Influence of nuclear de-excitation on observables relevant for space exploration

The composition of the space radiation environment inside spacecrafts is modified by the interaction with shielding material, with equipment and even with the astronauts' bodies. Accurate quantitative estimates of the effects of nuclear reactions are necessary, for example, for dose estimation and prediction of single-event-upset rates. To this end, it is necessary to construct predictive models for nuclear reactions, which usually consist of an intranuclear-cascade or quantum-molecular-dynamics stage, followed by a nuclear-de-excitation stage. While it is generally acknowledged that it is necessary to accurately simulate the first reaction stage, transport-code users often neglect or underestimate the importance of the choice of the de-excitation code. The purpose of this work is to prove that the de-excitation model is in fact a non-negligible source of uncertainty for the prediction of several observables of crucial importance for space applications. For some particular observables, the systematic uncertainty due to the de-excitation model actually dominates the total uncertainty. Our point will be illustrated by making use of nucleon-nucleus calculations performed with several intranuclear-cascade/de-excitation models, such as the Li\`{e}ge Intranuclear Cascade model (INCL) and Isabel (for the cascade part) and ABLA07, Dresner, GEM, GEMINI++ and SMM (on the de-excitation side).Comment: 12 pages, 6 figures. Presented at the 38th COSPAR Scientific Assembly (Bremen, Germany, 18-25 July 2010). Submitted to Advances in Space Researc

p63 is an alternative p53 repressor in melanoma that confers chemoresistance and a poor prognosis.

The role of apoptosis in melanoma pathogenesis and chemoresistance is poorly characterized. Mutations in TP53 occur infrequently, yet the TP53 apoptotic pathway is often abrogated. This may result from alterations in TP53 family members, including the TP53 homologue TP63. Here we demonstrate that TP63 has an antiapoptotic role in melanoma and is responsible for mediating chemoresistance. Although p63 was not expressed in primary melanocytes, up-regulation of p63 mRNA and protein was observed in melanoma cell lines and clinical samples, providing the first evidence of significant p63 expression in this lineage. Upon genotoxic stress, endogenous p63 isoforms were stabilized in both nuclear and mitochondrial subcellular compartments. Our data provide evidence of a physiological interaction between p63 with p53 whereby translocation of p63 to the mitochondria occurred through a codependent process with p53, whereas accumulation of p53 in the nucleus was prevented by p63. Using RNA interference technology, both isoforms of p63 (TA and ΔNp63) were demonstrated to confer chemoresistance, revealing a novel oncogenic role for p63 in melanoma cells. Furthermore, expression of p63 in both primary and metastatic melanoma clinical samples significantly correlated with melanoma-specific deaths in these patients. Ultimately, these observations provide a possible explanation for abrogation of the p53-mediated apoptotic pathway in melanoma, implicating novel approaches aimed at sensitizing melanoma to therapeutic agents

In-Cell Biochemistry Using NMR Spectroscopy

Biochemistry and structural biology are undergoing a dramatic revolution. Until now, mostly in vitro techniques have been used to study subtle and complex biological processes under conditions usually remote from those existing in the cell. We developed a novel in-cell methodology to post-translationally modify interactor proteins and identify the amino acids that comprise the interaction surface of a target protein when bound to the post-translationally modified interactors. Modifying the interactor proteins causes structural changes that manifest themselves on the interacting surface of the target protein and these changes are monitored using in-cell NMR. We show how Ubiquitin interacts with phosphorylated and non-phosphorylated components of the receptor tyrosine kinase (RTK) endocytic sorting machinery: STAM2 (Signal-transducing adaptor molecule), Hrs (Hepatocyte growth factor regulated substrate) and the STAM2-Hrs heterodimer. Ubiquitin binding mediates the processivity of a large network of interactions required for proper functioning of the RTK sorting machinery. The results are consistent with a weakening of the network of interactions when the interactor proteins are phosphorylated. The methodology can be applied to any stable target molecule and may be extended to include other post-translational modifications such as ubiquitination or sumoylation, thus providing a long-awaited leap to high resolution in cell biochemistry

Spallation reactions. A successful interplay between modeling and applications

The spallation reactions are a type of nuclear reaction which occur in space by interaction of the cosmic rays with interstellar bodies. The first spallation reactions induced with an accelerator took place in 1947 at the Berkeley cyclotron (University of California) with 200 MeV deuterons and 400 MeV alpha beams. They highlighted the multiple emission of neutrons and charged particles and the production of a large number of residual nuclei far different from the target nuclei. The same year R. Serber describes the reaction in two steps: a first and fast one with high-energy particle emission leading to an excited remnant nucleus, and a second one, much slower, the de-excitation of the remnant. In 2010 IAEA organized a worskhop to present the results of the most widely used spallation codes within a benchmark of spallation models. If one of the goals was to understand the deficiencies, if any, in each code, one remarkable outcome points out the overall high-quality level of some models and so the great improvements achieved since Serber. Particle transport codes can then rely on such spallation models to treat the reactions between a light particle and an atomic nucleus with energies spanning from few tens of MeV up to some GeV. An overview of the spallation reactions modeling is presented in order to point out the incomparable contribution of models based on basic physics to numerous applications where such reactions occur. Validations or benchmarks, which are necessary steps in the improvement process, are also addressed, as well as the potential future domains of development. Spallation reactions modeling is a representative case of continuous studies aiming at understanding a reaction mechanism and which end up in a powerful tool.Comment: 59 pages, 54 figures, Revie

The transverse proximity effect in the z ~ 2 Lyman-alpha forest suggests QSO episodic lifetimes of ~1 Myr

We look for signs of the H~I transverse proximity effect in the spectra of 130 QSO pairs, most with transverse separations in the plane of the sky of 0.1 -- 3 Mpc at z ~ 2.2. We expected to see a decrease in Lyman-alpha forest HI absorption in the spectrum of background QSOs near the position of foreground QSOs. Instead we see no change in the absorption in front of the foreground QSOs, and we see evidence for a 50% increase in the absorption out to 6 Mpc behind the foreground QSOs. Further, we see no change in the H I absorption along the line-of-sight to the foreground QSOs, the normal line-of-sight proximity effect. We may account for the lack of change in the H I absorption if the effect of extra UV photons is canceled by higher gas density around QSOs. If so, the increase in absorption behind the QSOs then suggests that the higher gas density there is not canceled by the UV radiation from the QSOs. We can explain our observations if QSOs have had their current UV luminosities for less than approximately a million years, a time scale that has been suggested for accretion disk instabilities and gas depletion.Comment: Submitted for publication in MNRA

Coexistent ARID1A–PIK3CA mutations promote ovarian clear-cell tumorigenesis through pro-tumorigenic inflammatory cytokine signalling

Ovarian clear-cell carcinoma (OCCC) is an aggressive form of ovarian cancer with high ARID1A mutation rates. Here we present a mutant mouse model of OCCC. We find that ARID1A inactivation is not sufficient for tumor formation, but requires concurrent activation of the phosphoinositide 3-kinase catalytic subunit, PIK3CA. Remarkably, the mice develop highly penetrant tumors with OCCC-like histopathology, culminating in hemorrhagic ascites and a median survival period of 7.5 weeks. Therapeutic treatment with the pan-PI3K inhibitor, BKM120, prolongs mouse survival by inhibiting tumor cell growth. Cross-species gene expression comparisons support a role for IL-6 inflammatory cytokine signaling in OCCC pathogenesis. We further show that ARID1A and PIK3CA mutations cooperate to promote tumor growth through sustained IL-6 overproduction. Our findings establish an epistatic relationship between SWI/SNF chromatin remodeling and PI3K pathway mutations in OCCC and demonstrate that these pathways converge on pro-tumorigenic cytokine signaling. We propose that ARID1A protects against inflammation-driven tumorigenesis

Clustering of Low-Redshift (z <= 2.2) Quasars from the Sloan Digital Sky Survey

We present measurements of the quasar two-point correlation function, \xi_{Q}, over the redshift range z=0.3-2.2 based upon data from the SDSS. Using a homogeneous sample of 30,239 quasars with spectroscopic redshifts from the DR5 Quasar Catalogue, our study represents the largest sample used for this type of investigation to date. With this redshift range and an areal coverage of approx 4,000 deg^2, we sample over 25 h^-3 Gpc^3 (comoving) assuming the current LCDM cosmology. Over this redshift range, we find that the redshift-space correlation function, xi(s), is adequately fit by a single power-law, with s_{0}=5.95+/-0.45 h^-1 Mpc and \gamma_{s}=1.16+0.11-0.16 when fit over s=1-25 h^-1 Mpc. Using the projected correlation function we calculate the real-space correlation length, r_{0}=5.45+0.35-0.45 h^-1 Mpc and \gamma=1.90+0.04-0.03, over scales of rp=1-130 h^-1 Mpc. Dividing the sample into redshift slices, we find very little, if any, evidence for the evolution of quasar clustering, with the redshift-space correlation length staying roughly constant at s_{0} ~ 6-7 h^-1 Mpc at z<2.2 (and only increasing at redshifts greater than this). Comparing our clustering measurements to those reported for X-ray selected AGN at z=0.5-1, we find reasonable agreement in some cases but significantly lower correlation lengths in others. We find that the linear bias evolves from b~1.4 at z=0.5 to b~3 at z=2.2, with b(z=1.27)=2.06+/-0.03 for the full sample. We compare our data to analytical models and infer that quasars inhabit dark matter haloes of constant mass M ~2 x 10^12 h^-1 M_Sol from redshifts z~2.5 (the peak of quasar activity) to z~0. [ABRIDGED]Comment: 28 pages, 26 figures, ApJ accepted. Online materials (including source code, catalogues and high-resolution figures) can be found at http://www.astro.psu.edu/users/npr/DR5

Extension of INCL4 between 2 and 15 GeV

The intranuclear cascade model INCL4 has been shown to be very successful for describing, without adjustable parameters, a whole set of data for p-induced reactions in the 40 MeV–2 GeV energy range. In view of its possible application to cosmic ray interactions, the INCL4 code has been extended to the 2–15 GeV energy range, so covering a large part of the spectrum of the incident energy of the cosmic rays. In this paper, the changes brought into the INCL4 code are discussed and some illustrative comparisons between the results given by the modified version of the code and experimental data are presented

Depressive Symptoms, Pain, and Quality of Life among Patients with Nonalcohol-Related Chronic Pancreatitis

Objective. The present study was conducted to determine if depressive symptoms were associated with variability in pain perception and quality of life among patients with nonalcohol-related chronic pancreatitis. Methods. The research design was cross-sectional, and self-report data was collected from 692 patients with nonalcohol-related, intractable pancreatitis. The mean age of the sample was 52.6 (); 41% of the sample were male. Participants completed the MOS SF12 Quality of Life Measure, the Center for Epidemiological Studies 10-item Depression Scale (CESD), and a numeric rating scale measure of “pain on average” from the Brief Pain Inventory. Results. Depressive symptoms were significantly related to participants’ reports of increased pain and decreased quality of life. The mean CESD score of the sample was 10.6 () and 52% of the sample scored above the clinical cutoff for the presence of significant depressive symptomology. Patients scoring above the clinical cutoff on the depression screening measure rated their pain as significantly higher than those below the cutoff () and had significantly lower physical quality of life () and lower mental quality of life (). Conclusion. Although causality cannot be determined based on cross-sectional, correlational data, findings suggest that among patients with nonalcoholic pancreatitis, the presence of depressive symptoms is common and may be a risk factor associated with increased pain and decreased quality of life. Thus, routine screening for depressive symptomology among patients with nonalcoholic pancreatitis may be warranted