305 research outputs found
Random billiards with wall temperature and associated Markov chains
By a random billiard we mean a billiard system in which the standard specular
reflection rule is replaced with a Markov transition probabilities operator P
that, at each collision of the billiard particle with the boundary of the
billiard domain, gives the probability distribution of the post-collision
velocity for a given pre-collision velocity. A random billiard with
microstructure (RBM) is a random billiard for which P is derived from a choice
of geometric/mechanical structure on the boundary of the billiard domain. RBMs
provide simple and explicit mechanical models of particle-surface interaction
that can incorporate thermal effects and permit a detailed study of
thermostatic action from the perspective of the standard theory of Markov
chains on general state spaces.
We focus on the operator P itself and how it relates to the
mechanical/geometric features of the microstructure, such as mass ratios,
curvatures, and potentials. The main results are as follows: (1) we
characterize the stationary probabilities (equilibrium states) of P and show
how standard equilibrium distributions studied in classical statistical
mechanics, such as the Maxwell-Boltzmann distribution and the Knudsen cosine
law, arise naturally as generalized invariant billiard measures; (2) we obtain
some basic functional theoretic properties of P. Under very general conditions,
we show that P is a self-adjoint operator of norm 1 on an appropriate Hilbert
space. In a simple but illustrative example, we show that P is a compact
(Hilbert-Schmidt) operator. This leads to the issue of relating the spectrum of
eigenvalues of P to the features of the microstructure;(3) we explore the
latter issue both analytically and numerically in a few representative
examples;(4) we present a general algorithm for simulating these Markov chains
based on a geometric description of the invariant volumes of classical
statistical mechanics
Role of endothelial kinin B(1) receptor on the membrane potential of transgenic rat aorta
The kinin receptors are classically involved in inflammation, pain and sepsis. The effects of the kinin B(1) receptor agonist des-Arg(9)-bradykinin (DBK) and lipopolysaccharide (LPS) were investigated by comparing the membrane potential responses of aortic rings from transgenic rats overexpressing the kinin B1 receptor (B1R) in the endothelium (TGR(Tie2B1)) and Sprague Dawley (SD) rats. No difference in the resting membrane potential in the aorta's smooth muscle from the transgenic and SD rats was observed. The aorta rings from SD rats hyperpolarized only to LPS but not to DBK, whereas the aorta rings from TGR(Tie2B(1)) responded by the administration of both drugs. DBK and LPS responses were inhibited by the B(1) receptor antagonist R715 and by iberiotoxin in both cases. Thapsigargin induced a hyperpolarization in the smooth muscle of SD rats that was not reversed by R715, but was reversed by iberiotoxin and this hyperpolarization was further augmented by DBK administration. These results show that the model of overexpression of vascular B(1) receptors in the TGR(Tie2B(1)) rats represent a good model to study the role of functional B(1) receptors in the absence of any pathological stimulus. The data also show that K(Ca) channels are the final mediators of the hyperpolarizing responses to DBK and LPS. In addition, we suggest an interaction between the B1R and TLR4, since the hyperpolarization induced by LPS could be abolished in the presence of R715
Effects of bromopride on the healing of left colon anastomoses of rats
Objetivo: Avaliar os efeitos da bromoprida sobre a formação de aderências e a cicatrização de anastomoses de cólon esquerdo de
ratos. Métodos: Foram incluídos 40 ratos, divididos em dois grupos contendo 20 animais, para administração de bromoprida (grupo
de estudo- E) ou solução fisiológica (grupo controle- C). Cada grupo foi dividido em subgrupos contendo 10 animais cada, para
eutanásia no terceiro (E3 e C3) ou no sétimo dia (E7 e C7) de pós-operatório. Os ratos foram submetidos à secção do cólon esquerdo
e anastomose término-terminal. No dia da relaparotomia, foi avaliada a quantidade total de aderências e removido um segmento
colônico contendo a anastomose para análise histopatológica, da força de ruptura e da concentração de hidroxiprolina. Resultados:
Não houve diferença entre os grupos em relação à evolução clínica. Dois animais do grupo de estudo apresentaram deiscência
de anastomose bloqueada. Os animais que receberam bromoprida apresentaram número de aderências intracavitárias e aderências
à anastomose semelhantes ao grupo controle. As anastomoses dos animais do grupo E3 apresentaram menor resistência de ruptura
do que as do grupo C3 (p=0,04). Este efeito não ocorreu no sétimo dia de pós-operatório (p=0,37). Não houve diferença significativa
entre os grupos em relação à histopatologia ou concentração de hidroxiprolina das anastomoses. Conclusão: O uso da bromoprida
está associado à diminuição da resistência tênsil de anastomoses do cólon esquerdo de ratos no terceiro dia de pós-operatório.Objective: To evaluate the effects of bromopride on the formation of adhesions and anastomotic healing in the left colon of rats.
Methods: We divided 40 rats into two groups of 20 animals, administration of bromopride (study group-E) or saline (control group-
C). Each group was divided into subgroups containing 10 animals each for euthanasia in the third (C3 and E3) or the seventh (E7 and
C7) postoperative days. The rats were submitted to section of the left colon and end-to-end anastomosis. On the day of reoperation,
we evaluated the total amount of adhesions and removed a colonic segment containing the anastomosis for histopathological
analysis, assessment of rupture strength and hydroxyproline concentration. Results: There was no difference between groups in
relation to clinical outcome. Two animals in the study group had blocked anastomotic leakage. The animals that received bromopride
had the number of intracavitary adhesions and adhesions to the anastomosis similar to the control group. The anastomoses from the
group E3 animals showed lower resistance to rupture the one from the C3 group (p = 0.04). This effect did not occur on the seventh
postoperative day (p = 0.37). There was no significant difference between groups in relation to histopathology and hydroxyproline
concentration in the anastomoses. Conclusion: The use of bromopride was associated with decreased tensile strength of left colon
anastomosis in rats in the third postoperative day
Estudo da formação de aderências e da cicatrização de anastomoses colônicas em ratos com sepse peritoneal induzida
OBJETIVO: Avaliar os efeitos da sepse abdominal sobre a formação de aderências e a cicatrização de anastomoses colônicas em ratos. MÉTODOS: 40 ratos distribuídos em dois grupos contendo 20 animais, para anastomose do cólon esquerdo na presença (grupo S) ou
ausência (grupo N) de indução de sepse por ligadura e punção do ceco (CLP). Cada grupo foi dividido em subgrupos para eutanásia no
terceiro (N3 e S3) ou sétimo (N7 e S7) dia de pós-operatório (DPO). Foi avaliada a quantidade de aderências e removido um segmento
colônico contendo a anastomose para análise histopatológica, força de ruptura, hidroxiprolina e conteúdo de colágeno tecidual. RESULTADOS: Os animais submetidos à CLP apresentaram maior quantidade de aderências intra-abdominais tanto no 3° DPO
(p=0,00) quanto no 7° DPO (p=0,00). Tiveram menores valores de força de ruptura no 3° DPO (p=0,00), porém maiores valores no 7°
DPO (p=0,00). Não houve diferença na variação da concentração de hidroxiprolina, conteúdo de colágeno e histopatologia. CONCLUSÕES: A infecção peritoneal desencadeada por CLP aumentou a quantidade de aderências intra-cavitárias. Houve diminuição da resistência de anastomoses cólicas no 3° DPO, com posterior aumento no 7° DPO, sem efeito sobre os outros parâmetros da cicatrização. ________________________________________________________________________________ ABSTRACTPURPOSE: To evaluate the effects of abdominal sepsis on adhesion formation and colon anastomosis healing in rats.
METHODS: Forty rats were distributed in two groups containing 20 rats each for left colon anastomosis in the presence (Group S) or
absence (Group N) of induced sepsis by cecal ligation and puncture. Each group was divided into subgroups for euthanasia on the third
(N3 and S3) or seventh (N7 or S7) post-operative day. The amount of adhesions was evaluated and a segment of the colon was removed
for histopathologic analysis, bursting strength assessment, hydroxyproline and the determination of tissue collagen.
RESULTS: The subjects which underwent cecal ligation and puncture presented a higher amount of intra-abdominal adherences in
both third (p=0,00) and seventh (p=0,00) post-operatory days. Smaller bursting strengths were found in the S3 subgroup, and greater
bursting strengths were found in the S7 subgroup. There was no difference in the variations on the concentrations of hydroxyproline,
tissue collagen and histopathology.
CONCLUSIONS: The peritoneal infection which was developed by cecal ligation and puncture raised the amount of intra-cavitary
adhesions. There was a decrease in the amount of colonic anastomosis on the third post-operatory day with a following raise on the
seventh without any effects on other healing parameters
Liberalismo igualitário e ação afirmativa: da teoria moral à política pública
O presente artigo examina a hipótese de que a teoria política e moral do liberalismo igualitário serve de justificação para políticas de ação afirmativa de recorte étnico-racial, hipótese essa que tem sido assumida como verdadeira por acadêmicos e importantes operadores do direito em nosso país. Buscamos estabelecer como autores fundamentais do liberalismo igualitário, como John Rawls, Ronald Dworkin, Thomas Nagel e Robert Taylor, trataram a questão das políticas de discriminação positiva. O método usado é a interpretação textual, tomando cuidado de trabalhar o mais próximo possível da linguagem e dos conceitos nos próprios textos dos autores e cobrindo a evolução do tema na obra de cada um, particularmente na de Rawls. Pretendemos mostrar que há uma gradação de opiniões em relação à questão, que vai da defesa à rejeição de tais políticas, passando por posições intermediárias que justificam algumas modalidades de ação afirmativa, mas não outras. Portanto, não há uma relação unívoca entre a teoria política e moral do liberalismo igualitário e a justificação de políticas de ação afirmativa de recorte étnico-racial, a despeito do senso comum e do fato de teóricos do liberalismo igualitário e defensores da ação afirmativa partilharem o mesmo lugar no espectro político das democracias liberais
The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase
Tumour metastasis is a complex process involving reciprocal interplay
between cancer cells and host stroma at both primary and secondary
sites, and is strongly influenced by microenvironmental
factors such as hypoxia. Tumour-secreted proteins play a crucial role
in these interactions and present strategic therapeutic potential.
Metastasis of breast cancer to the bone affects approximately 85%
of patients with advanced disease and renders them largely untreatable. Specifically, osteolytic bone lesions, where bone is destroyed,
lead to debilitating skeletal complications and increased patient morbidity
and mortality. The molecular interactions governing the
early events of osteolytic lesion formation are currently unclear.
Here we show hypoxia to be specifically associated with bone relapse
in patients with oestrogen-receptor negative breast cancer. Global
quantitative analysis of the hypoxic secretome identified lysyl oxidase
(LOX) as significantly associated with bone-tropism and relapse.
High expression of LOX in primary breast tumours or systemic delivery
of LOX leads to osteolytic lesion formation whereas silencing or
inhibition of LOX activity abrogates tumour-driven osteolytic lesion
formation. We identify LOX as a novel regulator of NFATc1-driven
osteoclastogenesis,independent of RANK ligand, which disrupts normal
bone homeostasisleading to the formation of focal pre-metastatic
lesions. We show that these lesions subsequently provide a platform
for circulating tumour cells to colonize and form bone metastases.
Our study identifies a novel mechanism of regulation of bone homeostasis
and metastasis, opening up opportunities for novel therapeutic
intervention with important clinical implications
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