Characterization of the precipitation in southwestern part of Greece with X-band Doppler radar, 2-D video disdrometer and rain gauges

International audienceWe document precipitation in the southwestern part of Greece with the National Observatory of Athens (NOA) X-band radar, NOA 2D video disdrometer and a network of rain gauges. The observations were collected between February and April 2004. Time evolution of the drop size distribution (DSD) is presented for the 9 March 2004 case where rain rate (computed on 1-min period) was measured up to 80 mm/h and reflectivity at the location of the disdrometer exceeded 40 dBZ. We then present the differences of DSD as function of the rain rate for the studied case as well as for the entire observations of the field experiment. It shows that higher the rain rate is, larger the range of the DSD and higher the concentration of the raindrops are

Synoptic environment related to rapid cyclogenesis in the Eastern Mediterranean

International audienceThis paper presents first results on the investigation of the synoptic conditions that led to the rapid development of a low-pressure system over the Aegean Sea. Indeed, during the period 21?22 January 2004, a very deep cyclone was observed over the Aegean Sea with a minimum central pressure of ~972 hPa, a value which is among the lowest observed over the entire Mediterranean Sea during the last 40 years. The rapid development was associated with a two-trough system that, under the influence of a very intense upper-level jet, was merged in one and then acquired a negative tilting. Additional information on the mesoscale organisation of the system is given, based on lightning data and space borne microwave and infrared observations

Assimilation of Meteosat Third Generation (MTG) Lightning Imager (LI) pseudo-observations in AROME-France – proof of concept

This study develops a lightning data assimilation (LDA) scheme for the regional, convection-permitting numerical weather prediction (NWP) model AROME-France. The LDA scheme intends to assimilate total lightning, i.e., cloud-to-ground (CG) and inter- and intra-cloud (IC), of the future Meteosat Third Generation (MTG) Lightning Imager (LI; MTG-LI). MTG-LI proxy data are created, and flash extent density (FED) fields are derived. An FED forward observation operator (FFO) is trained based on modeled, column-integrated graupel mass from 24 storm days in 2018. The FFO is successfully verified for 2 independent storm days. With the FFO, the LDA adapts a 1-dimensional Bayesian (1DBay) retrieval followed by a 3-dimensional variational (3DVar) assimilation approach that is currently run operationally in AROME-France for radar reflectivity data. The 1DBay retrieval derives relative humidity profiles from the background by comparing the FED observations to the FED inferred from the background. Retrieved relative humidity profiles are assimilated as sounding data. The evaluation of the LDA comprises different LDA experiments and four case studies. It is found that all LDA experiments can increase the background integrated water vapor (IWV) in regions where the observed FED exceeds the FED inferred from AROME-France outputs. In addition, IWV can be reduced where spurious FED is modeled. A qualitative analysis of 6 h accumulated rainfall fields reveals that the LDA is capable of locating and initiating some local precipitation fields better than a radar data assimilation (RDA) experiment. However, the LDA also leads to rainfall accumulations that are too high at some locations. Fractions skill scores (FSSs) of 6 h accumulated rainfall are overall similar for the developed LDA and RDA experiments. An approach aiming at mitigating effects due to differences in the optical extents of lightning flashes and the area of the corresponding cloud was developed and included in the LDA; however, it does not always improve the FSS.</p

Electric Fields, Cloud Microphysics, and Reflectivity in Anvils of Florida Thunderstorms

A coordinated aircraft - radar project that investigated the electric fields, cloud microphysics and radar reflectivity of thunderstorm anvils near Kennedy Space Center is described. Measurements from two cases illustrate the extensive nature of the microphysics and electric field observations. As the aircraft flew from the edges of anvils into the interior, electric fields very frequently increased abruptly from approx.1 to >10 kV/m even though the particle concentrations and radar reflectivity increased smoothly. The abrupt increase in field usually occurred when the aircraft entered regions with a reflectivity of 10 to 15 dBZ. It is suggested that the abrupt increase in electric field may be because the charge advection from the storm core did not occur across the entire breadth of the anvil and was not constant in time. Screening layers were not detected near the edges of the anvils. Some long-lived anvils showed subsequent enhancement of electric field and reflectivity and growth of particles, which if localized, might be a factor in explaining the abrupt change of field in some cases. Comparisons of electric field magnitude with particle concentration or reflectivity for a combined data set that included all anvil measurements showed a threshold behavior. When the average reflectivity, such as in a 3-km cube, was less than approximately 5 dBZ, the electric field magnitude was <3 kV/m. Based on these findings, the Volume Averaged Height Integrated Radar Reflectivity (VAHIRR) is now being used by NASA, the Air Force and Federal Aviation Administration in new Lightning Launch Commit Criteria as a diagnostic for high electric fields in anvils

Natalizumab affects T-cell phenotype in multiple sclerosis: implications for JCV reactivation

The anti-CD49d monoclonal antibody natalizumab is currently an effective therapy against the relapsing-remitting form of multiple sclerosis (RRMS). Natalizumab therapeutic efficacy is limited by the reactivation of the John Cunningham polyomavirus (JCV) and development of progressive multifocal leukoencephalopathy (PML). To correlate natalizumab-induced phenotypic modifications of peripheral blood T-lymphocytes with JCV reactivation, JCV-specific antibodies (serum), JCV-DNA (blood and urine), CD49d expression and relative abundance of peripheral blood T-lymphocyte subsets were longitudinally assessed in 26 natalizumab-treated RRMS patients. Statistical analyses were performed using GraphPad Prism and R. Natalizumab treatment reduced CD49d expression on memory and effector subsets of peripheral blood T-lymphocytes. Moreover, accumulation of peripheral blood CD8+ memory and effector cells was observed after 12 and 24 months of treatment. CD4+ and CD8+ T-lymphocyte immune-activation was increased after 24 months of treatment. Higher percentages of CD8+ effectors were observed in subjects with detectable JCV-DNA. Natalizumab reduces CD49d expression on CD8+ T-lymphocyte memory and effector subsets, limiting their migration to the central nervous system and determining their accumulation in peripheral blood. Impairment of central nervous system immune surveillance and reactivation of latent JCV, can explain the increased risk of PML development in natalizumab-treated RRMS subjects

Interferon β-1a in relapsing multiple sclerosis: four-year extension of the European IFNβ-1a Dose-C omparison Study

Background: Multiple sclerosis (MS) is a chronic disease requiring long-term monitoring of treatment. Objective: To assess the four-year clinical efficacy of intramuscular (IM) IFNb-1a in patients with relapsing MS from the European IFNb-1a Dose-C omparison Study. Methods: Patients who completed 36 months of treatment (Part 1) of the European IFNb-1a Dose-C omparison Study were given the option to continue double-blind treatment with IFNb-1a 30 mcg or 60 mcg IM once weekly (Part 2). Analyses of 48-month data were performed on sustained disability progression, relapses, and neutralizing antibody (NA b) formation. Results: O f 608/802 subjects who completed 36 months of treatment, 493 subjects continued treatment and 446 completed 48 months of treatment and follow-up. IFNb-1a 30 mcg and 60 mcg IM once weekly were equally effective for up to 48 months. There were no significant differences between doses over 48 months on any of the clinical endpoints, including rate of disability progression, cumulative percentage of patients who progressed (48 and 43, respectively), and annual relapse rates; relapses tended to decrease over 48 months. The incidence of patients who were positive for NAbs at any time during the study was low in both treatment groups. Conclusion: C ompared with 60-mcg IM IFNb-1a once weekly, a dose of 30 mcg IM IFNb-1a once weekly maintains the same clinical efficacy over four years

Cardiac Myosin Binding Protein C and MAP-Kinase Activating Death Domain-Containing Gene Polymorphisms and Diastolic Heart Failure

OBJECTIVE: Myosin binding protein C (MYBPC3) plays a role in ventricular relaxation. The aim of the study was to investigate the association between cardiac myosin binding protein C (MYBPC3) gene polymorphisms and diastolic heart failure (DHF) in a human case-control study. METHODS: A total of 352 participants of 1752 consecutive patients from the National Taiwan University Hospital and its affiliated hospital were enrolled. 176 patients diagnosed with DHF confirmed by echocardiography were recruited. Controls were matched 1-to-1 by age, sex, hypertension, diabetes, renal function and medication use. We genotyped 12 single nucleotide polymorphisms (SNPs) according to HapMap Han Chinese Beijing databank across a 40 kb genetic region containing the MYBPC3 gene and the neighboring DNA sequences to capture 100% of haplotype variance in all SNPs with minor allele frequencies ≥ 5%. We also analyzed associations of these tagging SNPs and haplotypes with DHF and linkage disequilibrium (LD) structure of the MYBPC3 gene. RESULTS: In a single locus analysis, SNP rs2290149 was associated with DHF (allele-specific p = 0.004; permuted p = 0.031). The SNP with a minor allele frequency of 9.4%, had an odds ratio 2.14 (95% CI 1.25-3.66; p = 0.004) for the additive model and 2.06 for the autosomal dominant model (GG+GA : AA, 95% CI 1.17-3.63; p = 0.013), corresponding to a population attributable risk fraction of 12.02%. The haplotypes in a LD block of rs2290149 (C-C-G-C) was also significantly associated with DHF (odds ratio 2.10 (1.53-2.89); permuted p = 0.029). CONCLUSIONS: We identified a SNP (rs2290149) among the tagging SNP set that was significantly associated with early DHF in a Chinese population

Cross-Species Transmission of a Novel Adenovirus Associated with a Fulminant Pneumonia Outbreak in a New World Monkey Colony

Adenoviruses are DNA viruses that naturally infect many vertebrates, including humans and monkeys, and cause a wide range of clinical illnesses in humans. Infection from individual strains has conventionally been thought to be species-specific. Here we applied the Virochip, a pan-viral microarray, to identify a novel adenovirus (TMAdV, titi monkey adenovirus) as the cause of a deadly outbreak in a closed colony of New World monkeys (titi monkeys; Callicebus cupreus) at the California National Primate Research Center (CNPRC). Among 65 titi monkeys housed in a building, 23 (34%) developed upper respiratory symptoms that progressed to fulminant pneumonia and hepatitis, and 19 of 23 monkeys, or 83% of those infected, died or were humanely euthanized. Whole-genome sequencing of TMAdV revealed that this adenovirus is a new species and highly divergent, sharing <57% pairwise nucleotide identity with other adenoviruses. Cultivation of TMAdV was successful in a human A549 lung adenocarcinoma cell line, but not in primary or established monkey kidney cells. At the onset of the outbreak, the researcher in closest contact with the monkeys developed an acute respiratory illness, with symptoms persisting for 4 weeks, and had a convalescent serum sample seropositive for TMAdV. A clinically ill family member, despite having no contact with the CNPRC, also tested positive, and screening of a set of 81 random adult blood donors from the Western United States detected TMAdV-specific neutralizing antibodies in 2 individuals (2/81, or 2.5%). These findings raise the possibility of zoonotic infection by TMAdV and human-to-human transmission of the virus in the population. Given the unusually high case fatality rate from the outbreak (83%), it is unlikely that titi monkeys are the native host species for TMAdV, and the natural reservoir of the virus is still unknown. The discovery of TMAdV, a novel adenovirus with the capacity to infect both monkeys and humans, suggests that adenoviruses should be monitored closely as potential causes of cross-species outbreaks

The Role of Mislocalized Phototransduction in Photoreceptor Cell Death of Retinitis Pigmentosa

Most of inherited retinal diseases such as retinitis pigmentosa (RP) cause photoreceptor cell death resulting in blindness. RP is a large family of diseases in which the photoreceptor cell death can be caused by a number of pathways. Among them, light exposure has been reported to induce photoreceptor cell death. However, the detailed mechanism by which photoreceptor cell death is caused by light exposure is unclear. In this study, we have shown that even a mild light exposure can induce ectopic phototransduction and result in the acceleration of rod photoreceptor cell death in some vertebrate models. In ovl, a zebrafish model of outer segment deficiency, photoreceptor cell death is associated with light exposure. The ovl larvae show ectopic accumulation of rhodopsin and knockdown of ectopic rhodopsin and transducin rescue rod photoreceptor cell death. However, knockdown of phosphodiesterase, the enzyme that mediates the next step of phototransduction, does not. So, ectopic phototransduction activated by light exposure, which leads to rod photoreceptor cell death, is through the action of transducin. Furthermore, we have demonstrated that forced activation of adenylyl cyclase in the inner segment leads to rod photoreceptor cell death. For further confirmation, we have also generated a transgenic fish which possesses a human rhodopsin mutation, Q344X. This fish and rd10 model mice show photoreceptor cell death caused by adenylyl cyclase. In short, our study indicates that in some RP, adenylyl cyclase is involved in photoreceptor cell death pathway; its inhibition is potentially a logical approach for a novel RP therapy