Design and application of a multi-modal process tomography system

This paper presents a design and application study of an integrated multi-modal system designed to support a range of common modalities: electrical resistance, electrical capacitance and ultrasonic tomography. Such a system is designed for use with complex processes that exhibit behaviour changes over time and space, and thus demand equally diverse sensing modalities. A multi-modal process tomography system able to exploit multiple sensor modes must permit the integration of their data, probably centred upon a composite process model. The paper presents an overview of this approach followed by an overview of the systems engineering and integrated design constraints. These include a range of hardware oriented challenges: the complexity and specificity of the front end electronics for each modality; the need for front end data pre-processing and packing; the need to integrate the data to facilitate data fusion; and finally the features to enable successful fusion and interpretation. A range of software aspects are also reviewed: the need to support differing front-end sensors for each modality in a generic fashion; the need to communicate with front end data pre-processing and packing systems; the need to integrate the data to allow data fusion; and finally to enable successful interpretation. The review of the system concepts is illustrated with an application to the study of a complex multi-component process

Gaze stabilization in the rabbit : three-dimensional organization and cholinergic floccular control

Whereas a large body of knowledge is available on the rabbit's optokinetic responses about a vertical axis, only fragmentary data have been obtained about horizontal-axis optokinetic responses. With emerging knowledge on the spatial organization of the three dimensional visual messages in the flocculus there is a need for a detailed description of three-dimensional optokinetic responses. We conducted a behavioral study of three-dimensional eye movements, elicited by optokinetic stimulation about horizontal axes, which will be presented in Chapter 2 of this thesis. Chapter 3 descnbes the positive modulatory effects of floccular injection of the cholinergic agonist carbachol and the AChE inhibitor eserine on the OKR and the VOR. A possible mechanism for the positive action of carbachol is proposed in Chapter 4, in the context of a synergistic action between injections of carbachol and the ,8-noradrenergic agonist isoproterenol. Specification of the receptor type involved in the action of carbachol is attempted in Chapter 5. The effects of bilateral and unilateral injections of carbachol on optokinetic nystagmus and afternystagmus are presented in Chapters 6 and 7, whereas Chapter 8 descnbes the effect of bilateral injection of carbachol on vestibular, post-rotatory nystagmus

PPARs and Tumor Microenvironment: The Emerging Roles of the Metabolic Master Regulators in Tumor Stromal-Epithelial Crosstalk and Carcinogenesis.

Peroxisome proliferator-activated receptors (PPARs) have been extensively studied for more than three decades. Consisting of three isotypes, PPARα, γ, and β/δ, these nuclear receptors are regarded as the master metabolic regulators which govern many aspects of the body energy homeostasis and cell fate. Their roles in malignancy are also increasingly recognized. With the growing interest in crosstalk between tumor stroma and epithelium, this review aims to highlight the current knowledge on the implications of PPARs in the tumor microenvironment. PPARγ plays a crucial role in the metabolic reprogramming of cancer-associated fibroblasts and adipocytes, coercing the two stromal cells to become substrate donors for cancer growth. Fibroblast PPARβ/δ can modify the risk of tumor initiation and cancer susceptibility. In endothelial cells, PPARβ/δ and PPARα are pro- and anti-angiogenic, respectively. Although the angiogenic role of PPARγ remains ambiguous, it is a crucial regulator in autocrine and paracrine signaling of cancer-associated fibroblasts and tumor-associated macrophages/immune cells. Of note, angiopoietin-like 4 (ANGPTL4), a secretory protein encoded by a target gene of PPARs, triggers critical oncogenic processes such as inflammatory signaling, extracellular matrix derangement, anoikis resistance and metastasis, making it a potential drug target for cancer treatment. To conclude, PPARs in the tumor microenvironment exhibit oncogenic activities which are highly controversial and dependent on many factors such as stromal cell types, cancer types, and oncogenesis stages. Thus, the success of PPAR-based anticancer treatment potentially relies on innovative strategies to modulate PPAR activity in a cell type-specific manner

Integrating access to care and tumor patterns by race and age in the Carolina Breast Cancer Study, 2008–2013

Purpose: Understanding breast cancer mortality disparities by race and age is complex due to disease heterogeneity, comorbid disease, and the range of factors influencing access to care. It is important to understand how these factors group together within patients. Methods: We compared socioeconomic status (SES) and comorbidity factors in the Carolina Breast Cancer Study Phase 3 (CBCS3, 2008–2013) to those for North Carolina using the 2010 Behavioral Risk Factor Surveillance Study. In addition, we used latent class analysis of CBCS3 data to identify covariate patterns by SES/comorbidities, barriers to care, and tumor characteristics and examined their associations with race and age using multinomial logistic regression. Results: Major SES and comorbidity patterns in CBCS3 participants were generally similar to patterns in the state. Latent classes were identified for SES/comorbidities, barriers to care, and tumor characteristics that varied by race and age. Compared to white women, black women had lower SES (odds ratio (OR) 6.3, 95% confidence interval (CI) 5.2, 7.8), more barriers to care (OR 5.6, 95% CI 3.9, 8.1) and several aggregated tumor aggressiveness features. Compared to older women, younger women had higher SES (OR 0.5, 95% CI 0.4, 0.6), more barriers to care (OR 2.1, 95% CI 1.6, 2.9) and aggregated tumor aggressiveness features. Conclusions: CBCS3 is representative of North Carolina on comparable factors. Patterns of access to care and tumor characteristics are intertwined with race and age, suggesting that interventions to address disparities will need to target both access and biology

Exploiting vulnerabilities of cancer by targeting nuclear receptors of stromal cells in tumor microenvironment.

The tumor microenvironment is a complex and dynamic cellular community comprising the tumor epithelium and various tumor-supporting cells such as immune cells, fibroblasts, immunosuppressive cells, adipose cells, endothelial cells, and pericytes. The interplay between the tumor microenvironment and tumor cells represents a key contributor to immune evasiveness, physiological hardiness and the local and systemic invasiveness of malignant cells. Nuclear receptors are master regulators of physiological processes and are known to play pro-/anti-oncogenic activities in tumor cells. However, the actions of nuclear receptors in tumor-supporting cells have not been widely studied. Given the excellent druggability and extensive regulatory effects of nuclear receptors, understanding their biological functionality in the tumor microenvironment is of utmost importance. Therefore, the present review aims to summarize recent evidence about the roles of nuclear receptors in tumor-supporting cells and their implications for malignant processes such as tumor proliferation, evasion of immune surveillance, angiogenesis, chemotherapeutic resistance, and metastasis. Based on findings derived mostly from cell culture studies and a few in vivo animal cancer models, the functions of VDR, PPARs, AR, ER and GR in tumor-supporting cells are relatively well-characterized. Evidence for other receptors, such as RARβ, RORγ, and FXR, is limited yet promising. Hence, the nuclear receptor signature in the tumor microenvironment may harbor prognostic value. The clinical prospects of a tumor microenvironment-oriented cancer therapy exploiting the nuclear receptors in different tumor-supporting cells are also encouraging. The major challenge, however, lies in the ability to develop a highly specific drug delivery system to facilitate precision medicine in cancer therapy

Black diholes in five dimensions

Using a generalized Weyl formalism, we show how stationary, axisymmetric solutions of the four-dimensional vacuum Einstein equation can be turned into static, axisymmetric solutions of five-dimensional dilaton gravity coupled to a two-form gauge field. This procedure is then used to obtain new solutions of the latter theory describing pairs of extremal magnetic black holes with opposite charges, known as black diholes. These diholes are kept in static equilibrium by membrane-like conical singularities stretching along two different directions. We also present solutions describing diholes suspended in a background magnetic field, and with unbalanced charges.Comment: 21 pages, 2 figures; reference adde

Rotating Circular Strings, and Infinite Non-Uniqueness of Black Rings

We present new self-gravitating solutions in five dimensions that describe circular strings, i.e., rings, electrically coupled to a two-form potential (as e.g., fundamental strings do), or to a dual magnetic one-form. The rings are prevented from collapsing by rotation, and they create a field analogous to a dipole, with no net charge measured at infinity. They can have a regular horizon, and we show that this implies the existence of an infinite number of black rings, labeled by a continuous parameter, with the same mass and angular momentum as neutral black rings and black holes. We also discuss the solution for a rotating loop of fundamental string. We show how more general rings arise from intersections of branes with a regular horizon (even at extremality), closely related to the configurations that yield the four-dimensional black hole with four charges. We reproduce the Bekenstein-Hawking entropy of a large extremal ring through a microscopic calculation. Finally, we discuss some qualitative ideas for a microscopic understanding of neutral and dipole black rings.Comment: 31 pages, 7 figures. v2: minor changes, added reference. v3: erroneous values of T_{ww} (eq.(3.39)) and n_p (eq.(5.20)) corrected, and accompanying discussion amended. In the journal version these corrections appear as an appended erratum. No major changes involve

First order Born-Infeld Hydrodynamics via Gauge/Gravity Duality

By performing a derivative expansion on a class of boosted Born-Infeld-AdS_5 black branes, we study the hydrodynamics of the dual field theory - in the spirit of AdS/CFT correspondence. We determine the fluid dynamical stress-energy tensor to first order, and find that the ratio of the shear viscosity to entropy density conforms to the universal value of $1/4\pi$ to all orders of the inverse of the Born-Infeld parameter.Comment: 14 pages, JHEP3, minor revision

Review of time in therapeutic range of warfarin in a tertiary centre in Malaysia

Anticoagulation management is a recognized challenge in medical care. Complications of supratherapeutic anticoagulation are hemorrhagic stroke, major bleeding, and death. There is an even greater risk of ischemic stroke in AF, worsening of VTE associated with subtherapeutic dosing