A study of the link between cosmic rays and clouds with a cloud chamber at the CERN PS

Recent satellite data have revealed a surprising correlation between galactic cosmic ray (GCR) intensity and the fraction of the Earth covered by clouds. If this correlation were to be established by a causal mechanism, it could provide a crucial step in understanding the long-sought mechanism connecting solar and climate variability. The Earth's climate seems to be remarkably sensitive to solar activity, but variations of the Sun's electromagnetic radiation appear to be too small to account for the observed climate variability. However, since the GCR intensity is strongly modulated by the solar wind, a GCR-cloud link may provide a sufficient amplifying mechanism. Moreover if this connection were to be confirmed, it could have profound consequences for our understanding of the solar contributions to the current global warming. The CLOUD (Cosmics Leaving OUtdoor Droplets) project proposes to test experimentally the existence a link between cosmic rays and cloud formation, and to understand the microphysical mechanism. CLOUD plans to perform detailed laboratory measurements in a particle beam at CERN, where all the parameters can be precisely controlled and measured. The beam will pass through an expansion cloud chamber and a reactor chamber where the atmosphere is to be duplicated by moist air charged with selected aerosols and trace condensable vapours. An array of external detectors and mass spectrometers is used to analyse the physical and chemical characteristics of the aerosols and trace gases during beam exposure. Where beam effects are found, the experiment will seek to evaluate their significance in the atmosphere by incorporating them into aerosol and cloud models.Recent satellite data have revealed a surprising correlation between galactic cosmic ray (GCR) intensity and the fraction of the Earth covered by clouds. If this correlation were to be established by a causal mechanism, it could provide a crucial step in understanding the long-sought mechanism connecting solar and climate variability. The Earth's climate seems to be remarkably sensitive to solar activity, but variations of the Sun's electromagnetic radiation appear to be too small to account for the observed climate variability. However, since the GCR intensity is strongly modulated by the solar wind, a GCR-cloud link may provide a sufficient amplifying mechanism. Moreover if this connection were to be confirmed, it could have profound consequences for our understanding of the solar contributions to the current global warming. The CLOUD (Cosmics Leaving OUtdoor Droplets) project proposes to test experimentally the existence a link between cosmic rays and cloud formation, and to understand the microphysical mechanism. CLOUD plans to perform detailed laboratory measurements in a particle beam at CERN, where all the parameters can be precisely controlled and measured. The beam will pass through an expansion cloud chamber and a reactor chamber where the atmosphere is to be duplicated by moist air charged with selected aerosols and trace condensable vapours. An array of external detectors and mass spectrometers is used to analyse the physical and chemical characteristics of the aerosols and trace gases during beam exposure. Where beam effects are found, the experiment will seek to evaluate their significance in the atmosphere by incorporating them into aerosol and cloud models

Fatigue properties of high strength titanium alloys at elevated temperatures (IMI 685)

SIGLETIB: RN 437 (86-19) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Oral Coenzyme Q10 supplementation leads to better preservation of kidney function in steroid-resistant nephrotic syndrome due to primary Coenzyme Q10 deficiency.

Primary Coenzyme Q10 (CoQ10) deficiency is an ultra-rare disorder caused by defects in genes involved in CoQ10 biosynthesis leading to multidrug-resistant nephrotic syndrome as the hallmark kidney manifestation. Promising early results have been reported anecdotally with oral CoQ10 supplementation. However, the long-term efficacy and optimal prescription remain to be established. In a global effort, we collected and analyzed information from 116 patients who received CoQ10 supplements for primary CoQ10 deficiency due to biallelic pathogenic variants in either the COQ2, COQ6 or COQ8B genes. Median duration of follow up on treatment was two years. The effect of treatment on proteinuria was assessed, and kidney survival was analyzed in 41 patients younger than 18 years with chronic kidney disease stage 1-4 at the start of treatment compared with that of an untreated cohort matched by genotype, age, kidney function, and proteinuria. CoQ10 supplementation was associated with a substantial and significant sustained reduction of proteinuria by 88% at 12 months. Complete remission of proteinuria was more frequently observed in COQ6 disease. CoQ10 supplementation led to significantly better preservation of kidney function (5-year kidney failure-free survival 62% vs. 19%) with an improvement in general condition and neurological manifestations. Side effects of treatment were uncommon and mild. Thus, our findings indicate that all patients diagnosed with primary CoQ10 deficiency should receive early and life-long CoQ10 supplementation to decelerate the progression of kidney disease and prevent further damage to other organs

Variation of the clinical spectrum and genotype-phenotype associations in Coenzyme Q10 deficiency associated glomerulopathy.

Primary Coenzyme Q10 deficiency is a rare mitochondriopathy with a wide spectrum of organ involvement, including steroid-resistant nephrotic syndrome mainly associated with disease-causing variants in the genes COQ2, COQ6 or COQ8B. We performed a systematic literature review, PodoNet, MitoNET, and CCGKDD registries queries and an online survey, collecting comprehensive clinical and genetic data of 251 patients spanning 173 published (47 updated) and 78 new cases. Kidney disease was first diagnosed at median age 1.0, 1.2 and 9.8 years in individuals with disease-causing variants in COQ2, COQ6 and COQ8B, respectively. Isolated kidney involvement at diagnosis occurred in 34% of COQ2, 10.8% of COQ6 and 70.7% of COQ8B variant individuals. Classic infantile multiorgan involvement comprised 22% of the COQ2 variant cohort while 47% of them developed neurological symptoms at median age 2.7 years. The association of steroid-resistant nephrotic syndrome and sensorineural hearing loss was confirmed as the distinctive phenotype of COQ6 variants, with hearing impairment manifesting at average age three years. None of the patients with COQ8B variants, but 50% of patients with COQ2 and COQ6 variants progressed to kidney failure by age five. At adult age, kidney survival was equally poor (20-25%) across all disorders. A number of sequence variants, including putative local founder mutations, had divergent clinical presentations, in terms of onset age, kidney and non-kidney manifestations and kidney survival. Milder kidney phenotype was present in those with biallelic truncating variants within the COQ8B variant cohort. Thus, significant intra- and inter-familial phenotype variability was observed, suggesting both genetic and non-genetic modifiers of disease severity

A fully validated microbiological assay to evaluate the potency of ceftriaxone sodium

Ceftriaxone (CFTX) sodium is a third-generation, broad-spectrum cephalosporin that is resistant to beta-lactamases. An alternative bioassay for the assessment of the potency of this drug in pharmaceutical formulations has not been previously reported. Thus, this paper reports the development and full validation of a 3 x 3 agar diffusion bioassay using a cylinder-plate method to quantify CFTX sodium in pharmaceutical samples. The strain Staphylococcus aureus ATCC 6538P was used as the test microorganism, and the results of the proposed bioassay displayed high linearity, precision, accuracy, specificity and robustness. All potency results were statistically analyzed using an analysis of variance (ANOVA) and were found to be linear (r=0.99999) in the range of 16-64 µg/mL, accurate (100.5%), and precise [repeatability: relative standard deviation (RSD)=1.4%; intermediate precision: between-day RSD=2.1% and between-analyst RSD=2.5%]. The specificity of the bioassay was determined by evaluating a degraded sample (50 ºC) at 0, 24 and 48 hours as compared against the results from the pharmacopeial liquid chromatography method for CFTX. The results validated the proposed microbiological assay, which allows reliable quantitation of CFTX in pharmaceutical samples. Moreover, it is a useful, simple and low-cost alternative method for monitoring the quality of this medicine