85 resultados para gain of function mutation


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Monte Carlo simulations are used to assess the adequacy of the Tanford-Kirkwood prescription for electrostatic interactions in macromolecules. Within a continuum dielectric framework, the approach accurately describes salt screening of electrostatic interactions for moderately charged systems consistent with common proteins at physiological conditions. The limitations of the Debye-Huckel theory, which forms the statistical mechanical basis for the Tanford-Kirkwood result, become apparent for highly charged systems. It is shown, both by an analysis of the Debye-Huckel theory and by numerical simulations, that the difference in dielectric permittivity between macromolecule and surrounding solvent does not play a significant role for salt effects if the macromolecule is highly charged. By comparison to experimental data, the continuum dielectric model (combined with either an approximate effective Hamiltonian as in the Tanford-Kirkwood treatment or with exact Monte Carlo simulations) satisfactorily predicts the effects of charge mutation on metal ion binding constants, but only if the macromolecule and solvent are assigned the same or similar permittivities.

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Comparative genomic hybridization (CGH) analysis was performed for the identification of chromosomal imbalances in two benign gynecomastias and one malignant breast carcinoma derived from patients with male breast disease and compared with cytogenetic analysis in two of the three cases. CGH analysis demonstrated overrepresentation of 8q in all three cases. One case of gynecomastia presented gain of 1p34.3similar topter. 11p14similar toq12. and 17p11.2similar toqter, and loss of 1q41similar toqter and 4q33similar toqter. The other gynecomastia presented del(1)(q41) as detected by both cytogenetic and CGH analysis. CGH analysis of the invasive ductal carcinoma confirmed a gain of 17p11.2similar toqter previously detected by cytogenetic analysis. These regions showed some similarity in their pattern of imbalance to the chromosomal alterations described in female and male breast cancer. (C) 2002 Elsevier B.V. All rights reserved.

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The chromosome number and meiotic cycle of triatomines were investigated. All five species presented the same diploid chromosome number, 2n = 22 (20A + XY in the male). Phylogenetic relationships based on chromosomal evidence and C-banded karyotypes in the subfamily are discussed. It is suggested that differences in DNA content are mainly due to variations in the amount of C-heterochromatin, which may be interpreted as loss and/or gain of C-regions. This interpretation is supported by the presence of meiotic and mitotic chromocentres which facilitate the transfer of C-positive material.

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This study was carried out to determine body composition and magnesium, potassium and sodium requirements for weight gain of Santa Ines lambs (hairy coat breed). Eighteen animals were used with average 15 kg initial LW. At the beginning of the experiment, six animals were slaughtered for the determination of the amount of each mineral retained in the body, and serving as reference animals in the comparative slaughter technique. The remaining 12 animals were divided in two groups: six were ad libitum fed and six animals were restricting fed at maintenance plus 20%. The animals from the ad libitum and restrict feeding groups started in the experimental period by pairs and they both were slaughtered when the animals from the ad libitum group reached 25 kg LW. The estimates of magnesium, potassium and sodium body composition were obtained through the prediction equations obtained by the logarithm regression of the amount of each present minerals in the empty body in function of the empty body weight (EBW). The net requirements for weight gain were obtained through the derivation of these prediction equations. The estimates of body composition per kg EBW for the animals from 15 to 25 kg were: 0.591 and 0,578 g for Mg: 2.914 and 2.776 g for K 1.830 and 1.637 g for Na; and the net requirements for kg weight gain were: 0.515 and 0.503 g for Mg: 2.408 and 2.294 g for K; 1.315 and 1.177 g for Na, respectively.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Chromosome analysis was performed on samples from 20 Brazilian patients with breast cancer. All the samples were from untreated patients who presented the clinical symptoms for months or years before surgical intervention. Six cases showed axillary lymph node metastases. Clonal chromosome abnormalities were detected in all cases. The numerical alterations most frequently observed involved the loss of chromosomes X, 19, 20, and 22 followed by gain of chromosomes 9 and 8. Among the structural anomalies observed, there was preferential involvement of chromosomes 11, 6, 1, 7, 3, and 12, supporting previous reports that these chromosomes may harbour genes of importance in the development of breast tumors. Two cases with a family history of breast cancer had in common total or partial trisomy 1.

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The objective of this experiment was to determine the protein requirements for hen pullets from 1 to 18 weeks of age, by factorial method, using the nitrogen balance and the comparative slaughtering techniques. Protein requirements for maintenance, was obtained by the nitrogen balance technique using four diets with different protein levels (18,9, 4 and 2% of CP) aiming to obtain positive balance, next to zero and negative nitrogen balance. The endogenous nitrogen losses (0.2575 g of N/kg·75/day) was obtained by regression of nitrogen balance (NB) on ingestion nitrogen (IN). The requirements of nitrogen for maintenance was estimated by the intercept of axis X (0.3831 g of N/kg·75/day). The slope of the straight line still supplied the efficiency of N of the diet (67.21%). The regression coefficients of the equation represented the requirements of net nitrogen for weight gain. Considering the conversion efficiencies of nitrogen of the diet into nitrogen for weight gain, the requirements of nitrogen were determined for weight gain of .065, .087g and .090 g of N per gram of weight gain, for the phases 1 to 6, 7 to 12, and 13 to 18 weeks of age, respectively. Based on the results, three equations of prediction of the daily nitrogen requirements were fitted in function of live weight (LW in kg) and daily weight gain (G in g): 1 to 6 weeks N=.3831 x BW·75 + G .065, 7 to 12 weeks N=.3831 × BW·75 + G .087, and 13 to 18 weeks N=.3831 × BW·75 + G .090.

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The design of a Gilbert Cell Mixer and a low noise amplifier (LNA), using GaAs PHEMT technology is presented. The compatibility is shown for co-integration of both block on the same chip, to form a high performance 1.9 GHz receiver front-end. The designed LNA shows 9.23 dB gain and 2.01 dB noise figure (NF). The mixer is designed to operate at RF=1.9 GHz, LO=2.0 GHz and IF=100 MHz with a gain of 14.3 dB and single sideband noise figure (SSB NF) of 9.6 dB. The mixer presents a bandwith of 8 GHz.

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This paper analyzes the thermal storage characteristics of aluminum plates in furnaces during their heating for lamination under two sources of heat: an electrical resistance bank and a combustion process carried out with natural gas. The set of equations to model the furnace under operation with electrical energy, for air as the fluid, is presented. This supports the theoretical analysis for the system under operation with natural gas combustion products. A numerical procedure, using the software ANSYS, is applied to determine the convection heat transfer coefficients for heating by the air flow. Temperatures measured in a plate inside a real furnace are used as parameters to determine these coefficients. Then convection and radiation heat transfer coefficients are determined for the natural gas combustion products. Results are compared, indicating a possible gain of 5.5 h in relation to a 19.5 h period of conventional electrical heating per plate.

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Ontogenetic changes in relative growth were studied in the hermit crab Calcinus tibicen in order to determine its growth phases with sexual maturity. Specimens were collected at 2-month intervals for two consecutive years. A total of 570 individuals was collected and analysed. Total mean animal size in terms of shield length was 5.14±1.23mm for males, 4.23±0.79mm for females and 4.53±0.60mm for ovigerous females. Sexual dimorphism in chela dimensions was stronger in males than in females. Differences between males and females were found in left propodus length (LPL) and height (LPH) versus shield length (SL) and wet weight (WW) versus SL relationships. Males showed a high positive allometry, while juveniles and adult females were isometric for the LPL/SL relationship. Negative allometry was observed in adult females in the LPL/SL relationship. The size at which a differentiation occurred in the growth of the chelipeds and in the weight gain of males and females was between 3.0 and 3.2mm SL, suggesting that sexual maturity occurs in small-sized individuals in the life cycle of C. tibicen.

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Loss of function, muscle inflammation, and pain are some of the signs and symptoms of temporomandibular dysfunction (TMD). Pharmacological strategies to minimize the clinical manifestation of these disorders often focus on blocking or inhibiting the pain-causing symptom. Resources such as muscle-relaxants, anxiety-relief drugs, and splint therapy are often used to reduce muscular hyperactivity related to TMD muscle pain. This study compares the effect of a randomly ordered association of occlusal splint therapy (S), nonsteroid anti-inflammatory with a muscle-relaxant drug (orphenadrine citrate) (O), and an anxiety-relief drug (benzodiazepine) (B), to ease painful TMD muscle symptoms. Clinical and anamnestic analyses were recorded in accordance with the Helkimo TMD index and applied before and after treatments. Twenty-one group two Helkimo TMD adult female patients were treated, all of whom were subjected to the three random therapeutic associations proposed: SBO, BOS, and OSB. The same operator applied the three specific associations over a period of 21 days in the proposed sequence, seven days for each therapy. The results show that all the groups presented the best results in terms of relief from pain after the therapeutic association (28.5% showed a decrease and 47.6% showed an absence of symptoms). No significant difference was observed among association therapeutic protocols. Copyright © 2003 by CHROMA, Inc.

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Objectives: To examine the change in health-related quality of life (HRQOL) and its determinants in children with juvenile idiopathic arthritis (JIA) treated with methotrexate (MTX). Methods: Patients were extracted from the PRINTO clinical trial which aimed to evaluate the efficacy and safety profile of MTX administered in standard, intermediate or higher doses (10, 15 and 30 mg/m2/week respectively). Children with polyarticular-course JIA, who were less than 18 years and had a complete HRQOL assessment were included. Results: A total of 521 children were included. At baseline, patients with JIA showed poorer HRQOL (p<0.01) than healthy children. In 207/412 (50%) and 63 (15%) children, HRQOL values were 2 standard deviations below the mean of healthy controls in the physical and psychosocial summary scale, respectively. After 6 months of treatment with standard dose MTX, there was a statistically significant improvement in all HRQOL health concepts, particularly the physical ones. Similar improvements were observed in those who did not respond to a standard dose of MTX and were subsequently randomised to a higher dose. The presence of marked disability at baseline was associated with a fivefold increased risk of retaining poor physical health after 6 months of active treatment with standard dose MTX. Other less important determinants of retaining poor physical well-being were the baseline level of systemic inflammation, pain intensity and an antinuclear-antibody-negative status. Conclusions: MTX treatment produces a significant improvement across a wide range of HRQOL components, particularly in the physical domains, in patients with JIA.

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The aim of this study was to determine the time to restore the biceps brachii (BB) electromyographic (EMG) activity after the biceps curl (BC) exercise, at different intensities. Ten males performed initially maximal voluntary isometric contractions (MVC) of the elbow flexors, followed by one isometric submaximal contraction at 50% MVC (reference contraction). After this, four bouts of the BC at 25%, 30%, 35%, and 40% 1 RM during 1 minute (randomly assigned, with 10 minutes rest between them) were performed. During the rest intervals at preestablished moments (15 seconds, 1, 3, 5, and 10 min), isometric 50% MVC were performed. The EMG variables (root mean square [RMS], zero crossings [ZC], median frequency, [MF] and peak power [PP]) at rest were compared with reference values. Immediately after the exercise, RMS and PP increased, while ZC and MF decreased, indicating fatigue. After 1 minute most of the variables were similar to the reference. Different load levels did not affect the EMG recovery. In conclusion, the EMG variables recovered after 1 minute rest, indicating the optimal muscular condition for subsequent bouts. Copyright © Taylor & Francis Group, LLC.

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Introduction: The aim of this study is to evaluate the serum activity of metalloproteinases (MMPs) -2 and -9 as predictors of pressure ulcer (PU), gait status and mortality 6 months after hip fracture. Methods: Eighty-seven patients over the age of 65 admitted to the orthopedic unit from January to December 2010 with hip fracture were prospectively evaluated. Upon admission, patient demographic information, including age, gender and concomitant diseases, was recorded. Blood samples were taken for analysis of MMP -2 and -9 activity by gel zymography and for biochemical examination within the first 72 hours of the patient's admission, after clinical stabilization. The fracture pattern (neck, trochanteric or subtrochanteric), time from admission to surgery, surgery duration and length of hospital stay were also recorded. Results: Two patients were excluded due to the presence of pathological fractures (related to cancer), and three patients were excluded due to the presence of PU before admission. Eighty-two patients, with a mean age of 80.4 ± 7.3 years, were included in the analysis. Among these patients, 75.6% were female, 59.8% had PU, and 13.4% died 6 months after hip fracture. All patients underwent hip fracture repair. In a univariate analysis, there were no differences in serum MMP activity between hip fracture patients with or without PU. In addition, the multiple logistic regression analysis models, which were adjusted by age, gender, length of hospital stay and C-reactive protein, showed that the pro-MMP-9 complexed with neutrophil gelatinase-associated lipocalin form (130 kDa) was associated with gait status recovery 6 months after hip fracture. Conclusions: In conclusion, serum pro-MMP-9 is a predictor of gait status recovery 6 months after hip fracture. © 2013 Gumieiro et al.