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Systemic chemotherapy-induced microsatellite instability in the mononuclear cell fraction of women with breast cancer can be reproduced in vitro and abrogated by amifostine

PINTO, Jorge L. F.; FONSECA, Fernando L. A.; MARSICANO, Sarah R.; DELGADO, Pamela O.; SANT`ANNA, Aleksandra V. L.; COELHO, Patricia G.; MAEDA, Patrica; GIGLIO, Auro Del
Fonte: WILEY-BLACKWELL PUBLISHING, INC Publicador: WILEY-BLACKWELL PUBLISHING, INC
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
36.23%
Objectives Microsatellite instability (MSI) induction by alkylating agent-based chemotherapy (ACHT) may underlie both tumor resistance to chemotherapy and secondary leukaemias in cancer patients. We investigated if ACHT could induce MSI in tumor-derived plasma-circulating DNA (pfDNA) and in normal peripheral blood mononuclear (PBMN) cells. We also evaluated if amifostine could interfere with this process in an in-vitro model. Methods MSI was determined in pfDNA, PBMN cells and urine cell-free DNA (ufDNA) of 33 breast cancer patients before and after ACHT. MCF-7 cells and PBMN from normal donors were exposed in vitro to melphalan, with or without amifostine. Results We observed at least one MSI event in PBMN cells, pfDNA or ufDNA of 87, 80 and 80% of patients, respectively. In vitro, melphalan induced MSI in both MCF-7 and normal PBMN cells. In PBMN cells, ACHT-induced MSI occurred together with a significant decrease in the expression of the DNA mismatch repair gene hMSH2. Amifostine decreased hMSH2 expression and also prevented MSI induction only in normal PBMN cells. Conclusions ACHT induced MSI in PBMN cells and in tumour-derived pfDNA. Because of its protective effect against ACHT induction of MSI in normal PBMN cells in vitro...

Modeling the size dependent pull-in instability of beam-type NEMS using strain gradient theory

Koochi,Ali; Sedighi,Hamid M.; Abadyan,Mohamadreza
Fonte: Associação Brasileira de Ciências Mecânicas Publicador: Associação Brasileira de Ciências Mecânicas
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2014 EN
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36.32%
It is well recognized that size dependency of materials characteristics, i.e. size-effect, often plays a significant role in the performance of nano-structures. Herein, strain gradient continuum theory is employed to investigate the size dependent pull-in instability of beam-type nano-electromechanical systems (NEMS). Two most common types of NEMS i.e. nano-bridge and nano-cantilever are considered. Effects of electrostatic field and dispersion forces i.e. Casimir and van der Waals (vdW) attractions have been considered in the nonlinear governing equations of the systems. Two different solution methods including numerical and Rayleigh-Ritz have been employed to solve the constitutive differential equations of the system. Effect of dispersion forces, the size dependency and the importance of coupling between them on the instability performance are discussed.

Genomic instability in human actinic keratosis and squamous cell carcinoma

Cabral,Luciana Sanches; Festa Neto,Cyro; Sanches Jr,José A.; Ruiz,Itamar R. G.
Fonte: Faculdade de Medicina / USP Publicador: Faculdade de Medicina / USP
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2011 EN
Relevância na Pesquisa
36.32%
OBJECTIVE: To compare the repetitive DNA patterns of human actinic keratoses and squamous cell carcinomas to determine the genetic alterations that are associated with malignant transformation. INTRODUCTION: Cancer cells are prone to genomic instability, which is often due to DNA polymerase slippage during the replication of repetitive DNA and to mutations in the DNA repair genes. The progression of benign actinic keratoses to malignant squamous cell carcinomas has been proposed by several authors. MATERIAL AND METHODS: Eight actinic keratoses and 24 squamous cell carcinomas (SCC), which were pair-matched to adjacent skin tissues and/or leucocytes, were studied. The presence of microsatellite instability (MSI) and the loss of heterozygosity (LOH) in chromosomes 6 and 9 were investigated using nine PCR primer pairs. Random Amplified Polymorphic DNA patterns were also evaluated using eight primers. RESULTS: MSI was detected in two (D6S251, D9S50) of the eight actinic keratosis patients. Among the 8 patients who had squamous cell carcinoma-I and provided informative results, a single patient exhibited two LOH (D6S251, D9S287) and two instances of MSI (D9S180, D9S280). Two LOH and one example of MSI (D6S251) were detected in three out of the 10 patients with squamous cell carcinoma-II. Among the four patients with squamous cell carcinoma-III...

From Wrinkles to Creases in Elastomers: The Instability and Imperfection-Sensitivity of Wrinkling

Cao, Yanping; Hutchinson, John W.
Fonte: The Royal Society Publicador: The Royal Society
Tipo: Artigo de Revista Científica
EN_US
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The stability of the wrinkling mode experienced by a compressed half-space of neo-Hookean material is investigated using analytical and numerical methods to study the post-bifurcation behaviour of periodic solutions. It is shown that wrinkling is highly unstable owing to the nonlinear interaction among the multiple modes associated with the critical compressive state. Concomitantly, wrinkling is sensitive to exceedingly small initial imperfections that significantly reduce the compressive strain at which the instability occurs. The study provides insight into the connection between wrinkling and an alternative surface mode, the finite amplitude crease or sulcus. The shape of the critical combination of wrinkling modes has the form of an incipient crease, and a tiny initial imperfection can trigger a wrinkling instability that collapses into a crease.; Engineering and Applied Sciences

Total Factor Productivity and Macroeconomic Instability

Berument, Hakan; Nergiz Dincer, N.; Mustafaoglu, Zafer
Fonte: Taylor and Francis Publicador: Taylor and Francis
Tipo: Artigo de Revista Científica
EN_US
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36.32%
Total factor productivity (TFP) is an important component of growth for most countries. This paper assesses the role of macroeconomic instability on TFP growth. We consider volatility in inflation, openness of an economy and financial market deepness as measures of macroeconomic instability. Empirical evidence provided from Turkey suggests that volatility of openness and financial market deepness reduce TFP growth, whereas volatility of inflation increases TFP growth.

Non-axisymmetric instability in the Taylor-Couette flow of fiber suspension

Wan, Z.; Lin, J.; You, Z.
Fonte: Zheijiang University Press Publicador: Zheijiang University Press
Tipo: Artigo de Revista Científica
Publicado em //2005 EN
Relevância na Pesquisa
36.32%
An analysis of the instability in the Taylor-Couette flow of fiber suspensions with respect to the non-axisymmetric disturbances was performed. The constitutive model proposed by Ericksen was used to represent the role of fiber additives on the stress tensor. The generalized eigenvalue equation governing the hydrodynamic stability of the system was solved using a direct numerical procedure. The results showed that the fiber additives can suppress the instability of the flow. At the same time, the non-axisymmetric disturbance is the preferred mode that makes the fiber suspensions unstable when the ratio of the angular velocity of the outer cylinder to that of the inner cylinder is a large negative number.; Zhan-hong Wan, Jian-zhong Lin and Zhen-jiang You

Targeting chromosomal instability: screening and characterization of CIN killers.

Shaukat, Zeeshan
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Tese de Doutorado
Publicado em //2014
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36.32%
Chromosomal INstability (CIN), a hallmark of cancer cells, refers to a state in which cells have an increased rate of gain or loss of whole chromosomes or large chromosomal fractions. CIN is linked to the progression of tumours with poor clinical outcomes such as drug resistance and metastasis. Chromosomal instability is mainly caused by defective chromosomal segregation during mitosis and normally prevented by cellular checkpoints. As CIN is not found in normal cells, it offers a cancer-specific target for therapy, which may be particularly valuable because CIN is common in advanced tumours that are resistant to conventional therapy. In this study, to identify targets which can specifically induce apoptosis in CIN cells, a CIN model was generated by knocking down the spindle assembly checkpoint in Drosophila. Defects in the checkpoint lead to high rate of chromosomal segregation defects (lagging chromosomes and chromosome bridges). An RNAi screening approach was used and the set of kinases and phosphatases was screened to identify those candidates that induce apoptosis only in CIN cells. Genes identified include those involved in JNK signaling pathways, mitotic cytoskeletal regulation and metabolic pathways. This screen demonstrates that it is feasible to selectively kill cells with CIN induced by spindle checkpoint defects. It has identified candidates that are currently being pursued as cancer therapy targets (e.g. Nek2: NIMA related kinase 2)...

Characteristics of palatal instability in Thoroughbred racehorses and their association with the development of dorsal displacement of the soft palate

Allen, K.; Franklin, S.
Fonte: Wiley Publicador: Wiley
Tipo: Artigo de Revista Científica
Publicado em //2013 EN
Relevância na Pesquisa
36.32%
REASON FOR PERFORMING STUDY: Two forms of dynamic upper respiratory tract obstruction affecting racehorses that involve the soft palate have been described: palatal instability (PI) and dorsal displacement of the soft palate (DDSP). Observation of DDSP is straightforward in that it is an all or nothing event, whereas observation of PI is subjective and interpretation may vary between clinicians. OBJECTIVES: The aim of this study was to attempt to characterise PI and to investigate endoscopic features that precede DDSP. METHODS: A retrospective study on the endoscopic observations of Thoroughbred racehorses referred for high-speed treadmill endoscopy was performed. Endoscopic observations were reviewed during the last 10 s of the exercise test or the last 10 s prior to DDSP. The degree of axial deviation of the aryepiglottic folds (ADAF), the conformation of the epiglottis, the conformation of the soft palate and the amount of obstruction of the rima glottidis by the soft palate (i.e. soft palate stability) were assessed. RESULTS: A total of 72 horses were included in this study, of which 7 showed no evidence of PI. Of the 65 horses with PI, 30 (46%) developed DDSP. There were significant associations between the stability of the soft palate...

Geologic Controls on Instability in WWI Excavations, Canadian National Memorial Site, Vimy, France

White, Maureen C.
Fonte: Quens University Publicador: Quens University
Tipo: Tese de Doutorado Formato: 18262950 bytes; application/pdf
EN; EN
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36.32%
The Canadian National Memorial Site, near Vimy, Artois, France, commemorates the WWI Battle of Vimy Ridge; where all four divisions of the young Canadian Corps fought together with the British Forces to liberate the French ridge. Today, trench systems and an extensive subterranean network of tunnels underlie the gentle landscape of the park, which is visited each year by hundreds of thousands of tourists. Failure within these excavations is expressed as local subsidence and is potentially hazardous to the public. The following research identifies the geologic factors that influence instability in the excavations and how these factors vary both with depth and lateral extent. The Artois region of northern France is underlain by Upper Cretaceous chalk with a thin veneer of Paleocene sediments. Structure is dominated by the northwest-southeast trending Weald-Boulonnais anticlinorium. Three principle geological controls govern failure within the excavations at the Vimy site; lithologic variations, structural geometry and carbonate dissolution. An extensive stratigraphic study identified variable horizons such as chalk marls, nodular chalks, hardgrounds and flint seams, which affect the strength, permeability and structure of the rockmass. Structural geometry in the chalk varies with depth and clay content. Orthogonal fracture patterns are typical in pure carbonate rockmasses whereas inclined conjugate sets occur in clay-rich chalk. Three failure mechanisms were observed in the Vimy excavations that vary with structure and lithology. Beam failure via block fall-out is observed in pure chalk with subhorizontal and subvertical structures. Ravelling...

New method for the measurement of fibres orientation on the paper faces applied to the analysis of hygro-instability in paper sheets

Pereira, M.J.T.; Costa, A.P.; Trindade, A.C.; Fiadeiro, P. T.; Silvy, J.; Tosio, J.M.Serra
Fonte: Universidade da Beira Interior Publicador: Universidade da Beira Interior
Tipo: Artigo de Revista Científica
Publicado em 28/04/2010 ENG
Relevância na Pesquisa
36.32%
For a given change in the humidity of a paper the hygro-instability of the sheet depends of two main factors:  the sheet structural parameters which reflects its structure: the sheet porosity, the fibres orientation distribution mainly in the sheet plane and the variations of these parameters across the paper sheet thickness.  the water reactivity of the components of the paper sheet which depends mainly of the sheet composition: the cellulosic and the fillers content, the nature of the fibres, softwood or hardwood, their degree of delignification, the beating degree of the pulp, the fines content, the conditions of the sheet drying with a more or less conditions of restraint. In this research initiated at the University of Beira Interior (UBI) with the collaboration of the Ecole Française de Papeterie (EFPG), we have tried to identify these main parameters of the paper hygro-instability. For this purpose we characterise the sheet structural parameters by optical methods developed at the Optical Centre of UBI.

Functional Anatomy, Pathomechanics, and Pathophysiology of Lateral Ankle Instability

Hertel, Jay
Fonte: National Athletic Trainers Association Publicador: National Athletic Trainers Association
Tipo: Artigo de Revista Científica
Publicado em //2002 EN
Relevância na Pesquisa
36.32%
Objective: To describe the functional anatomy of the ankle complex as it relates to lateral ankle instability and to describe the pathomechanics and pathophysiology of acute lateral ankle sprains and chronic ankle instability.

Is There a Link Between Chronic Ankle Instability and Postural Instability?

Riemann, Bryan L.
Fonte: National Athletic Trainers Association Publicador: National Athletic Trainers Association
Tipo: Artigo de Revista Científica
Publicado em //2002 EN
Relevância na Pesquisa
36.32%
Objective: To provide clinicians and researchers with an expanded perspective on the association between functional ankle instability and postural control.

Faraday’s Instability for Viscous Fluids

Tirapegui, Enrique; Cerda, Enrique
Fonte: Universidade do Chile Publicador: Universidade do Chile
Tipo: Artículo de revista
EN_US
Relevância na Pesquisa
36.32%
We derive an exact equation which is nonlocal in time for the linear evolution of the surface of a viscous fluid, and show that this equation becomes local and of second order in an interesting limit. We use our local equation to study Faraday’s instability in a strongly dissipative regime and find a new scenario which is the analog of the Rayleigh-Taylor instability. Analytic and numerical calculations are presented for the threshold of the forcing and for the most unstable mode with impressive agreement with experiments and numerical work on the exact Navier-Stokes equations. [S0031-9007(96)02234-X]

Genomic instability in human actinic keratosis and squamous cell carcinoma

Cabral, Luciana Sanches; Festa Neto, Cyro; Sanches Jr, José A.; Ruiz, Itamar R. G.
Fonte: Universidade de São Paulo. Faculdade de Medicina Publicador: Universidade de São Paulo. Faculdade de Medicina
Tipo: info:eu-repo/semantics/article; info:eu-repo/semantics/publishedVersion; ; ; ; ; ; Formato: application/pdf
Publicado em 01/01/2011 ENG
Relevância na Pesquisa
36.32%
OBJECTIVE: To compare the repetitive DNA patterns of human actinic keratoses and squamous cell carcinomas to determine the genetic alterations that are associated with malignant transformation. INTRODUCTION: Cancer cells are prone to genomic instability, which is often due to DNA polymerase slippage during the replication of repetitive DNA and to mutations in the DNA repair genes. The progression of benign actinic keratoses to malignant squamous cell carcinomas has been proposed by several authors. MATERIAL AND METHODS: Eight actinic keratoses and 24 squamous cell carcinomas (SCC), which were pair-matched to adjacent skin tissues and/or leucocytes, were studied. The presence of microsatellite instability (MSI) and the loss of heterozygosity (LOH) in chromosomes 6 and 9 were investigated using nine PCR primer pairs. Random Amplified Polymorphic DNA patterns were also evaluated using eight primers. RESULTS: MSI was detected in two (D6S251, D9S50) of the eight actinic keratosis patients. Among the 8 patients who had squamous cell carcinoma-I and provided informative results, a single patient exhibited two LOH (D6S251, D9S287) and two instances of MSI (D9S180, D9S280). Two LOH and one example of MSI (D6S251) were detected in three out of the 10 patients with squamous cell carcinoma-II. Among the four patients with squamous cell carcinoma-III...

Prognostic significance of extensive microsatellite instability in sporadic clinicopathological stage C colorectal cancer

Wright, Crispin; Dent, Owen; Barker, M; Newland, R; Chapuis, P; Bokey, E; Young, J P; Leggett, B; Jass, Jeremy; Macdonald, Graham J
Fonte: Blackwell Publishing Ltd Publicador: Blackwell Publishing Ltd
Tipo: Artigo de Revista Científica
Relevância na Pesquisa
36.32%
Background: Colorectal cancers exhibiting microsatellite instability (MSI) appear to have unique biological behaviour. This study analyses the association between extensive MSI (MSI-H), clinicopathological features and survival in an unselected group of patients with sporadic Australian Clinico-Pathological Stage (ACPS) C (tumour node metastasis stage III) colorectal cancer. Methods: Some 255 patients who underwent resection for sporadic ACPS C colorectal cancer between 1986 and 1992 were studied. No patient had received chemotherapy. Minimum follow-up for all patients was 5 years. Archival normal and tumour DNA was extracted and amplified by polymerase chain reaction using a radioactive labelling technique. MSI-H was defined as instability in 40 per cent or more of seven markers. Results: Twenty-one patients showed MSI-H. No association was found between MSI and age or sex. Tumours exhibiting MSI-H were more commonly right sided (P<0.00001), larger (P=0.002) and more likely to be high grade (P=0.049). After adjustment for age, sex and other pathological variables, patients whose cancers exhibited MSI-H had improved survival (P=0.015). Conclusion: Recognition of MSI-H in sporadic ACPS C tumours identifies a subset of cancers with improved prognosis. Such stratification should be considered in trials of adjuvant therapy and may be relevant to therapeutic decision making.

MAPPING THE REGION OF INSTABILITY FOR ADIABATIC PACKED BED REACTORS USING A HOMOTOPY CONTINUATION METHOD

GUTIÉRREZ-HERNANDEZ,JUAN PABLO; FONTALVO ALZATE,JAVIER; GÓMEZ GARCÍA,MIGUEL ÁNGEL
Fonte: DYNA Publicador: DYNA
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/09/2010 EN
Relevância na Pesquisa
36.32%
The pioneer schematic ideas of Kimura and Levenspiel (Ind. Eng. Chem. Proc. Des. Dev., 16 (1977) 145 - 148) have been developed to find numerically the region of instability for adiabatic packed bed reactors. Three different cases of special industrial interest and complexity are presented. The highly exothermic gas-phase reactions: ammonia synthesis, methanol production from syn-gas, and SO2 oxidation. Equations were parameterized and solved according to a continuation homotopy numerical method. The results showed that concentration of inerts and total pressure influences the size of the instability region.

Mechanical instability quantification of slopes at Cofre de Perote volcano, eastern Mexico

Díaz Castellón,Rodolfo; Carrasco Núñez,Gerardo; Álvarez-Manilla Aceves,Alfonso
Fonte: Sociedad Geológica Mexicana, A.C. Publicador: Sociedad Geológica Mexicana, A.C.
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2008 EN
Relevância na Pesquisa
36.32%
Cofre de Perote (CP) volcano is located at the eastern end of the Trans-Mexican Volcanic Belt (TMVB) at 19°30' Lat N, 97°10' Long W. At a height of 4,282 m.a. s.l, it comprises one of the most massive structures within the Citlaltépetl - Cofre de Perote volcanic range (CCPVR), which constitutes an important physiographic barrier that separates the central altiplano, also known as Serdán Oriental, from the coastal plains of the Gulf of Mexico. This massive structure has repeatedly collapsed, and at least two of the collapse events occurred long after activity ceased, suggesting that even extinct volcanoes may pose an important hazard to nearby populated areas. In the present work, volcanic instability is approached through both quantitative and descriptive methods that include combined numerical analysis of limit equilibrium, calculated with Bishop's modified method, and finite element analysis. The combined techniques were applied after attaining mechanical parameters in the laboratory, the field and through careful geological observations in order to obtain a model that approaches structural conditions prior to the destruction of the volcano. Reconstruction of the ancient volcano was used to propose an instability model for the modern summit...

Goal instability, self-esteem, and vocational identity of high school Portuguese students

Santos,Paulo Jorge
Fonte: Instituto Superior de Psicologia Aplicada Publicador: Instituto Superior de Psicologia Aplicada
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/04/2003 EN
Relevância na Pesquisa
36.32%
According to the self-psychology of Heinz Kohut, development of a healthy narcissism that is reflected in a secure sense of self, permits individuals to set and pursue meaningful life goals and maintain a sense of well-being, particularly in periods of transition and change. Based on this perspective, the primary purpose of this study was to assess the contribution of goal instability and self-esteem to the vocational identity of Portuguese high school students using a sample of 375 individuals. Additionally, the effect of gender and age on vocational identity was assessed. A regression equation accounted for 32% of the variance of the dependent variable with goal instability emerging as the strongest predictor. Implications for career theory and counseling are discussed.

Hydraulic support instability mechanism and its control in a fully-mechanized steep coal seam working face with large mining height

Yuan,Y.; Tu,S.H.; Wang,F.T.; Zhang,X.G.; Li,B.
Fonte: Journal of the Southern African Institute of Mining and Metallurgy Publicador: Journal of the Southern African Institute of Mining and Metallurgy
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/05/2015 EN
Relevância na Pesquisa
36.32%
Hydraulic support instability (HSI) is one of the most common causes of disasters in underground coal mining, posing a threat to the safety of mine workers and normal operation of the equipment. It is prone to occur in fully-mechanized mining faces with a large mining height (FMMLMH), especially when the dip angle of the coal seam is large. The key to controlling HSI is to deduce its mechanism and employ effective control techniques. This paper focuses on the analysis of HSI types, the key parameters and techniques to control HSI in FMMLMH, the establishment of a model of HSI in FMMLMH, and a multi-parameter sensitivity mechanical model of different HSI forms in the no. 7(2)19 longwall face in Xutuan Coal Mine, Huaibei Mining Group, by using sensitivity analysis . The results show that HSI mainly presents in three forms: hydraulic support gliding (HSG), hydraulic support tilting (HST), and hydraulic support tail twisting (HSTT). The occurrence of the above three forms depends mainly on support anti-instability capability. In the no. 7219 longwall face, HSG and HST are the main two forms of HSI. The dip angle of the working face and the friction coefficient between floor and hydraulic support are the sensitive parameters for HSG, while HST is strongly dependent on the dip angle of the working face and the friction coefficient between roof and hydraulic support. By the applications of measures such as the oblique layout of the working face...

The X-Ray Knee instability and Degenerative Score (X-KIDS) to determine the preference for a partial or a total knee arthroplasty (PKA/TKA)

Oosthuizen,CR; Burger,S; Vermaak,DP; Goldschmidt,P; Spangenberg,R
Fonte: SA Orthopaedic Journal Publicador: SA Orthopaedic Journal
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/09/2015 EN
Relevância na Pesquisa
36.32%
The X-ray Knee Instability and Degenerative Score (X-KIDS) was developed as a tool based on the degenerative and instability patterns seen on routine X-ray views of the weight-bearing compartments and tested on 336 knees, average age 64 years and followed up for 24 months. It is a study to evaluate the X-KIDS scoring method, which quantifies whether a PKA or TKA is the procedure of choice, comparing it to the surgical procedure done and to a stress X-ray evaluation as a stand-alone when contemplating knee arthroplasty. Points are allocated to the following features: narrowing (N), osteophytes (O), and subluxations (S). The assessed score is out of 10. A patient with a score of at least 3 but less than 5 is suitable for a PKA, a score of 5 could be suitable for a PKA or a TKA and a score exceeding 5 requires a TKA. There was a 95.82% (321) evaluator consensus with the X-KIDS on the X-ray sequence for a PKA or TKA. 92.3% (310) received the procedure assessed by X-KIDS and 2.98% (10) could have received the procedure evaluated. 90.78% of the stress views indicated the preferred procedure and is not as reliable as X-KIDS to determine the procedure.