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

Multiscaling analysis of high resolution space-time lidar-rainfall

In this study, we report results from scaling analysis of 2.5 m spatial and 1 s temporal resolution lidar-rainfall data. The high resolution spatial and temporal data from the same observing system allows us to investigate the variability of rainfall at very small scales ranging from few meters to ~1 km in space and few seconds to ~30 min in time. The results suggest multiscaling behaviour in the lidar-rainfall with the scaling regime extending down to the resolution of the data. The results also indicate the existence of a space-time transformation of the form <i>t</i>~<i>L<sup>z</sup></i> at very small scales, where <i>t</i> is the time lag, <i>L</i> is the spatial averaging scale and <i>z</i> is the dynamic scaling exponent

Impact of the indexed effective orifice area on mid-term cardiac-related mortality after aortic valve replacement

Background There has been ongoing controversy as to whether prosthesis-patient mismatch (PPM, defined as indexed effective orifice area (EOAI) <0.85 m(2)/cm(2)) influences mortality after aortic valve replacement (AVR). In most studies, PPM is anticipated by reference tables based on mean EOAs as opposed to individual assessment. These reference values may not reflect the actual in vivo EOAI and hence, the presence or absence of PPM may be based on false assumptions. Objective To assess the impact of small prosthesis EOA on survival after aortic valve replacement AVR. Methods 645 patients had undergone an AVR between 2000 and 2007 entered the study. All patients underwent transthoracic echocardiography for determination of the actual EOAI within 6 months postoperatively. In order to predict time from surgery to death a proportional hazards model for competing risks (cardiac death vs death from other causes) was used. EOAI was entered as a continuous variable. Results PPM occurred in 40% of the patients. After a median follow-up of 2.35 years, 92.1% of the patients were alive. The final Cox regression model showed a significantly increased risk for cardiac death among patients with a smaller EOAI (HR=0.32, p=0.022). The effect of EOAI on the 2-5 year mortality risk was demonstrated by risk plots. Conclusions In contrast to previous studies these EOAI values were obtained through postoperative echocardiography, substantially improving the accuracy of measurement, and the EOAI was modelled as a continuous variable. There was a significantly improved survival for larger EOAIs following AVR. Strategies to avoid PPM should become paramount during AVR

Systematic analysis of a novel human renal glomerulus-enriched gene expression dataset.

Glomerular diseases account for the majority of cases with chronic renal failure. Several genes have been identified with key relevance for glomerular function. Quite a few of these genes show a specific or preferential mRNA expression in the renal glomerulus. To identify additional candidate genes involved in glomerular function in humans we generated a human renal glomerulus-enriched gene expression dataset (REGGED) by comparing gene expression profiles from human glomeruli and tubulointerstitium obtained from six transplant living donors using Affymetrix HG-U133A arrays. This analysis resulted in 677 genes with prominent overrepresentation in the glomerulus. Genes with 'a priori' known prominent glomerular expression served for validation and were all found in the novel dataset (e.g. CDKN1, DAG1, DDN, EHD3, MYH9, NES, NPHS1, NPHS2, PDPN, PLA2R1, PLCE1, PODXL, PTPRO, SYNPO, TCF21, TJP1, WT1). The mRNA expression of several novel glomerulus-enriched genes in REGGED was validated by qRT-PCR. Gene ontology and pathway analysis identified biological processes previously not reported to be of relevance in glomeruli of healthy human adult kidneys including among others axon guidance. This finding was further validated by assessing the expression of the axon guidance molecules neuritin (NRN1) and roundabout receptor ROBO1 and -2. In diabetic nephropathy, a prevalent glomerulopathy, differential regulation of glomerular ROBO2 mRNA was found.In summary, novel transcripts with predominant expression in the human glomerulus could be identified using a comparative strategy on microdissected nephrons. A systematic analysis of this glomerulus-specific gene expression dataset allows the detection of target molecules and biological processes involved in glomerular biology and renal disease

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

Correction of stratospheric age-of-air derived from SF 6 for the effect of chemical sinks

Observational monitoring of the stratospheric transport circulation, the Brewer-Dobson-Circulation (BDC), is crucial to estimate any decadal to long-term changes therein, a prerequisite to interpret trends in stratospheric composition and to constrain the consequential impacts on climate. The transport time along the BDC (i.e., the mean age of stratospheric air, AoA) can best be deduced from trace gas measurements of tracers which increase linearly in time and are chemically passive. The gas SF6 is often used to deduce AoA, because it has been increasing monotonically since the ~1950s, and previously its chemical sinks in the mesosphere have been assumed to be negligible for AoA estimates. However, recent studies have shown that the chemical sinks of SF6 are stronger than assumed, and become increasingly relevant with rising SF6 concentrations. To adjust biases in AoA that result from the chemical SF6 sinks, we here propose a simple correction scheme for SF6-based AoA estimates accounting for the time-dependent effects of chemical sinks. The correction scheme is based on theoretical considerations with idealized assumptions, resulting in a relation between ideal AoA and apparent AoA which is a function of the tropospheric reference time-series of SF6 and of the AoA-dependent effective lifetime of SF6. The correction method is thoroughly tested within a self-consistent data set from a climate model that includes explicit calculation of chemical SF6 sinks. It is shown within the model that the correction successfully reduces biases in SF6-based AoA to less than 5 % for mean ages below 5 years. Tests with using only sub-sampled data for deriving the fit coefficients show that applying the correction scheme even with imperfect knowledge of the sink is far superior to not applying a sink correction. Further, we show that based on currently available measurements, we are not able to constrain the fit parameters of the correction scheme based on observational data alone. However, the model-based correction curve lies within the observational uncertainty, and we thus recommend to use the model-derived fit coefficients until more high-quality measurements will be able to further constrain the correction scheme. The application of the correction scheme to AoA from satellites and in-situ data suggests that it is highly beneficial to reconcile different observational estimates of mean AoA

The microbial diversity of the Su Bentu cave, Italy and the influence of human exploration.

Introduction: The microbial diversity in the Su Bentu Cave (Sardinia, Italy) was investigated by means of Illumina MiSeq analysis. The hypogean environment is of great interest for astrobiological research as cave conditions may resemble those in extra-terrestrial regions. Furthermore, they hold high potential to identify novel, extremely adapted organisms to severely oligo-trophic habitats. However, the influence of human is not neglectable and in-depth investigations are needed to determine the impact of exploration on an otherwise mostly pristine ecosystem. The cave investigated in this study develops for several kilometres into the mountain, two hundred metres below the topographic surface and is characterized by a strong air circulation. Its structure is composed of huge passages carved in limestone where an ephemeral underground stream creates some lakes, close to which seven samples of visible calcite rafts, manganese deposits and moonmilk (a hydrated calcium carbonate speleothem), were sampled during an expedition in 2014. Other samples were re-trieved from a frequently used campsite and from some dry cave passages leading deeper into the cave

Contrast sensitivity and night driving in older people: Quantifying the relationship between visual acuity, contrast sensitivity, and hazard detection distance in a night-time driving simulator

Purpose: (i) To assess how well contrast sensitivity (CS) predicts night-time hazard detection distance (one key component of night driving ability), in normally sighted older drivers, relative to a conventional measure of high contrast visual acuity (VA); (ii) To evaluate whether CS can be accurately quantified within a night driving simulator. Methods: Participants were fifteen (five female) ophthalmologically healthy adults, aged 55 to 81 years. CS was measured in a driving simulator using Landolt Cs, presented under static or dynamic driving conditions, and with or without glare. In the dynamic driving condition, the participant was asked to simultaneously maintain a (virtual) speed of 60 km/h on a country road. In the (dynamic) with glare condition, two calibrated LED arrays, moved by cable robots, simulated the trajectories and luminance characteristics of the (low beam) headlights of an approaching car. For comparison, CS was also measured clinically (with & without glare) using a Optovist I instrument (Vistec Inc., Olching/FRG). Visual acuity (VA) thresholds were also assessed at high and low contrast using the Freiburg Visual Acuity Test (FrACT) under photopic conditions. As a measure of driving performance, median hazard detection distance (MHDD) was computed, in meters, across three kinds of simulated obstacles of varying contrast. Results: CS and low contrast VA were both significantly associated with driving performance (both P < 0.01), whereas conventional high contrast acuity was not (P = 0.10). There was good correlation (P < 0.01) between CS measured in the driving simulator and a conventional clinical instrument (Optovist). As expected, CS was shown to decrease in the presence of glare, in dynamic driving conditions, and as a function of age (all P < 0.01). Conclusions: CS and low contrast VA predict night-time hazard detection ability in a manner that conventional high contrast VA does not. Either may therefore provide a useful metric for assessing fitness to drive at night, particularly in older individuals. CS measurements can be made within a driving simulator, and the data are in good agreement with conventional clinical methods (Optovist I)