Event Signaling Within Higher Performance Network Systems

The afterburner ATM link Adapter has allowed us to evaluate three event-signaling schemes: polling, traditional interrupts and the clocked interrupts first investigated in our operating system work in AURORA. The schemes are evaluated in the context of a single-copy TCP/IP stack. The experimental results indicate that clocked interrupts can provide throughput comparable with traditional interrupts for dedicated machines (up to over 144 Mbps, the highest TCP/IP/ATM throughput reported), and better performance when the machines are loaded with an artificial workload. Polling, implemented to be used with an unmodified netperf measurement tool, was competitive for small TCP/IP socket buffer sizes (¡32KB). We concluded that clocked interrupts may be preferable for applications requiring high throughput on systems with heavy processing workloads, such as servers

FSVPy: A Python-based Package for Fluorescent Streak Velocimetry (FSV)

Predictive constitutive equations that connect easy-to-measure transport properties (e.g., viscosity and conductivity) with system performance variables (e.g., power consumption and efficiency) are needed to design advanced thermal and electrical systems. In this work, we explore the use of fluorescent particle-streak analysis to directly measure the local velocity field of a pressure-driven flow, introducing a new Python package (FSVPy) to perform the analysis. Fluorescent streak velocimetry (FSV) combines high-speed imaging with highly fluorescent particles to produce images that contain fluorescent streaks, whose length and intensity can be related to the local flow velocity. By capturing images throughout the sample volume, the three-dimensional velocity field can be quantified and reconstructed. We demonstrate this technique by characterizing the channel flow profiles of several non-Newtonian fluids: micellar Cetylpyridinium Chloride solution, Carbopol 940, and Polyethylene Glycol. We then explore more complex flows, where significant acceleration is created due to micro-scale features encountered within the flow. We demonstrate the ability of FSVPy to process streaks of various shapes, and use the variable intensity along the streak to extract position-specific velocity measurements from individual images. Thus, we demonstrate that FSVPy is a flexible tool that can be used to extract local velocimetry measurements from a wide variety of fluids and flow conditions

Self-hybridization in Leishmania major

Genetic exchange between differen

Beryllium and Alpha-Element Abundances in a Large Sample of Metal-Poor Stars

The light elements, Li, Be, and B, provide tracers for many aspects of astronomy including stellar structure, Galactic evolution, and cosmology. We have taken spectra of Be in 117 metal-poor stars ranging in metallicity from [Fe/H] = -0.5 to -3.5 with Keck I + HIRES at a resolution of 42,000 and signal-to-noise ratios of near 100. We have determined the stellar parameters spectroscopically from lines of Fe I, Fe II, Ti I and Ti II. The abundances of Be and O were derived by spectrum synthesis techniques, while abundances of Fe, Ti, and Mg were found from many spectral line measurements. There is a linear relationship between [Fe/H] and A(Be) with a slope of +0.88 +-0.03 over three orders of magnitude in [Fe/H]. We fit the relationship between A(Be) and [O/H] with both a single slope and with two slopes. The relationship between [Fe/H] and [O/H] seems robustly linear and we conclude that the slope change in Be vs. O is due to the Be abundance. Although Be is a by-product of CNO, we have used Ti and Mg abundances as alpha-element surrogates for O in part because O abundances are rather sensitive to both stellar temperature and surface gravity. We find that A(Be) tracks [Ti/H] very well with a slope of 1.00 +-0.04. It also tracks [Mg/H] very well with a slope of 0.88 +-0.03. We find that there are distinct differences in the relationships of A(Be) and [Fe/H] and of A(Be) and [O/H] for our dissipative stars and our accretive stars. We suggest that the Be in the dissipative stars was primarily formed by GCR spallation and Be in the accretive stars was formed in the vicinity of SN II.Comment: Accepted for Ap.J. Nov. 10, 2011, v. 741 70 pages, 27 figures, 5 table

Genomic and phenotypic characterization of in vitro-generated Chlamydia trachomatis recombinants

Background: Pre-genomic and post-genomic studies demonstrate that chlamydiae actively recombine in vitro and in vivo, although the molecular and cellular biology of this process is not well understood. In this study, we determined the genome sequence of twelve Chlamydia trachomatis recombinants that were generated in vitro under antibiotic selection. These strains were used to explore the process of recombination in Chlamydia spp., including analysis of candidate recombination hotspots, and to correlate known C. trachomatis in vitro phenotypes with parental phenotypes and genotypes. Results: Each of the 190 examined recombination events was the product of homologous recombination, and no candidate targeting motifs were identified at recombination sites. There was a single deletion event in one recombinant progeny that resulted in the removal of 17.1 kilobases between two rRNA operons. There was no evidence for preference for any specific region of the chromosome for recombination, and analyses of a total of over 200 individual recombination events do not provide any support for recombination hotspots in vitro. Two measurable phenotypes were analyzed in these studies. First, the efficiency of attachment to host cells in the absence of centrifugation was examined, and this property segregated to regions of the chromosome that carry the polymorphic membrane protein (Pmp) genes. Second, the formation of secondary inclusions within cells varied among recombinant progeny, but this did not cleanly segregate to specific regions of the chromosome. Conclusions: These experiments examined the process of recombination in C. trachomatis and identified tools that can be used to associate phenotype with genotype in recombinant progeny. There were no data supporting the hypothesis that particular nucleotide sequences are preferentially used for recombination in vitro. Selected phenotypes can be segregated by analysis of recombination, and this technology may be useful in preliminary analysis of the relationship of genetic variation to phenotypic variation in the chlamydiae.Keywords: Attachment, Chlamydia, Secondary inclusions, Recombination, Hotspo

A Regional Assessment of Medicaid Access to Outpatient Orthopaedic Care: The Influence of Population Density and Proximity to Academic Medical Centers on Patient Access

Access to care is limited for patients with Medicaid with many conditions, but data investigating this relationship in the orthopaedic literature are limited. The purpose of this study was to investigate the relationship between health insurance status and access to care for a diverse group of adult orthopaedic patients, specifically if access to orthopaedic care is influenced by population density or distance from academic teaching hospitals

MYSM1 attenuates DNA damage signals triggered by physiologic and genotoxic DNA breaks

BACKGROUND: Patients with deleterious variants in MYSM1 have an immune deficiency characterized by B-cell lymphopenia, hypogammaglobulinemia, and increased radiosensitivity. MYSM1 is a histone deubiquitinase with established activity in regulating gene expression. MYSM1 also localizes to sites of DNA injury but its function in cellular responses to DNA breaks has not been elucidated. OBJECTIVES: This study sought to determine the activity of MYSM1 in regulating DNA damage responses (DDRs) to DNA double-stranded breaks (DSBs) generated during immunoglobulin receptor gene (Ig) recombination and by ionizing radiation. METHODS: MYSM1-deficient pre- and non-B cells were used to determine the role of MYSM1 in DSB generation, DSB repair, and termination of DDRs. RESULTS: Genetic testing in a newborn with abnormal screen for severe combined immune deficiency, T-cell lymphopenia, and near absence of B cells identified a novel splice variant in MYSM1 that results in nearly absent protein expression. Radiosensitivity testing in patient\u27s peripheral blood lymphocytes showed constitutive γH2AX, a marker of DNA damage, in B cells in the absence of irradiation, suggesting a role for MYSM1 in response to DSBs generated during Ig recombination. Suppression of MYSM1 in pre-B cells did not alter generation or repair of Ig DSBs. Rather, loss of MYSM1 resulted in persistent DNA damage foci and prolonged DDR signaling. Loss of MYSM1 also led to protracted DDRs in U2OS cells with irradiation induced DSBs. CONCLUSIONS: MYSM1 regulates termination of DNA damage responses but does not function in DNA break generation and repair

Activation of a Metabolic Gene Regulatory Network Downstream of mTOR Complex 1

Aberrant activation of the mammalian target of rapamycin complex 1 (mTORC1) is a common molecular event in a variety of pathological settings, including genetic tumor syndromes, cancer, and obesity. However, the cell-intrinsic consequences of mTORC1 activation remain poorly defined. Through a combination of unbiased genomic, metabolomic, and bioinformatic approaches, we demonstrate that mTORC1 activation is sufficient to stimulate specific metabolic pathways, including glycolysis, the oxidative arm of the pentose phosphate pathway, and de novo lipid biosynthesis. This is achieved through the activation of a transcriptional program affecting metabolic gene targets of hypoxia-inducible factor (HIF1α) and sterol regulatory element-binding protein (SREBP1 and SREBP2). We find that SREBP1 and 2 promote proliferation downstream of mTORC1, and the activation of these transcription factors is mediated by S6K1. Therefore, in addition to promoting protein synthesis, mTORC1 activates specific bioenergetic and anabolic cellular processes that are likely to contribute to human physiology and disease

Initial experience with an electron FLASH research extension (FLEX) for the Clinac system

Purpose: Radiotherapy delivered at ultra-high-dose-rates (≥40 Gy/s), that is, FLASH, has the potential to effectively widen the therapeutic window and considerably improve the care of cancer patients. The underlying mechanism of the FLASH effect is not well understood, and commercial systems capable of delivering such dose rates are scarce. The purpose of this study was to perform the initial acceptance and commissioning tests of an electron FLASH research product for preclinical studies. Methods: A linear accelerator (Clinac 23EX) was modified to include a nonclinical FLASH research extension (the Clinac-FLEX system) by Varian, a Siemens Healthineers company (Palo Alto, CA) capable of delivering a 16 MeV electron beam with FLASH and conventional dose rates. The acceptance, commissioning, and dosimetric characterization of the FLEX system was performed using radiochromic film, optically stimulated luminescent dosimeters, and a plane-parallel ionization chamber. A radiation survey was conducted for which the shielding of the pre-existing vault was deemed sufficient. Results: The Clinac-FLEX system is capable of delivering a 16 MeV electron FLASH beam of approximately 1 Gy/pulse at isocenter and reached amaximum dose rate \u3e3.8 Gy/pulse near the upper accessory mount on the linac gantry. The percent depth dose curves of the 16 MeV FLASH and conventional modes for the 10 × 10 cm2 applicator agreed within 0.5 mm at a range of 50% of the maximum dose. Their respective profiles agreed well in terms of flatness but deviated for field sizes \u3e10 × 10 cm2. The output stability of the FLASH system exhibited a dose deviation of \u3c1%.Preliminary cell studies showed that the FLASH dose rate (180 Gy/s) had much less impact on the cell morphology of 76N breast normal cells compared to the non-FLASH dose rate (18 Gy/s), which induced large-size cells. Conclusion: Our studies characterized the non-clinical Clinac-FLEX system as a viable solution to conduct FLASH research that could substantially increase access to ultra-high-dose-rate capabilities for scientists