Specimen dimensions influence the measurement of material properties in tendon fascicles

Stress, strain and modulus are regularly used to characterize material properties of tissue samples. However, when comparing results from different studies it is evident the reported material properties, particularly failure strains, vary hugely. The aim of our study was to characterize how and why specimen length and cross-sectional area (CSA) appear to influence failure stress, strain and modulus in fascicles from two functionally different tendons. Fascicles were dissected from five rat tails and five bovine foot extensors, their diameters determined by a laser micrometer, and loaded to failure at a range of grip-to-grip lengths. Strain to failure significantly decreased with increasing in specimen length in both rat and bovine fascicles, while modulus increased. Specimen length did not influence failure stress in rat tail fascicles, although in bovine fascicles it was significantly lower in the longer 40 mm specimens compared to 5 and 10 mm specimens. The variations in failure strain and modulus with sample length could be predominantly explained by end-effects. However, it was also evident that strain fields along the sample length were highly variable and notably larger towards the ends of the sample than the mid-section even at distances in excess of 5 mm from the gripping points. Failure strain, stress and modulus correlated significantly with CSA at certain specimen lengths. Our findings have implications for the mechanical testing of tendon tissue: while it is not always possible to control for fascicle length and/or CSA, these parameters have to be taken into account when comparing samples of different dimensions

A Current Mode Detector Array for Gamma-Ray Asymmetry Measurements

We have built a CsI(Tl) gamma-ray detector array for the NPDGamma experiment to search for a small parity-violating directional asymmetry in the angular distribution of 2.2 MeV gamma-rays from the capture of polarized cold neutrons by protons with a sensitivity of several ppb. The weak pion-nucleon coupling constant can be determined from this asymmetry. The small size of the asymmetry requires a high cold neutron flux, control of systematic errors at the ppb level, and the use of current mode gamma-ray detection with vacuum photo diodes and low-noise solid-state preamplifiers. The average detector photoelectron yield was determined to be 1300 photoelectrons per MeV. The RMS width seen in the measurement is therefore dominated by the fluctuations in the number of gamma rays absorbed in the detector (counting statistics) rather than the intrinsic detector noise. The detectors were tested for noise performance, sensitivity to magnetic fields, pedestal stability and cosmic background. False asymmetries due to gain changes and electronic pickup in the detector system were measured to be consistent with zero to an accuracy of $10^{-9}$ in a few hours. We report on the design, operating criteria, and the results of measurements performed to test the detector array.Comment: 33 pages, 20 figures, 2 table

Precision Measurement of PArity Violation in Polarized Cold Neutron Capture on the Proton: the NPDGamma Experiment

The NPDGamma experiment at the Los Alamos Neutron Science Center (LANSCE) is dedicated to measure with high precision the parity violating asymmetry in the $\gamma$ emission after capture of spin polarized cold neutrons in para-hydrogen. The measurement will determine unambiguously the weak pion-nucleon-nucleon ($\pi NN$) coupling constant {\it f$^1_{\pi}$}Comment: Proceedings of the PANIC'05 Conference, Santa Fe, NM, USA, October 24-28, 2005, 3 pages, 2 figure

Parity nonconservation in deuteron photoreactions

We calculate the asymmetries in parity nonconserving deuteron photodisintegration due to circularly polarized photons gamma+d to n+p with the photon laboratory energy ranging from the threshold up to 10 MeV and the radiative capture of thermal polarized neutrons by protons n+p to gamma+d. We use the leading order electromagnetic Hamiltonian neglecting the smaller nuclear exchange currents. Comparative calculations are done by using the Reid93 and Argonne v18 potentials for the strong interaction and the DDH and FCDH "best" values for the weak couplings in a weak one-meson exchange potential. A weak NDelta transition potential is used to incorporate also the Delta(1232)-isobar excitation in the coupled-channels formalism.Comment: 14 pages, 13 figures (18 eps files), LaTeX2

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Euclid preparation: XVIII. The NISP photometric system

Galaxie

Somatic Mutational Landscape of Splicing Factor Genes and Their Functional Consequences across 33 Cancer Types

Hotspot mutations in splicing factor genes have been recently reported at high frequency in hematological malignancies, suggesting the importance of RNA splicing in cancer. We analyzed whole-exome sequencing data across 33 tumor types in The Cancer Genome Atlas (TCGA), and we identified 119 splicing factor genes with significant non-silent mutation patterns, including mutation over-representation, recurrent loss of function (tumor suppressor-like), or hotspot mutation profile (oncogene-like). Furthermore, RNA sequencing analysis revealed altered splicing events associated with selected splicing factor mutations. In addition, we were able to identify common gene pathway profiles associated with the presence of these mutations. Our analysis suggests that somatic alteration of genes involved in the RNA-splicing process is common in cancer and may represent an underappreciated hallmark of tumorigenesis

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although the MYC oncogene has been implicated in cancer, a systematic assessment of alterations of MYC, related transcription factors, and co-regulatory proteins, forming the proximal MYC network (PMN), across human cancers is lacking. Using computational approaches, we define genomic and proteomic features associated with MYC and the PMN across the 33 cancers of The Cancer Genome Atlas. Pan-cancer, 28% of all samples had at least one of the MYC paralogs amplified. In contrast, the MYC antagonists MGA and MNT were the most frequently mutated or deleted members, proposing a role as tumor suppressors. MYC alterations were mutually exclusive with PIK3CA, PTEN, APC, or BRAF alterations, suggesting that MYC is a distinct oncogenic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such as immune response and growth factor signaling; chromatin, translation, and DNA replication/repair were conserved pan-cancer. This analysis reveals insights into MYC biology and is a reference for biomarkers and therapeutics for cancers with alterations of MYC or the PMN. We present a computational study determining the frequency and extent of alterations of the MYC network across the 33 human cancers of TCGA. These data, together with MYC, positively correlated pathways as well as mutually exclusive cancer genes, will be a resource for understanding MYC-driven cancers and designing of therapeutics