Prostate cancer is the most common cancer in men from Western industrialized countries and a significant proportion of patients progress to advanced metastatic disease, for which currently no ...curative treatment exists. Therefore, new therapeutic approaches need to be considered. Prostate specific membrane antigen (PSMA) is an integral, non-shed type 2 membrane protein that is highly and specifically expressed on prostate epithelial cells and strongly upregulated in prostate cancer. PSMA is also present in the neovasculature of other solid tumors. These findings have spurred the development of PSMA-targeted therapies and first-generation products have entered clinical testing. The proposed strategies range from targeted toxins and radionuclides to immunotherapeutic agents. The present review provides an overview of these approaches.
Unfolding and Validation of SREM Fluxes Sandberg, I.; Daglis, I. A.; Anastasiadis, A. ...
IEEE transactions on nuclear science,
08/2012, Letnik:
59, Številka:
4
Journal Article
Recenzirano
Odprti dostop
The Standard Radiation Environment Monitor (SREM) belongs to a second generation of instruments in a program established by the European Research and Technology Centre of the European Space Agency ...(ESA) to provide minimum intrusive particle radiation detectors on ESA spacecraft for space weather applications, which are also suitable for scientific investigations.
Summary
Capnography (ETCO2) is routinely used as a non‐invasive estimate of arterial carbon dioxide (PaCO2) levels in order to modify ventilatory settings, whereby it is assumed that there is a ...positive gap between PaCO2 and ETCO2 of approximately 0.5 kPa. However, negative values (ETCO2 > PaCO2) can be observed. We retrospectively analysed arterial to end‐tidal carbon dioxide differences in 799 children undergoing general anaesthesia with mechanical ventilation of the lungs in order to elucidate predictors for a negative gap. A total of 2452 blood gas analysis readings with complete vital sign monitoring, anaesthesia gas analysis and spirometry data were analysed. Mean arterial to end‐tidal carbon dioxide difference was −0.18 kPa (limits of 95% agreement −1.10 to 0.74) and 71.2% of samples demonstrated negative values. The intercept model revealed PaCO2 to be the strongest predictor for a negative PaCO2‐ETCO2 difference. A decrease in PaCO2 by 1 kPa resulted in a decrease in the PaCO2‐ETCO2 difference by 0.23 kPa. This study demonstrates that ETCO2 monitoring in children whose lungs are mechanically ventilated may paradoxically lead to overestimation of ETCO2 (ETCO2 > PaCO2) with a subsequent risk of unrecognised hypocarbia.
X-ray spectroscopy of kaonic atoms provides a versatile tool to study the strong interaction at low energies via a direct observation of its influence on the ground state of kaonic hydrogen atoms. ...The SIDDHARTA experiment provided precise results on the energy shift and width of the kaonic hydrogen 1s state induced by the strong interaction. To enable the extraction of the antikaon-nucleon scattering lengths a0 and a1, SIDDHARTA-2 aims to determine the energy shift and width in kaonic deuterium with precisions of 30 eV and 75 eV, respectively. This measurement is aggravated by the low kaonic deuterium X-ray yield and a high background environment and will only be possible by implementing a severe upgrade on the SIDDHARTA apparatus.
Pionic hydrogen and deuterium Gotta, D.; Amaro, F.D.; Anagnostopoulos, D.F. ...
EPJ Web of conferences,
2022, Letnik:
262
Journal Article
Recenzirano
Odprti dostop
The strong-interaction effects both in pionic hydrogen and deuterium atoms have been re-determined with improved precision. The hadronic shift and width in pionic hydrogen together with the hadronic ...shift in pionic deuterium constitute a one-fold constraint for the two independent pion-nucleon scattering lengths. Furthermore, the hadronic width in pionic deuterium measures the transition strength of s-wave pions on an isoscalar nucleon-nucleon pair which is an independent quantity not related to the pion-nucleon scattering lengths. The experiment was performed at the Paul Scherrer Institute by stopping a high-intensity low-energy pion beam in gaseous targets using the cyclotron trap. The X-rays emitted by the πH and πD atoms were analysed with a high resolution Bragg spectrometer equipped with spherically bent crystals. The pion-nucleon scattering lengths and other physical quantities extracted from the atom data are in good agreement with the results obtained from pionnucleon and nucleon-nucleon scattering experiments and confirm that a consistent picture is achieved for the low-energy pion-nucleon sector with respect to the expectations of chiral perturbation theory.
Background
Although cancer of the prostate is one of the most commonly diagnosed cancers in men, no curative treatment currently exists after its progression beyond resectable boundaries. Therefore, ...new agents for targeted treatment strategies are needed. Cross-linking of tumor antigens with T-cell associated antigens by bispecific monoclonal antibodies have been shown to increase antigen-specific cytotoxicity in T-cells. Since the prostate-specific membrane antigen (PSMA) represents an excellent tumor target, immunotherapy with bispecific diabodies could be a promising novel treatment option for prostate cancer.
Methods
A heterodimeric diabody specific for human PSMA and the T-cell antigen CD3 was constructed from the DNA of anti-CD3 and anti-PSMA single chain Fv fragments (scFv). It was expressed in
E. coli
using a vector containing a bicistronic operon for co-secretion of the hybrid scFv V
H
CD3-V
L
PSMA and V
H
PSMA-V
L
CD3. The resulting PSMAxCD3 diabody was purified from the periplasmic extract by immobilized metal affinity chromatography (IMAC). The binding properties were tested on PSMA-expressing prostate cancer cells and PSMA-negative cell lines as well as on Jurkat cells by flow cytometry. For in vitro functional analysis, a cell viability test (WST) was used. For in vivo evaluation the diabody was applied together with human peripheral blood lymphocytes (PBL) in a C4-2 xenograft-SCID mouse model.
Results
By Blue Native gel electrophoresis, it could be shown that the PSMAxCD3 diabody is mainly a tetramer. Specific binding both to CD3-expressing Jurkat cells and PSMA-expressing C4-2 cells was shown by flow cytometry. In vitro, the diabody proved to be a potent agent for retargeting PBL to lyze C4-2 prostate cancer cells. Treatment of SCID mice inoculated with C4-2 tumor xenografts with the diabody and PBL efficiently inhibited tumor growth.
Conclusions
The PSMAxCD3 diabody bears the potential for facilitating immunotherapy of prostate cancer and for the elimination of minimal residual disease.
Ischemic brain damage has been reported in healthy patients after beach chair position for surgery due to cerebral hypoperfusion. Near-infrared spectroscopy has been described as a non-invasive, ...continuous method to monitor cerebral oxygen saturation. However, its impact on neurobehavioral outcome comparing different anesthesia regimens has been poorly described.
In this prospective, assessor-blinded study, 90 patients undergoing shoulder surgery in beach chair position following general (G-group, n=45) or regional anesthesia (R-group; n=45) were enrolled to assess the prevalence of cerebral desaturation events comparing anesthesia regimens and their impact on neurobehavioral and neurological outcome. Anesthesiologists were blinded to regional cerebral oxygen saturation values. Baseline data assessed the day before surgery included neurological and neurobehavioral tests, which were repeated the day after surgery. The baseline data for regional cerebral oxygen saturation/bispectral index and invasive blood pressure both at heart and auditory meatus levels were taken prior to anesthesia, 5 min after induction of anesthesia, 5 min after beach chair positioning, after skin incision and thereafter all 20 min until discharge.
Patients in the R-group showed significantly less cerebral desaturation events (p<0.001), drops in regional cerebral oxygen saturation values (p<0.001), significantly better neurobehavioral test results the day after surgery (p<0.001) and showed a greater hemodynamic stability in the beach chair position compared to patients in the G-group.
The incidence of regional cerebral oxygen desaturations seems to influence the neurobehavioral outcome. Regional anesthesia offers more stable cardiovascular conditions for shoulder surgery in beach chair position influencing neurobehavioral test results at 24h.
Mars' polar layered deposits record its climate history. However, no deposit yet analyzed provides a global water cycle record that can be tied to a specific orbital history. Here, I fill this gap by ...analyzing H2O ice layer formation in Mars' south polar Massive CO2 Ice Deposit (MCID), a 510,000‐year climate record. Statistical analyses of ∼109 formation model runs compared to observed stratigraphy indicate a variable H2O deposition rate of ∼1, 0.1, and 0.01 mm yr−1 at 20, 24, and 28° ^{\circ}$ obliquity, respectively—likely recording the obliquity‐dependent midlatitude‐to‐pole H2O transport rate. The MCID record allows unprecedented obliquity‐driven H2O ice deposition rate derivation because of its well‐defined age relative to other deposits and its CO2 cold‐trapping effect, which simplifies local seasonal and long‐term H2O flux. The recovery of an orbit‐resolved H2O transport rate is an essential step in elucidating Mars' global, orbit‐driven water cycle.
Plain Language Summary
Mars' south pole hosts a deposit of alternating CO2 and H2O ice layers, which contain a record of global H2O and CO2 transport as Mars' orbit evolved during the past 510 thousand years. I created a numerical model to simulate the build‐up of the layers over time and ran the model approximately one billion times, each time using a different governing function of H2O ice deposition as a function of Mars' orbital configuration. Using statistical analysis, I found that an H2O ice deposition function that exponentially decreases as a function of obliquity (spin‐axis tilt) best recreates the observed layer sequence. Recovery of a south polar H2O‐ice‐deposition‐versus‐obliquity function is novel and important for elucidating how Mars' global water cycle is driven by its orbital variations.
Key Points
H2O ice layers in Mars' Massive CO2 Ice Deposit record obliquity‐mediated rates of midlatitude‐to‐pole H2O transport over the past 510 kyr
The record's unique CO2 cold‐trapping environment isolates the orbit‐forcing signal from other processes, simplifying its interpretation
Orbit‐resolved H2O transport rates place an important new quantitative bound on processes driving Mars' recent (∼3.5 Myr) global water cycle
The PANDA Barrel DIRC detector Hoek, M.; Dzhygadlo, R.; Gerhardt, A. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
12/2014, Letnik:
766
Journal Article
Recenzirano
The PANDA experiment at the new Facility for Antiproton and Ion Research in Europe (FAIR) at GSI, Darmstadt, will study fundamental questions of hadron physics and QCD using high-intensity cooled ...antiproton beams with momenta between 1.5 and 15 GeV/c. Efficient Particle Identification for a wide momentum range and the full solid angle is required for reconstructing the various physics channels of the PANDA program. Hadronic Particle Identification in the barrel region of the detector will be provided by a DIRC counter. The design is based on the successful BABAR DIRC with important improvements, such as focusing optics and fast photon timing. Several of these improvements, including different radiator geometries and optics, were tested in particle beams at GSI and at CERN. The evolution of the conceptual design of the PANDA Barrel DIRC and the performance of complex prototypes in test beam campaigns will be discussed.
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