885 resultados para Inducers of resistance


Relevância:

90.00% 90.00%

Publicador:

Resumo:

Slow intrinsic fluctuations of resistance, also known as the flicker noise or 1/f-noise, in the surface transport of strong topological insulators (TIs) is a poorly understood phenomenon. Here, we have systematically explored the 1/f-noise in field-effect transistors (FET) of mechanically exfoliated Bi1.6Sb0.4Te2Se TI films when transport occurs predominantly via the surface states. We find that the slow kinetics of the charge disorder within the bulk of the TI induces mobility fluctuations at the surface, providing a new source of intrinsic 1/f-noise that is unique to bulk TI systems. At small channel thickness, the noise magnitude can be extremely small, corresponding to the phenomenological Hooge parameter gamma(H) as low as approximate to 10(-4), but it increases rapidly when channel thickness exceeds similar to 1 mu m. From the temperature (T)-dependence of noise, which displayed sharp peaks at characteristic values of T, we identified generation-recombination processes from interband transitions within the TI bulk as the dominant source of the mobility fluctuations in surface transport. Our experiment not only establishes an intrinsic microscopic origin of noise in TI surface channels, but also reveals a unique spectroscopic information on the impurity bands that can be useful in bulk TI systems in general.

Relevância:

90.00% 90.00%

Publicador:

Resumo:

PURPOSE: The main goals of the present study were: 1) to review some recommendations about how to increase lean body mass; 2) to analyse whether following scientific sources of current recommendations, visible changes can be shown or not in a participant (body composition, strength and blood analyses). METHODS: One male athlete completed 12 weeks of resistance training program and following a diet protocol. Some test were determined such as, strength 6RM, blood analyses, skindfold measurements, body perimeters and impedance test. Body composition measurements were taken 3 times during the program (before-T1, after 6 weeks of intervention period-T2 and at the end of the program-T3). On the other hand, strength tests and blood analyses were performed twice (before and after the program). RESULTS: Strength was increased in general; blood analyses showed that Creatine kinase was increased a 104% and Triglycerides level was decreased a 22.5%; in the impedance test, body mass (1.6%), lean body mass (3.5%) and Body mass index (1.7%) were increased, whereas fat mass was decreased (15.5%); relaxed and contracted biceps perimeters were also increased. CONCLUSION: A muscle hypertrophy training program mixed with an appropriate diet during 12 weeks leads to interesting adaptations related to increase in body weight, lean body mass, biceps perimeters, strength and creatine kinase levels, and a decrease in fat mass.

Relevância:

90.00% 90.00%

Publicador:

Resumo:

The application of principles from evolutionary biology has long been used to gain new insights into the progression and clinical control of both infectious diseases and neoplasms. This iterative evolutionary process consists of expansion, diversification and selection within an adaptive landscape - species are subject to random genetic or epigenetic alterations that result in variations; genetic information is inherited through asexual reproduction and strong selective pressures such as therapeutic intervention can lead to the adaptation and expansion of resistant variants. These principles lie at the center of modern evolutionary synthesis and constitute the primary reasons for the development of resistance and therapeutic failure, but also provide a framework that allows for more effective control.

A model system for studying the evolution of resistance and control of therapeutic failure is the treatment of chronic HIV-1 infection by broadly neutralizing antibody (bNAb) therapy. A relatively recent discovery is that a minority of HIV-infected individuals can produce broadly neutralizing antibodies, that is, antibodies that inhibit infection by many strains of HIV. Passive transfer of human antibodies for the prevention and treatment of HIV-1 infection is increasingly being considered as an alternative to a conventional vaccine. However, recent evolution studies have uncovered that antibody treatment can exert selective pressure on virus that results in the rapid evolution of resistance. In certain cases, complete resistance to an antibody is conferred with a single amino acid substitution on the viral envelope of HIV.

The challenges in uncovering resistance mechanisms and designing effective combination strategies to control evolutionary processes and prevent therapeutic failure apply more broadly. We are motivated by two questions: Can we predict the evolution to resistance by characterizing genetic alterations that contribute to modified phenotypic fitness? Given an evolutionary landscape and a set of candidate therapies, can we computationally synthesize treatment strategies that control evolution to resistance?

To address the first question, we propose a mathematical framework to reason about evolutionary dynamics of HIV from computationally derived Gibbs energy fitness landscapes -- expanding the theoretical concept of an evolutionary landscape originally conceived by Sewall Wright to a computable, quantifiable, multidimensional, structurally defined fitness surface upon which to study complex HIV evolutionary outcomes.

To design combination treatment strategies that control evolution to resistance, we propose a methodology that solves for optimal combinations and concentrations of candidate therapies, and allows for the ability to quantifiably explore tradeoffs in treatment design, such as limiting the number of candidate therapies in the combination, dosage constraints and robustness to error. Our algorithm is based on the application of recent results in optimal control to an HIV evolutionary dynamics model and is constructed from experimentally derived antibody resistant phenotypes and their single antibody pharmacodynamics. This method represents a first step towards integrating principled engineering techniques with an experimentally based mathematical model in the rational design of combination treatment strategies and offers predictive understanding of the effects of combination therapies of evolutionary dynamics and resistance of HIV. Preliminary in vitro studies suggest that the combination antibody therapies predicted by our algorithm can neutralize heterogeneous viral populations despite containing resistant mutations.

Relevância:

90.00% 90.00%

Publicador:

Resumo:

Two topics in plane strain perfect plasticity are studied using the method of characteristics. The first is the steady-state indentation of an infinite medium by either a rigid wedge having a triangular cross section or a smooth plate inclined to the direction of motion. Solutions are exact and results include deformation patterns and forces of resistance; the latter are also applicable for the case of incipient failure. Experiments on sharp wedges in clay, where forces and deformations are recorded, showed a good agreement with the mechanism of cutting assumed by the theory; on the other hand the indentation process for blunt wedges transforms into that of compression with a rigid part of clay moving with the wedge. Finite element solutions, for a bilinear material model, were obtained to establish a correspondence between the response of the plane strain wedge and its axi-symmetric counterpart, the cone. Results of the study afford a better understanding of the process of indentation of soils by penetrometers and piles as well as the mechanism of failure of deep foundations (piles and anchor plates).

The second topic concerns the plane strain steady-state free rolling of a rigid roller on clays. The problem is solved approximately for small loads by getting the exact solution of two problems that encompass the one of interest; the first is a steady-state with a geometry that approximates the one of the roller and the second is an instantaneous solution of the rolling process but is not a steady-state. Deformations and rolling resistance are derived. When compared with existing empirical formulae the latter was found to agree closely.

Relevância:

90.00% 90.00%

Publicador:

Resumo:

Escritores/as pós-coloniais têm se engajado em denunciar o doloroso legado da escravidão e do colonialismo, através da recuperação de histórias previamente apropriadas e distorcidas por narrativas mestras. A investigação e a narrativização do passado esquecido de ex-colônias têm sido uma estratégia empregada no sentido de se reconstruir identidades que foram fragmentadas devido às múltiplas opressões sofridas ou testemunhadas por autores. Michelle Cliff é uma romancista, poeta, e ensaísta diaspórica, nascida na Jamaica e que vive nos Estados Unidos. Ela é uma das muitas vozes pós-coloniais comprometidas com uma literatura de resistência que luta pela descolonização cultural e encoraja o sentimento de pertencimento. O objetivo dessa dissertação é analisar os romances de cunho autobiográfico de Cliff, Abeng (1984) e No Telephone to Heaven (1987), que lidam com questões relacionadas às práticas coloniais e pós-coloniais. Os dois romances retratam a saga da protagonista Clare Savage, através da qual Cliff revela o impacto da colonização no Caribe, denuncia as configurações de poder geradas a partir dos imbricamentos entre raça, gênero e classe, e critica a maneira deturpada como a história da Jamaica é transmitida e disseminada através da educação colonial à qual os Jamaicanos são submetidos. A autora também explora os efeitos que as diásporas exercem no processo de construção identitária e o movimento de resgate e recriação de uma história própria por parte dos sujeitos diaspóricos

Relevância:

90.00% 90.00%

Publicador:

Resumo:

The sensitivity of 61 cultures of bacteria isolated from fish towards chlortetracycline (CTC) at 5 ppm and 20 ppm levels has been determined on two solid media: sea water agar (SWA) and a distilled water based medium consisting of peptone, beef extract, glucose and NaCI (PBGA). The cultures employed consisted of (i) gram-negative rods of marine origin (Achromobacter, Pseudomonas, Vibrio and Flavobacterium) and (ii) gram positive organisms (Micrococci and Corynebacterium). Depending on the inhibition zone diameter, the order of CTC sensitivity was found to be Pseudomonasof 5 and 20 ppm. The SWA enhanced the development of resistance in majority of the cultures as compared to PBGA. PBG broth containing CTC at less than 10 ppm exerted a bacteriostatic effect only while that containing 10 ppm or more exerted a bactericidal effect on Achromobacter, Pseudomonas and Micrococci cultures. The significance of these results in fish preservation by CTC is discussed.

Relevância:

90.00% 90.00%

Publicador:

Resumo:

A simple ac resistance bridge is proposed. The stability of the design is better than 10(-6), which is especially suitable for detecting tiny changes of resistance. An example of magnetoresistance measurement for a 220 nm Au film shows the good performance of the bridge. (C) 2009 American Institute of Physics. [DOI: 10.1063/1.3202284]

Relevância:

90.00% 90.00%

Publicador:

Resumo:

We report the measurements of conductivity, I-V curve, and magnetoresistance of a single Au/polyaniline microfiber with a core-shell structure, on which a pair of platinum microleads was attached by focused ion beam. The Au/polyaniline microfiber shows a much higher conductivity (similar to 110 S/cm at 300 K) and a much weaker temperature dependence of resistance [R(4 K)/R(300 K)=5.1] as compared with those of a single polyaniline microtube [sigma(RT)=30-40 S/cm and R(4 K)/R(300 K)=16.2]. The power-law dependence of R(T)proportional to T-beta, with beta=0.38, indicates that the measured Au/polyaniline microfiber is lying in the critical regime of the metal-insulator transition. In addition, the microfiber shows a H-2 dependent positive magnetoresistance at 2, 4, and 6 K.

Relevância:

90.00% 90.00%

Publicador:

Resumo:

Dysprosium and ytterbium monophosphides have been prepared by the solid state reaction. The optical and electrical properties have been studied. Evidence that DyP and YbP are semiconductors has been obtained from the study of the absorption spectrum, the negative temperature coefficient of resistance and the rectifying effect. Their energy gaps are determined as 1.15 eV for DyP and 1.30 eV for YbP, electric conduction type is n-type, resistivities are about 10(-2) ohm cm and Hall mobility is 8.5-80 cm2/Vs. The p-n junction is formed on the LnP/Si.

Relevância:

90.00% 90.00%

Publicador:

Resumo:

The objective of this paper is to analyze the characteristics of protein permeability in alainate-polylysine-alginate (APA) and alginate-chitosan-alginate (ACA) microcapsules by mathematical models based on the balance of chemical potential. The comparison between calculated results and experimental data shows that the models can describe the process of protein diffusion from microcapsule and protein release into microcapsule successfully. The influences of membrane composition on the permeability of ACA microcapsule have been investigated and analyzed. The effect of resistance on the mass transfer is further analyzed theoretically with the aid of mathematical modeling. (c) 2005 Elsevier B.V. All rights reserved.

Relevância:

90.00% 90.00%

Publicador:

Resumo:

This article presents a new method for predicting viral resistance to seven protease inhibitors from the HIV-1 genotype, and for identifying the positions in the protease gene at which the specific nature of the mutation affects resistance. The neural network Analog ARTMAP predicts protease inhibitor resistance from viral genotypes. A feature selection method detects genetic positions that contribute to resistance both alone and through interactions with other positions. This method has identified positions 35, 37, 62, and 77, where traditional feature selection methods have not detected a contribution to resistance. At several positions in the protease gene, mutations confer differing degress of resistance, depending on the specific amino acid to which the sequence has mutated. To find these positions, an Amino Acid Space is introduced to represent genes in a vector space that captures the functional similarity between amino acid pairs. Feature selection identifies several new positions, including 36, 37, and 43, with amino acid-specific contributions to resistance. Analog ARTMAP networks applied to inputs that represent specific amino acids at these positions perform better than networks that use only mutation locations.

Relevância:

90.00% 90.00%

Publicador:

Resumo:

Due to the increasing incidence of antibiotic resistant strains, the use of novel antimicrobials, such as bacteriocins, has become an ever more likely prospect. Lacticin 3147 (of which there are two components, Ltnα and Ltnβ) and nisin belong to the subgroup of bacteriocins called the lantibiotics, which has attracted much attention in recent years. The lantibiotics are antimicrobial peptides that contain unusual amino acids resulting from a series of enzyme-mediated post translational modifications. Given that there have been relatively few examples of lantibiotic-specific resistance; these antimicrobials appear to represent valid alternatives to classical antibiotics. However, the fact that lantibiotics are naturally only produced in small amounts often hinders their commercialisation. In order to overcome this bottleneck, several approaches can be employed. For example, we can create a situation that reduces the quantity of a lantibiotic required to inhibit a target by combining it with other antimicrobials. Here, following an initial screen involving lacticin 3147 and several classical antibiotics, it was observed between lacticin 3147 and the commercial antibiotics polymyxin B/E function synergistically. This reduced the amounts of the individual antimicrobials required for kill and broadened the spectrum of inhibition of both agents. Upon combination with polymyxins, lacticin 3147, which has been associated with Gram positive targets only, actively targeted Gram negative species such as Escherichia coli and Cronobacter sp. An alternative means of addressing problems associated with lantibiotic yield is to better understand how production is regulated, and ultimately use this information to enhance peptide levels. With this in mind the regulation of lacticin 3147 production from the promoter Pbac was investigated using a green fluorescent protein (GFP) expression reporter system. This revealed that elements within both of the divergent operons of the lacticin 3147 gene cluster are involved in Pbac regulation. That is, LtnR, already established as a negative regulator of itself and the lacticin 3147 associated immunity genes, also acts as an activator of Pbac transcription. In contrast, an enhanced level of expression is observed in the absence of the lacticin 3147 structural genes, ltnA1 and ltnA2, indicating that these genes/gene products are involved in Pbac repression. In fact, through complementation of the ltnA2 gene, it was revealed that this regulation is more likely to be dependent on the presence of the gene transcript rather that the corresponding prepropeptide or modified Ltnβ. It may be that if lacticin 3147 production is successfully enhanced, the ability of the producing cell to protect itself may become an issue. To prepare for such a possibility a bioengineered derivative of the lacticin 3147 immunity protein LtnI (LtnI I81V) which provides enhanced protection was discovered through an in depth investigation involving the site and saturation mutagenesis of this protein. In addition, the creation of truncated forms of LtnI allowed the identification of important and essential regions of this immunity protein. Finally, as mentioned, self-immunity is essential to prevent self-killing. However the discovery of nisin U immunity and regulatory gene homologues (spiFEGRR’K) within the pathogenic strain S. infantarius subsp. infantarius is a cause for concern as it represents an example of immune mimicry, a form of lantibiotic-specific resistance. The ability of spiFEG to confer protection was apparent when they successfully provided protection to nisin A, F, Z, Q and U when expressed heterologously in the nisin sensitive L. lactis HP host. As a consequence of the studies presented in this thesis, it is likely that strategies will emerge that will facilitate the production of greater levels of lacticin 3147 production and lead to enhanced immunity in lactococcal backgrounds. Alternatively the need for enhanced production could be avoided through the use of antimicrobial combinations. In addition, providing awareness of the threats of the emergence of resistance through immune mimicry can allow researchers to develop strategies to prevent this phenomenon from leading to the dissemination of lantibiotic resistance.

Relevância:

90.00% 90.00%

Publicador:

Resumo:

M66 an X-ray induced mutant of winter wheat (Triticum aestivum) cv. Guardian exhibits broad-spectrum resistance to powdery mildew (Blumeria graminis f. sp. tritici), yellow rust (Puccinia striiformis f. sp. tritici), and leaf rust (Puccinia recondita f. sp. tritici), along with partial resistance to stagnonospora nodorum blotch (caused by the necrotroph Stagonosporum nodorum) and septoria tritici blotch (caused by the hemibiotroph Mycosphaerella graminicola) compared to the parent plant ‘Guardian’. Analysis revealed that M66 exhibited no symptoms of infection following artificial inoculation with Bgt in the glasshouse after adult growth stage (GS 45). Resistance in M66 was associated with widespread leaf flecking which developed during tillering. Flecking also occurred in M66 leaves without Bgt challenge; as a result grain yields were reduced by approximately 17% compared to ‘Guardian’ in the absence of disease. At the seedling stage, M66 exhibited partial resistance. M66, along with Tht mutants (Tht 12, Tht13), also exhibit increased tolerance to environmental stresses (abiotic), such as drought and heat stress at seedling and adult growth stages, However, adult M66 exhibited increased susceptibility to the aphid Schizaphis graminum compared to ‘Guardian’. Resistance to Bgt in M66 was characterized with increased and earlier H2O2 accumulation at the site of infection which resulted in increased papilla formation in epidermal cells, compared to ‘Guardian’. Papilla formation was associated with reduced pathogen ingress and haustorium formation, indicating that the primary cause of resistance in M66 was prevention of pathogen penetration. Heat treatment at 46º C prior to challenge with Bgt also induced partial disease resistance to Blumeria graminis f. sp. tritici in ‘Guardian’ and M66 seedlings. This was characterized by a delay in primary infection, due to increased production of ROS species, such as hydrogen peroxide, ROS-scavenging enzymes and Hsp70, resulting in cross-linking of cell wall components prior to inoculation. This actively prevented the fungus from penetrating the epidermal cell wall. Proteomics analysis using 2-D gel electrophoresis identified primary and secondary disease resistance effects in M66 including detection of ROS scavenging enzymes (4, 24 hai), such as ascorbate peroxidase and a superoxidase dismutase isoform (CuZnSOD) in M66 which were absent from ‘Guardian’. Chitinase (PR protein) was also upregulated (24 hai) in M66 compared to ‘Guardian’.Monosomic and ditelosomic analysis of M66 revealed that the mutation in M66 is located on the long arm of chromosome 2B (2BL). Chromosome 2BL is known to have key genes involved in resistance to pathogens such as those causing stripe rust and powdery mildew. The TaMloB1 gene, an orthologue of the barley Mlo gene, is also located on chromosome 2BL. Sanger sequencing of part of the coding sequence revealed no deletions in the TaMloB1 gene between ‘Guardian’ and M66.

Relevância:

90.00% 90.00%

Publicador:

Resumo:

This thesis explores the meaning-making practices of migrant and non-migrant children in relation to identities, race, belonging and childhood itself in their everyday lives and in the context of ‘normalizing’ discourses and spaces in Ireland. The relational, spatial and institutional contexts of children’s worlds are examined in the arenas of school, home, family, peer groups and consumer culture. The research develops a situated account of children’s complex subject positions, belongings and exclusions, as negotiated within discursive constructs, emerging in the ‘in-between’ spaces explored with other children and with adults. As a peripheral EU area both geographically and economically, Ireland has traditionally been a country of net emigration. This situation changed briefly in the late 1990s to early 2000s, sparking broad debate on Ireland’s perceived ‘new’ ethnic, cultural and linguistic diversity arising from the arrival of migrant people both from within and beyond the EU as workers and as asylum seekers, and drawing attention to issues of race, identity, equality and integration in Irish society. Based in a West of Ireland town where migrant children and children of migrants comprise very small minorities in classroom settings, this research engages with a particular demographic of children who have started primary school since these changes have occurred. It seeks to represent the complexities of the processes which constitute children’s subjectivities, and which also produce and reproduce race and childhood itself in this context. The role of local, national and global spaces, relational networks and discursive currents as they are experienced and negotiated by children are explored, and the significance of embodied, sensory and affective processes are integrated into the analysis. Notions of the functions and rhetorics of play and playfulness (Sutton-Smith 1997) form a central thread that runs throughout the thesis, where play is both a feature of children’s cultural worlds and a site of resistance or ‘thinking otherwise’. The study seeks to examine how children actively participate in (re)producing definitions of both childhood and race arising in local, national and global spaces, demonstrating that while contestations of the boundaries of childhood discourses are contingently successful, race tends to be strongly reiterated, clinging to bodies and places and compromising belonging. In addition, it explores how children access belongings through agentic and imaginative practices with regard to peer and family relationships, particularly highlighting constructions of home, while also illustrating practices of excluding children positioned as unintelligible, including the role of silences in such situations. Finally, drawing on teachers’ understandings and on children’s playful micro-level negotiations of race, the study argues that assumptions of childhood innocence contribute to justifying depoliticised discourses of race in the early primary school years, and also tend to silence children’s own dialogues with this issue. Central throughout the thesis is an emphasis on the productive potentials of children’s marginal positioning in processes of transgressing definitional boundaries, including the generation of post-race conceptualisations that revealed the borders of race as performative and fluid. It suggests that interrupting exclusionary raced identities in Irish primary schools requires engagement with children’s world-making practices and the multiple resources that inform their lives.

Relevância:

90.00% 90.00%

Publicador:

Resumo:

BACKGROUND: A major challenge in oncology is the selection of the most effective chemotherapeutic agents for individual patients, while the administration of ineffective chemotherapy increases mortality and decreases quality of life in cancer patients. This emphasizes the need to evaluate every patient's probability of responding to each chemotherapeutic agent and limiting the agents used to those most likely to be effective. METHODS AND RESULTS: Using gene expression data on the NCI-60 and corresponding drug sensitivity, mRNA and microRNA profiles were developed representing sensitivity to individual chemotherapeutic agents. The mRNA signatures were tested in an independent cohort of 133 breast cancer patients treated with the TFAC (paclitaxel, 5-fluorouracil, adriamycin, and cyclophosphamide) chemotherapy regimen. To further dissect the biology of resistance, we applied signatures of oncogenic pathway activation and performed hierarchical clustering. We then used mRNA signatures of chemotherapy sensitivity to identify alternative therapeutics for patients resistant to TFAC. Profiles from mRNA and microRNA expression data represent distinct biologic mechanisms of resistance to common cytotoxic agents. The individual mRNA signatures were validated in an independent dataset of breast tumors (P = 0.002, NPV = 82%). When the accuracy of the signatures was analyzed based on molecular variables, the predictive ability was found to be greater in basal-like than non basal-like patients (P = 0.03 and P = 0.06). Samples from patients with co-activated Myc and E2F represented the cohort with the lowest percentage (8%) of responders. Using mRNA signatures of sensitivity to other cytotoxic agents, we predict that TFAC non-responders are more likely to be sensitive to docetaxel (P = 0.04), representing a viable alternative therapy. CONCLUSIONS: Our results suggest that the optimal strategy for chemotherapy sensitivity prediction integrates molecular variables such as ER and HER2 status with corresponding microRNA and mRNA expression profiles. Importantly, we also present evidence to support the concept that analysis of molecular variables can present a rational strategy to identifying alternative therapeutic opportunities.