97 research outputs found
Inhibitory effects of somatostatin on rat hepatocyte proliferation are mediated by cyclic AMP,
Get PDFSomatostatin (SS-14) is known as an antigrowth factor for a variety of cell types, including gastrointestinal mucosa, exocrine pancreas, lymphocytes, and some tumors. We have recently identified and biochemically characterized SS-14-binding protein on rat liver plasma membranes (S. E. Raper, P. C. Kothary, and J. DelValle, Gastroenterology 96: A408, 1989; P. C. Kothary et al., Digestion 46(Suppl 1): 58, 1990). We hypothesized that SS-14 may affect liver growth as well and investigated cellular mechanisms of this phenomenon focusing on the second messenger cAMP. Freshly isolated rat hepatocytes were plated on tissue culture dishes coated with Matrigel (laminin, heparan sulfate, and type IV collagen). The medium was not supplemented with serum or hormones. Either dibutyryl-cAMP (1 mM) or isobutylmethylxanthine (IBMX, 0.1 mM) was added in the presence or absence of SS-14 (10 nM). DNA synthesis was estimated by the rate of [3H]thymidine incorporation into DNA and by the labeling index (an autoradiographic measurement of the number of labeled nuclei). SS-14 significantly inhibited both [3H]thymidine incorporation and labeling index of rat hepatocytes stimulated by dibutyryl-cAMP or IBMX. SS-14 also inhibited intracellular cAMP accumulation stimulated by IBMX. We conclude that SS-14 exerts at least part of its antiproliferative effects via the adenylate cyclase system. Further study using other signal transduction systems may yield more information about mechanisms of hepatocyte growth.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29185/1/0000238.pd
Set up errors in Brain tumours – A retrospective study to review the current practice of PTV margins in the institution
Get PDFSet up errors in Brain tumours – A retrospective study to review the current practice of PTV margins in the institution
Chaturvedi D.1 , Mehta A.2 , Kumar P.3*
1 Diksha Chaturvedi, Junior Resident, Department of Radiation Oncology, Shri Ram Murti Institute of Medical Sciences, Bareilly, Uttar Pradesh, India.
2 Ankita Mehta, Senior Resident, Department of Radiation Oncology, Shri Ram Murti Institute of Medical Sciences, Bareilly, Uttar Pradesh, India.
3* Piyush Kumar, Professor and Head, Department of Radiation Oncology, Shri Ram Murti Institute of Medical Sciences, Bareilly, Uttar Pradesh, India.
Corresponding Author: Dr. Piyush Kumar, Professor and Head, Department of Radiation Oncology, all authors are affiliated to Shri Ram Murti Institute of Medical Sciences, Bareilly, Uttar Pradesh, India, E-mail: [email protected]
Abstract
Background
Radiotherapy in brain tumors needs accuracy and reproducibility of the patient’s position. There may be set up errors which are taken care by adding planning target volume (PTV) margin. Lesser PTV margins may lead to tumor miss or greater margins may lead to unnecessary radiation of normal brain tissue. The present study is done to evaluate whether the current practice of PTV margins in our institute is optimum or not.
Materials and methods
Eleven patients of brain tumours who received adjuvant radiotherapy were retrospectively selected for determining the setup errors. These patients were immobilised in supine position and contrast enhanced CT of head was taken for radiotherapy planning. Delineation of gross tumor volume and clinical target volume was done with 5 mm PTV margin. The treatment was delivered by 3-Dimensional Conformal Radiotherapy or Intensity Modulated Radiotherapy Technique. The set up errors in three dimensions were determined retrospectively for all images. PTV margins were calculated using International Commission on Radiation Units And Measurements Report 62, Stroom’s and Van Herk formulae.
Results
The overall population set up error was 0.034,-0.048, 0.028 in X, Y, Z directions respectively. The population systematic error was calculated to be 0.107, 0.069, 0.092 and population random error was 0.221, 0.202, 0.217 in X, Y, Z directions respectively. The calculated setup margin as per the three formulas was less than 5 mm in all directions.
Conclusion
The present study showed that the institutional protocol of 5 mm is optimum to counter the setup errors. 
NH2-Terminal of gastrin-17 in duodenal ulcer disease: Identification of progastrin-17
No full textSerum gastrin concentrations were measured using antisera with specificity for the carboxyl and amino terminus of gastrin-17 in 50 healthy subjects and 18 patients with active duodenal ulcer disease (DU). The amino terminal of gastrin-17 immunoreactivity was significantly higher in DU patients than in healthy subjects. NH2-terminus of gastrin-17 immunopurified material from serum of DU patients was subjected to Sephadex G50 column chromatography and eluates were monitored by an additional antiserum EG10 that recognizes COOH-terminally extended gastrin. Besides the NH2 terminal tridecapeptide of gastrin-17, COOH-terminally extended progastrin was found. This may reflect abnormal processing of gastrin in patients with active duodenal ulcer disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26637/1/0000179.pd
Anisotropic diffusion in spherical coordinates: Steady state wizard
No full textThe theory is developed in a peer reviewed paper, whose bibliographic information will appear here once published.
The GUI executable files are packaged in a tar archive for each operating system. The relevant MATLAB Runtime version appears in the name. For MacOS and Linux the archive also includes instructions and a shell script (on MacOS the executable might be run as a clickable application or from a shell)
A Possible Impaired Signaling Mechanism in Human Retinal Pigment Epithelial Cells from Patients with Macular Degeneration
No full textMetabolic heterogeneity in microbial populations
Get PDFNo two living cells are exactly the same. Even cells from a clonal population with identical genomes living in the same environment will express proteins in different numbers simply due to the random nature of the chemistry involved in gene expression. The consequences of this stochastic gene expression are complex and not well understood, especially at the level of large reaction networks like metabolism. Here we investigate how variability in the copy numbers of metabolic enzymes affects how individual cells extract nourishment from their environment and grow. We model independent microbial cells, each with their own set of enzyme copy numbers sampled from experimental distributions, and use flux balance analysis (FBA) to compute the optimal way that each cell can use its metabolic pathways—an approach we dubbed Population FBA. We find that enzyme variability gives rise to a wide distribution of growth rates, and several metabolic phenotypes—subpopulations relying on diverse metabolic pathways.
First we use Population FBA in investigating the effects of single cell proteomics data on the metabolic behavior of an in silico E. coli population. We use the latest metabolic reconstruction integrated with transcriptional regulatory data to model realistic cells growing in a glucose minimal medium under aerobic conditions. The modeled population exhibits a broad distribution of growth rates, and principal component analysis was used to identify well-defined subpopulations that differ in terms of their pathway usage. The cells differentiate into slow-growing acetate-secreting cells and fast-growing CO2-secreting cells, and a large population growing at intermediate rates shift from glycolysis to Entner-Doudoroff (ED) pathway usage. Constraints imposed by integrating regulatory data have a large impact on NADH oxidizing pathway usage within the cell. Finally we find that stochasticity in the expression of only a few genes may be sufficient to capture most of the metabolic variability of the entire population.
Next, we extend the methodology to account for correlations in protein expression arising from the co-regulation of genes and apply it to study the growth of independent Saccharomyces cerevisiae cells in two different growth media. We find the partitioning of flux between fermentation and respiration predicted by our model agrees with recent 13C fluxomics experiments, and that our model largely recovers the Crabtree effect (the experimentally known bias among certain yeast species toward fermentation with the production of ethanol even in the presence of oxygen), while FBA without proteomics constraints predicts respirative metabolism almost exclusively. The comparisons to the 13C study showed improvement upon inclusion of the correlations and motivated a technique to systematically identify inconsistent kinetic parameters in the literature. The minor secretion fluxes for glycerol and acetate are underestimated by our method, which indicate a need for further refinements to the metabolic model. For yeast cells grown in synthetic defined (SD) medium, the calculated broad distribution of growth rates matches experimental observations from single cell studies, and we characterize several metabolic phenotypes within our modeled populations that make use of diverse pathways. Fast growing yeast cells perform significant amount of respiration, use serine- glycine cycle and produce ethanol in mitochondria as opposed to slow growing cells. We also investigate the degeneracy of the sets of protein-associated constraints that are necessary to give rise to the growth rate distributions seen experimentally. We find that a core set of 51 constraints are essential but that additional constraints are still necessary to reproduce the observed growth rate distributions in SD medium.Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2019-08-01The student, Piyush Labhsetwar, accepted the attached license on 2017-07-06 at 19:36.The student, Piyush Labhsetwar, submitted this Dissertation for approval on 2017-07-06 at 19:43.This Dissertation was approved for publication on 2017-07-09 at 16:17.DSpace SAF Submission Ingestion Package generated from Vireo submission #11328 on 2017-09-29 at 11:14:32Made available in DSpace on 2017-09-29T16:39:20Z (GMT). No. of bitstreams: 3
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Identification and partial characterization of a somatostatin-14 binding protein on rat liver plasma membranes
Get PDFBinding of somatostatin-14 to rat liver plasma membranes was characterized with 125 -labeled[tyr 11 ] somatostatin-14. Binding at 24° C reached a plateau at 50 min and was reversible by synthetic somatostatin-14. Scatchard analysis revealed a single class of binding sites (affinity constant = 2.4 ± 0.2 nmol/L, binding capacity = 148 ± 0.02 fmol/mg protein). Specificity for somatostatin-14 was demonstrated by the inhibition of 125 I-[tyr 11 ]somatostatin-14 binding by biologically active somatostatin analogs but not by a biologically inactive somatostatin analog or unrelated peptides. The radioiodinated binding site complex could be cross-linked with disuccinimidyl suberate. Analysis by sodium dodecyl sulfate–polyacrylamide gel electrophoresis and gel autoradiography revealed a 70,000-Da band. Dithiothreitol, a reducing reagent, did not alter the mobility of the band, and the band could be abolished in the presence of 10 Μmol/L synthetic somatostatin-14. Covalently crosslinked, iodinated binding protein complexes could be solubilized by the nonreducing detergents Zwittergent 3–12 and 3-([3-cholamidopropyl] diethylammonio)-1-propanesulfonic acid (CHAPS). Solubilized complex bound to wheat-germ agglutinin–agarose columns and was eluted by N, N′, N′-triacetylchitotriose. Binding to wheat-germ agglutinin agarose columns was lost after pretreatment with endo-Β- N -acetylglucosaminidase F. Binding studies with liver plasma membranes, 125 I-labeled[tyrosine 11 ]somatostatin-14 and guanine nucleotides showed inhibition of binding in the presence of guanine nucleotides. These results indicate that the purified rat liver plasma membranes contain a specific binding protein for somatostatin-14, the binding protein appears to be glycosylated and somatostatin-14 binding to rat liver plasma membranes may be regulated by G proteins. (H EPATOLOGY 1992;16:433–439.)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38379/1/1840160223_ftp.pd
Tropical oceanic mesoscale cold pools in observations and models
No full textConvective cold pools over oceans contribute to the atmosphere-ocean exchange of heat and moisture across the globe. Beyond cold pools’ physical properties, cold pools and their intersections are important mechanisms controlling the life cycle of tropical convective systems. However, few observational techniques are available to routinely observe the properties of cold pools and their association with convection. The primary goal of the first part of this study is to demonstrate a new technique using gradient in remotely-sensed ocean vector winds as a proxy for the structure and characteristics of tropical oceanic cold pools. Using Advanced Scatterometer (ASCAT) vector wind retrievals with field of view of 12.5 km, regions of enhanced gradients in surface winds are identified as gradient features (or GFs). A 3-km Weather Research and Forecasting (WRF) model simulation was carried out to illustrate the technique over the Indian Ocean during the 2011 DYNAmics of the Madden-Julian Oscillation (DYNAMO) field campaign. A forward operator was applied to the model wind fields, allowing direct comparisons of wind gradients and virtual temperature-defined cold pool thermodynamic and kinematic properties. In situ buoy measurements of air temperature were also used to validate ASCAT-identified cold pools. Quantitative skill metrics demonstrate that the technique has a low false alarm rate (85%), and a low bias (~1). The GF technique was then applied to ASCAT-retrieved ocean vector winds, revealing global variations in cold pool properties. These properties are shown to be related to the properties of global convective systems observed by the Tropical Rainfall Measurement Mission (TRMM). The results from the first objective of this study are explained in Chapter 2 of this dissertation.
Once the GF technique was well-validated against independent buoy observations and a model simulation, it was applied on NASA’s RapidScat scatterometer in the second objective. Compared to ASCAT (sun-synchronous orbit), RapidScat was in a non-sun-synchronous orbit onboard the International Space Station (ISS) from 2014-2016 and thus was able to provide the diurnal cycle of ocean vector winds. Since the field of view and underlying scatterometry principles of both the scatterometers were similar, ASCAT GF methodology was effectively replicated on RapidScat ocean vector winds for the two-year period to identify diurnally-resolved cold pool properties. This similarity also allowed us to compare the tropical oceanic cold pool properties across the basins and thus helped identify how different wavelengths, swath width, and rain-flag algorithms would change the cold pool properties. Buoy data over the Pacific, Atlantic, and Indian Ocean was also used to validate RapidScat-observed diurnal cycle of cold pool number and precipitation. GF- and buoy-observed cold pool number and precipitation exhibits a similar bimodal diurnal variability with a dominant morning and a secondary afternoon maxima, thus establishing confidence in using GF as a proxy to observe cold pools over tropical oceans. NASA globally-merged (MERGIR) infrared brightness temperature (TB) and ERA5 reanalysis’ total column water vapor (TCWV) is then used to obtain a conceptual understanding of the bimodal diurnal behavior of tropical oceanic mesoscale cold pools. Results from this objective are explained in Chapter 3 of this dissertation.
In the recent years, global kilometer-scale convection-permitting models have shown promising results in producing realistic convection and precipitation. Cold pools are identified as one of the major mesoscale processes responsible for modulating the life cycle of mesoscale organized convection in these models. Once an observational perspective of diurnally-resolved global tropical oceanic cold pool properties was obtained in the first two objectives, the third and final objective of this study is to find out if the global high-resolution cloud-resolving model simulations produce realistic cold pool properties across tropical oceanic basins. In this objective, a 2.5 km global Icosahedral Nonhydrostatic (ICON) model simulation run for 40 days (06 UTC 01 Aug – 23 UTC 10 Aug 2016) from the Dynamics of the Atmospheric general circulation Modeled On Non-hydrostatic Domains (DYAMOND) initiative is used to identify thermal cold pools (using Tv) over the tropical oceans. Model-simulated cold pools are compared against RapidScat-observed diurnal climatology of GFs and NASA’s Integrated Multi-satellite Retrievals for Global Precipitation Measurement (IMERG) precipitation. Overall, the model-simulated global cold pool climatology is similar to RapidScat across oceanic basins, but ICON portrays a near-unimodal distribution in cold pool diurnal cycle. Environmental properties such as column water vapor, surface fluxes, vertical wind shear, and convective available potential energy (CAPE) are analyzed to identify controls on cold pool strength, density, and size. A random forest regression model was then applied to identify statistically significant features important in modulating cold pool properties across the global tropics. Regional difference in relationship between environment and cold pool properties is explored and it was observed that EPAC and AO cold pool activity is strongly controlled by synoptic-scale waves while WPAC and AO have strong mesoscale controls on cold pools. Results from the third objective are depicted in the Chapter 4 of this dissertation.Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2023-08-01The student, Piyush Garg, accepted the attached license on 2021-06-21 at 16:18.The student, Piyush Garg, submitted this Dissertation for approval on 2021-06-21 at 16:19.This Dissertation was approved for publication on 2021-06-24 at 10:04.DSpace SAF Submission Ingestion Package generated from Vireo submission #16703 on 2022-01-12 at 12:52:22Made available in DSpace on 2022-01-12T22:34:46Z (GMT). No. of bitstreams: 3
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Movie rating prediction using multimedia content and modeling as a classification problem
No full textThis paper presents the method proposed for the recommender system task in Mediaeval 2018 on predicting user global ratings given to movies and their standard deviation through the audiovisual content and the associated metadata. In the proposed work, we model the rating prediction problem as a classification problem and employ different classifiers for the prediction task. Furthermore, in order to obtain a video-level representation of features from clip-level features, we employ statistical summarization functions. Results are promising and show the potential of leveraging the audiovisual content for improving the quality of existing movie recommendation systems in service. Copyright held by the owner/author(s)
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