Biomedical subjects

A Rangarajan

Publications and source records attributed to A Rangarajan.

10 recordsLinked to original sources

PubMed2001

Activated Notch1 signaling cooperates with papillomavirus oncogenes in transformation and generates resistance to apoptosis on matrix withdrawal through PKB/Akt.

Invasive cervical tumors, a major subset of human epithelial neoplasms, are characterized by the consistent presence of papillomavirus oncogenes 16 or 18 E6 and E7 products. Cervical tumors also consistently exhibit cytosolic and nuclear forms of Notch1, suggesting the possible persistent activation of the Notch pathway. Here we show that activated Notch1 synergizes with papillomavirus oncogenes in transformation of immortalized epithelial cells and leads to the generation of resistance to anoikis, an apoptotic response induced on matrix withdrawal. This resistance to anoikis by activated Notch1 is mediated through the activation of PKB/Akt, a key effector of activated Ras in transformation. We suggest that activated Notch signaling may serve to substitute for the lack of activated Ras mutations in the majority of human cervical neoplasms.

Apoptosis↗

PubMed2001

Notch signaling is a direct determinant of keratinocyte growth arrest and entry into differentiation.

The role of Notch signaling in growth/differentiation control of mammalian epithelial cells is still poorly defined. We show that keratinocyte-specific deletion of the Notch1 gene results in marked epidermal hyperplasia and deregulated expression of multiple differentiation markers. In differentiating primary keratinocytes in vitro endogenous Notch1 is required for induction of p21WAF1/Cip1 expression, and activated Notch1 causes growth suppression by inducing p21WAF1/Cip1 expression. Activated Notch1 also induces expression of 'early' differentiation markers, while suppressing the late markers. Induction of p21WAF1/Cip1 expression and early differentiation markers occur through two different mechanisms. The RBP-Jkappa protein binds directly to the endogenous p21 promoter and p21 expression is induced specifically by activated Notch1 through RBP-Jkappa-dependent transcription. Expression of early differentiation markers is RBP-Jkappa-independent and can be induced by both activated Notch1 and Notch2, as well as the highly conserved ankyrin repeat domain of the Notch1 cytoplasmic region. Thus, Notch signaling triggers two distinct pathways leading to keratinocyte growth arrest and differentiation.

Animals↗

PubMed1999

Convergence properties of the softassign quadratic assignment algorithm.

The softassign quadratic assignment algorithm is a discrete-time, continuous-state, synchronous updating optimizing neural network. While its effectiveness has been shown in the traveling salesman problem, graph matching, and graph partitioning in thousands of simulations, its convergence properties have not been studied. Here, we construct discrete-time Lyapunov functions for the cases of exact and approximate doubly stochastic constraint satisfaction, which show convergence to a fixed point. The combination of good convergence properties and experimental success makes the softassign algorithm an excellent choice for neural quadratic assignment optimization.

Algorithms↗

PubMed1999

A minimax entropy registration framework for patient setup verification in radiotherapy.

In external beam radiotherapy (EBRT), patient setup verification over the entire course of fractionated treatment is necessary for accurate delivery of a specified dose to the tumor. We are working on the development of a minimax entropy registration framework for patient setup verification using dual portal images and the treatment planning 3D CT dataset. In this paper, we present an overview of our registration framework, where an iteratively and automatically estimated segmentation of the portal image is utilized to more accurately and robustly register the portal image to the 3D treatment-planning CT data. In addition, we describe initial testing of this approach. We note that, due to low resolution and low contrast of the portal images, this registration presents a difficult problem. We also note that the registration of the images in our proposed method is guided by the bony structure visible in the portal and the 3D CT images. However, since the prostate can move with respect to the pelvic bone, we propose using ultrasound images to quantify this movement.

Algorithms↗

PubMed1999

Rigid point feature registration using mutual information.

We have developed a new mutual information-based registration method for matching unlabeled point features. In contrast to earlier mutual information-based registration methods, which estimate the mutual information using image intensity information, our approach uses the point feature location information. A novel aspect of our approach is the emergence of correspondence (between the two sets of features) as a natural by-product of joint density estimation. We have applied this algorithm to the problem of geometric alignment of primate autoradiographs. We also present preliminary results on three-dimensional robust matching of sulci derived from anatomical magnetic resonance images. Finally, we present an experimental comparison between the mutual information approach and other recent approaches which explicitly parameterize feature correspondence.

Algorithms↗

PubMed1998

Young unwed fathers of AFDC children: do they provide support?

We examine the support provided by fathers of children born to disadvantaged teenage mothers. Our sample includes the fathers of 6,009 children born over a two-year period to 3,855 teenage mothers receiving AFDC in three economically depressed inner cities. These fathers provide little social and economic support to their children. Support declines as their children age from infants to toddlers and as fathers' relationships with the mothers grow more distant. Fathers' employment status and educational attainment positively affect the amount of economic support that they provide but do not strongly influence the amount of social support they provide.

Adolescent↗

PubMed1997

The human transcription enhancer factor-1, TEF-1, can substitute for Drosophila scalloped during wingblade development.

The human transcription enhancer factor-1 (TEF-1) belongs to a family of evolutionarily conserved proteins that have a DNA binding TEA domain. TEF-1 shares a 98% homology with Drosophila scalloped (sd) in the DNA binding domain and a 50% similarity in the activation domain. We have expressed human TEF-1 in Drosophila under the hsp-70 promoter and find that it can substitute for Sd function. The transformants rescue the wingblade defects as well as the lethality of loss-of-function alleles. Observation of reporter activity in the imaginal wing discs of the enhancer-trap alleles suggests that TEF-1 is capable of promoting sd gene regulation. The functional capability of the TEF-1 product was assessed by comparing the extent of rescue by heat shock (hs)-TEF-1 with that of hs-sd. The finding that TEF-1 can function in vivo during wingblade development offers a potent genetic system for the analysis of its function and in the identification of the molecular partners of TEF-1.

Amino Acid Sequence↗

PubMed1997

A robust point-matching algorithm for autoradiograph alignment.

We present a novel method for the geometric alignment of autoradiographs of the brain. The method is based on finding the spatial mapping and the one-to-one correspondences (or homologies) between point features extracted from the images and rejecting non-homologies as outliers. In this way, we attempt to account for the local, natural and artifactual differences between the autoradiograph slices. We have used the resulting automated algorithm on a set of left prefrontal cortex autoradiograph slices, specifically demonstrated its ability to perform point outlier rejection, validated its robustness property using synthetically generated spatial mappings and provided an anecdotal visual comparison with the well-known iterated closest-point (ICP) algorithm. Visualization of a stack of aligned left prefrontal cortex autoradiograph slices is also provided.

Algorithms↗

PubMed1997

Oxidative glucose metabolism in rat brain during single forepaw stimulation: a spatially localized 1H[13C] nuclear magnetic resonance study.

In the alpha-chloralose-anesthetized rat during single forepaw stimulation, a spatially localized 1H[13C] nuclear magnetic resonance spectroscopic method was used to measure the rate of cerebral [C4]-glutamate isotopic turnover from infused [1,6-(13)C]glucose. The glutamate turnover data were analyzed using a mathematical model of cerebral glucose metabolism to evaluate the tricarboxylic acid (TCA) cycle flux (V(TCA)). During stimulation the value of V(TCA) in the sensorimotor region increased from 0.47 +/- 0.06 (at rest) to 1.44 +/- 0.41 micromol x g(-1) x min(-1) (P < 0.01) in the contralateral hemispheric compartment (24 mm3) and to 0.65 +/- 0.10 micromol x g(-1) x min(-1) (P < 0.03) in the ipsilateral side. Each V(TCA) value was converted to the cerebral metabolic rates of glucose oxidation (oxidative-CMR(glc)) and oxygen consumption (CMR(O2)). These rates were corrected for partial-volume based on activation maps obtained by blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI). The percent increase and the absolute value of oxidative-CMR(glc) in the activated regions are similar to values reported previously for total-CMR(glc) using the same activation paradigm. This indicates that the large majority of energy required for brain activation, in going from the resting to an activated state, is supplied by glucose oxidation. The level of activity during stimulation is relevant to awake animals because the oxidative-CMR(glc) (1.05 +/- 0.28 micromol x g(-1) x min(-1); current study) is in the range of total-CMR(glc) previously reported for awake rats undergoing physiologic activation (0.7-1.4 micromol x g(-1) x min(-1)). It is concluded that oxidative glycolysis is the main source of energy for increased brain activity and a positive BOLD fMRI signal-change occurs in conjunction with a large increase in CMR(O2).

Animals↗

PubMed1997

The link between integration and expression of human papillomavirus type 16 genomes and cellular changes in the evolution of cervical intraepithelial neoplastic lesions.

We have matched a PCR assay which detects disruptions in the E2 reading frame of human papillomavirus type 16, with RNA in situ hybridization patterns and shown that in 15 out of 16 cervical intraepithelial neoplastic (CIN) III lesions and in 19 out of 19 tumours, the E2 gene is disrupted with no detectable E2 transcripts. Varying levels of E6-E7 transcripts are detected in CIN III lesions, with stronger signals in tumours. The cytokeratin profile of most tumours: cytokeratin 10-, 14- and 19-positive and 4-, 13- and 18-negative, is also detected in CIN III lesions. The changes in levels of alpha 2, beta 1 and beta 4 integrins, CD44 and E-cadherin occur during the evolution of high-grade CIN lesions. Increases in the levels of expression of CD44 and E6-E7 transcripts, coupled with changes in the cellular localization of the Notch protein, define the transition from CIN III lesions to tumours.

Cadherins↗