Computational Method for Phase Space Transport with Applications to Lobe Dynamics and Rate of Escape

Lobe dynamics and escape from a potential well are general frameworks introduced to study phase space transport in chaotic dynamical systems. While the former approach studies how regions of phase space are transported by reducing the flow to a two-dimensional map, the latter approach studies the phase space structures that lead to critical events by crossing periodic orbit around saddles. Both of these frameworks require computation with curves represented by millions of points-computing intersection points between these curves and area bounded by the segments of these curves-for quantifying the transport and escape rate. We present a theory for computing these intersection points and the area bounded between the segments of these curves based on a classification of the intersection points using equivalence class. We also present an alternate theory for curves with nontransverse intersections and a method to increase the density of points on the curves for locating the intersection points accurately.The numerical implementation of the theory presented herein is available as an open source software called Lober. We used this package to demonstrate the application of the theory to lobe dynamics that arises in fluid mechanics, and rate of escape from a potential well that arises in ship dynamics.Comment: 33 pages, 17 figure

The tumor suppressor TERE1 (UBIAD1) prenyltransferase regulates the elevated cholesterol phenotype in castration resistant prostate cancer by controlling a program of ligand dependent SXR target genes.

Castrate-Resistant Prostate Cancer (CRPC) is characterized by persistent androgen receptor-driven tumor growth in the apparent absence of systemic androgens. Current evidence suggests that CRPC cells can produce their own androgens from endogenous sterol precursors that act in an intracrine manner to stimulate tumor growth. The mechanisms by which CRPC cells become steroidogenic during tumor progression are not well defined. Herein we describe a novel link between the elevated cholesterol phenotype of CRPC and the TERE1 tumor suppressor protein, a prenyltransferase that synthesizes vitamin K-2, which is a potent endogenous ligand for the SXR nuclear hormone receptor. We show that 50% of primary and metastatic prostate cancer specimens exhibit a loss of TERE1 expression and we establish a correlation between TERE1 expression and cholesterol in the LnCaP-C81 steroidogenic cell model of the CRPC. LnCaP-C81 cells also lack TERE1 protein, and show elevated cholesterol synthetic rates, higher steady state levels of cholesterol, and increased expression of enzymes in the de novo cholesterol biosynthetic pathways than the non-steroidogenic prostate cancer cells. C81 cells also show decreased expression of the SXR nuclear hormone receptor and a panel of directly regulated SXR target genes that govern cholesterol efflux and steroid catabolism. Thus, a combination of increased synthesis, along with decreased efflux and catabolism likely underlies the CRPC phenotype: SXR might coordinately regulate this phenotype. Moreover, TERE1 controls synthesis of vitamin K-2, which is a potent endogenous ligand for SXR activation, strongly suggesting a link between TERE1 levels, K-2 synthesis and SXR target gene regulation. We demonstrate that following ectopic TERE1 expression or induction of endogenous TERE1, the elevated cholesterol levels in C81 cells are reduced. Moreover, reconstitution of TERE1 expression in C81 cells reactivates SXR and switches on a suite of SXR target genes that coordinately promote both cholesterol efflux and androgen catabolism. Thus, loss of TERE1 during tumor progression reduces K-2 levels resulting in reduced transcription of SXR target genes. We propose that TERE1 controls the CPRC phenotype by regulating the endogenous levels of Vitamin K-2 and hence the transcriptional control of a suite of steroidogenic genes via the SXR receptor. These data implicate the TERE1 protein as a previously unrecognized link affecting cholesterol and androgen accumulation that could govern acquisition of the CRPC phenotype

Diffusion tensor imaging metrics associated with future disability in multiple sclerosis

The relationship between brain diffusion microstructural changes and disability in multiple sclerosis (MS) remains poorly understood. We aimed to explore the predictive value of microstructural properties in white (WM) and grey matter (GM), and identify areas associated with mid-term disability in MS patients. We studied 185 patients (71% female; 86% RRMS) with the Expanded Disability Status Scale (EDSS), timed 25-foot walk (T25FW), nine-hole peg test (9HPT), and Symbol Digit Modalities Test (SDMT) at two time-points. We used Lasso regression to analyse the predictive value of baseline WM fractional anisotropy and GM mean diffusivity, and to identify areas related to each outcome at 4.1 years follow-up. Motor performance was associated with WM (T25FW: RMSE = 0.524, R2 = 0.304; 9HPT dominant hand: RMSE = 0.662, R2 = 0.062; 9HPT non-dominant hand: RMSE = 0.649, R2 = 0.139), and SDMT with GM diffusion metrics (RMSE = 0.772, R2 = 0.186). Cingulum, longitudinal fasciculus, optic radiation, forceps minor and frontal aslant were the WM tracts most closely linked to motor dysfunction, and temporal and frontal cortex were relevant for cognition. Regional specificity related to clinical outcomes provide valuable information that can be used to develop more accurate predictive models that could improve therapeutic strategies

Living with AIDS in Uganda: a qualitative study of patients' and families' experiences following referral to hospice

Background: Globally, the majority of people with HIV/AIDS live in sub-Saharan Africa. While the increasing availability of antiretroviral therapy is improving the outlook for many, its effects are yet to reach all of those in need and patients still present with advanced disease. This paper reports findings from qualitative interviews with patients living with AIDS and their caregivers who were receiving palliative care from Hospice Africa Uganda (HAU). We aimed to understand what motivated patients and their families to seek formal healthcare, whether there were any barriers to help- seeking and how the help and support provided to them by HAU was perceived. Methods: We invited patients with AIDS and their relatives who were newly referred to HAU to participate in qualitative interviews. Patients and carers were interviewed in their homes approximately four weeks after the patient’s enrolment at HAU. Interviews were translated, transcribed and analysed using narrative and thematic approaches. Results: Interviews were completed with 22 patients (10 women and 12 men) and 20 family caregivers, nominated by patients. Interviews revealed the extent of suffering patients endured and the strain that family caregivers experienced before help was sought or accessed. Patients reported a wide range of severe physical symptoms. Patients and their relatives reported worries about the disclosure of the AIDS diagnosis and fear of stigma. Profound poverty framed all accounts. Poverty and stigma were, depending on the patient and family situation, both motivators and barriers to help seeking behaviour. Hospice services were perceived to provide essential relief of pain and symptoms, as well as providing rehabilitative support and a sense of caring. The hospice was perceived relieve utter destitution, although it was unable to meet all the expectations that patients had. Conclusion: Hospice care was highly valued and perceived to effectively manage problems such as pain and other symptoms and to provide rehabilitation. Participants noted a strong sense of being “cared for”. However, poverty and a sense of stigma were widespread. Further research is needed to understand how poverty and stigma can be effectively managed in hospice care for patients for advanced AIDS and their families

Time-Frequency based Feature Selection for Discrimination of non stationary Biosignals.

This research proposes a generic methodology for dimensionality reduction upon time-frequency representations applied to the classification of different types of biosignals. The methodology directly deals with the highly redundant and irrelevant data contained in these representations, combining a first stage of irrelevant data removal by variable selection, with a second stage of redundancy reduction using methods based on linear transformations. The study addresses two techniques that provided a similar performance: the first one is based on the selection of a set of the most relevant time?frequency points, whereas the second one selects the most relevant frequency bands. The first methodology needs a lower quantity of components, leading to a lower feature space; but the second improves the capture of the time-varying dynamics of the signal, and therefore provides a more stable performance. In order to evaluate the generalization capabilities of the methodology proposed it has been applied to two types of biosignals with different kinds of non-stationary behaviors: electroencephalographic and phonocardiographic biosignals. Even when these two databases contain samples with different degrees of complexity and a wide variety of characterizing patterns, the results demonstrate a good accuracy for the detection of pathologies, over 98%.The results open the possibility to extrapolate the methodology to the study of other biosignals

Semiclassical analysis of the quantum interference corrections to the conductance of mesoscopic systems

The Kubo formula for the conductance of a mesoscopic system is analyzed semiclassically, yielding simple expressions for both weak localization and universal conductance fluctuations. In contrast to earlier work which dealt with times shorter than $O(\log \hbar^{-1})$, here longer times are taken to give the dominant contributions. For such long times, many distinct classical orbits may obey essentially the same initial and final conditions on positions and momenta, and the interference between pairs of such orbits is analyzed. Application to a chain of $k$ classically ergodic scatterers connected in series gives the following results: $-{1 \over 3} [ 1 - (k+1)^{-2} ]$ for the weak localization correction to the zero--temperature dimensionless conductance, and ${2 \over 15} [ 1 - (k+1)^{-4} ]$ for the variance of its fluctuations. These results interpolate between the well known ones of random scattering matrices for $k=1$, and those of the one--dimensional diffusive wire for $k \rightarrow \infty$.Comment: 53 pages, using RevTeX, plus 3 postscript figures mailed separately. A short version of this work is available as cond-mat/950207