Gastrointestinal stromal tumors (GISTs): Point mutations matter in management, a review

The therapeutic implications of the genomic alterations seen within the drivers of gastrointestinal stromal tumors (GIST) are among the best understood in all of solid tumors. Sequencing of cKIT and PDGFRα should be considered standard practice for the treatment of GIST patients. In this article, we will review the common mutations and how they are utilized in clinical management. In addition, we will review the rare D842V PDGFRα mutation and the diverse molecular group that lacks a mutation in either cKIT or PDGFRα (wild-type GIST) which are best treated on clinical trial. Finally, we will look forward at the future therapies that are ever evolving for management of GIST. Taken together, the scientific advances in understanding the molecular basis of GIST validates the importance of knowing and understanding the mutations that are present in any one patient

Can GPR4 be a potential therapeutic target for COVID-19?

This study was supported in part by the North Carolina COVID-19 Special State Appropriations. Research in the author's laboratory was also supported by a grant from the National Institutes of Health (R15DK109484, to LY).Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first emerged in late 2019 and has since rapidly become a global pandemic. SARS-CoV-2 infection causes damages to the lung and other organs. The clinical manifestations of COVID-19 range widely from asymptomatic infection, mild respiratory illness to severe pneumonia with respiratory failure and death. Autopsy studies demonstrate that diffuse alveolar damage, inflammatory cell infiltration, edema, proteinaceous exudates, and vascular thromboembolism in the lung as well as extrapulmonary injuries in other organs represent key pathological findings. Herein, we hypothesize that GPR4 plays an integral role in COVID-19 pathophysiology and is a potential therapeutic target for the treatment of COVID-19. GPR4 is a pro-inflammatory G protein-coupled receptor (GPCR) highly expressed in vascular endothelial cells and serves as a “gatekeeper� to regulate endothelium-blood cell interaction and leukocyte infiltration. GPR4 also regulates vascular permeability and tissue edema under inflammatory conditions. Therefore, we hypothesize that GPR4 antagonism can potentially be exploited to mitigate the hyper-inflammatory response, vessel hyper-permeability, pulmonary edema, exudate formation, vascular thromboembolism and tissue injury associated with COVID-19.ECU Open Access Publishing Support Fun

Towards a New Science of a Clinical Data Intelligence

In this paper we define Clinical Data Intelligence as the analysis of data generated in the clinical routine with the goal of improving patient care. We define a science of a Clinical Data Intelligence as a data analysis that permits the derivation of scientific, i.e., generalizable and reliable results. We argue that a science of a Clinical Data Intelligence is sensible in the context of a Big Data analysis, i.e., with data from many patients and with complete patient information. We discuss that Clinical Data Intelligence requires the joint efforts of knowledge engineering, information extraction (from textual and other unstructured data), and statistics and statistical machine learning. We describe some of our main results as conjectures and relate them to a recently funded research project involving two major German university hospitals.Comment: NIPS 2013 Workshop: Machine Learning for Clinical Data Analysis and Healthcare, 201

Empirical comparison of high gradient achievement for different metals in DC and pulsed mode

For the SwissFEL project, an advanced high gradient low emittance gun is under development. Reliable operation with an electric field, preferably above 125 MV/m at a 4 mm gap, in the presence of an UV laser beam, has to be achieved in a diode configuration in order to minimize the emittance dilution due to space charge effects. In the first phase, a DC breakdown test stand was used to test different metals with different preparation methods at voltages up to 100 kV. In addition high gradient stability tests were also carried out over several days in order to prove reliable spark-free operation with a minimum dark current. In the second phase, electrodes with selected materials were installed in the 250 ns FWHM, 500 kV electron gun and tested for high gradient breakdown and for quantum efficiency using an ultra-violet laser.Comment: 25 pages, 13 figures, 5 tables. Follow up from FEL 2008 conference (Geyongju Korea 2008) New Title in JVST A (2010) : Vacuum breakdown limit and quantum efficiency obtained for various technical metals using DC and pulsed voltage source

Studies on charge production from Cs2Te photocathodes in the PITZ L-band normal conducting radio frequency photo injector

This paper discusses the behavior of electron bunch charge produced in an L-band normal conducting radio frequency cavity (RF gun) from Cs2Te photocathodes illuminated with ps-long UV laser pulses when the laser transverse distribution consists of a flat-top core with Gaussian-like decaying halo. The produced charge shows a linear dependence at low laser pulse energies as expected in the quantum efficiency limited emission regime, while its dependence on laser pulse energy is observed to be much weaker for higher values, due to space charge limited emission. However, direct plug-in of experimental parameters into the space charge tracking code ASTRA yields lower output charge in the space charge limited regime compared to measured values. The rate of increase of the produced charge at high laser pulse energies close to the space charge limited emission regime seems to be proportional to the amount of halo present in the radial laser profile since the charge from the core has saturated already. By utilizing core + halo particle distributions based on measured radial laser profiles, ASTRA simulations and semi-analytical emission models reproduce the behavior of the measured charge for a wide range of RF gun and laser operational parameters within the measurement uncertainties.Comment: 15 pages, 16 figures, 2 table

Photocathode laser based bunch shaping for high transformer ratio plasma wakefield acceleration

Beam driven plasma acceleration is one of the most promising candidates for future compact particle accelerator technologies. In this scheme a particle bunch drives a wake in a plasma medium. The fields inside of the wake can be used to accelerate a trailing witness bunch. To maximise the ratio between acceleration of the witness to deceleration of the drive bunch, the so called transformer ratio, several methods have been proposed. The ones yielding the most favorable results are based on shaped drive bunches that are long in terms of the plasma wavelength. We present here methods to create such drive bunches employing temporally shaped UV-laser pulses for the extraction of electron bunches from a photo-electron gun. Theoretical considerations, experimental results and possibilities for further improvements are discussed