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Biomedical subjects

L Pinsky

Publications and source records attributed to L Pinsky.

At least 19 recordsLinked to original sources
PubMed2006

Human exposure to space radiation: role of primary and secondary particles.

Human exposure to space radiation implies two kinds of risk, both stochastic and deterministic. Shielding optimisation therefore represents a crucial goal for long-term missions, especially in deep space. In this context, the use of radiation transport codes coupled with anthropomorphic phantoms allows to simulate typical radiation exposures for astronauts behind different shielding, and to calculate doses to different organs. In this work, the FLUKA Monte Carlo code and two phantoms, a mathematical model and a voxel model, were used, taking the Galactic Cosmic Rays (GCR) spectra from the model of Badhwar and O'Neill. The time integral spectral proton fluence of the August 1972 Solar Particle Event (SPE) was represented by an exponential function. For each aluminium shield thickness, besides total doses the contributions from primary and secondary particles for different organs and tissues were calculated separately. More specifically, organ-averaged absorbed doses, dose equivalents and a form of 'biological dose', defined on the basis of initial (clustered) DNA damage, were calculated. As expected, the SPE doses dramatically decreased with increasing shielding, and doses in internal organs were lower than in skin. The contribution of secondary particles to SPE doses was almost negligible; however it is of note that, at high shielding (10 g cm(-2)), most of the secondaries are neutrons. GCR organ doses remained roughly constant with increasing Al shielding. In contrast to SPE results, for the case of cosmic rays, secondary particles accounted for a significant fraction of the total dose.

Astronauts↗
PubMed2005

Omega- and Omega+ production in central Pb + Pb collisions at 40 and 158A GeV.

Results are presented on Omega production in central Pb+Pb collisions at 40 and 158A GeV beam energy. For the first time in heavy ion reactions, rapidity distributions and total yields were measured for the sum Omega(-) + Omega(+) at 40A GeV and for Omega(-) and Omega(+) separately at 158A GeV. The yields are strongly underpredicted by the string-hadronic UrQMD model but agree better with predictions from hadron gas models.

Journal Article↗
PubMed2005

System-size dependence of strangeness production in nucleus-nucleus collisions at squareroot[sNN]=17.3 GeV.

Emission of pi+/-, K+/-, phi, and Lambda was measured in near-central C+C and Si+Si collisions at 158 AGeV beam energy. Together with earlier data for p+p, S+S, and Pb+Pb, the system-size dependence of relative strangeness production in nucleus-nucleus collisions is obtained. Its fast rise and the saturation observed at about 60 participating nucleons can be understood as the onset of the formation of coherent systems of increasing size.

Journal Article↗
PubMed2005

The FLUKA code: new developments and application to 1 GeV/n iron beams.

The modeling of ion transport and interactions in matter is a subject of growing interest, driven by the continuous increase of possible application fields. These include hadron therapy, dosimetry, and space missions, but there are also several issues involving fundamental research, accelerator physics, and cosmic ray physics, where a reliable description of heavy ion induced cascades is important. In the present work, the capabilities of the FLUKA code for ion beams will be briefly recalled and some recent developments presented. Applications of the code to the simulation of therapeutic carbon, nitrogen and oxygen ion beams, and of iron beams, which are of direct interest for space mission related experiments, will be also presented together with interesting consideration relative to the evaluation of dosimetric quantities. Both applications involve ion beams in the AGeV range.

Carbon↗
PubMed2005

The application of FLUKA to dosimetry and radiation therapy.

The FLUKA Monte Carlo code has been evolving over the last several decades and is now widely used for radiation shielding calculations. In order to facilitate the use of FLUKA in dosimetry and therapy applications, supporting software has been developed to allow the direct conversion of the output files from standard CT-scans directly into a voxel geometry for transport within FLUKA. Since the CT-scan information essentially contains only the electron density information over the scanned volume, one needs the specific compositions for each voxel individually. We present here the results of a simple algorithm to assign tissues in the human body to one of four categories: soft-tissue, hard-bone, trabecular-bone and porous-lung. In addition, we explore the problem of the pathlength distributions in porous media such as trabecular bone. A mechanism will be implemented within FLUKA to allow for variable multipal fixed density materials to accommodate the pathlength distributions discovered.

Algorithms↗
PubMed2004

Lambda and lambda production in central Pb-Pb collisions at 40, 80, and 158A GeV.

Production of Lambda and Antilambda hyperons was measured in central Pb-Pb collisions at 40, 80, and 158A GeV beam energy on a fixed target. Transverse mass spectra and rapidity distributions are given for all three energies. The Lambda/pi ratio at midrapidity and in full phase space shows a pronounced maximum between the highest BNL Alternating Gradient Synchrotron and 40A GeV CERN Super Proton Synchrotron energies, whereas the Lambda/pi ratio exhibits a monotonic increase.

Journal Article↗
PubMed2004

Evidence for an exotic S= -2, Q= -2 baryon resonance in proton-proton collisions at the CERN SPS.

Results of resonance searches in the Xi(-)pi(-), Xi(-)pi(+), Xi;(+)pi(-), and Xi;(+)pi(+) invariant mass spectra in proton-proton collisions at sqrt[s]=17.2 GeV are presented. Evidence is shown for the existence of a narrow Xi(-)pi(-) baryon resonance with mass of 1.862+/-0.002 GeV/c(2) and width below the detector resolution of about 0.018 GeV/c(2). The significance is estimated to be above 4.2sigma. This state is a candidate for the hypothetical exotic Xi(--)(3/2) baryon with S=-2, I=3 / 2, and a quark content of (dsdsū). At the same mass, a peak is observed in the Xi(-)pi(+) spectrum which is a candidate for the Xi(0)(3/2) member of this isospin quartet with a quark content of (dsus[-]d). The corresponding antibaryon spectra also show enhancements at the same invariant mass.

Journal Article↗
PubMed2004

Overview of the Martian radiation environment experiment.

Space radiation presents a hazard to astronauts, particularly those journeying outside the protective influence of the geomagnetosphere. Crews on future missions to Mars will be exposed to the harsh radiation environment of deep space during the transit between Earth and Mars. Once on Mars, they will encounter radiation that is only slightly reduced, compared to free space, by the thin Martian atmosphere. NASA is obliged to minimize, where possible, the radiation exposures received by astronauts. Thus, as a precursor to eventual human exploration, it is necessary to measure the Martian radiation environment in detail. The MARIE experiment, aboard the 2001 Mars Odyssey spacecraft, is returning the first data that bear directly on this problem. Here we provide an overview of the experiment, including introductory material on space radiation and radiation dosimetry, a description of the detector, model predictions of the radiation environment at Mars, and preliminary dose-rate data obtained at Mars.

Astronauts↗
PubMed2004

Heavy ion observations by MARIE in cruise phase and Mars orbit.

The charged particle spectrum for nuclei from protons to neon, (charge Z=10) was observed during the cruise phase and orbit around Mars by the MARIE charged particle spectrometer on the Odyssey spacecraft. The cruise data were taken between April 23, 2001 and mid-August 2001. The Mars orbit data were taken March 5, 2002 through May 2002 and are scheduled to continue until August 2004. Charge peaks are clearly separated for charges up to Z=10. Especially prominent are the carbon and oxygen peaks, with boron and nitrogen also clearly visible. Although heavy ions are much less abundant than protons in the cosmic ray environment, it is important to determine their abundances because their ionization energy losses (proportional to Z2) are far more dangerous to humans and to instruments. Thus the higher charged nuclei make a significant contribution to dose and dose equivalent received in space. Results of the charged particle spectrum measurements will be reported.

Calibration↗
PubMed2002

Cloning and characterization of an androgen receptor N-terminal-interacting protein with ubiquitin-protein ligase activity.

The androgen receptor (AR) N-terminal domain plays a critical role in androgen-responsive gene regulation. A novel AR N-terminal-interacting protein (ARNIP) was isolated using the yeast two-hybrid system and its interaction with amino acids 11-172 of the normal or corresponding region of the polyglutamine-expanded human AR confirmed by glutathione S-transferase pulldown assays. ARNIP cDNAs cloned from NSC-34 (mouse neuroblastoma/spinal cord) or PC-3 (human prostate adenocarcinoma) mRNA encoded highly homologous 30 kDa (261 amino acids) cysteine-rich proteins with a RING-H2 (C3H2C3 zinc finger) domain; this motif is highly conserved in predicted ARNIP-homologous proteins from several other species. Expression of the approximately 1.7 kb ARNIP mRNA was detected in various tissues by Northern blotting, but was highest in mouse testes, kidney and several neuronal cell lines. In addition, the human ARNIP protein was found to be encoded by nine exons spanning 32 kb on chromosome 4q21. In COS-1 cells, coexpression of ARNIP and AR did not affect AR ligand-binding kinetics, nor did ARNIP act as a coactivator or corepressor in transactivation assays. However, AR N-terminal:C-terminal interaction was reduced in the presence of ARNIP. Intriguingly, ARNIP, and in particular its RING-H2 domain, functioned as a ubiquitin-protein ligase in vitro in the presence of a specific ubiquitin-conjugating enzyme, Ubc4-1. Mutation of a single cysteine residue in the ARNIP RING-H2 domain (Cys145Ala) abolished this E3 ubiquitin ligase activity. Fluorescent protein tagging studies revealed that AR-ARNIP interaction was hormone-independent in COS-1 cells, and suggest that colocalization of both AR and ARNIP to the nucleus upon androgen addition may allow ARNIP to play a role in nuclear processes. Thus, identification of a novel AR-interacting protein with ubiquitin ligase activity will stimulate further investigation into the role of ubiquitination and the ubiquitin-proteasome system in AR-mediated cellular functions.

Amino Acid Sequence↗
PubMed2001

Event-by-event fluctuations of the Kaon-to-Pion ratio in central Pb+Pb collisions at 158 GeV per nucleon.

We present the first measurement of fluctuations from event to event in the production of strange particles in collisions of heavy nuclei. The ratio of charged kaons to charged pions is determined for individual central Pb+Pb collisions. After accounting for the fluctuations due to detector resolution and finite number statistics we derive an upper limit on genuine nonstatistical fluctuations, which could be related to a first- or second-order QCD phase transition. Such fluctuations are shown to be very small.

Journal Article↗
PubMed2001

Genetic counseling and interpretation of genetic tests in familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer.

PURPOSE: Genetic counseling and interpreting genetic test results can be complex. Moreover, without knowing the limitations of the methods used and the lifetime probability of developing cancer in individuals who carry a gene that predisposes to cancer, misinterpretation may lead to false assurance. The purpose of this review is to discuss how genetic counseling will benefit patients and their family, the genetic tests available for hereditary colorectal cancer syndromes, and the interpretation of results. METHODS: Current literature was reviewed and our clinical and research experiences were incorporated. RESULTS: This review serves as a guide to enable various health care providers to better counsel patients in their quest for advice on prevention, early detection, and surveillance for colorectal cancer. Notable topics of discussion are who should undergo genetic counseling and consider testing and how the interpretation of test results can be misleading; for example, understanding the difference between a no mutation detected vs. a negative test result. CONCLUSIONS: Genetic counseling is of paramount importance for patients to fully understand the limitations of genetic testing and will aid in the management of patients who are susceptible to colorectal cancer.

Adenomatous Polyposis Coli↗
PubMed2001

Role of molecular diagnostic testing in familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer families.

PURPOSE: Genetic tests are available for familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer. The goal of this review was to develop an algorithm for application of molecular diagnostic techniques to the management of hereditary colorectal carcinoma and to familiarize the clinician with the vocabulary of molecular genetic testing for hereditary colorectal carcinoma. METHODS: Studies examining the clinical use of genetic testing for hereditary colorectal carcinoma syndromes are evaluated. Recent advances in molecular genetic technology are reviewed, and clinical management as practiced here and elsewhere is outlined. RESULTS: This review is a guide to the most reliable molecular diagnostic techniques. Three key questions are answered: who, when, and how to test. CONCLUSIONS: When integrated with existing testing protocols for colorectal carcinoma and when applied with appropriate caveats, particularly regarding interpretation of negative results, genetic testing can result in improved management of patients and families.

Adenomatous Polyposis Coli↗
PubMed2001

Characterization of intracellular aggregates using fluorescently-tagged polyglutamine-expanded androgen receptor.

Spinal bulbar muscular atrophy (SBMA) is a classic CAG-repeat neurodegenerative disease. It is caused by expansion of a polyglutamine (polyGln) tract in the androgen receptor (AR). Recent evidence has indicated a potential role for nuclear and cytoplasmic inclusions in the pathogenesis of these diseases. We have used blue and green fluorescently-tagged AR to show that both wild-type (WT) and poly-Gln-expanded full-length AR can form aggregates and that aggregation is not related to cytotoxicity. Twenty to thirty-five percent of all cell types transfected into COS cells showed aggregation containing both amino- and carboxy-terminal fluorescent tags. The aggregates reacted with (F39.4.1), an anti-AR antibody and with IC2, an expanded polyGln tract antibody. Western analysis of protein extracts revealed little evidence of proteolysis although some cleavage of the fusion proteins was seen. The general caspase inhibitor, Z-DEVD-FMK, did not affect aggregation in either wild type or polyGln-expanded GFP-AR transfected cells. Surprisingly, addition of Mibolerone a synthetic androgen significantly decreased inclusion formation in both WT and polyGln-expanded AR-transfected cells. Overall, we show that both WT and polyGln expanded full-length AR are found in aggregates and that proteolysis is not a requirement for aggregation. Our results also suggest that toxicity is not related to intracellular aggregation of polyGln expanded AR.

Journal Article↗
PubMed2001

Simulation of Space Shuttle neutron measurements with FLUKA.

FLUKA is an integrated particle transport code that has enhanced multigroup low-energy neutron transport capability similar to the well-known MORSE transport code. Gammas are produced in groups but many important individual lines are specifically included, and subsequently transported by the main FLUKA routines which use a modified version of EGS4 for electromagnetic (EM) transport. Recoil protons are also transported by the primary FLUKA transport simulation. The neutron cross-section libraries employed within FLUKA were supplied by Giancarlo Panini (ENEA, Italy) based upon the most recent data from JEF-1, JEF-2.2, ENDF/B-VI, JENDL-3, etc. More than 60 different materials are included in the FLUKA databases with temperature ranges including down to cryogenic temperatures. This code has been used extensively to model the neutron environments near high-energy physics experiment shielding. A simulation of the Space Shuttle based upon a spherical aluminum equivalent shielding distribution has been performed with reasonable results. There are good prospects for extending this calculation to a more realistic 3-D geometrical representation of the Shuttle including an accurate representation of its composition, which is an essential ingredient for the improvement of the predictions. A proposed project to develop a combined analysis and simulation package based upon FLUKA and the analysis infrastructure provided by the ROOT software is under active consideration. The code to be developed for this project will be of direct application to the problem of simulating the neutron environment in space, including the albedo effects.

Aluminum↗
PubMed2001

The polymorphic CAG repeat of the androgen receptor gene: a potential role in breast cancer in women over 40.

Previous investigations into the relationship of CAG-repeat lengths in the androgen receptor (AR) gene to female breast cancer (BC) have yielded somewhat confusing results. Decreased AR transactivational activity lowers androgen:estrogen balance, and may thereby effect functional hyperestrogenicity. This may promote the pathogenesis of BC. To elucidate whether longer CAG repeats of the AR gene (AR), which correlate with lower transactivational activity of the AR, are associated with BC in women over 40, we examined the distribution of CAG-repeat lengths in BC tissue from this population. The BC tissue was histologically graded as: Grade 1, well differentiated (WD); Grade 2, moderately differentiated (MD); and Grade 3, poorly-differentiated (PD). Analysis showed significant differences as compared to controls when CAG lengths greater than 21 were examined, and that alleles with > or = 26 repeats were 2.4-fold more frequent in BC samples than in constitutional samples from a normal population. A significant shift to greater CAG-repeat lengths, appeared in WD and MD tumors only. Our results give some indication as to the progression of BC by suggesting that hypotransactive ARs with long polyglutamine (polyGln) tracts may have a role in the initiation and/or progression of BC. PD tumors tended to have shorter than normal CAG-repeat lengths. In this case it is hypothesized that the ARs have now become hypertransactive, possibly coinciding with the estrogen resistance that is associated with PD tumors. Whether this shift is of germline or somatic origin was not clear, though the appearance in 14% of the BC samples of a third CAG-repeat length indicates that it may be somatic.

Adult↗