A study of concept options for the evolution of Space Station Freedom

Two conceptual evolution configurations for Space Station Freedom, a research and development configuration, and a transportation node configuration are described and analyzed. Results of pertinent analyses of mass properties, attitude control, microgravity, orbit lifetime, and reboost requirements are provided along with a description of these analyses. Also provided are brief descriptions of the elements and systems that comprise these conceptual configurations

An Examination of Western Stemmed Tradition Settlement-Subsistence, Territoriality, and Lithic Technological Organization in the Northwestern Great Basin

A paucity of stratified, open-air Western Stemmed Tradition (WST) sites has long been an issue for Great Basin researchers. Most Paleoindian sites are near-surface lithic scatters that lack subsistence residues, perishable technology, and materials that can be radiocarbon dated. While surface sites pose a number of interpretive challenges, they remain essential to our understanding of WST lifeways in the Great Basin. In this dissertation, I evaluate current models of WST settlement-subsistence and lithic technological organization in the northwestern Great Basin through analyses of recently discovered and previously reported lithic assemblages. I also explore novel methods of analyzing lithic and source provenance data to strengthen interpretations of surface assemblages and source profiles. My results suggests that: (1) WST groups in the northwestern Great Basin were residentially mobile, focused on wetlands, and likely moved base camps regularly; (2) toolstone procurement strategies were based on maximizing productivity within a wetland-oriented lifestyle; and (3) the northwestern Great Basin contained a single highly connected Paleoindian network that was likely a product of unrestricted socio-political boundaries, low population densities, limited resource competition, and a mobile settlement-subsistence strategy

Dust Control at Yucca Mountain Project

This report describes actions taken to control silica dust at the Yucca Mountain Exploratory Studies Facility, a tunnel located in Southern Nevada that is part of a scientific program to determine site suitability for a potential nuclear waste repository. The rock is a volcanic tuff containing significant percentages of both quartz and cristobalite. Water use for dust control was limited because of scientific test requirements, and this limitation made dust control a difficult task. Results are reported for two drifts, called the Main Loop Drift and the Cross Drift. In the Main Loop Drift, dust surveys and tracer gas tests indicated that air leakage from the TBM head, the primary ventilation duct, and movement of the conveyor belt were all significant sources of dust. Conventional dust control approaches yielded no significant reductions in dust levels. A novel alternative was to install an air cleaning station on a rear deck of the TBM trailing gear. It filtered dust from the contaminated intake air and discharged clean air towards the front of the TBM. The practical effect was to produce dust levels below the exposure limit for all TBM locations except close to the head. In the Cross Drift, better ventilation and an extra set of dust seals on the TBM served to cut down the leakage of dust from the TBM cutter head. However, the conveyor belt was much dustier than the belt in the main loop drift. The problem originated with dirt on the bottom of the belt return side and muck spillage from the belt top side. Achieving lower dust levels in hard rock tunneling operations will require new approaches as well as a more meticulous application of existing technology. Planning for dust control will require specific means to deal with dust that leaks from the TBM head, dust that originates with leaky ventilation systems, and dust that comes from conveyor belts. Also, the application of water could be more efficient if automatic controls were used to adjust the water flow rate to the mining rate

The Effects of Apelin on the Electrical Activity of Hypothalamic Magnocellular Vasopressin and Oxytocin Neurons and Somatodendritic Peptide Release

Apelin, a novel peptide originally isolated from bovine stomach tissue extracts, is widely but selectively distributed throughout the nervous system. Vasopressin and oxytocin are synthesised in the magnocellular neurons of the hypothalamic supraoptic (SON) and paraventricular nuclei (PVN), which are apelin-rich regions in the central nervous system. We made extracellular electrophysiological recordings from the transpharyngeally exposed SON of urethane-anaesthetised rats to assess the role of apelin in the control of the firing activity of identified magnocellular vasopressin and oxytocin neurons in vivo. Apelin-13 administration onto SON neurons via microdialysis revealed cell-specific responses; apelin-13 increased the firing rates of vasopressin cells, but had no effect on the firing rate of oxytocin neurons. A direct excitatory effect of apelin-13 on vasopressin cell activity is also supported by our in vitro studies showing depolarisation of membrane potential and increase in action potential firing. To assess the effects of apelin-13 on somato/dendritic peptide release we used in vitro release studies from SON explants in combination with highly sensitive and specific radioimmunoassays. Apelin-13 decrease basal (by 78%, p<0.05, n=6) and potassium-stimulated (by 57%, p<0.05, n=6) vasopressin release but had no effect on somato/dendritic oxytocin release. Taken together, our data suggest a local autocrine feedback action of apelin on magnocellular vasopressin neurons. Furthermore, these data show a marked dissociation between axonal and dendritic vasopressin release with a decrease in somato/dendritic release but an increase in electrical activity at the cell bodies, indicating that release from these two compartments can be regulated wholly independently

Design of a TSR-based project learning strategy for biochemistry undergraduate teaching and research labs: a case study

Given the exponential growth of biochemical data and deep effect of computational methods on life sciences, there is a need to rethink undergraduate curricula. A project-oriented learning approach based on the Triangular Spatial Relationship (TSR) algorithm has been developed. The TSR-based method was designed for protein 3D structural comparison, motif discovery and probing molecular interactions. The uniqueness of the method benefits students’ learning of big data and computational methods. Specifically, students learn (i) how to search proteins of interest from the PDB archive, (ii) basic supercomputer skills, (iii) how to prepare datasets, (iv) how to perform protein structure and sequence analyses, (v) how to interpret the results, visualize protein structures and make graphs. Five specific strategies have been developed to achieve students’ highest potentials. (i) This lab exercise is designed as a project-oriented learning approach. (ii) The skills-first and concept-second approach is used. (iii) Students choose the proteins based on their interests. (iv) Students are encouraged to learn from each other to promote student–student interactions. (v) Students are required to write a report and/or present their studies. To assess students’ performance, we have developed an assessment rubric that includes (i) demonstration of supercomputer skills in job script preparation, submission and monitoring, (ii) skills in preparation of datasets, (iii) data analytical skills, (iv) project report, (v) presentation, and (vi) integration of the TSR-based method with other computational methods (e.g., molecular 3D structural visualization and protein sequence analysis). This project has been introduced in undergraduate biochemistry research and teaching labs for 4 years. Most students have learned the basic supercomputer skills as well as structure data analysis skills. Students’ feedback is positive and encouraging. It can be further developed as a module for an integrated computational chemistry lecture course

A Fine-Mapping Study of 7 Top Scoring Genes from a GWAS for Major Depressive Disorder

Major depressive disorder (MDD) is a psychiatric disorder that is characterized -amongst others- by persistent depressed mood, loss of interest and pleasure and psychomotor retardation. Environmental circumstances have proven to influence the aetiology of the disease, but MDD also has an estimated 40% heritability, probably with a polygenic background. In 2009, a genome wide association study (GWAS) was performed on the Dutch GAIN-MDD cohort. A non-synonymous coding single nucleotide polymorphism (SNP) rs2522833 in the PCLO gene became only nominally significant after post-hoc analysis with an Australian cohort which used similar ascertainment. The absence of genome-wide significance may be caused by low SNP coverage of genes. To increase SNP coverage to 100% for common variants (m.a.f.>0.1, r2>0.8), we selected seven genes from the GAIN-MDD GWAS: PCLO, GZMK, ANPEP, AFAP1L1, ST3GAL6, FGF14 and PTK2B. We genotyped 349 SNPs and obtained the lowest P-value for rs2715147 in PCLO at P = 6.8E−7. We imputed, filling in missing genotypes, after which rs2715147 and rs2715148 showed the lowest P-value at P = 1.2E−6. When we created a haplotype of these SNPs together with the non-synonymous coding SNP rs2522833, the P-value decreased to P = 9.9E−7 but was not genome wide significant. Although our study did not identify a more strongly associated variant, the results for PCLO suggest that the causal variant is in high LD with rs2715147, rs2715148 and rs2522833

CNS targets of adipokines

This is the author accepted manuscript. The final version is available from American Physiological Society via the DOI in this record.Our understanding of adipose tissue as an endocrine organ has been transformed over the last twenty years. During this time a number of adipocyte-derived factors or adipokines have been identified. This paper will review evidence for how adipokines acting via the central nervous system (CNS) regulate normal physiology and disease pathology. The reported CNS-mediated effects of adipokines are varied and include the regulation of energy homeostasis, autonomic nervous system activity, the reproductive axis, neurodevelopment, cardiovascular function, and cognition. Due to the wealth of information available and the diversity of their known functions, the archetypal adipokines leptin and adiponectin will be the focused on extensively. Other adipokines with established CNS actions will also be discussed. Due to the difficulties associated with studying CNS function on a molecular level in humans, the majority of our knowledge, and as such the studies described in this paper, comes from work in experimental animal models; however, where possible the relevant data from human studies are also highlighted