950 resultados para Copy number variations and polymorphisms


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Design aspects of the Transversally Laminated Anisotropic (TLA) Synchronous Reluctance Motor (SynRM) are studied and the machine performance analysis compared to the Induction Motor (IM) is done. The SynRM rotor structure is designed and manufactured for a30 kW, four-pole, three-phase squirrel cage induction motor stator. Both the IMand SynRM were supplied by a sensorless Direct Torque Controlled (DTC) variablespeed drive. Attention is also paid to the estimation of the power range where the SynRM may compete successfully with a same size induction motor. A technicalloss reduction comparison between the IM and SynRM in variable speed drives is done. The Finite Element Method (FEM) is used to analyse the number, location and width of flux barriers used in a multiple segment rotor. It is sought for a high saliency ratio and a high torque of the motor. It is given a comparison between different FEM calculations to analyse SynRM performance. The possibility to take into account the effect of iron losses with FEM is studied. Comparison between the calculated and measured values shows that the design methods are reliable. A new application of the IEEE 112 measurement method is developed and used especially for determination of stray load losses in laboratory measurements. The study shows that, with some special measures, the efficiency of the TLA SynRM is equivalent to that of a high efficiency IM. The power factor of the SynRM at rated load is smaller than that of the IM. However, at lower partial load this difference decreases and this, probably, brings that the SynRM gets a better power factor in comparison with the IM. The big rotor inductance ratio of the SynRM allows a good estimating of the rotor position. This appears to be very advantageous for the designing of the rotor position sensor-less motor drive. In using the FEM designed multi-layer transversally laminated rotor with damper windings it is possible to design a directly network driven motor without degrading the motorefficiency or power factor compared to the performance of the IM.

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The 16p11.2 600 kb copy-number variants (CNVs) are associated with mirror phenotypes on BMI, head circumference, and brain volume and represent frequent genetic lesions in autism spectrum disorders (ASDs) and schizophrenia. Here we interrogated the transcriptome of individuals carrying reciprocal 16p11.2 CNVs. Transcript perturbations correlated with clinical endophenotypes and were enriched for genes associated with ASDs, abnormalities of head size, and ciliopathies. Ciliary gene expression was also perturbed in orthologous mouse models, raising the possibility that ciliary dysfunction contributes to 16p11.2 pathologies. In support of this hypothesis, we found structural ciliary defects in the CA1 hippocampal region of 16p11.2 duplication mice. Moreover, by using an established zebrafish model, we show genetic interaction between KCTD13, a key driver of the mirrored neuroanatomical phenotypes of the 16p11.2 CNV, and ciliopathy-associated genes. Overexpression of BBS7 rescues head size and neuroanatomical defects of kctd13 morphants, whereas suppression or overexpression of CEP290 rescues phenotypes induced by KCTD13 under- or overexpression, respectively. Our data suggest that dysregulation of ciliopathy genes contributes to the clinical phenotypes of these CNVs.

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Classic semiquantitative proteomic methods have shown that all organisms respond to a mild heat shock by an apparent massive accumulation of a small set of proteins, named heat-shock proteins (HSPs) and a concomitant slowing down in the synthesis of the other proteins. Yet unexplained, the increased levels of HSP messenger RNAs (mRNAs) may exceed 100 times the ensuing relative levels of HSP proteins. We used here high-throughput quantitative proteomics and targeted mRNA quantification to estimate in human cell cultures the mass and copy numbers of the most abundant proteins that become significantly accumulated, depleted, or unchanged during and following 4 h at 41 °C, which we define as mild heat shock. This treatment caused a minor across-the-board mass loss in many housekeeping proteins, which was matched by a mass gain in a few HSPs, predominantly cytosolic HSPCs (HSP90s) and HSPA8 (HSC70). As the mRNAs of the heat-depleted proteins were not significantly degraded and less ribosomes were recruited by excess new HSP mRNAs, the mild depletion of the many housekeeping proteins during heat shock was attributed to their slower replenishment. This differential protein expression pattern was reproduced by isothermal treatments with Hsp90 inhibitors. Unexpectedly, heat-treated cells accumulated 55 times more new molecules of HSPA8 (HSC70) than of the acknowledged heat-inducible isoform HSPA1A (HSP70), implying that when expressed as net copy number differences, rather than as mere "fold change" ratios, new biologically relevant information can be extracted from quantitative proteomic data. Raw data are available via ProteomeXchange with identifier PXD001666.

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Low-copy-number molecules are involved in many functions in cells. The intrinsic fluctuations of these numbers can enable stochastic switching between multiple steady states, inducing phenotypic variability. Herein we present a theoretical and computational study based on Master Equations and Fokker-Planck and Langevin descriptions of stochastic switching for a genetic circuit of autoactivation. We show that in this circuit the intrinsic fluctuations arising from low-copy numbers, which are inherently state-dependent, drive asymmetric switching. These theoretical results are consistent with experimental data that have been reported for the bistable system of the gallactose signaling network in yeast. Our study unravels that intrinsic fluctuations, while not required to describe bistability, are fundamental to understand stochastic switching and the dynamical relative stability of multiple states.

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Three-dimensional reconstruction of reservoir analogues can be improved combining data from different geophysical methods. Ground Penetrating Radar (GPR) and Electrical Resistivity Tomography (ERT) data are valuable tools, since they provide subsurface information from internal architecture and facies distribution of sedimentary rock bodies, enabling the upgrading of depositional models and heterogeneity reconstruction. The Lower Eocene Roda Sandstone is a well-known deltaic complex widely studied as a reservoir analogue that displays a series of sandstone wedges with a general NE to SW progradational trend. To provide a better understanding of internal heterogeneity of a 10m-thick progradational delta-front sandstone unit, 3D GPR data were acquired. In addition, common midpoints (CMP) to measure the sandstone subsoil velocity, test profiles with different frequency antennas (25, 50 and 100MHz) and topographic data for subsequent correction in the geophysical data were also obtained. Three ERT profiles were also acquired to further constrain GPR analysis. These geophysical results illustrate the geometry of reservoir analogue heterogeneities both depositional and diagenetic in nature, improving and complementing previous outcrop-derived data. GPR interpretation using radar stratigraphy principles and attributes analysis provided: 1)tridimensional geometry of major stratigraphic surfaces that define four units in the GPR Prism, 2) image the internal architecture of the units and their statistical study of azimuth and dips, useful for a quick determination of paleocurrent directions. These results were used to define the depositional architecture of the progradational sandbody that shows an arrangement in very-high-frequency sequences characterized by clockwise paleocurrent variations and decrease of the sedimentary flow, similar to those observed at a greater scale in the same system. This high-frequency sequential arrangement has been attributed to the autocyclic dynamics of a supply-dominated delta- front where fluvial and tidal currents are in competition. The resistivity models enhanced the viewing of reservoir quality associated with cement distribution caused by depositional and early diagenetic processes related to the development of transgressive and regressive systems tracts in igh-frequency sequences.

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Different types of aerosolization and deagglomeration testing systems exist for studying the properties of nanomaterial powders and their aerosols. However, results are dependent on the specific methods used. In order to have well-characterized aerosols, we require a better understanding of how system parameters and testing conditions influence the properties of the aerosols generated. In the present study, four experimental setups delivering different aerosolization energies were used to test the resultant aerosols of two distinct nanomaterials (hydrophobic and hydrophilic TiO2). The reproducibility of results within each system was good. However, the number concentrations and size distributions of the aerosols created varied across the four systems; for number concentrations, e.g., from 10(3) to 10(6) #/cm(3). Moreover, distinct differences were also observed between the two materials with different surface coatings. The article discusses how system characteristics and other pertinent conditions modify the test results. We propose using air velocity as a suitable proxy for estimating energy input levels in aerosolization systems. The information derived from this work will be especially useful for establishing standard operating procedures for testing nanopowders, as well as for estimating their release rates under different energy input conditions, which is relevant for occupational exposure.

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Background: A substantial proportion of NSCLC has been shown to harbour specific molecular alterations affecting tumour proliferation and resulting in sensitivity to inhibition of the corresponding activated oncogenic pathway by targeted therapies. Comprehensive tumor profiling can diagnose such alterations and may identify new alterations opening additional treatment options for all distinct NSCLC subtypes. Methods: Over 6,700 non-small cell lung cancer cases referred to Caris Life Sciences between 2009 and 2014 were evaluated; clinical diagnoses and detailed tumor pathology were collected from referring physicians. Specific profiling was performed per physician request and included a combination of sequencing (Sanger, NGS or pyrosequencing), protein expression (IHC), gene amplification/rearrangement (CISH or FISH), and/or RNA fragment analysis within potential cancer-related genes and pathways. Results: Patients were grouped into cohorts according to histological subtype - adenocarcinoma (AD) (n=4,286), squamous cell carcinoma (SCC) (n=1,280), large cell carcinoma (LCC) (n=153) and bronchioalveolar carcinoma (BAC) (n=94). Protein overexpression of cMET (>2+ in >50% cells) was higher in AD (35.9%) compared to other subgroups (12-20%) while RRM1 and TOP2A levels were lower in AD. ALK or ROS1 were rearranged in 5.3% of patients with AD compared to 3.7% of patients with LCC and 1.2% of patients with SCC. EGFR mutations were found at low prevalence in both the LCC (0%) and SCC cohorts (2.8%) compared to 21% in AD. Similar lower rates of BRAF mutations were observed in the LCC and SCC cohorts compared to AD (0%, 1.1% and 5.1%). Pathway analysis showed activating mutations in the ERK pathway in 40% of patients with AD. Only 10-12% of patients with LCC or SCC had activating mutations in the ERK pathway. Conclusions: Despite the limitations of this retrospective series, we report comprehensive profiling of the largest cohort of NSCLC. Tumor profiling reveals that ADs may be more addicted to the ERK pathway than other histological subtypes. Drugs which target cMET may also have most utility in AD. Full analysis by histological subtype and additional correlative data on protein expression, gene copy number and mutations will be presented.

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Whole-genome duplication (WGD) is usually followed by gene loss and karyotype repatterning. Despite evidence of new adaptive traits associated with WGD, the underpinnings and evolutionary significance of such genome fractionation remain elusive. Here, we use Buckler mustard (Biscutella laevigata) to infer processes that have driven the retention of duplicated genes after recurrent WGDs. In addition to the β- and α-WGD events shared by all Brassicaceae, cytogenetic and transcriptome analyses revealed two younger WGD events that occurred at times of environmental changes in the clade of Buckler mustard (Biscutelleae): a mesopolyploidy event from the late Miocene that was followed by considerable karyotype reshuffling and chromosome number reduction and a neopolyploidy event during the Pleistocene. Although a considerable number of the older duplicates presented signatures of retention under positive selection, the majority of retained duplicates arising from the younger mesopolyploidy WGD event matched predictions of the gene balance hypothesis and showed evidence of strong purifying selection as well as enrichment in gene categories responding to abiotic stressors. Retention of large stretches of chromosomes for both genomic copies supported the hypothesis that cycles of WGD and biased fractionation shaped the genome of this stress-tolerant polypolyloid, promoting the adaptive recruitment of stress-responding genes in the face of environmental challenges.

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Objective: To analyze anatomical variations associated with celiac plexus complex by means of computed tomography simulation, assessing the risk for organ injury as the transcrural technique is utilized. Materials and Methods: One hundred eight transaxial computed tomography images of abdomen were analyzed. The aortic-vertebral, celiac trunk (CeT)-vertebral, CeT-aortic and celiac-aortic-vertebral topographical relationships were recorded. Two needle insertion pathways were drawn on each of the images, at right and left, 9 cm and 4.5 cm away from the midline. Transfixed vital organs and gender-related associations were recorded. Results: Aortic-vertebral - 45.37% at left and 54.62% in the middle; CeT-vertebral - T12, 36.11%; T12-L1, 32.4%; L1, 27.77%; T11-T12, 2.77%; CeT-aortic - 53.7% at left and 46.3% in the middle; celiac-aortic-vertebral - L-l, 22.22%; M-m, 23.15%; L-m, 31.48%; M-l, 23.15%. Neither correspondence on the right side nor significant gender-related associations were observed. Conclusion: Considering the wide range of abdominal anatomical variations and the characteristics of needle insertion pathways, celiac plexus block should not be standardized. Imaging should be performed prior to the procedure in order to reduce the risks for injuries or for negative outcomes to patients. Gender-related anatomical variations involved in celiac plexus block should be more deeply investigated, since few studies have addressed the subject.

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ABSTRACT Climatic conditions stimulates the cambial activity of plants, and cause significant changes in trunk diameter growth and wood characteristics. The objective of this study was to evaluate the influence of climate variables in the diameter growth rate of the stem and the wood density of Eucalyptus grandis trees in different classes of the basal area. A total of 25 Eucalyptus trees at 22 months of age were selected according to the basal area distribution. Dendrometer bands were installed at the height of 1.30 meters (DBH) to monitor the diameter growth every 14 days, for 26 months. After measuring growth, the trees were felled and wood discs were removed at the DBH level to determine the radial density profile through x-ray microdensitometry and then re-scale the average values every 14 days. Climatic variables for the monitoring period were obtained and grouped every 14 days. The effect of the climate variables was determined by maximum and minimum growth periods in assessing trunk growth. These growth periods were related with precipitation, average temperature and relative air humidity. The re-scaled wood density values, calculated using the radial growth of the tree trunks measured accurately with steel dendrometers, enabled the determination of the relationship of small changes in wood density and the effect of the climatic variations and growth rate of eucalyptus tree trunks. A high sensitivity of the wood density to variation in precipitation levels was found.

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ABSTRACTThe objective of this study was to determine the energy balance of the poultry-shed system and its effect on broiler performance during the production cycle. The experimental design was completely random with sub-divided blocks. The blocks were composed of five different types of sheds and the sub-blocks of the evaluation times (00:00 h to 23:00 h), allowing an analysis of variance and a comparison between means with the Tukey test. There were no significant differences between the mean values of the exchanges of sensible, latent and total heat between the poultry sheds but the differences for the evaluation times were significant (P<0.05). There was no significant difference between sheds 1 and 4 for broiler productive performance regarding weight gain, feed consumption and feed conversion. Bird performance was significant (P<0.05) for the remaining poultry sheds. The productive indexes remained below the ranges considered ideal for broilers and values in the final weeks were characterized by the poor installation efficiency in controlling temperature variations and, consequently, the energy balance in the system, which adversely affected bird productive performance.

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CHARGE syndrome, Sotos syndrome and 3p deletion syndrome are examples of rare inherited syndromes that have been recognized for decades but for which the molecular diagnostics only have been made possible by recent advances in genomic research. Despite these advances, development of diagnostic tests for rare syndromes has been hindered by diagnostic laboratories having limited funds for test development, and their prioritization of tests for which a (relatively) high demand can be expected. In this study, the molecular diagnostic tests for CHARGE syndrome and Sotos syndrome were developed, resulting in their successful translation into routine diagnostic testing in the laboratory of Medical Genetics (UTUlab). In the CHARGE syndrome group, mutation was identified in 40.5% of the patients and in the Sotos syndrome group, in 34%, reflecting the use of the tests in routine diagnostics in differential diagnostics. In CHARGE syndrome, the low prevalence of structural aberrations was also confirmed. In 3p deletion syndrome, it was shown that small terminal deletions are not causative for the syndrome, and that testing with arraybased analysis provides a reliable estimate of the deletion size but benign copy number variants complicate result interpretation. During the development of the tests, it was discovered that finding an optimal molecular diagnostic strategy for a given syndrome is always a compromise between the sensitivity, specificity and feasibility of applying a new method. In addition, the clinical utility of the test should be considered prior to test development: sometimes a test performing well in a laboratory has limited utility for the patient, whereas a test performing poorly in the laboratory may have a great impact on the patient and their family. At present, the development of next generation sequencing methods is changing the concept of molecular diagnostics of rare diseases from single tests towards whole-genome analysis.

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Passive immunity transfer (PIT) evaluation is an essential tool for the maintenance of healthy calves during the first months of life. Since lactation number and breed have been proven to influence immunoglobulin levels in colostrum, the aim of this study was to evaluate PIT from primiparous and multiparous Canchim cows to their calves. Blood samples were collected from the calves before colostrum intake and 1, 2, 7, 15 and 30 days thereafter, while colostrum samples from the cows were taken immediately after parturition. Activities of gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and concentrations of total protein, albumin, globulins, immunoglobulin A (IgA), immunoglobulin G (IgG), total and ionized calcium, inorganic phosphorus, magnesium, sodium and potassium were evaluated in calves' serum and activities of GGT and ALP and concentrations of total protein, IgA and IgG were assessed in cow's colostrum whey. Immunoglobulins concentrations were evaluated by electrophoresis in polyacrylamide gels. Serum biochemistry evaluations revealed an increase in gamma-glutamyl transferase and alkaline phosphatase activities and in total protein, globulins, immunoglobulin A and immunoglobulin G levels in calves' serum after colostrum intake. Only total protein and light chain immunoglobulin G levels in colostrum whey were affected by the cows' lactation number. Phosphorus and magnesium levels in blood serum increased after colostrum intake, while sodium and potassium levels oscillated in the experimental period. PIT was influenced by the cows' lactation number but was efficient in both groups.

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Two field experiments were conducted at the experimental farm of the National Research Centre at Shalakan, Kalubia Governorate, Egypt, during 2006 and 2007 seasons, to study the effect of three pre-emergence herbicides, prometryn [at the rate of 0.75, 1.5 and 2.25 kg ha-1], oxadiargyl [at the rate of 240, 480 and 720 g ha-1] and butralin [at the rate of 1.20, 2.40 and 3.36 kg ha-1], two hand hoeing treatments and a nonweeded check, on weed infestation, nodulation, growth, yield and yield attributes of soybean plants. Two hand hoeing treatments resulted in the highest weed depression expressed as the lowest fresh and dry weights of broadleaved, grassy and total weeds. The reduction percentage in weed dry matter compared to the nonweeded treatment was 98.3, 92.64 and 96.9% in broadleaved, grassy and total weeds, respectively. Application of the three herbicides at higher or recommended doses significantly reduced fresh and dry weight of the weeds compared to the nonweeded treatment. The results indicated that all the three herbicides at rates higher than the recommended markedly decreased the number, fresh and dry weight of nodules as well as root, shoot and total dry weight plant-1, while application of two hand hoeing treatments significantly increased these traits. Two hand hoeing treatments and pre-emergence herbicides at the recommended rates markedly increased soybean yield and its attributes. Two hand hoeing treatments gave the highest values of number of pods per plant-1, weight of pods per plant-1 and number of seeds per plant-1 by 140.7, 150.0 and 59.8%, respectively, compared to the nonweeded treatment. On the other hand, oxadiargyl at the recommended rate (480 g ha-1) was the best treatment for promoting seed yield (g plant-1), seed yield (kg ha-1) and biological yield (g plant-1) compared to the nonweeded treatment by 87.3, 85.0 and 88.2%, respectively. Prometryn at the rate of 1.50 kg ha-1, followed by two hand hoeing treatments, produced the highest shoot and seed protein percentage as well as seed oil percentage, compared to the other weed control treatments.