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Biomedical subjects

R Srinivasan

Publications and source records attributed to R Srinivasan.

At least 109 records · Page 6Linked to original sources

Effect of selected in-vehicle route guidance systems on driver reaction times.

Experiments were conducted in a fixed-base, high-fidelity simulator to evaluate selected in-vehicle route guidance systems. Drivers navigated a simulated network using five route guidance systems: paper map, head-down turn-by-turn display, head-down electronic route map, head-up turn-by-turn display, and an audio guidance system. The primary measure of driving performance was the reaction time to a scanning task. Other measures included navigation errors, workload, and perception ratings. Censored regression models were developed to study the effect of route guidance type on reaction times. Results indicated that the drivers responded the fastest while using the audio system and the slowest while using the paper map. The head-up turn-by-turn display was associated with lower reaction times compared with an identically designed head-down turn-by-turn display. The head-down electronic map, despite its complexity, performed better than the head-down turn-by-turn display.

Adult↗

Thorotrast and the liver--revisited.

BACKGROUND: Thorotrast, a radiological contrast medium that was widely used from 1928-1955 is a thorium dioxide colloid that has been neutralized and stabilized by colloid, composed of dextran. The major site of deposition is the reticuloendothelial system where it is retained for a long time. CASE REPORTS: Complications occurring late after exposure to thorotrast are described in two patients. RESULTS: One patient had angiosarcoma of liver metastatic to bone and bone marrow failure after a 43 year latency period. The other patient had a thorotrast granuloma and angiosarcoma of the liver after 22 year and 28 year latency periods respectively. CONCLUSIONS: Complications due to thorotrast appear to represent consequences of chronic alpha irradiation.

Aged↗

In vitro characterization of a zinc based bioceramic.

Six different blends of zinc calcium phosphorous oxide ceramics (ZCAP) were prepared by mixing and calcining powders (ZnO:CaO:P2O5) of weight percent ratio: 50:30:20, 48:32:20, 44:20:26, 40:40:20, 30:40:30, and 30:30:40. ZCAP is a resorbable bioceramic and has been used to repair bone defects and deliver drugs in a continuous manner. The chemical composition, porosity, and elements released on exposure to buffered Tris HCl were measured for each blend of ZCAP. The products of mixing and thermal reaction were beta-Ca3(PO4)2, alpha-CaZn2(PO4)2, and 2CaO.P2O5. Free calcium and/or zinc oxide was present in several blends. The components of ZCAP and their volume percentages influenced the interconnected porosity of ZCAP bioceramics. The interconnected porosity for all blends of ZCAP ranged from 35 to 38%. Pore sizes from these six blends of ZCAP ranged from less 1 micron to greater than 100 microns. Results of the 12 hour dissolution study showed that more calcium was released than zinc or phosphorous from all blends of ZCAP. Zinc was released in trace amounts from all blends of ZCAP. Release of phosphorous from the different blends of ZCAP was not detected by the procedures used to detect phosphorous in this investigation. These blends of ZCAP have the potential to be used as bone substitutes and probably long term treatment of zinc deficiency in humans.

Biocompatible Materials↗

A cellular protein activates the sequence-specific DNA-binding of p53 by interacting with the central conserved region.

Mutational inactivation of the p53 gene product is one of the most common genetic aberations so far identified in human cancers. The p53 protein suppresses the transformed phenotype by transactivation or repression of genes involved in cell growth control. Missense mutations in the p53 protein coding sequence observed in human cancers are clustered within a central conserved (conformational) domain spanning amino acid residues 100-300 of a total of 393. Using the conformational domain of p53 fused with protein A, we have shown that the p53 conformational domain possesses Zn+2-dependent, sequence-specific DNA-binding activity. In addition to binding DNA, this domain interacts with at least five cellular proteins ranging in sizes from 30K to 90K M(r) and with the SV40 large T antigen viral oncoprotein. We investigated these cellular proteins for their modulatory effects on the sequence-specific DNA binding activity of full-length wild-type p53. A mixture of p53 conformational domain-binding proteins in bulk enhanced the DNA-binding activity of p53 greater than two-fold. Selective elution of the p53-binding proteins from the p53 hybrid protein by using a sequential step-wise NaCl gradient implicated one protein of 35K M(r) as contributing to a greater than four-fold activation of p53 DNA-binding activity. A p53 conformational domain protein containing a tumor-derived mutation at amino acid 175 failed to associate with the 35K M(r) protein. We propose that proteins interacting with the conformational domain of wild type p53 regulate the DNA-binding activity of p53, thus providing a biochemical basis for the alterations in its function induced by point mutations.

Base Sequence↗

Spatial sampling and filtering of EEG with spline laplacians to estimate cortical potentials.

The electroencephalogram (EEG) is recorded by sensors physically separated from the cortex by resistive skull tissue that smooths the potential field recorded at the scalp. This smoothing acts as a low-pass spatial filter that determines the spatial bandwidth, and thus the required spatial sampling density, of the scalp EEG. Although it is better appreciated in the time domain, the Nyquist frequency for adequate discrete sampling is evident in the spatial domain as well. A mathematical model of the low-pass spatial filtering of scalp potentials is developed, using a four concentric spheres (brain, CSF, skull, and scalp) model of the head and plausible estimates of the conductivity of each tissue layer. The surface Laplacian estimate of radial skull current density or cortical surface potential counteracts the low-pass filtering of scalp potentials by shifting the spatial spectrum of the EEG, producing a band-passed spatial signal that emphasizes local current sources. Simulations with the four spheres model and dense sensor arrays demonstrate that progressively more detail about cortical potential distribution is obtained as sampling is increased beyond 128 channels.

Cerebral Cortex↗

Pattern recognition approach to nucleic acid sequences.

A pattern recognition method through the two dimensional matrix representation of the nucleic acids sequence is developed. This approach of two dimensional plotting primarily enables to visualize all types of bonding between different bases in a RNA or DNA. The two dimensional matrix uses the capability of intramolecular Watson-Crick type (A-U and C-G) and Wobble type (G-U) base pairing. The method discusses both parallel and anti-parallel stranded base pairing. The application of the method to tRNA is shown.

Base Composition↗

A new simple method of representing relative orientation of bases in DNA helical structures.

It is shown that the strandwise correlation of the torsion angles in Nucleic acid structures can throw light on the aspects like helical distortion, in double helical and other associated forms. The single crystal X-ray coordinates for 7 A-DNA, 29 B-DNA, 8 Z-DNA and 4 tRNA structures are used to calculate the glycosyl angle chi and they are plotted in a two dimensional plot. A new torsion angle pi is defined as O4'-C1'-N1(9)-X, where X is a fictitious atom on the normal at N1(9). The chi 1 vs. chi 2 plots (where 1 and 2 refer to I and II-strand of DNA respectively) show the characteristic clustering features of A, B and Z DNAs. They are also compactly reflected in the modified graphical representation like (chi 1 + chi 2) vs. magnitude of chi 1 - chi 2 plot. chi 1 vs. chi 2 plot of the Hoogsteen type of base pairing obtained from the tRNA structures is off diagonal. The distortions due to complexing of the structures under each category, in particular, B-DNAs is readily observed. The observed points of A/B hybrid form clusters between A and B uncomplexed forms. The new torsion angle pi shows similar behavior as that of chi.

Base Composition↗

Corneal phaeohyphomycosis due to Exserohilum rostratum. A case report and brief review.

We report a rare case of corneal phaeohyphomycosis due to Exserohilum rostratum following organic trauma. A known cause of cutaneous and subcutaneous phaeohyphomycosis, this fungus has been very rarely associated with infections of the eye. Being a plant pathogen, along with other saprophytic dematiaceous fungi the possible role in keratomycosis is discussed.

Cornea↗

Spread of lymphatic filariasis, re-emergence of leishmaniasis & threat of babesiosis in India.

The impact of unabated population growth and consequent ecological changes is felt in the spread of vector-borne diseases also. Filariasis, once considered to be more associated with urban areas and urbanization, is rapidly emerging as a major problem in rural areas. The need to delimit the endemic areas through a new rapid assessment procedure and the possible control methods of rural filariasis are discussed. Leishmaniasis has re-emerged with a vengeance in some parts of the country and the reasons for this are analyzed. Babesiosis, though zoonotic, has the potential to invade the domain of man in India.

Animals↗

Modeling unfolded states of peptides and proteins.

The hydrophobic effect is the major factor that drives a protein molecule toward collapse and folding. In this process, residues with apolar side chains associate to form a solvent-shielded hydrophobic core. Often, this hydrophobic contribution to folding is quantified by measuring buried apolar surface area, reckoned as the difference in area between hydrophobic groups in the folded protein and in a standard state. Typically, the standard state area of a residue is obtained from tripeptide models, with the results taken to implicitly represent values appropriate for the unfolded state. Here, we show that a tripeptide is a poor descriptor of the unfolded state, and its widespread use has prompted erroneous conclusions about folding. As an alternative, we explore two limiting models, chosen to bracket the expected behavior of the unfolded chain between reliable extremes. One extreme is represented by simulated hard-sphere peptides and shown to behave like a homopolymer with excluded volume in a good solvent. The other extreme is represented by fragments excised from folded proteins and conjectured to approximate the time-average behavior of a thermally denatured protein at Tm, the midpoint of the unfolding transition. Using these models, it is shown that the area buried by apolar side chains upon folding is considerably less than earlier estimates. For example, upon transfer from the unfolded state to the middle of an alpha-helix, an alanine side chain buries negligible area and, surprisingly, a valine side chain actually gains area. Among other applications, an improved model of the unfolded state can be used to better evaluate the driving force for helix formation in peptides and proteins.

Amino Acids↗

NOE enhancements and T1 relaxation times of phosphorylated metabolites in human calf muscle at 1.5 Tesla.

Nuclear Overhauser effect (NOE) enhancements and relaxation times of 31P metabolites in human calf were measured in 12 volunteers (4 men and 8 women) at 1.5 T using a dual tuned four-ring birdcage. The NOE enhancements of inorganic phosphate (Pi), phosphocreatine (PCr), gamma-, alpha-, and beta-nucleoside triphosphate (NTP) from 19 measurements were 0.51 +/- 0.10, 0.64 +/- 0.03, 0.53 +/- 0.03, 0.56 +/- 0.08, and 0.47 +/- 0.05, respectively. The relaxation times were independent of proton irradiation and from 23 measurements were 3.49 +/- 0.35, 4.97 +/- 0.58, 4.07 +/- 0.36, 2.90 +/- 0.25, and 3.61 +/- 0.25 s for Pi, PCr, gamma-, alpha-, and beta-NTP, respectively. No significant differences between gender and age were observed for either NOE enhancements or relaxation times. Also, among nine volunteers, we observed no significant differences in T1 between the coupled and decoupled cases.

Adolescent↗

LINUS: a hierarchic procedure to predict the fold of a protein.

We describe LINUS, a hierarchic procedure to predict the fold of a protein from its amino acid sequence alone. The algorithm, which has been implemented in a computer program, was applied to large, overlapping fragments from a diverse test set of 7 X-ray-elucidated proteins, with encouraging results. For all proteins but one, the overall fragment topology is well predicted, including both secondary and supersecondary structure. The algorithm was also applied to a molecule of unknown conformation, groES, in which X-ray structure determination is presently ongoing. LINUS is an acronym for Local Independently Nucleated Units of Structure. The procedure ascends the folding hierarchy in discrete stages, with concomitant accretion of structure at each step. The chain is represented by simplified geometry and folds under the influence of a primitive energy function. The only accurately described energetic quantity in this work is hard sphere repulsion--the principal force involved in organizing protein conformation [Richards, F. M. Ann. Rev. Biophys. Bioeng. 6:151-176, 1977]. Among other applications, the method is a natural tool for use in the human genome initiative.

Algorithms↗

Light-dependent and tissue-specific expression of the H-protein of the glycine decarboxylase complex.

Glycine decarboxylase is a mitochondrial enzyme complex, which is the site of photorespiratory CO2 and NH3 release. Although the proteins that constitute the complex are located within the mitochondria, because of their intimate association with photosynthesis their expression is controlled by light. Comparisons of the kinetics of mRNA accumulation between the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase and the H-protein of glycine decarboxylase during the greening of etiolated Arabidopsis thaliana suggest that their expression is controlled in parallel. A genomic clone for the H-protein (gdcH) was isolated from Arabidopsis and sequenced. The upstream region from -856 to +62 was fused to the beta-glucuronidase (GUS) reporter gene, and this construct was transformed into tobacco. This 5' upstream regulatory region appears to control GUS expression in a manner very similar to that of the endogenous H-protein gene. Constructs with deletions in the 5' upstream region were transformed into tobacco. These deletions revealed that light-dependent and tissue-specific expression was largely controlled by a 259-bp region between -376 and -117 bp. This region contains several putative GT boxes with the GGTTAA consensus core sequence. Once these strong light-dependent elements were removed, a second level of control was revealed. In constructs in which the gdcH 5' regulatory region was shortened to -117 bp or less, there was more GUS activity in the roots than in the leaves, and in dark-grown plants than in light-grown plants. This suggests that more proximal control elements may be responsible for the constitutive low levels of gene expression noted in all nonphotosynthetic tissues.

Amino Acid Oxidoreductases↗

Tuberculous uteroenterocutaneous fistula--a rare post-caesarean complication.

A case of uteroenterocutaneous fistula which developed after lower segment Caesarean section is described. A total abdominal hysterectomy with removal of a tuboovarian mass with excision of the fistulous tract and repair of a small gut fistula were performed. The tuberculous aetiology of this fistula was established after surgery by a positive endometrial culture of acid fast bacilli and the demonstration of epithelioid granulomas in the surgical specimen. Antituberculosis therapy was started and the postoperative recovery was uneventful. The description of the nature of the fistula, its rarity and its presence in a woman with unimpaired fertility are discussed.

Adult↗

Performance on three-point vernier acuity targets as a function of age.

With certain (but not all) vernier acuity (VeA) stimulus displays observers exhibit no or slight performance decrements with aging. Because three-point VeA test displays are much more easily applied experimentally and clinically, we examined visual performance on this task as a function of age. Ages of groups tested ranged from 20 to 70+ years (some individuals were 90+ years old). Eyes were examined monocularly. We tested three- and two-point sharply defined VeA arrays and a three-point ground-glass-degraded display (simulating a 20/100 nuclear cataract). Gap or feature separations were varied. Results obtained with the three-point display showed little alteration with age. Image degradation resulted in reduction in performance when small gap separations were used between the test points, but only slight decrements for large gap separations were recorded. The finding that performance with certain VeA targets is largely unaffected by age is confirmed and is expanded.

Adult↗

Analysis of codon usage: positional preference in various organisms.

The degree of preference of the four nucleotides C, G, A and U in the three positions I, II and III of the codons of 15137 genes of various individual organisms is examined using the nucleotide sequence data obtained from the GenBank Genetic Sequence Data Bank (Release 65.0, Sep., 1990). It is found that G, A and C, are preferred maximally in the three positions respectively. Similarly, U, G and A are preferred minimally in these positions. The analysis shows a correlation in the positional base preference which discriminates against codons with the same base in all three positions or in the adjacent positions.

Animals↗