Data Augmentation for Neutron Spectrum Unfolding with Neural Networks

Neural networks require a large quantity of training spectra and detector responses in order to learn to solve the inverse problem of neutron spectrum unfolding. In addition, due to the under-determined nature of unfolding, non-physical spectra which would not be encountered in usage should not be included in the training set. While physically realistic training spectra are commonly determined experimentally or generated through Monte Carlo simulation, this can become prohibitively expensive when considering the quantity of spectra needed to effectively train an unfolding network. In this paper, we present three algorithms for the generation of large quantities of realistic and physically motivated neutron energy spectra. Using an IAEA compendium of 251 spectra, we compare the unfolding performance of neural networks trained on spectra from these algorithms, when unfolding real-world spectra, to two baselines. We also investigate general methods for evaluating the performance of and optimizing feature engineering algorithms

USP7 Enforces Heterochromatinization of p53 Target Promoters by Protecting SUV39H1 from MDM2-Mediated Degradation

SummaryThe H3K9me3 repressive histone conformation of p53 target promoters is abrogated in response to p53 activation by MDM2-mediated SUV39H1 degradation. Here, we present evidence that the USP7 deubiquitinase protects SUV39H1 from MDM2-mediated ubiquitination in the absence of p53 stimulus. USP7 occupies p53 target promoters in unstressed conditions, a process that is abrogated with p53 activation associated with loss of the H3K9me3 mark on these same promoters. Mechanistically, USP7 forms a trimeric complex with MDM2 and SUV39H1, independent of DNA, and modulates MDM2-dependent SUV39H1 ubiquitination. Furthermore, we show that this protective function of USP7 on SUV39H1 is independent of p53. Finally, USP7 blocking cooperates with p53 in inducing apoptosis by enhancing p53 promoter occupancy and dependent transactivation of target genes. These results uncover a layer of the p53 transcriptional program mediated by USP7, which restrains relaxation of local chromatin conformation at p53 target promoters

Fast-, Light-Cured Scintillating Plastic for 3D-Printing Applications

Additive manufacturing techniques enable a wide range of possibilities for novel radiation detectors spanning simple to highly complex geometries, multi-material composites, and metamaterials that are either impossible or cost prohibitive to produce using conventional methods. The present work identifies a set of promising formulations of photocurable scintillator resins capable of neutron-gamma pulse shape discrimination (PSD) to support the additive manufacturing of fast neutron detectors. The development of these resins utilizes a step-by-step, trial-and-error approach to identify different monomer and cross-linker combinations that meet the requirements for 3D printing followed by a 2-level factorial parameter study to optimize the radiation detection performance, including light yield, PSD, optical clarity, and hardness. The formulations resulted in hard, clear, PSD-capable plastic scintillators that were cured solid within 10 s using 405 nm light. The best-performing scintillator produced a light yield 83% of EJ-276 and a PSD figure of merit equaling 1.28 at 450–550 keVee

An analysis of the carbon balance of the Arctic Basin from 1997 to 2006

Author Posting. © The Authors, 2010. This is the author's version of the work. It is posted here by permission of John Wiley & Sons for personal use, not for redistribution. The definitive version was published in Tellus B 62 (2010): 455-474, doi:10.1111/j.1600-0889.2010.00497.x.This study used several model-based tools to analyze the dynamics of the Arctic Basin between 1997 and 2006 as a linked system of land-ocean-atmosphere C exchange. The analysis estimates that terrestrial areas of the Arctic Basin lost 62.9 Tg C yr-1 and that the Arctic Ocean gained 94.1 Tg C yr-1. Arctic lands and oceans were a net CO2 sink of 108.9 Tg C yr-1, which is within the range of uncertainty in estimates from atmospheric inversions. Although both lands and oceans of the Arctic were estimated to be CO2 sinks, the land sink diminished in strength because of increased fire disturbance compared to previous decades, while the ocean sink increased in strength because of increased biological pump activity associated with reduced sea ice cover. Terrestrial areas of the Arctic were a net source of 41.5 Tg CH4 yr-1 that increased by 0.6 Tg CH4 yr-1 during the decade of analysis, a magnitude that is comparable with an atmospheric inversion of CH4. Because the radiative forcing of the estimated CH4 emissions is much greater than the CO2 sink, the analysis suggests that the Arctic Basin is a substantial net source of green house gas forcing to the climate system.This study was supported, in part, by the NSF Arctic System Science Program as part of the Arctic Carbon Cycle Synthesis Project (ARC-0531047, 0531082, 0531119, and 0554811)

Distinct mechanisms control genome recognition by p53 at its target genes linked to different cell fates.

The tumor suppressor p53 integrates stress response pathways by selectively engaging one of several potential transcriptomes, thereby triggering cell fate decisions (e.g., cell cycle arrest, apoptosis). Foundational to this process is the binding of tetrameric p53 to 20-bp response elements (REs) in the genome (RRRCWWGYYYN0-13RRRCWWGYYY). In general, REs at cell cycle arrest targets (e.g. p21) are of higher affinity than those at apoptosis targets (e.g., BAX). However, the RE sequence code underlying selectivity remains undeciphered. Here, we identify molecular mechanisms mediating p53 binding to high- and low-affinity REs by showing that key determinants of the code are embedded in the DNA shape. We further demonstrate that differences in minor/major groove widths, encoded by G/C or A/T bp content at positions 3, 8, 13, and 18 in the RE, determine distinct p53 DNA-binding modes by inducing different Arg248 and Lys120 conformations and interactions. The predictive capacity of this code was confirmed in vivo using genome editing at the BAX RE to interconvert the DNA-binding modes, transcription pattern, and cell fate outcome

Circulating free insulin-like growth factor-I and prostate cancer: a case-control study nested in the European prospective investigation into cancer and nutrition

Background: Circulating total insulin-like growth factor-I (IGF-I) is an established risk factor for prostate cancer. However, only a small proportion of circulating IGF-I is free or readily dissociable from IGF-binding proteins (its bioavailable form), and few studies have investigated the association of circulating free IGF-I with prostate cancer risk. Methods: We analyzed data from 767 prostate cancer cases and 767 matched controls nested within the European Prospective Investigation into Cancer and Nutrition cohort, with an average of 14-years (interquartile range = 2.9) follow-up. Matching variables were study center, length of follow-up, age, and time of day and fasting duration at blood collection. Circulating free IGF-I concentration was measured in serum samples collected at recruitment visit (mean age 55 years old; standard deviation = 7.1) using an enzyme-linked immunosorbent assay (ELISA). Conditional logistic regressions were performed to examine the associations of free IGF-I with risk of prostate cancer overall and subdivided by time to diagnosis (≤ 14 and > 14 years), and tumor characteristics. Results: Circulating free IGF-I concentrations (in fourths and as a continuous variable) were not associated with prostate cancer risk overall (odds ratio [OR] = 1.00 per 0.1 nmol/L increment, 95% CI: 0.99, 1.02) or by time to diagnosis, or with prostate cancer subtypes, including tumor stage and histological grade. Conclusions: Estimated circulating free IGF-I was not associated with prostate cancer risk. Further research may consider other assay methods that estimate bioavailable IGF-I to provide more insight into the well-substantiated association between circulating total IGF-I and subsequent prostate cancer risk

Simultaneous quantification of 12 different nucleotides and nucleosides released from renal epithelium and in human urine samples using ion-pair reversed-phase HPLC

Nucleotides and nucleosides are not only involved in cellular metabolism but also act extracellularly via P1 and P2 receptors, to elicit a wide variety of physiological and pathophysiological responses through paracrine and autocrine signalling pathways. For the first time, we have used an ion-pair reversed-phase high-performance liquid chromatography ultraviolet (UV)-coupled method to rapidly and simultaneously quantify 12 different nucleotides and nucleosides (adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, adenosine, uridine triphosphate, uridine diphosphate, uridine monophosphate, uridine, guanosine triphosphate, guanosine diphosphate, guanosine monophosphate, guanosine): (1) released from a mouse renal cell line (M1 cortical collecting duct) and (2) in human biological samples (i.e., urine). To facilitate analysis of urine samples, a solid-phase extraction step was incorporated (overall recovery rate ? 98 %). All samples were analyzed following injection (100 ?l) into a Synergi Polar-RP 80 Å (250 × 4.6 mm) reversed-phase column with a particle size of 10 ?m, protected with a guard column. A gradient elution profile was run with a mobile phase (phosphate buffer plus ion-pairing agent tetrabutylammonium hydrogen sulfate; pH 6) in 2-30 % acetonitrile (v/v) for 35 min (including equilibration time) at 1 ml min(-1) flow rate. Eluted compounds were detected by UV absorbance at 254 nm and quantified using standard curves for nucleotide and nucleoside mixtures of known concentration. Following validation (specificity, linearity, limits of detection and quantitation, system precision, accuracy, and intermediate precision parameters), this protocol was successfully and reproducibly used to quantify picomolar to nanomolar concentrations of nucleosides and nucleotides in isotonic and hypotonic cell buffers that transiently bathed M1 cells, and urine samples from normal subjects and overactive bladder patients

Local invertibility in Sobolev spaces with applications to nematic elastomers and magnetoelasticity

We define a class of deformations in W^1,p(\u3a9,R^n), p>n 121, with positive Jacobian that do not exhibit cavitation. We characterize that class in terms of the non-negativity of the topological degree and the equality between the distributional determinant and the pointwise determinant of the gradient. Maps in this class are shown to satisfy a property of weak monotonicity, and, as a consequence, they enjoy an extra degree of regularity. We also prove that these deformations are locally invertible; moreover, the neighbourhood of invertibility is stable along a weak convergent sequence in W^1,p, and the sequence of local inverses converges to the local inverse. We use those features to show weak lower semicontinuity of functionals defined in the deformed configuration and functionals involving composition of maps. We apply those results to prove existence of minimizers in some models for nematic elastomers and magnetoelasticity

Skp2B Overexpression Alters a Prohibitin-p53 Axis and the Transcription of PAPP-A, the Protease of Insulin-Like Growth Factor Binding Protein 4

We previously reported that the degradation of prohibitin by the SCF(Skp2B) ubiquitin ligase results in a defect in the activity of p53. We also reported that MMTV-Skp2B transgenic mice develop mammary gland tumors that are characterized by an increased proteolytic cleavage of the insulin-like growth factor binding protein 4 (IGFBP-4), an inhibitor of IGF signaling. However, whether a link exists between a defect in p53 activity and proteolysis of IGFBP-4 was not established.We analyzed the levels of pregnancy-associated plasma protein A (PAPP-A), the protease of IGFBP-4, in MMTV-Skp2B transgenic mice and found that PAPP-A levels are elevated. Further, we found a p53 binding site in intron 1 of the PAPP-A gene and that both wild type and mutant p53 bind to this site. However, binding of wild type p53 results in the transcriptional repression of PAPP-A, while binding of mutant p53 results in the transcriptional activation of PAPP-A. Since MMTV-Skp2B mice express wild type p53 and yet show elevated levels of PAPP-A, at first, these observations appeared contradictory. However, further analysis revealed that the defect in p53 activity in Skp2B overexpressing cells does not only abolish the activity of wild type of p53 but actually mimics that of mutant p53. Our results suggest that in absence of prohibitin, the half-life of p53 is increased and like mutant p53, the conformation of p53 is denatured.These observations revealed a novel function of prohibitin as a chaperone of p53. Further, they suggest that binding of denatured p53 in intron 1 causes an enhancer effect and increases the transcription of PAPP-A. Therefore, these findings indicate that the defect in p53 function and the increased proteolysis of IGFBP-4, we had observed, represent two components of the same pathway, which contributes to the oncogenic function of Skp2B