Automated thermal treatment of metals with a mechanically fluidized vacuum machine. Final report

The ERIP project {open_quotes}Automated Thermal Treatment of Metals with a Mechanically Fluidized Vacuum Machine{close_quotes} produced more benefits in unintended areas than in the original intent of the program. The first project was directed to heat treating of solid parts using a retort half filled with fine powder. The treatment of metal powders was not originally envisioned at the time of proposal preparation. This second application, where the powder itself is being treated, has turned out to be multi-billion dollar market in which the Mechanical Fluidized Vacuum machine can create revolutionary changes. Consequently most efforts in recent years have been dedicated to further growth of the powder markets. These efforts procured a second ERIP grant titled {open_quotes}Thermal Heat and Diffusion Treatment of Bulk Powders.{close_quotes

Mitochondrial function and oxygen supply in normal and in chronically ischemic muscle: A combined 31P magnetic resonance spectroscopy and near infrared spectroscopy study in vivo

AbstractPurpose: We used 31P magnetic resonance spectroscopy (MRS) and near-infrared spectroscopy (NIRS) as a means of quantifying abnormalities in calf muscle oxygenation and adenosine triphosphate (ATP) turnover in peripheral vascular disease (PVD). Methods: Eleven male patients with PVD (mean age, 65 years; range, 55-76 years) and nine male control subjects of similar age were observed in a case-control study in vascular outpatients. Inclusion criteria were more than 6 months' calf claudication (median, 1.5 years; range, 0.6-18 years); proven femoropopliteal or iliofemoral occlusive or stenotic disease; maximum treadmill walking distance (2 km/h, 10° gradient) of 50 to 230 m (mean, 112 m); ankle-brachial pressure index of 0.8 or less during exercise (mean, 0.47; range, 0.29-0.60). Exclusion criteria included diabetes mellitus, anemia, and magnet contraindications. Simultaneous 31P MRS and NIRS of lateral gastrocnemius was conducted during 2 to 4 minutes of voluntary 0.5 Hz isometric plantarflexion at 50% and 75% maximum voluntary contraction force (MVC), followed by 5 minutes recovery. Each subject was studied three times, and the results were combined. Results: Compared with control subjects, patients with PVD showed (1) normal muscle cross-sectional area, MVC, ATP turnover, and contractile efficiency (ATP turnover per force/area); (2) larger phosphocreatine (PCr) changes during exercise (ie, increased shortfall of oxidative ATP synthesis) and slower PCr recovery (47% ± 7% [mean ± SEM] decrease in functional capacity for oxidative ATP synthesis, P =.001); (3) faster deoxygenation during exercise and slower postexercise reoxygenation (59% ± 7% decrease in rate constant, P =.0009), despite reduced oxidative ATP synthesis; (4) correlation between PCr and NIRS recovery rate constants (P <.02); and (5) correlations between smaller walking distance, slower PCr recovery, and reduced MVC (P <.001). The precision of the key measurements (rate constants and contractile efficiency) was 12% to 18% interstudy and 30% to 40% intersubject. Conclusion: The primary lesion in oxygen supply dominates muscle metabolism. Reduced force-generation in patients who are affected more may protect muscle from metabolic stress. (J Vasc Surg 2001;34:1103-10.

An assessment of the durability and susceptibility of scab resistance in apple cultivars

Durable resistance to scab (Venturia inaequalis) of newly introduced cultivars is needed to achieve a considerable reduction of pesticide use. However, the assessment in the field on the level and durability of scab resistance is time and space consuming. A proper and fast indoor test should be a convenient tool to discard cultivars with a limited level of resistance at an early stage. As a result, field tests can include only the better cultivars. This approach has been tried out by comparing field data with data from a glasshouse test, comprising twelve new and seven well-known susceptible and resistant (with and without Vf) cultivars which have been tested with six isolates of scab from different origins, virulence and aggressiveness, including race 6 and 7. Young trees on M.9 rootstock were infected and after a 17 day period at high humidity, sporulation and chlorosis have been observed. If the set of isolates is broad and well-chosen it seems possible to assess susceptibility and possibly also durability. To optimize the choice of isolates, it is desirable to know the pedigree of the cultivars that are tested. In addition, this procedure allows the use of highly virulent and aggressive races, that should be avoided in field tests for the risk of spreadin

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

Volume I. Introduction to DUNE

The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay—these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. The Deep Underground Neutrino Experiment (DUNE) is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. This TDR is intended to justify the technical choices for the far detector that flow down from the high-level physics goals through requirements at all levels of the Project. Volume I contains an executive summary that introduces the DUNE science program, the far detector and the strategy for its modular designs, and the organization and management of the Project. The remainder of Volume I provides more detail on the science program that drives the choice of detector technologies and on the technologies themselves. It also introduces the designs for the DUNE near detector and the DUNE computing model, for which DUNE is planning design reports. Volume II of this TDR describes DUNE\u27s physics program in detail. Volume III describes the technical coordination required for the far detector design, construction, installation, and integration, and its organizational structure. Volume IV describes the single-phase far detector technology. A planned Volume V will describe the dual-phase technology

The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

Renal cell carcinoma(RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD) ChRCC that associated with extremely poor survival

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