965 resultados para Hoffmann, Dietrich
Resumo:
We propose a new satellite mission to deliver high quality measurements of upper air water vapour. The concept centres around a LiDAR in limb sounding by occultation geometry, designed to operate as a very long path system for differential absorption measurements. We present a preliminary performance analysis with a system sized to send 75 mJ pulses at 25 Hz at four wavelengths close to 935 nm, to up to 5 microsatellites in a counter-rotating orbit, carrying retroreflectors characterized by a reflected beam divergence of roughly twice the emitted laser beam divergence of 15 µrad. This provides water vapour profiles with a vertical sampling of 110 m; preliminary calculations suggest that the system could detect concentrations of less than 5 ppm. A secondary payload of a fairly conventional medium resolution multispectral radiometer allows wide-swath cloud and aerosol imaging. The total weight and power of the system are estimated at 3 tons and 2,700 W respectively. This novel concept presents significant challenges, including the performance of the lasers in space, the tracking between the main spacecraft and the retroreflectors, the refractive effects of turbulence, and the design of the telescopes to achieve a high signal-to-noise ratio for the high precision measurements. The mission concept was conceived at the Alpbach Summer School 2010.
Resumo:
A nitric oxide synthase (NOS)-like activity has been demonstrated in human red blood cells (RBCs), but doubts about its functional significance, isoform identity and disease relevance remain. Using flow cytometry in combination with the NO-imaging probe DAF-FM we find that all blood cells form NO intracellularly, with a rank order of monocytes > neutrophils > lymphocytes > RBCs > platelets. The observation of a NO-related fluorescence within RBCs was unexpected given the abundance of the NO-scavenger oxyhemoglobin. Constitutive normoxic NO formation was abolished by NOS inhibition and intracellular NO scavenging, confirmed by laser-scanning microscopy and unequivocally validated by detection of the DAF-FM reaction product with NO using HPLC and LC-MS/MS. Employing immunoprecipitation, ESI-MS/MS-based peptide sequencing and enzymatic assay we further demonstrate that human RBCs contain an endothelial NOS (eNOS) that converts L-3H-Arginine to L-3H-Citrulline in a Ca2+/Calmodulin-dependent fashion. Moreover, in patients with coronary artery disease, red cell eNOS expression and activity are both lower than in age-matched healthy individuals and correlate with the degree of endothelial dysfunction. Thus, human RBCs constitutively produce NO under normoxic conditions via an active eNOS isoform the activity of which is compromised in patients with coronary artery disease.
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During each of the late Pleistocene glacial–interglacial transitions, atmospheric carbon dioxide concentrations rose by almost 100 ppm. The sources of this carbon are unclear, and efforts to identify them are hampered by uncertainties in the magnitude of carbon reservoirs and fluxes under glacial conditions. Here we use oxygen isotope measurements from air trapped in ice cores and ocean carbon-cycle modelling to estimate terrestrial and oceanic gross primary productivity during the Last Glacial Maximum. We find that the rate of gross terrestrial primary production during the Last Glacial Maximum was about 40±10 Pg C yr−1, half that of the pre-industrial Holocene. Despite the low levels of photosynthesis, we estimate that the late glacial terrestrial biosphere contained only 330 Pg less carbon than pre-industrial levels. We infer that the area covered by carbon-rich but unproductive biomes such as tundra and cold steppes was significantly larger during the Last Glacial Maximum, consistent with palaeoecological data. Our data also indicate the presence of an inert carbon pool of 2,300 Pg C, about 700 Pg larger than the inert carbon locked in permafrost today. We suggest that the disappearance of this carbon pool at the end of the Last Glacial Maximum may have contributed to the deglacial rise in atmospheric carbon dioxide concentrations.
Resumo:
We present a new speleothem record of atmospheric Δ14C between 28 and 44 ka that offers considerable promise for resolving some of the uncertainty associated with existing radiocarbon calibration curves for this time period. The record is based on a comprehensive suite of AMS 14C ages, using new low-blank protocols, and U–Th ages using high precision MC-ICPMS procedures. Atmospheric Δ14C was calculated by correcting 14C ages with a constant dead carbon fraction (DCF) of 22.7 ± 5.9%, based on a comparison of stalagmite 14C ages with the IntCal04 (Reimer et al., 2004) calibration curve between 15 and 11 ka. The new Δ14C speleothem record shows similar structure and amplitude to that derived from Cariaco Basin foraminifera (Hughen et al., 2004, 2006), and the match is further improved if the latter is tied to the most recent Greenland ice core chronology (Svensson et al., 2008). These data are however in conflict with a previously published 14C data set for a stalagmite record from the Bahamas — GB-89-24-1 (Beck et al., 2001), which likely suffered from 14C analytical blank subtraction issues in the older part of the record. The new Bahamas speleothem ∆14C data do not show the extreme shifts between 44 and 40 ka reported in the previous study (Beck et al., 2001). Causes for the observed structure in derived atmospheric Δ14C variation based on the new speleothem data are investigated with a suite of simulations using an earth system model of intermediate complexity. Data-model comparison indicates that major fluctuations in atmospheric ∆14C during marine isotope stage 3 is primarily a function of changes in geomagnetic field intensity, although ocean–atmosphere system reorganisation also played a supporting role.
Resumo:
Approximately 20 % of individuals with Parkinson's disease (PD) report a positive family history. Yet, a large portion of causal and disease-modifying variants is still unknown. We used exome sequencing in two affected individuals from a family with late-onset PD to identify 15 potentially causal variants. Segregation analysis and frequency assessment in 862 PD cases and 1,014 ethnically matched controls highlighted variants in EEF1D and LRRK1 as the best candidates. Mutation screening of the coding regions of these genes in 862 cases and 1,014 controls revealed several novel non-synonymous variants in both genes in cases and controls. An in silico multi-model bioinformatics analysis was used to prioritize identified variants in LRRK1 for functional follow- up. However, protein expression, subcellular localization, and cell viability were not affected by the identified variants. Although it has yet to be proven conclusively that variants in LRRK1 are indeed causative of PD, our data strengthen a possible role for LRRK1 in addition to LRRK2 in the genetic underpinnings of PD but, at the same time, highlight the difficulties encountered in the study of rare variants identified by next-generation sequencing in diseases with autosomal dominant or complex patterns of inheritance.
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Sudden stratospheric warmings (SSWs) are the most prominent vertical coupling process in the middle atmosphere, which occur during winter and are caused by the interaction of planetary waves (PWs) with the zonal mean flow. Vertical coupling has also been identified during the equinox transitions, and is similarly associated with PWs. We argue that there is a characteristic aspect of the autumn transition in northern high latitudes, which we call the “hiccup”, and which acts like a “mini SSW”, i.e. like a small minor warming. We study the average characteristics of the hiccup based on a superimposed epoch analysis using a nudged version of the Canadian Middle Atmosphere Model, representing 30 years of historical data. Hiccups can be identified in about half the years studied. The mesospheric zonal wind results are compared to radar observations over Andenes (69N,16E) for the years 2000–2013. A comparison of the average characteristics of hiccups and SSWs shows both similarities and differences between the two vertical coupling processes.
Resumo:
Systematic review (SR) is a rigorous, protocol-driven approach designed to minimise error and bias when summarising the body of research evidence relevant to a specific scientific question. Taking as a comparator the use of SR in synthesising research in healthcare, we argue that SR methods could also pave the way for a “step change” in the transparency, objectivity and communication of chemical risk assessments (CRA) in Europe and elsewhere. We suggest that current controversies around the safety of certain chemicals are partly due to limitations in current CRA procedures which have contributed to ambiguity about the health risks posed by these substances. We present an overview of how SR methods can be applied to the assessment of risks from chemicals, and indicate how challenges in adapting SR methods from healthcare research to the CRA context might be overcome. Regarding the latter, we report the outcomes from a workshop exploring how to increase uptake of SR methods, attended by experts representing a wide range of fields related to chemical toxicology, risk analysis and SR. Priorities which were identified include: the conduct of CRA-focused prototype SRs; the development of a recognised standard of reporting and conduct for SRs in toxicology and CRA; and establishing a network to facilitate research, communication and training in SR methods. We see this paper as a milestone in the creation of a research climate that fosters communication between experts in CRA and SR and facilitates wider uptake of SR methods into CRA.
Resumo:
Structure of inflorescences and flowers and flowering behaviour are reported for the woody liana Anchietea pyrifolia (Violaceae) from Brazil. The specimen studied is grown for some decades now in the greenhouses of Halle Botanical Garden and turned out unisexually male, which adds a further example of dioecism to the family Violaceae, in which this type of sex distribution is rarely encountered. The flowers are exceptional also for the strongly asymmetric anterior petal, which represents a rare case of a species with enantiomorphic flowers pollinated by Lepidoptera. They have a fully developed gynoecium with a complicated architecture comparable to the pistil of bisexual Violaceae flowers, though without ovules. The style head is capable to release viscose liquid on tactile stimulation or pressure, which is known to act as pollen-gathering mechanism in bisexual Violaceae species with usually dry pollen and buzz-pollination. This function has switched in male A. pyrifolia to a mechanism for efficient pollen release mediated by insect pollinators from its short-lived flowers. (C) 2009 Elsevier GmbH. All rights reserved.
Resumo:
Although most of effects of Angiotensin II (Ang II) related to cardiac remodelling can be attributed to type 1 Ang II receptor (AT(1)R), the type 2 receptor (AT(2)R) has been shown to be involved in the development of some cardiac hypertrophy models. In the present study, we investigated whether the thyroid hormone (TH) action leading to cardiac hypertrophy is also mediated by increased Ang II levels or by change on AT(1)R and AT(2)R expression, which could contribute to this effect. In addition, we also evaluated the possible contribution of AT(2)R in the activation of Akt and in the development of TH-induced cardiac hypertrophy. To address these questions, Wistar rats were treated with thyroxine (T(4), 0.1 mg/kg BW/day, i.p.), with or without AT(2)R blocker (PD123319), for 14 days. Cardiac hypertrophy was identified based on heart/body weight ratio and confirmed by analysis of atrial natriuretic factor mRNA expression. Cardiomyocyte cultures were used to exclude the influence of TH-related hemodynamic effects. Our results demonstrate that the cardiac Ang II levels were significantly increased (80%, P < 0.001) as well as the AT(2)R expression (50%, P < 0.05) in TH-induced cardiac hypertrophy. The critical involvement of AT(2)R to the development of this cardiac hypertrophy in vivo was evidenced after administration of AT(2) blocker, which was able to prevent in 40% (P < 0.01) the cardiac mass gain and the Akt activation induced by TH. The role of AT(2)R to the TH-induced cardiomyocyte hypertrophy was also confirmed after using PD123319 in the in vitro studies. These findings improve understanding of the cardiac hypertrophy observed in hyperthyroidism and provide new insights into the generation of future therapeutic strategies.
Resumo:
Background Depression symptomatology was assessed with the Beck Depression Inventory (BDI) in a sample of Jewish adolescents, in order to compare the frequency and severity of depression with non-Jewish adolescents as well as examine gender difference of the expression of depressive symptomatology. Method Subjects comprised 475 students from Jewish private schools, aged 13-17 years, who were compared with an age-matched non-Jewish sample (n = 899). Kendall`s definition was adopted to classify these adolescents according to level of depressive symptoms. The frequency of depression was calculated for ethnicity, gender and age strata. Discriminant analysis and principal component analysis were performed to assess the importance of depression-specific and non-specific items, along with the factor structure of the BDI, respectively. Results The overall mean score on the BDI in the Jewish and the non-Jewish sample was 9.0 (SD = 6.4) and 8.6 (SD = 7.2), respectively. Jewish girls and boys had comparable mean BDI scores, contrasting with non-Jewish sample, where girls complained more of depressive symptoms than boys (p < 0.001). The frequency of depression, adopting a BDI cutoff of 20, was 5.1% for the Jewish sample and 6.3% for the non-Jewish sample. The frequency of depression for Jewish girls and boys was 5.5% (SE = 1.4) and 4.6% (SE = 1.5), respectively. On the other hand, the frequency of depression for non-Jewish girls and boys was 8.4% (SE = 1.2) and 4.0% (SE = 1.0), respectively. The female/male ratio of frequency of BDI-depression was 1.2 in the Jewish sample, but non-Jewish girls were twice (2.1) as likely to report depression as boys. Discriminant analysis showed that the BDI highly discriminates depressive symptomatology among Jewish adolescents, and measured specific aspects of depression. Factor analysis revealed two meaningful factors for the total sample and each gender (cognitive-affective dimension and somatic dimension), evidencing a difference between Jewish boys and Jewish girls in the symptomatic expression of depression akin to non-Jewish counterparts. Conclusions Ethnic-cultural factor might play a role in the frequency, severity and symptomatic expression of depressive symptoms in Jewish adolescents. The lack of gender effect on depression, which might persist from adolescence to adulthood among Jewish people, should be investigated in prospective studies.
Resumo:
The Plasmodium falciparum var gene family encodes large variant antigens, which are important virulence factors, and also targets of the humoral host response. The frequently observed mild outcomes of falciparum malaria in many places of the Amazon area prompted us to ask whether a globally restricted variant (var) gene repertoire is present in currently circulating and older isolates of this area. By exhaustive analysis of var gene tags from 89 isolates and clones taken during many years from all over the Brazilian Amazon, we estimate that there are probably no more than 350-430 distinct sequence types, less than for any similar sized area studied so far. Detailed analysis of the var tags from genetically distinct clones obtained from single isolates revealed restricted and redundant repertoires suggesting either a low incidence of infective bites or restricted variant gene diversity in inoculated parasites. Additionally, we found a structuring of var gene repertoires observed as a higher pairwise typing sharing in isolates from the same microregion compared to isolates from different regions. Fine analysis of translated var tags revealed that certain Distinct Sequence Identifiers (DSIDs) were differently represented in Brazilian/South American isolates when compared to datasets from other continents. By global alignment of worldwide var DBL alpha sequences and sorting in groups with more than 76% identity, 125 clusters were formed and more than half of all genes were found in nine clusters with 50 or more sequences. While Brazilian/South American sequences were represented only in 64 groups, African sequences were found in the majority of clusters. DSID type 1 related sequences accumulated almost completely in one single cluster, indicating that limited recombination occurs in these specific var gene types. These data demonstrate the so far highest pairwise type sharing values for the var gene family in isolates from all over an entire subcontinent. The apparent lack of specific sequences types suggests that the P. falciparum transmission dynamics in the whole Amazon are probably different from any other endemic region studied and possibly interfere with the parasite`s ability to efficiently diversify its variant gene repertoires. (C) 2010 Elsevier B.V. All rights reserved.