after stimulation. In part 2, patients who participated in part 1 will receive a 4 week iTBS treatment of the left DLPFC, performed daily for 5 days per week. Psychometric evaluation will be performed periodically and at 1 month treatment follow-up. Statistical analysis will include a conventional, as well as a machine learning approach.Ethics and disseminationEthics approval was obtained from the Institutional Review Board. Findings will be disseminated through scientific journals, conferences and university courses.Trial registration numberNCT04526002.
BRCA1 or BRCA2-mutated breast cancers are sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors and platinum agents owing to deficiency in homologous recombination repair of DNA damage. In this ...trial, we compared veliparib versus placebo in combination with carboplatin and paclitaxel, and continued as monotherapy if carboplatin and paclitaxel were discontinued before progression, in patients with HER2-negative advanced breast cancer and a germline BRCA1 or BRCA2 mutation.
BROCADE3 was a randomised, double-blind, placebo-controlled, phase 3 trial done at 147 hospitals in 36 countries. Eligible patients (aged ≥18 years) had deleterious germline BRCA1 or BRCA2 mutation-associated, histologically or cytologically confirmed advanced HER2-negative breast cancer, an Eastern Cooperative Oncology Group performance status of 0–2, and had received up to two previous lines of chemotherapy for metastatic disease. Patients were randomly assigned (2:1) by interactive response technology by means of permuted blocks within strata (block size of 3 or 6) to carboplatin (area under the concentration curve 6 mg/mL per min intravenously) on day 1 and paclitaxel (80 mg/m2 intravenously) on days 1, 8, and 15 of 21-day cycles combined with either veliparib (120 mg orally twice daily, on days −2 to 5) or matching placebo. If patients discontinued carboplatin and paclitaxel before progression, they could continue veliparib or placebo at an intensified dose (300 mg twice daily continuously, escalating to 400 mg twice daily if tolerated) until disease progression. Patients in the control group could receive open-label veliparib monotherapy after disease progression. Randomisation was stratified by previous platinum use, history of CNS metastases, and oestrogen and progesterone receptor status. The primary endpoint was investigator-assessed progression-free survival per Response Evaluation Criteria in Solid Tumors version 1.1. Efficacy analyses were done by intention to treat, which included all randomly assigned patients with a centrally confirmed BRCA mutation, and safety analyses included all patients who received at least one dose of velilparib or placebo. This study is ongoing and is registered with ClinicalTrials.gov, NCT02163694.
Between July 30, 2014, and Jan 17, 2018, 2202 patients were screened, of whom 513 eligible patients were enrolled and randomly assigned. In the intention-to-treat population (n=509), 337 patients were assigned to receive veliparib plus carboplatin–paclitaxel (veliparib group) and 172 were assigned to receive placebo plus carboplatin–paclitaxel (control group). Median follow-up at data cutoff (April 5, 2019) was 35·7 months (IQR 24·9–43·6) in the veliparib group and 35·5 months (23·1–45·9) in the control group. Median progression-free survival was 14·5 months (95% CI 12·5–17·7) in the veliparib group versus 12·6 months (10·6–14·4) in the control group (hazard ratio 0·71 95% CI 0·57–0·88, p=0·0016). The most common grade 3 or worse adverse events were neutropenia (272 81% of 336 patients in the veliparib group vs 143 84% of 171 patients in the control group), anaemia (142 42% vs 68 40%), and thrombocytopenia (134 40% vs 48 28%). Serious adverse events occurred in 115 (34%) patients in the veliparib group versus 49 (29%) patients in the control group. There were no study drug-related deaths.
The addition of veliparib to a highly active platinum doublet, with continuation as monotherapy if the doublet were discontinued, resulted in significant and durable improvement in progression-free survival in patients with germline BRCA mutation-associated advanced breast cancer. These data indicate the utility of combining platinum and PARP inhibitors in this patient population.
AbbVie.
The new INFN-CHNet neutron imaging facility Gelli, N.; Giuntini, L.; Cantini, F. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
June 2023, 2023-06-00, Letnik:
1051
Journal Article
Recenzirano
In this paper, NICHE (Neutron Imaging for Cultural HEritage), the new neutron imaging facility of the Italian National Institute of Nuclear Physics (INFN) is shortly presented. We report on the main ...features of the beamline, the specifications of the detection set-up, and the performances of the imaging system. NICHE is installed at the TRIGA reactor of LENA (Laboratorio Energia Nucleare Applicata) Pavia University laboratory (Italy). The imaging facility was designed during 2020, installed in the spring 2021, and has been in operation since May 2021. NICHE is the first Italian neutron imaging station open to national external users through the INFN-CHNet network application system. NICHE allows users to obtain neutron radiographies and tomographies, thus allowing for morphological characterisation of samples. First results to highlight the potential of the facility are reported. In particular, we show the first results about spatial resolution measurement and 3D reconstruction to provide morphological analysis capabilities.
Exposure of cells to colloidal nanoparticles (NPs) can have concentration-dependent harmful effects. Mostly, such effects are monitored with biochemical assays or probes from molecular biology, i.e., ...viability assays, gene expression profiles, etc., neglecting that the presence of NPs can also drastically affect cellular morphology. In the case of polymer-coated Au NPs, we demonstrate that upon NP internalization, cells undergo lysosomal swelling, alterations in mitochondrial morphology, disturbances in actin and tubulin cytoskeleton and associated signaling, and reduction of focal adhesion contact area and number of filopodia. Appropriate imaging and data treatment techniques allow for quantitative analyses of these concentration-dependent changes. Abnormalities in morphology occur at similar (or even lower) NP concentrations as the onset of reduced cellular viability. Cellular morphology is thus an important quantitative indicator to verify harmful effects of NPs to cells, without requiring biochemical assays, but relying on appropriate staining and imaging techniques.
Fragility fractures, a major public health concern, are expected to further increase due to aging of the world populations because age remains a cardinal, independent determinant of fracture risk. ...With aging the balance between bone formation and resorption during the remodeling process becomes negative, with increased resorption and reduced formation. Bisphosphonates (BPs) are widely prescribed anti-resorptive agents that inhibit osteoclasts attachment to bone matrix and enhance osteoclast apoptosis. BPs can be divided into nitrogen-containing (N-BPs) and non-nitrogen-containing BPs (non-N-BPs). Both classes induce apoptosis but they evoke it differently. Several studies have examined the molecular mechanisms underlying BPs’ effects on osteoclasts and bone remodeling. N-BPs (alendronate, risedronate, zoledronate) inhibit the intracellular mevalonate pathway and protein isoprenylation, via the enzyme farnesyl pyrophosphate synthase. N-BPs act by competition, binding to the natural substrate-binding site of the enzyme. The less potent non-N-BPs (etidronate, clodronate), do not inhibit the mevalonate pathway and protein isoprenylation, but are metabolized intracellularly to metabolites, which are cytotoxic analogs of ATP. N-BPs represent the first choice treatment for diseases associated with excessive bone resorption, such as fragility fractures (due to postmenopausal-, male, glucocorticoid- and transplant-induced osteoporosis), Paget’s disease of bone, and bone metastasis. Better understanding of BPs’ effects on osteoblasts/osteocytes (e.g., preventing apoptosis) and differential distribution may further help explain anti-fracture benefit and bone quality effects. Lower affinity BPs (e.g., risedronate) may allow better access to osteocyte network. Effects of BPs on bone senescence, cancer cells apoptosis and prevention of cardiovascular calcifications may open new avenues for biogerontological research.
•An Eco-friendly electro-organic synthetic method for 2-(4,5-diphenyl-1H-imidazol-2-yl)phenol (DIP) using two electrode system.•DIP was synthesized in aqueous medium with good economical yield and ...showed excellent capacitance behaviour.•DIP as a monomer itself exhibited pseudocapacitive behaviour.•DIP showed 93.7% specific capacitance retention in the supercapacitor measurement.
An efficient cost-effective and eco-friendly electro-organic synthesis of 2-(4,5-diphenyl-1H-imidazol-2-yl)phenol (DIP) in aqueous medium and its application as an electrode material for supercapacitor are reported here. The as-synthesized derivative was characterized by various spectral and analytical techniques. The optical and physical properties were analyzed by PL studies and by XRD, SEM, BET, TG- DTA and DSC techniques. The electrochemical studies of the electroactive material, DIP were carried out using Cyclic Voltammetry (CV), Galvanostatic Charge – Discharge analysis (GCD) and Electrochemical Impedence Spectroscopy (EIS). DFT calculation of DIP was also performed to evaluate the bandgap energy theoretically. DIP as a monomer exhibited a good capacitive behavior with a specific capacitance of 325F/g at the scan rate of 5mV/s. The results revealed that DIP can be potentially used as a promising electrode material for high performance supercapacitor applications.
Over the last few decades, analyses of wind-driven rain exposure on building façades have been conducted in multiple regions. Sometimes, these studies also included the driving rain wind pressure, ...thereby characterising both critical factors contributing to rainwater penetration into façade materials. However, practitioners typically rely on performance results obtained from standardised watertightness tests to make façade design decisions, even though these tests do not recreate the specific exposure combinations that can occur on each façade. Consequently, there is no quantitative correlation between the traditionally identified exposures and actual façade designs, resulting in pure qualitative choices and poorly optimised designs. This study addresses this issue by correcting the existing methodological deficiencies in a prior calculation procedure, which aims to relate the exposure parameters that the façade configuration withstood during any watertightness test to the expected climate exposures at its design operating conditions. New contributions are presented to enhance the method reliability as well as to reduce calculation effort and reliance on exhaustive weather data. The various climate parameters required to establish this relationship were analysed and tabulated for the Netherlands, enabling a truly performance-based design of façades to resist rainwater penetration throughout the country. Different methods of implementing this procedure, according to the availability of weather data, were also compared for façade case studies located in Amsterdam and Maastricht.
•Quantitative approach for designing façades resistant to rainwater penetration.•Conceptual and mathematical improvements to reduce calculation uncertainties.•Enhanced applicability by reducing method reliance on exhaustive weather records.•Functional database for the performance-based design of Dutch façades.•Method implementation according availability of weather data in two case studies.
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