Low noise buffer amplifiers and buffered phase comparators for precise time and frequency measurement and distribution

Extremely low noise, high performance, wideband buffer amplifiers and buffered phase comparators were developed. These buffer amplifiers are designed to distribute reference frequencies from 30 KHz to 45 MHz from a hydrogen maser without degrading the hydrogen maser's performance. The buffered phase comparators are designed to intercompare the phase of state of the art hydrogen masers without adding any significant measurement system noise. These devices have a 27 femtosecond phase stability floor and are stable to better than one picosecond for long periods of time. Their temperature coefficient is less than one picosecond per degree C, and they have shown virtually no voltage coefficients

Multisystem proteinopathy due to a homozygous p.Arg159His VCP mutation : a tale of the unexpected

ObjectiveTo assess the clinical, radiologic, myopathologic, and proteomic findings in a patient manifesting a multisystem proteinopathy due to a homozygous valosin-containing protein gene (VCP) mutation previously reported to be pathogenic in the heterozygous state.MethodsWe studied a 36-year-old male index patient and his father, both presenting with progressive limb-girdle weakness. Muscle involvement was assessed by MRI and muscle biopsies. We performed whole-exome sequencing and Sanger sequencing for segregation analysis of the identified p.Arg159His VCP mutation. To dissect biological disease signatures, we applied state-of-the-art quantitative proteomics on muscle tissue of the index case, his father, 3 additional patients with VCP-related myopathy, and 3 control individuals.ResultsThe index patient, homozygous for the known p.Arg159His mutation in VCP, manifested a typical VCP-related myopathy phenotype, although with a markedly high creatine kinase value and a relatively early disease onset, and Paget disease of bone. The father exhibited a myopathy phenotype and discrete parkinsonism, and multiple deceased family members on the maternal side of the pedigree displayed a dementia, parkinsonism, or myopathy phenotype. Bioinformatic analysis of quantitative proteomic data revealed the degenerative nature of the disease, with evidence suggesting selective failure of muscle regeneration and stress granule dyshomeostasis.ConclusionWe report a patient showing a multisystem proteinopathy due to a homozygous VCP mutation. The patient manifests a severe phenotype, yet fundamental disease characteristics are preserved. Proteomic findings provide further insights into VCP-related pathomechanisms

Size-resolved aerosol emission factors and new particle formation/growth activity occurring in Mexico City during the MILAGRO 2006 Campaign

Measurements of the aerosol size distribution from 11 nm to 2.5 microns were made in Mexico City in March 2006, during the MILAGRO (Megacity Initiative: Local and Global Research Observations) field campaign. Observations at the urban supersite, referred to as T0, could often be characterized by morning conditions with high particle mass concentrations, low mixing heights, and highly correlated particle number and CO<sub>2</sub> concentrations, indicative that particle number is controlled by primary emissions. Average size-resolved and total number- and volume-based emission factors for combustion sources impacting T0 have been determined using a comparison of peak sizes in particle number and CO<sub>2</sub> concentration. Peaks are determined by subtracting the measured concentration from a calculated baseline concentration time series. The number emission and volume emission factors for particles from 11 nm to 494 nm are 1.56 × 10<sup>15</sup> particles, and 9.48 × 10<sup>11</sup> cubic microns per kg of carbon, respectively. The uncertainty of the number emission factor is approximately plus or minus 50 %. The mode of the number emission factor was between 25 and 32 nm, while the mode of the volume factor was between 0.25 and 0.32 microns. These emission factors are reported as log normal model parameters and are compared with multiple emission factors from the literature. In Mexico City in the afternoon, the CO<sub>2</sub> concentration drops during ventilation of the polluted layer, and the coupling between CO<sub>2</sub> and particle number breaks down, especially during new particle formation events when particle number is no longer controlled by primary emissions. Using measurements of particle number and CO<sub>2</sub> taken aboard the NASA DC-8, the determined primary emission factor was applied to the Mexico City Metropolitan Area (MCMA) plume to quantify the degree of secondary particle formation in the plume; the primary emission factor accounts for less than 50 % of the total particle number and the surplus particle count is not correlated with photochemical age. Primary particle volume and number in the size range 0.1–2 μm are similarly too low to explain the observed volume distribution. Contrary to the case for number, the apparent secondary volume increases with photochemical age. The size distribution of the apparent increase, with a mode at ~250 nm, is reported

Risk of recurrence after a first unprovoked venous thromboembolism : external validation of the Vienna Prediction Model with pooled individual patient data

Background: In order to stratify patients with a first unprovoked venous thromboembolism (VTE) according to their recurrence risk and to identify those who would actually benefit from indefinite anticoagulation, three prediction models have been developed so far; none of them has been yet externally validated. Objective: To externally validate the Vienna Prediction Model (VPM), a prediction guide for estimating the recurrence risk after a first unprovoked VTE developed through Cox modeling and including sex, D-dimer and index VTE site as predictors. Patients/Methods: Nine hundred and four patients pooled from five prospective studies evaluating the prognostic value of D-dimer for VTE recurrence served as the validation cohort. The validity of the VPM in stratifying patients according to their relative recurrence risk (discrimination) and in predicting the absolute recurrence risk (calibration) was tested with survival analysis methods. Results: The ability of the VPM to distinguish patients' risk for recurrent VTE in the validation cohort was at least as good as in the original cohort, with a calibration slope of 1.17 (95% confidence interval 0.71-1.64; P\ua0=\ua00.456 for the hypothesis of a significant difference from 1), and a c-statistic of 0.626 (vs. 0.651 in the original derivation cohort). The VPM absolute predictions in terms of cumulative rates tended to underestimate the observed recurrence rates at 12\ua0months. Conclusions: By using a pooled individual patient database as a validation cohort, we confirmed the ability of the VPM to stratify patients with a first unprovoked VTE according to their risk of recurrence

Bio-electrospraying and aerodynamically assisted bio-jetting the model eukaryotic Dictyostelium discoideum: assessing stress and developmental competency post treatment

Bio-electrospraying (BES) and aerodynamically assisted bio-jetting (AABJ) have recently been established as important novel biospray technologies for directly manipulating living cells. To elucidate their potential in medical and clinical sciences, these bio-aerosol techniques have been subjected to increasingly rigorous investigations. In parallel to these studies, we wish to introduce these unique biotechnologies for use in the basic biological sciences, for handling a wide range of cell types and systems, thus increasing the range and the scope of these techniques for modern research. Here, the authors present the analysis of the new use of these biospray techniques for the direct handling of the simple eukaryotic biomedical model organism Dictyostelium discoideum. These cells are widely used as a model for immune cell chemotaxis and as a simple model for development. We demonstrate that AABJ of these cells did not cause cell stress, as defined by the stress-gene induction, nor affect cell development. Furthermore, although BES induced the increased expression of one stress-related gene (gapA), this was not a generalized stress response nor did it affect cell development. These data suggest that these biospray techniques can be used to directly manipulate single cells of this biomedical model without inducing a generalized stress response or perturbing later development

Localizing Defects in Multithreaded Programs by Mining Dynamic Call Graphs

Writing multithreaded software for multicore computers confronts many developers with the difficulty of finding parallel programming errors. In the past, most parallel debugging techniques have concentrated on finding race conditions due to wrong usage of synchronization constructs. A widely unexplored issue, however, is that a wrong usage of non-parallel programming constructs may also cause wrong parallel application behavior. This paper presents a novel defect-localization technique for multithreaded shared-memory programs that is based on analyzing execution anomalies. Compared to race detectors that report just on wrong synchronization, this method can detect a wider range of defects affecting parallel execution. It works on a condensed representation of the call graphs of multithreaded applications and employs data-mining techniques to locate a method containing a defect. Our results from controlled application experiments show that we found race conditions, but also other programming errors leading to incorrect parallel program behavior. On average, our approach reduced in our benchmark the amount of code to be inspected to just 7.1% of all methods

Entamoeba Shows Reversible Variation in Ploidy under Different Growth Conditions and between Life Cycle Phases

Under axenic growth conditions, trophozoites of Entamoeba histolytica contain heterogenous amounts of DNA due to the presence of both multiple nuclei and different amounts of DNA in individual nuclei. In order to establish if the DNA content and the observed heterogeneity is maintained during different growth conditions, we have compared E. histolytica cells growing in xenic and axenic cultures. Our results show that the nuclear DNA content of E. histolytica trophozoites growing in axenic cultures is at least 10 fold higher than in xenic cultures. Re-association of axenic cultures with their bacterial flora led to a reduction of DNA content to the original xenic values. Thus switching between xenic and axenic growth conditions was accompanied by significant changes in the nuclear DNA content of this parasite. Changes in DNA content during encystation-excystation were studied in the related reptilian parasite E. invadens. During excystation of E. invadens cysts, it was observed that the nuclear DNA content increased approximately 40 fold following emergence of trophozoites in axenic cultures. Based on the observed large changes in nuclear size and DNA content, and the minor differences in relative abundance of representative protein coding sequences, rDNA and tRNA sequences, it appears that gain or loss of whole genome copies may be occurring during changes in the growth conditions. Our studies demonstrate the inherent plasticity and dynamic nature of the Entamoeba genome in at least two species