Two seasons of excavation at the 1865 office building at scenic Hudson\u27s West Point foundry preserve

In 1865 Robert P. Parrott ordered a stately office building be built as a symbol of the West Point Foundry\u27s national prestige and success. Once constructed, the building\u27s distinctive cupola was easily visible from various places in the landscape, including locations throughout the factory, the worker and management housing on Mount Rascal, and from West Point and ships passing on the Hudson River. As the physical and symbolic center of administrative power on the site, the office was an important part of the productive process. Archaeological excavation permitted a detailed reconstruction of the building\u27s construction, use, reuse and abandonment

Managing Environmental, Health, and Safety Risks: A Comparative Assessment of the Minerals Management Service and Other Agencies

This study compares and contrasts regulatory and related practices—in particular, regulatory decisionmaking, risk assessment and planning processes, inspection and compliance, and organization structure, budgets, and training—of the Minerals Management Service (MMS, now the Bureau of Ocean Energy Management, Regulation, and Enforcement, or BOEMRE) with those of the Federal Aviation Administration (FAA) and the Environmental Protection Agency (EPA). Comparing MMS practices with those of other federal agencies that also manage low-probability but high-consequence environmental risks provides a basis for identifying opportunities for enhancing regulatory capacity and safety performance in managing deepwater energy exploration and production. Our research finds important differences in processes for setting standards; peer review contribution to the rulemaking process; establishment of tolerable risk thresholds; and training of key staff. The paper concludes with several recommendations for how various EPA and FAA practices might be modified and used at BOEMRE to strengthen its regulatory and risk management processes.Minerals Management Service, Federal Aviation Administration, Environmental Protection Agency, risk management

Historic Resources Study of Pullman National Monument, Illinois

This Historic Resource Study is a Baseline Research Report for Pullman National Monument. This HRS summarizes the historical writings about Pullman, provides context for the significant themes identified in its founding document, collates collections of primary documents and historical resources that are important sources of information on those themes, and recommends questions that will require additional study. These cultural resources include primary historical materials in archives and oral history collections, as well as architectural, archaeological, museum collections, or landscape resources. While this report includes new historical narrative based in original archival research, other sections present synthetic reviews of existing publications. National Park Service staff will use this document and included resources as they make management decisions and design interpretive programming. In addition to this report and its appendices—which are only published digitally—the research team deposited its entire library with the monument staff, including nearly 2,000 references and thousands of pages of digitally-imaged archival documents

Bricks and an Evolving Industrial Landscape: The West Point Foundry and New York\u27s Hudson River Valley

Ongoing archaeological research at Scenic Hudson’s West Point Foundry Preserve in Cold Spring, New York, has permitted systematic collection of data related to fire and common brick brands that appear throughout the foundry’s campus. Archaeologists have begun to correlate the varied ceramic building material with periods in the evolution of this 19th-century industrial landscape. Hudson River Valley brick making provides an interesting comparison to the foundry’s history since both industries were tied to the overall development of New York City’s urban fabric

Three male germline-specific aldolase A isozymes are generated by alternative splicing and retrotransposition

Enzymes in the glycolytic pathway of mammalian sperm are modified extensively and are localized in the flagellum, where several are tightly bound to the fibrous sheath. This study provides the first evidence for three novel aldolase isozymes in mouse sperm, two encoded by Aldoart1 and Aldoart2 retrogenes on different chromosomes and another by Aldoa_v2, a splice variant of Aldoa. Phylogenetic analyses and comparative genomics indicate that the retrogenes and splice variant have remained functional and have been under positive selection for millions of years. Their expression is restricted to the male germline and is tightly regulated at both transcriptional and translational levels. All three isozymes are present only in spermatids and sperm and have distinctive features that may be important for localization in the flagellum and/or altered metabolic regulation. Both ALDOART1 and ALDOA_V2 have unusual N-terminal extensions not found in other aldolases. The N-terminal extension of ALDOA_V2 is highly conserved in mammals, suggesting a conserved function in sperm. We hypothesize that the N-terminal extensions are responsible for localizing components of the glycolytic pathway to the fibrous sheath and that this localization is required to provide sufficient ATP along the length of the flagellum to support sperm motility

Loss of GPVI and GPIbα contributes to trauma-induced platelet dysfunction in severely injured patients

Trauma-induced coagulopathy (TIC) is a complex, multifactorial failure of hemostasis that occurs in 25% of severely injured patients and results in a fourfold higher mortality. However, the role of platelets in this state remains poorly understood. We set out to identify molecular changes that may underpin platelet dysfunction after major injury and to determine how they relate to coagulopathy and outcome. We performed a range of hemostatic and platelet-specific studies in blood samples obtained from critically injured patients within 2 hours of injury and collected prospective data on patient characteristics and clinical outcomes. We observed that, although platelet counts were preserved above critical levels, circulating platelets sampled from trauma patients exhibited a profoundly reduced response to both collagen and the selective glycoprotein VI (GPVI) agonist collagen-related peptide, compared with those from healthy volunteers. These responses correlated closely with overall clot strength and mortality. Surface expression of the collagen receptors GPIbα and GPVI was reduced on circulating platelets in trauma patients, with increased levels of the shed ectodomain fragment of GPVI detectable in plasma. Levels of shed GPVI were highest in patients with more severe injuries and TIC. Collectively, these observations demonstrate that platelets experience a loss of GPVI and GPIbα after severe injury and translate into a reduction in the responsiveness of platelets during active hemorrhage. In turn, they are associated with reduced hemostatic competence and increased mortality. Targeting proteolytic shedding of platelet receptors is a potential therapeutic strategy for maintaining hemostatic competence in bleeding and improving the efficacy of platelet transfusions

Distinct tau prion strains propagate in cells and mice and define different tauopathies

Prion-like propagation of tau aggregation might underlie the stereotyped progression of neurodegenerative tauopathies. True prions stably maintain unique conformations (“strains”) in vivo that link structure to patterns of pathology. We now find that tau meets this criterion. Stably expressed tau repeat domain indefinitely propagates distinct amyloid conformations in a clonal fashion in culture. Reintroduction of tau from these lines into naive cells reestablishes identical clones. We produced two strains in vitro that induce distinct pathologies in vivo as determined by successive inoculations into three generations of transgenic mice. Immunopurified tau from these mice recreates the original strains in culture. We used the cell system to isolate tau strains from 29 patients with 5 different tauopathies, finding that different diseases are associated with different sets of strains. Tau thus demonstrates essential characteristics of a prion. This might explain the phenotypic diversity of tauopathies and could enable more effective diagnosis and therapy

Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.

Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis