812 resultados para 68T40 (secondary)


Relevância:

20.00% 20.00%

Publicador:

Resumo:

Fibroblast-like cells of secondary lymphoid organs (SLO) are important for tissue architecture. In addition, they regulate lymphocyte compartmentalization through the secretion of chemokines, and participate in the orchestration of appropriate cell-cell interactions required for adaptive immunity. Here, we provide data demonstrating the functional importance of SLO fibroblasts during Notch-mediated lineage specification and immune response. Genetic ablation of the Notch ligand Delta-like (DL)1 identified splenic fibroblasts rather than hematopoietic or endothelial cells as niche cells, allowing Notch 2-driven differentiation of marginal zone B cells and of Esam(+) dendritic cells. Moreover, conditional inactivation of DL4 in lymph node fibroblasts resulted in impaired follicular helper T cell differentiation and, consequently, in reduced numbers of germinal center B cells and absence of high-affinity antibodies. Our data demonstrate previously unknown roles for DL ligand-expressing fibroblasts in SLO niches as drivers of multiple Notch-mediated immune differentiation processes.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Background: Post-surgical management of stage I seminoma includes: surveillance with repeated CT-scans and treatment reserved for those who relapse, or adjuvant treatment with either immediate radiation therapy (RT) or carboplatin. The cancer specific survival is close to 100%. Cure without long-term sequelae of treatment is the aim. Our goal is to estimate the risk of radiation-induced secondary cancers (SC) death from for patients undergoing S, adjuvant RT or adjuvant carboplatin (AC).Materials and Methods: We measured organ doses from CT scans (3 phases each one) of a seminoma patient who was part of the active surveillance strategy and from a man undergoing adjuvant RT 20-Gy and a 30-Gy salvage RT treatment to the para-aortic area using helical Intensity Modulated RT (Tomotherapy®) with accurate delineation of organs at risk and a CTV to PTV expansion of 1 cm. Effective doses to organs in mSv were estimated according to the tissue-weighting factors recommendations of the International Commission on Radiological Protection 103 (Ann ICRP 2007). We estimated SC incidence and mortality for a 10,000 people population based on the excess absolute risk model from the Biological Effects of Ionizing Radiation (BEIR) VII (Health Risk of Exposure to Low Levels of Ionizing Radiation, NCR, The National Academies Press Washington, DC, 2006) assuming a seminoma diagnosis at age 30, a total life expectancy of 80 years.Results: The nominal risk for a fatal secondary cancers was calculated 1.5% for 15 abdominal CT scans, 14.8% for adjuvant RT (20 Gy paraaortic field) and 22.2% for salvage RT (30 Gy). The calculation assumed that the risk of relapse on surveillance and adjuvant AC was 15% and 4% respectively and that all patients were salvaged at relapse with RT. n CT abdomen/Pelvis = secondary cancer % RT Dose and % receiving treatment = secondary cancer % Total secondary cancer risk in % Active surveillance 15 = 1.5% 30 Gy in 15% of pts = 3.3% 4.8 Adjuvant carboplatin 7 = 0.7% 30 Gy in 4% of pts = 0.88% 1.58 Adjuvant radiotherapy 7 = 0.7% 20 Gy in 100% of pts = 14.8% 15.5Conclusions: These data suggest that: 1) Adjuvant radiotherapy is harmful and should not anymore be regarded as a standard option for seminoma stage I. 2) AC seems to be an option to reduce radiation induced cancers. Limitations: the study does not consider secondary cancers due to chemotherapy with AC (unknown). The use of BEIR VII for risk modeling with higher doses of RT needs to be validated.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

BACKGROUND AND AIMS: In a mixed-ploidy population, strong frequency-dependent mating will lead to the elimination of the less common cytotype, unless prezygotic barriers enhance assortative mating. However, such barriers favouring cytotype coexistence have only rarely been explored. Here, an assessment is made of the mechanisms involved in formation of mixed-ploidy populations and coexistence of diploid plants and their closely related allotetraploid derivates from the Centaurea stoebe complex (Asteraceae). METHODS: An investigation was made of microspatial and microhabitat distribution, life-history and fitness traits, flowering phenology, genetic relatedness of cytotypes and intercytotype gene flow (cpDNA and microsatellites) in six mixed-ploidy populations in Central Europe. KEY RESULTS: Diploids and tetraploids were genetically differentiated, thus corroborating the secondary origin of contact zones. The cytotypes were spatially segregated at all sites studied, with tetraploids colonizing preferentially drier and open microhabitats created by human-induced disturbances. Conversely, they were rare in more natural microsites and microsites with denser vegetation despite their superior persistence ability (polycarpic life cycle). The seed set of tetraploid plants was strongly influenced by their frequency in mixed-ploidy populations. Triploid hybrids originated from bidirectional hybridizations were extremely rare and almost completely sterile, indicating a strong postzygotic barrier between cytotypes. CONCLUSIONS: The findings suggest that tetraploids are later immigrants into already established diploid populations and that anthropogenic activities creating open niches favouring propagule introductions were the major factor shaping the non-random distribution and habitat segregation of cytotypes at fine spatial scale. Establishment and spread of tetraploids was further facilitated by their superior persistence through the perennial life cycle. The results highlight the importance of non-adaptive spatio-temporal processes in explaining microhabitat and microspatial segregation of cytotypes.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Along with the decrease in kidney function arises a secondary hyperparathyroidism, which constitutes one of the most important risk factor for mortality in patients suffering from renal insufficiency. Treating secondary hyperparathyroidism is challenging, as most of the parameters of mineral metabolism are interconnected. We review here the pathophysiology and treatment options of this entity.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

In the vast majority of bottom-up proteomics studies, protein digestion is performed using only mammalian trypsin. Although it is clearly the best enzyme available, the sole use of trypsin rarely leads to complete sequence coverage, even for abundant proteins. It is commonly assumed that this is because many tryptic peptides are either too short or too long to be identified by RPLC-MS/MS. We show through in silico analysis that 20-30% of the total sequence of three proteomes (Schizosaccharomyces pombe, Saccharomyces cerevisiae, and Homo sapiens) is expected to be covered by Large post-Trypsin Peptides (LpTPs) with M(r) above 3000 Da. We then established size exclusion chromatography to fractionate complex yeast tryptic digests into pools of peptides based on size. We found that secondary digestion of LpTPs followed by LC-MS/MS analysis leads to a significant increase in identified proteins and a 32-50% relative increase in average sequence coverage compared to trypsin digestion alone. Application of the developed strategy to analyze the phosphoproteomes of S. pombe and of a human cell line identified a significant fraction of novel phosphosites. Overall our data indicate that specific targeting of LpTPs can complement standard bottom-up workflows to reveal a largely neglected portion of the proteome.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Children with unresolved brachial plexus palsy frequently develop a disabling internal rotation contracture of the shoulder. Several surgical options, including soft tissue procedures such as muscle releases and/or transfers, and bone operations such as humeral osteotomy are available to correct this deformity. This study describes the effect of subscapularis muscle release performed in isolation. Thirteen patients (5 boys, 8 girls) were reviewed at an average of 3.5 years after their surgery (range, 2-7 years). Their mean age at operation was 4.7 years (range, 1-8 years). Three children had C5-C6 palsies, 8 had C5-C7 palsies, and 2 had C5-C8 palsies. Postoperatively, patients presented significant gains in shoulder active lateral rotation (+49 degrees, from 5 to 54 degrees), active abduction (+30 degrees, from 63 to 93 degrees), active flexion (+46 degrees, from 98 to 144 degrees), and active extension (+23 degrees, from 7 to 30 degrees). Gains were also observed in passive range of motion, but of a lesser degree. Subscapularis muscle release is a procedure we found to have few significant complications and was highly effective in increasing active range of motion and restoring shoulder function.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

County engineers in Iowa face the dual problems of rapidly escalating costs and a decreasing rate of growth of revenues. Various priority systems are in use, ranking projects for inclusion in road improvement programs, but they generally have weaknesses when used to compare one project with another in a different location. The sufficiency rating system has proven to be a useful tool in developing a priority list of projects for primary road systems, but there are none currently in use for secondary road systems. The research reported here was undertaken to develop a sufficiency rating system which could be used for secondary roads in Iowa and to produce the necessary forms and instructions to aid county engineering personnel in their efforts to complete the ratings for roads within their county.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Pseudomonas fluorescens CHA0, an antagonist of phytopathogenic fungi in the rhizosphere of crop plants, elaborates and excretes several secondary metabolites with antibiotic properties. Their synthesis depends on three small RNAs (RsmX, RsmY, and RsmZ), whose expression is positively controlled by the GacS-GacA two-component system at high cell population densities. To find regulatory links between primary and secondary metabolism in P. fluorescens and in the related species Pseudomonas aeruginosa, we searched for null mutations that affected central carbon metabolism as well as the expression of rsmY-gfp and rsmZ-gfp reporter constructs but without slowing down the growth rate in rich media. Mutation in the pycAB genes (for pyruvate carboxylase) led to down-regulation of rsmXYZ and secondary metabolism, whereas mutation in fumA (for a fumarase isoenzyme) resulted in up-regulation of the three small RNAs and secondary metabolism in the absence of detectable nutrient limitation. These effects required the GacS sensor kinase but not the accessory sensors RetS and LadS. An analysis of intracellular metabolites in P. fluorescens revealed a strong positive correlation between small RNA expression and the pools of 2-oxoglutarate, succinate, and fumarate. We conclude that Krebs cycle intermediates (already known to control GacA-dependent virulence factors in P. aeruginosa) exert a critical trigger function in secondary metabolism via the expression of GacA-dependent small RNAs.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

There are approximately 800 installations of destination lighting at secondary road intersections in Iowa. Approximately 90% of these have only a single luminaire. The other installations have two luminaires. No warrants currently exist for justifying the use of this type of lighting. Previous research has examined the safety benefits from full lighting of rural intersections that generally serve substantially higher traffic volumes than secondary road intersections in Iowa. However, the safety benefit of destination lighting at intersections carrying relatively low volumes has not been the subject of previous research. The research reported here, sponsored by the Iowa Department of Transportation, was undertaken to identify locations where destination lighting could be expected to improve highway safety. If destination lighting were shown to reduce accident frequency, warrants for its use on secondary roads could be developed. An inventory of secondary road lighting installations in Iowa was assembled. From this inventory, two samples were constituted that would permit two separate comparisons of the accident experience with and without destination lighting. Before and after comparisons were made for the same locations if accident records were available for at least one full year both preceding and following the installation of destination lighting. Accident records for this purpose were available from a statewide computerized record system covering the period from 1977 through 1982. The accident experience at locations having destination lighting installed before 1978 was compared with a sample of comparable locations not having destination lighting. The sample of secondary road intersections used for the before and after comparison included 91 locations. The sample of continuously lighted locations included 102 intersections. Accident experience at these locations was compared with the experience at 102 intersections that were not lighted. The intersections included in these samples averaged only 0.31 accidents per year. The accident rate at secondary road intersections that had destination lighting did not differ significantly from the accident rate at intersections that were not lighted. This conclusion was derived from both comparisons, the before and after experience and the comparison of experience at intersections that were continuously lighted with that at unlighted locations. Furthermore, no significant differences were noted between lighted and unlighted locations in the proportion of accidents that occurred at night. The distribution of accidents by type also did not differ between unlighted intersections and those having destination lighting. It was not possible to formulate warrants for destination lighting since analyses directed toward identifying specific characteristics of an intersection that could be correlated with highway safety did not yield any useful relationships. However, it was noted that the average damages for night accidents that occurred at lighted intersections were lower than for accidents at unlighted intersections. Even in the absence of a more definitive demonstration of beneficial effects, destination lighting is perceived by officials in most of the counties having such installations as yielding desirable effects and is recognized as helpful to motorists in performing the guidance function in driving. Given this benefit and a relatively low cost (an average of $74 per year for one luminaire), and given that the subjective criteria that have been used in the past to justify the installation of destination lighting have led to a high degree of public acceptance and satisfaction, it is recommended that the same subjective criteria continue to be used in lieu of definitive warrants.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

The goal of this study is to develop a usable sufficiency rating system for secondary roads. There are several assumptions that have been made at the outset. These are: 1. County engineers currently use at least a limited set of decision criteria to make decisions regarding project priorities. 2. Some degree of consensus exists among the county engineers in terms of which are the most important criteria and that there is some agreement on their relative importance. Accordingly, a questionnaire was developed which could be used as a survey tool. The results of the survey were used to develop a final list of weighted rating elements which were used as part of the proposed sufficiency rating system. State and local jurisdictions from other states were also surveyed to determine the status of the use of sufficiency rating systems for secondary roads outside of Iowa and to gather some applicable data.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Snow removal on the 90,000 mile Iowa secondary road system is a major concern of county engineers. Rural residents rely almost entirely on motor vehicles for travel. They have come to expect passable roads during all types of weather and as most county engineers know, the public is less tolerant of problems in snow removal than in any other highway department function. To avoid snow removal problems, maintenance personnel begin preparation before the winter maintenance season. The slide tape presentation, "Snow Removal on Iowa's Secondary Roads", was developed to assist in training and retraining maintenance personnel each year prior to winter. The program covers preparation for winter, snow and ice removal, and after storm care of equipment.