908 resultados para Biological, pharmacological and toxicological tests
Resumo:
The problem of identification of stiffness, mass and damping properties of linear structural systems, based on multiple sets of measurement data originating from static and dynamic tests is considered. A strategy, within the framework of Kalman filter based dynamic state estimation, is proposed to tackle this problem. The static tests consists of measurement of response of the structure to slowly moving loads, and to static loads whose magnitude are varied incrementally; the dynamic tests involve measurement of a few elements of the frequency response function (FRF) matrix. These measurements are taken to be contaminated by additive Gaussian noise. An artificial independent variable τ, that simultaneously parameterizes the point of application of the moving load, the magnitude of the incrementally varied static load and the driving frequency in the FRFs, is introduced. The state vector is taken to consist of system parameters to be identified. The fact that these parameters are independent of the variable τ is taken to constitute the set of ‘process’ equations. The measurement equations are derived based on the mechanics of the problem and, quantities, such as displacements and/or strains, are taken to be measured. A recursive algorithm that employs a linearization strategy based on Neumann’s expansion of structural static and dynamic stiffness matrices, and, which provides posterior estimates of the mean and covariance of the unknown system parameters, is developed. The satisfactory performance of the proposed approach is illustrated by considering the problem of the identification of the dynamic properties of an inhomogeneous beam and the axial rigidities of members of a truss structure.
Resumo:
The rapid increase in allergic diseases in developed, high-income countries during recent decades is attributed to several changes in the environment such as urbanization and improved hygiene. This relative lack of microbial stimulation is connected to a delay in maturation of the infantile immune system and seems to predispose especially genetically prone infants to allergic diseases. Probiotics, which are live ingestible health-promoting microbes, may compensate for the lack of microbial stimulation of the developing gut immune system and may thus be beneficial in prevention of allergies. Prebiotics, which are indigestible nutrients by us, promote the growth and activity of a number of bacterial strains considered beneficial for the gut. In a large cohort of 1 223 infants at hereditary risk for allergies we studied in a double-blind placebo-controlled manner whether probiotics administered in early life prevent allergic diseases from developing. We also evaluated their safety and their effects on common childhood infections, vaccine antibody responses, and intestinal immune markers. Pregnant mothers used a mixture of four probiotic bacteria or a placebo, from their 36th week of gestation. Their infants received the same probiotics plus prebiotic galacto-oligosaccharides for 6 months. The 2-year follow-up consisted of clinical examinations and allergy tests, fecal and blood sampling, and regular questionnaires. Among the 925 infants participating in the 2-year follow-up the cumulative incidence of any allergic disease (food allergy, eczema, asthma, rhinitis) was comparable in the probiotic (32%) and the placebo (35%) group. However, eczema, which was the most common manifestation (88%) of all allergic diseases, occurred less frequently in the probiotic (26%) than in the placebo group (32%). The preventive effect was more pronounced against atopic (IgE-associated) eczema which, of all atopic diseases, accounted for 92%. The relative risk reduction of eczema was 26% and of atopic eczema 34%. To prevent one case of eczema, the number of mother-infant pairs needed to treat was 16. Probiotic treatment was safe without any undesirable outcome for neonatal morbidity, feeding-related behavior, serious adverse events, growth, or for vaccine-induced antibody responses. Fewer infants in the probiotic than in the placebo group received antibiotics during their first 6 months of life and thereafter to age 2 years suffered from fewer respiratory tract infections. As a novel finding, we discovered that high fecal immunoglobulin A (IgA) concentrations at age 6 months associated with reduced risk for atopic (IgE-associated) diseases by age 2 years. In conclusion, although feeding probiotics to high-risk newborn infants showed no preventive effect on the cumulative incidence of any allergic diseases by age 2, they apparently prevented eczema. This probiotic effect was more pronounced among IgE-sensitized infants. The treatment was safe and seemed to stimulate maturation of the immune system as indicated by increased resistance to respiratory infections and improved vaccine antibody responses.
Resumo:
Given the increasing aetiological importance of Streptococcus dysgalactiae subspecies equisimilis in diseases which are primarily attributed to S. pyogenes, molecular markers are essential to distinguish these species and delineate their epidemiology more precisely. Many clinical microbiology laboratories rely on agglutination reactivity and biochemical tests to distinguish them. These methods have limitations which are particularly exacerbated when isolates with mixed properties are encountered. In order to provide additional distinguishing parameters that could be used to unequivocally discriminate these two common pathogens, we assess here three molecular targets: the speB gene, intergenic region upstream of the scpG gene (IRSG) and virPCR. Of these, the former two respectively gave positive and negative results for S. pyogenes, and negative and positive results for S. dysgalactiae subsp. equisimilis. Thus,a concerted use of these nucleic acid-based methods is particularly helpful in epidemiological surveillance to accurately assess the relative contribution of these species to streptococcal infections and diseases.
Resumo:
The enzymes involved in the biosynthesis of isoleucine and valine have been shown to be present in cell-free extracts of Mycobacterium tuberculosis H37Rv. In addition to the known enzymes of the pathway, cell-free extracts of this organism contain a new enzyme. When cell-free extracts were incubated with acetolactate and Image -ascorbic acid, without reduced nicotinamide adenine dinucleotide phosphate, the isomer of acetolactate, viz., α-keto-β-hydroxyisovalerate, was found to accumulate and was identified by different methods. The reaction is enzymic, and Image -ascorbic acid cannot be replaced by other reducing agents such as hydroquinone, 2,6-dichlorophenol indophenol, or glutathione; by derivatives of Image -ascorbic acid such as dehydroascorbic acid or dimethyl ascorbic acid; or by cobamide coenzyme. Since the extracts also isomerize α-acetohydroxybutyrate to α-keto-β-hydroxy-β-methylvalerate, the enzyme catalyzing the reaction has been termed “acetohydroxy acid isomerase.” This is the first time that the presence of acetohydroxy acid isomerase has been reported in any biological system and that a specific metabolic role has been assigned for Image -ascorbic acid. The extract also possesses reductase activity to convert α-keto-β-hydroxyisovalerate to α,β-dihydroxyisovalerate in the presence of reduced nicotinamide adenine dinucleotide phosphate.
Resumo:
Autoimmune diseases are more common in dogs than in humans and are already threatening the future of some highly predisposed dog breeds. Susceptibility to autoimmune diseases is controlled by environmental and genetic factors, especially the major histocompatibility complex (MHC) gene region. Dogs show a similar physiology, disease presentation and clinical response as humans, making them an excellent disease model for autoimmune diseases common to both species. The genetic background of canine autoimmune disorders is largely unknown, but recent annotation of the dog genome and subsequent development of new genomic tools offer a unique opportunity to map novel autoimmune genes in various breeds. Many autoimmune disorders show breed-specific enrichment, supporting a strong genetic background. Furthermore, the presence of hundreds of breeds as genetic isolates facilitates gene mapping in complex autoimmune disorders. Identification of novel predisposing genes establishes breeds as models and may reveal novel candidate genes for the corresponding human disorders. Genetic studies will eventually shed light on common biological functions and interactions between genes and the environment. This study aimed to identify genetic risk factors in various autoimmune disorders, including systemic lupus erythematosus (SLE)-related diseases, comprising immune-mediated rheumatic disease (IMRD) and steroid-responsive meningitis arteritis (SMRA) as well as Addison s disease (AD) in Nova Scotia Duck Tolling Retrievers (NSDTRs) and chronic superficial keratitis (CSK) in German Shepherd dogs (GSDs). We used two different approaches to identify genetic risk factors. Firstly, a candidate gene approach was applied to test the potential association of MHC class II, also known as a dog leukocyte antigen (DLA) in canine species. Secondly, a genome-wide association study (GWAS) was performed to identify novel risk loci for SLE-related disease and AD in NSDTRs. We identified DLA risk haplotypes for an IMRD subphenotype of SLE-related disease, AD and CSK, but not in SMRA, and show that the MHC class II gene region is a major genetic risk factor in canine autoimmune diseases. An elevated risk was found for IMRD in dogs that carried the DLA-DRB1*00601/DQA1*005011/DQB1*02001 haplotype (OR = 2.0, 99% CI = 1.03-3.95, p = 0.01) and for ANA-positive IMRD dogs (OR = 2.3, 99% CI = 1.07-5.04, p-value 0.007). We also found that DLA-DRB1*01502/DQA*00601/DQB1*02301 haplotype was significantly associated with AD in NSDTRs (OR = 2.1, CI = 1.0-4.4, P = 0.044) and the DLA-DRB1*01501/DQA1*00601/DQB1*00301 haplotype with the CSK in GSDs (OR=2.67, CI=1.17-6.44, p= 0.02). In addition, we found that homozygosity for the risk haplotype increases the risk for each disease phenotype and that an overall homozygosity for the DLA region predisposes to CSK and AD. Our results have enabled the development of genetic tests to improve breeding practices by avoiding the production of puppies homozygous for risk haplotypes. We also performed the first successful GWAS for a complex disease in dogs. With less than 100 cases and 100 controls, we identified five risk loci for SLE-related disease and AD and found strong candidate genes involved in a novel T-cell activation pathway. We show that an inbred dog population has fewer risk factors, but each of them has a stronger genetic risk. Ongoing studies aim to identify the causative mutations and bring new knowledge to help diagnostics, treatment and understanding of the aetiology of SLE-related diseases.
Resumo:
The protein kinases (PKs) belong to the largest single family of enzymes, phosphotransferases, which catalyze the phosphorylation of other enzymes and proteins and function primarily in signal transduction. Consequently, PKs regulate cell mechanisms such as growth, differentiation, and proliferation. Dysfunction of these cellular mechanisms may lead to cancer, a major predicament in health care. Even though there is a range of clinically available cancer-fighting drugs, increasing number of cancer cases and setbacks such as drug resistance, constantly keep cancer research active. At the commencement of this study an isophthalic acid derivative had been suggested to bind to the regulatory domain of protein kinase C (PKC). In order to investigate the biological effects and structure-activity relationships (SARs) of this new chemical entity, a library of compounds was synthesized. The best compounds induced apoptosis in human leukemia HL-60 cells and were not cytotoxic in Swiss 3T3 fibroblasts. In addition, the best apoptosis inducers were neither cytotoxic nor mutagenic. Furthermore, results from binding affinity assays of PKC isoforms revealed the pharmacophores of these isophthalic acid derivatives. The best inhibition constants of the tested compounds were measured to 210 nM for PKCα and to 530 nM for PKCδ. Among natural compounds targeting the regulatory domain of PKC, the target of bistramide A has been a matter of debate. It was initially found to activate PKCδ; however, actin was recently reported as the main target. In order to clarify and to further study the biological effects of bistramide A, the total syntheses of the natural compound and two isomers were performed. Biological assays of the compounds revealed accumulation of 4n polyploid cells as the primary mode of action and the compounds showed similar overall antiproliferative activities. However, each compound showed a distinct distribution of antimitotic effect presumably via actin binding, proapoptotic effect presumably via PKCδ, and pro-differentiation effect as evidenced by CD11b expression. Furthermore, it was shown that the antimitotic and proapoptotic effects of bistramide A were not secondary effects of actin binding but independent effects. The third aim in this study was to synthesize a library of a new class of urea-based type II inhibitors targeted at the kinase domain of anaplastic lymphoma kinase (ALK). The best compounds in this library showed IC50 values as low as 390 nM for ALK while the initial low cellular activities were successfully increased even by more than 70 times for NPM-ALK- positive BaF3 cells. More importantly, selective antiproliferative activity on ALK-positive cell lines was achieved; while the best compound affected the BaF3 and SU-DHL-1 cells with IC50 values of 0.5 and 0.8 μM, respectively, they were less toxic to the NPM-ALK-negative human leukemic cells U937 (IC50 = 3.2 μM) and BaF3 parental cells (IC50 = 5.4 μM). Furthermore, SAR studies of the synthesized compounds revealed functional groups and positions of the scaffold, which enhanced the enzymatic and cellular activities.
Resumo:
Model building and molecular mechanics studies have been carried out to examine the potential structures for d(GGC/GCC)5 and d(CAG/CTG)5 that might relate to their biological function and association with triplet repeat expansion diseases. Model building studies suggested that hairpin and quadruplex structures could be formed with these repeat sequences. Molecular mechanics studies have demonstrated that the hairpin and hairpin dimmer structures of triplet repeat sequences formed by looping out of the two strands are as favourable as the corresponding B-DNA type hetero duplex structures. Further, at high salt condition, Greek key type quadruplex structures are energetically comparable with hairpin dimer and B-DNA type duplex structures. All tetrads in the quadruplex structures are well stacked and provide favourable stacking energy values. Interestingly, in the energy minimized hairpin dimer and Greek key type quadruplex structures, all the bases even in the non-G tetrads are cyclically hydrogen bonded, even though the A, C and T-tetrads were not hydrogen bonded in the starting structures.
Resumo:
Bad breath or oral malodour can be related to gingival diseases, trimethylaminuria, various inflammation diseases of upper respiratory tract, foreign bodies in nasal cavity etc. Bad breath is usually, in 85 % to 95 % of cases, inflicted by gram negative anaerobic bacteria in tongue coating. These bacteria have a tendency of producing foul-smelling sulphur containing gases called volatile sulphur compounds or VSC. Main cause of bad breath is parodontitis or postnasal drip into posterior part of the tongue. Detecting bad breath is most efficiently done by organoleptic method. By skilled analyser the reason for oral malodour can be determined with great accuracy. For scientific study the most effective method is gas chromatography (GC) with flame photometric detector (FPD). With it almost every component of exhaled air can be detected both quantitative and qualitative. Effective chairside methods include portable sulphur monitors and saliva tests.
Resumo:
Lithium-containing aluminium alloys are of considerable current interest in the aerospace and aircraft industries because lithium additions to aluminium improve the modulus and decrease the density compared to conventional aluminium alloys. Few commercial aluminium-lithium alloys have emerged for use in the aerospace industry. One such candidate is 8090, a precipitation-hardenable Al-Li-Cu-Mg alloy. The influence of electron-beam welding on the microstructure and mechanical properties of alloy 8090 material has been evaluated through microscopical observations and mechanical tests. Microscopic observations of the electronbeam welds revealed an absence of microporosity and hot cracking, but revealed presence of microporosity in the transverse section of the weld. Mechanical tests revealed the electronbeam weld to have lower strength, elongation and joint efficiency. A change in microscopic fracture mode was observed for the welded material when compared to the unwelded counterpart. An attempt is made to rationalize the behaviour in terms of competing mechanistic effects involving the grain structure of the material, the role of matrix deformation characteristics, grain-boundary chemistry and grain-boundary failure.
Resumo:
The influence of strain rate and state-of-stress on the formation of ferrite in stainless steel type AISI 304L, 304 and 304 as-cast, during hot working has been studied. Compression and torsion tests were conducted in the temperature range 1100 to 1250 degrees C and strain rate range 0.001 to 100 s(-1) on these materials, Ferrite formation occurs during deformation at temperatures above 1150 degrees C and strain rates above 10 s(-1), in stainless steel type AISI 304L and 304. The tendency for the formation of ferrite is more in as-cast 304 than in wrought 304, In as-cast 304 the ferrite forms at lower temperatures and strain rates, The tendency for the ferrite formation is more in torsion than in compression.
Resumo:
In this work, a procedure is presented for the reconstruction of biological organs from image sequences obtained through CT-scan. Although commercial software, which can accomplish this task, are readily available, the procedure presented here needs only free software. The procedure has been applied to reconstruct a liver from the scan data available in literature. 3D biological organs obtained this way can be used for the finite element analysis of biological organs and this has been demonstrated by carrying out an FE analysis on the reconstructed liver.
Resumo:
Animals communicate in non-ideal and noisy conditions. The primary method they use to improve communication efficiency is sender-receiver matching: the receiver's sensory mechanism filters the impinging signal based on the expected signal. In the context of acoustic communication in crickets, such a match is made in the frequency domain. The males broadcast a mate attraction signal, the calling song, in a narrow frequency band centred on the carrier frequency (CF), and the females are most sensitive to sound close to this frequency. In tree crickets, however, the CF changes with temperature. The mechanisms used by female tree crickets to accommodate this change in CF were investigated at the behavioural and biomechanical level. At the behavioural level, female tree crickets were broadly tuned and responded equally to CFs produced within the naturally occurring range of temperatures (18 to 27 degrees C). To allow such a broad response, however, the transduction mechanisms that convert sound into mechanical and then neural signals must also have a broad response. The tympana of the female tree crickets exhibited a frequency response that was even broader than suggested by the behaviour. Their tympana vibrate with equal amplitude to frequencies spanning nearly an order of magnitude. Such a flat frequency response is unusual in biological systems and cannot be modelled as a simple mechanical system. This feature of the tree cricket auditory system not only has interesting implications for mate choice and species isolation but may also prove exciting for bio-mimetic applications such as the design of miniature low frequency microphones.
Resumo:
The Indian Ocean earthquake of 26 December 2004 led to significant ground deformation in the Andaman and Nicobar region, accounting for ~800 km of the rupture. Part of this article deals with coseismic changes along these islands, observable from coastal morphology, biological indicators, and Global Positioning System (GPS) data. Our studies indicate that the islands south of 10° N latitude coseismically subsided by 1–1.5 m, both on their eastern and western margins, whereas those to the north showed a mixed response. The western margin of the Middle Andaman emerged by >1 m, and the eastern margin submerged by the same amount. In the North Andaman, both western and eastern margins emerged by >1 m. We also assess the pattern of long-term deformation (uplift/subsidence) and attempt to reconstruct earthquake/tsunami history, with the available data. Geological evidence for past submergence includes dead mangrove vegetation dating to 740 ± 100 yr B.P., near Port Blair and peat layers at 2–4 m and 10–15 m depths observed in core samples from nearby locations. Preliminary paleoseismological/tsunami evidence from the Andaman and Nicobar region and from the east coast of India, suggest at least one predecessor for the 2004 earthquake 900–1000 years ago. The history of earthquakes, although incomplete at this stage, seems to imply that the 2004-type earthquakes are infrequent and follow variable intervals
Resumo:
In order to improve the tracking and erosion performance of outdoor polymeric silicone rubber (SR) insulators used in HV power transmission lines, micron sized inorganic fillers are usually added to the base SR matrix. In addition, insulators used in high voltage dc transmission lines are designed to have increased creepage distance to mitigate the tracking and erosion problems. ASTM D2303 standard gives a procedure for finding the tracking and erosion resistance of outdoor polymeric insulator weathershed material samples under laboratory conditions for ac voltages. In this paper, inclined plane (IP) tracking and erosion tests similar to ASTM D2303 were conducted under both positive and negative dc voltages for silicone rubber samples filled with micron and nano sized particles to understand the phenomena occurring during such tests. Micron sized Alumina Trihydrate (ATH) and nano sized alumina fillers were added to silicone rubber matrix to improve the resistance to tracking and erosion. The leakage current during the tests and the eroded mass at the end of the tests were monitored. Scanning Electron Microscopy (SEM) and Energy dispersive Xray (EDX) studies were conducted to understand the filler dispersion and the changes in surface morphology in both nanocomposite and microcomposite samples. The results suggest that nanocomposites performed better than microcomposites even for a small filler loading (4%) for both positive and negative dc stresses. It was also seen that the tracking and erosion performance of silicone rubber is better under negative dc as compared to positive dc voltage. EDX studies showed migration of different ions onto the surface of the sample during the IP test under positive dc which has led to an inferior performance as compared to the performance under negative dc.
Resumo:
Competition theory predicts that local communities should consist of species that are more dissimilar than expected by chance. We find a strikingly different pattern in a multicontinent data set (55 presence-absence matrices from 24 locations) on the composition of mixed-species bird flocks, which are important sub-units of local bird communities the world over. By using null models and randomization tests followed by meta-analysis, we find the association strengths of species in flocks to be strongly related to similarity in body size and foraging behavior and higher for congeneric compared with noncongeneric species pairs. Given the local spatial scales of our individual analyses, differences in the habitat preferences of species are unlikely to have caused these association patterns; the patterns observed are most likely the outcome of species interactions. Extending group-living and social-information-use theory to a heterospecific context, we discuss potential behavioral mechanisms that lead to positive interactions among similar species in flocks, as well as ways in which competition costs are reduced. Our findings highlight the need to consider positive interactions along with competition when seeking to explain community assembly.