287 Matching Results

Search Results

Advanced search parameters have been applied.

Measuring Light Reflectance of BGO Crystal Surfaces

Description: A scintillating crystal's surface reflectance has to be well understood in order to accurately predict and optimize the crystal?s light collection through Monte Carlo simulations. In this paper, we measure the inner surface reflectance properties for BGO. The measurements include BGO crystals with a mechanically polished surface, rough-cut surface, and chemically etched surface, and with various reflectors attached, both air- coupled and with coupling compound. The measurements are performed with a laser aimed at the center of a hemispherical shaped BGO crystal. The hemispherical shape eliminates any non-perpendicular angles for light entering and exiting the crystal. The reflected light is collected with an array of photodiodes. The laser can be set at an arbitrary angle, and the photodiode array is rotated to fully cover 2? of solid angle. The current produced in the photodiodes is readout with a digital multimeter connected through a multiplexer. The two rows of photodiodes achieve 5-degree by 4-degree resolution, and the current measurement has a dynamic range of 10^5:1. The acquired data was not described by the commonly assumed linear combination of specular and diffuse (Lambertian) distributions, except for a very few surfaces. Surface roughness proved to be the most important parameter when choosing crystal setup. The reflector choice was of less importance and of almost no consequence for rough-cut surfaces. Pure specular reflection distribution for all incidence angles was measured for polished surfaces with VM2000 film, while the most Lambertian distribution for any surface finish was measured for titanium dioxide paint. The distributions acquired in this paper will be used to create more accurate Monte Carlo models for light reflection distribution within BGO crystals.
Date: July 28, 2008
Creator: Janecek, Martin & Moses, William
Partner: UNT Libraries Government Documents Department

Putting Tumors in Context

Description: The interactions between cancer cells and their micro- and macroenvironment create a context that promotes tumor growth and protects it from immune attack. The functional association of cancer cells with their surrounding tissues forms a new 'organ' that changes as malignancy progresses. Investigation of this process might provide new insights into the mechanisms of tumorigenesis and could also lead to new therapeutic targets. Under normal conditions, ORGANS are made up of TISSUES that exchange information with other cell types via cell-cell contact, cytokines and the EXTRACELLULAR MATRIX (ECM). The ECM, which is produced by collaboration between STROMAL fibroblasts and EPITHELIAL cells, provides structural scaffolding for cells, as well as contextual information. The endothelial vasculature provides nutrients and oxygen, and cells of the immune system combat pathogens and remove apoptotic cells. Epithelial cells associate into intact, polarized sheets. These tissues communicate through a complex network of interactions: physically, through direct contact or through the intervening ECM, and biochemically, through both soluble and insoluble signalling molecules. In combination, these interactions provide the information that is necessary to maintain cellular differentiation and to create complex tissue structures. Occasionally, the intercellular signals that define the normal context become disrupted. Alterations in epithelial tissues can lead to movement of epithelial sheets and proliferation - for example, after activation of mesenchymal fibroblasts due to wounding.Normally, these conditions are temporary and reversible, but when inflammation is sustained, an escalating feedback loop ensues.Under persistent inflammatory conditions, continual upregulation of enzymes such as matrix metalloproteinases (MMPs) by stromal fibroblasts can disrupt the ECM, and invading immune cells can overproduce factors that promote abnormal proliferation. As this process progresses, the normal organization of the organ is replaced by a functional disorder. If there are pre-existing epithelial cells within this changing context that possess tumorigenic potential, they can start to proliferate. ...
Date: October 1, 2001
Creator: Bissell, Mina & Radisky, Derek
Partner: UNT Libraries Government Documents Department

Overexpressed of RAD51 suppresses recombination defects: a possible mechanism to reverse genomic instability

Description: RAD51, a key protein in the homologous recombinational DNA repair (HRR) pathway, is the major strand-transferase required for mitotic recombination. An important early step in HRR is the formation of single-stranded DNA (ss-DNA) coated by RPA (a ss-DNA binding protein). Displacement of RPA by RAD51 is highly regulated and facilitated by a number of different proteins known as the 'recombination mediators'. To assist these recombination mediators, a second group of proteins also is required and we are defining these proteins here as 'recombination co-mediators'. Defects in either recombination mediators or comediators, including BRCA1 and BRCA2, lead to impaired HRR that can genetically be complemented for (i.e. suppressed) by overexpression of RAD51. Defects in HRR have long been known to contribute to genomic instability leading to tumor development. Since genomic instability also slows cell growth, precancerous cells presumably require genomic restabilization to gain a growth advantage. RAD51 is overexpressed in many tumors, and therefore, we hypothesize that the complementing ability of elevated levels of RAD51 in tumors with initial HRR defects limits genomic instability during carcinogenic progression. Of particular interest, this model may also help explain the high frequency of TP53 mutations in human cancers, since wild-type p53 represses RAD51.
Date: October 15, 2009
Creator: Schild, David & Wiese, Claudia
Partner: UNT Libraries Government Documents Department

Single cell analysis: the new frontier in 'Omics'

Description: Cellular heterogeneity arising from stochastic expression of genes, proteins, and metabolites is a fundamental principle of cell biology, but single cell analysis has been beyond the capabilities of 'Omics' technologies. This is rapidly changing with the recent examples of single cell genomics, transcriptomics, proteomics, and metabolomics. The rate of change is expected to accelerate owing to emerging technologies that range from micro/nanofluidics to microfabricated interfaces for mass spectrometry to third- and fourth-generation automated DNA sequencers. As described in this review, single cell analysis is the new frontier in Omics, and single cell Omics has the potential to transform systems biology through new discoveries derived from cellular heterogeneity.
Date: January 14, 2010
Creator: Wang, Daojing & Bodovitz, Steven
Partner: UNT Libraries Government Documents Department

Simulating Scintillator Light Collection Using Measured Optical Reflectance

Description: To accurately predict the light collection from a scintillating crystal through Monte Carlo simulations, it is crucial to know the angular distribution from the surface reflectance. Current Monte Carlo codes allow the user to set the optical reflectance to a linear combination of backscatter spike, specular spike, specular lobe, and Lambertian reflections. However, not all light distributions can be expressed in this way. In addition, the user seldom has the detailed knowledge about the surfaces that is required for accurate modeling. We have previously measured the angular distributions within BGO crystals and now incorporate these data as look-up-tables (LUTs) into modified Geant4 and GATE Monte Carlo codes. The modified codes allow the user to specify the surface treatment (ground, etched, or polished), the attached reflector (Lumirror(R), Teflon(R), ESR film, Tyvek(R), or TiO paint), and the bonding type (air-coupled or glued). Each LUT consists of measured angular distributions with 4o by 5o resolution in theta and phi, respectively, for incidence angles from 0? to 90? degrees, in 1o-steps. We compared the new codes to the original codes by running simulations with a 3 x 10 x 30 mm3 BGO crystal coupled to a PMT. The simulations were then compared to measurements. Light output was measured by counting the photons detected by the PMT with the 3 x 10, 3 x 30, or 10 x 30 mm2 side coupled to the PMT, respectively. Our new code shows better agreement with the measured data than the current Geant4 code. The new code can also simulate reflector materials that are not pure specular or Lambertian reflectors, as was previously required. Our code is also more user friendly, as no detailed knowledge about the surfaces or light distributions is required from the user.
Date: January 28, 2010
Creator: Janecek, Martin & Moses, William
Partner: UNT Libraries Government Documents Department

DNA Repair Decline During Mouse Spermiogenesis Results in the Accumulation of Heritable DNA Damage

Description: The post-meiotic phase of mouse spermatogenesis (spermiogenesis) is very sensitive to the genomic effects of environmental mutagens because as male germ cells form mature sperm they progressively lose the ability to repair DNA damage. We hypothesized that repeated exposures to mutagens during this repair-deficient phase result in the accumulation of heritable genomic damage in mouse sperm that leads to chromosomal aberrations in zygotes after fertilization. We used a combination of single or fractionated exposures to diepoxybutane (DEB), a component of tobacco smoke, to investigate how differential DNA repair efficiencies during the three weeks of spermiogenesis affected the accumulation of DEB-induced heritable damage in early spermatids (21-15 days before fertilization, dbf), late spermatids (14-8 dbf) and sperm (7-1 dbf). Analysis of chromosomal aberrations in zygotic metaphases using PAINT/DAPI showed that late spermatids and sperm are unable to repair DEB-induced DNA damage as demonstrated by significant increases (P<0.001) in the frequencies of zygotes with chromosomal aberrations. Comparisons between single and fractionated exposures suggested that the DNA repair-deficient window during late spermiogenesis may be less than two weeks in the mouse and that during this repair-deficient window there is accumulation of DNA damage in sperm. Finally, the dose-response study in sperm indicated a linear response for both single and repeated exposures. These findings show that the differential DNA repair capacity of post-meioitic male germ cells has a major impact on the risk of paternally transmitted heritable damage and suggest that chronic exposures that may occur in the weeks prior to fertilization because of occupational or lifestyle factors (i.e, smoking) can lead to an accumulation of genetic damage in sperm and result in heritable chromosomal aberrations of paternal origin.
Date: December 1, 2007
Creator: Marchetti, Francesco; Marchetti, Francesco & Wyrobek, Andrew J.
Partner: UNT Libraries Government Documents Department

DNA repair decline during mouse spermiogenesis results in the accumulation of heritable DNA damage

Description: The post-meiotic phase of mouse spermatogenesis (spermiogenesis) is very sensitive to the genomic effects of environmental mutagens because as male germ cells form mature sperm they progressively lose the ability to repair DNA damage. We hypothesized that repeated exposures to mutagens during this repair-deficient phase result in the accumulation of heritable genomic damage in mouse sperm that leads to chromosomal aberrations in zygotes after fertilization. We used a combination of single or fractionated exposures to diepoxybutane (DEB), a component of tobacco smoke, to investigate how differential DNA repair efficiencies during the three weeks of spermiogenesis affected the accumulation of DEB-induced heritable damage in early spermatids (21-15 days before fertilization, dbf), late spermatids (14-8 dbf) and sperm (7- 1 dbf). Analysis of chromosomalaberrations in zygotic metaphases using PAINT/DAPI showed that late spermatids and sperm are unable to repair DEB-induced DNA damage as demonstrated by significant increases (P<0.001) in the frequencies of zygotes with chromosomal aberrations. Comparisons between single and fractionated exposures suggested that the DNA repair-deficient window during late spermiogenesis may be less than two weeks in the mouse and that during this repair-deficient window there is accumulation of DNA damage in sperm. Finally, the dose-response study in sperm indicated a linear response for both single and repeated exposures. These findings show that the differential DNA repair capacity of post-meioitic male germ cells has a major impact on the risk of paternally transmitted heritable damage and suggest that chronic exposures that may occur in the weeks prior to fertilization because of occupational or lifestyle factors (i.e, smoking) can lead to an accumulation of genetic damage in sperm and result in heritable chromosomal aberrations of paternal origin.
Date: February 21, 2008
Creator: Marchetti, Francesco; Marchetti, Francesco & Wryobek, Andrew J
Partner: UNT Libraries Government Documents Department

Translating the cancer genome: Going beyond p values

Description: Cancer cells are endowed with diverse biological capabilities driven by myriad inherited and somatic genetic and epigenetic aberrations that commandeer key cancer-relevant pathways. Efforts to elucidate these aberrations began with Boveri's hypothesis of aberrant mitoses causing cancer and continue today with a suite of powerful high-resolution technologies that enable detailed catalogues of genomic aberrations and epigenomic modifications. Tomorrow will likely bring the complete atlas of reversible and irreversible alteration in individual cancers. The challenge now is to discern causal molecular abnormalities from genomic and epigenomic 'noise', to understand how the ensemble of these aberrations collaborate to drive cancer pathophysiology. Here, we highlight lessons learned from now classical examples of successful translation of genomic discoveries into clinical practice, lessons that may be used to guide and accelerate translation of emerging genomic insights into practical clinical endpoints that can impact on practice of cancer medicine.
Date: April 3, 2008
Creator: Chin, Lynda; Chin, Lynda & Gray, Joe W.
Partner: UNT Libraries Government Documents Department

Unraveling the microenvironmental influences on the normal mammary gland and induction and progression of breast cancer

Description: The normal mammary gland and invasive breast cancer are both complex 'organs' composed of multiple cell types as well as extracellular matrix (ECM) in three-dimensional (3D) space. Conventionally, both normal and malignant breast cells are studied in vitro as two-dimensional (2D) monolayers of epithelial cells, which results in the loss of structure and tissue function. Many laboratories are now investigating regulation of signaling function in normal mammary gland using 3D cultures. However, it is important also to assay malignant breast cells ex vivo in a physiologically relevant environment to more closely mimic tumor architecture, signal transduction regulation and tumor behavior in vivo. Here we present the potential of these 3D models for drug testing, target validation and guidance of patient selection for clinical trials. We argue also that in order to get full insight into the biology of the normal and malignant breast, and to create in vivo-like models for therapeutic approaches in humans, we need to continue to create more complex heterotypic models to approach the full context the cells encounter in the human body.
Date: June 26, 2008
Creator: Weigelt, Britta & Bissell, Mina J.
Partner: UNT Libraries Government Documents Department

A review of ground-based heavy-ion radiobiology relevant to space radiation risk assessment: Part II. Cardiovascular and immunological effects

Description: The future of manned space flight depends on an analysis of the numerous potential risks of travel into deep space. Currently no radiation dose limits have been established for these exploratory missions. To set these standards more information is needed about potential acute and late effects on human physiology from appropriate radiation exposure scenarios, including pertinent radiation types and dose rates. Cancer risks have long been considered the most serious late effect from chronic daily relatively low-dose exposures to the complex space radiation environment. However, other late effects from space radiation exposure scenarios are under study in ground-based accelerator facilities and have revealed some unique particle radiation effects not observed with conventional radiations. A comprehensive review of pertinent literature that considers tissue effects of radiation leading to functional detriments in specific organ systems has recently been published (NCRP National Council on Radiation Protection and Measurements, Information Needed to Make Radiation Protection Recommendations for Space Missions Beyond Low-Earth Orbit, Report 153, Bethesda, MD, 2006). This paper highlights the review of two non-cancer concerns from this report: cardiovascular and immunological effects.
Date: February 26, 2007
Creator: Blakely, Eleanor A. & Chang, Polly Y.
Partner: UNT Libraries Government Documents Department


Description: Relatively large values of objective-lens defocus must normally be used to produce detectable levels of image contrast for unstained biological specimens, which are generally weak phase objects. As a result, a subsequent restoration operation must be used to correct for oscillations in the contrast transfer function (CTF) at higher resolution. Currently used methods of CTF-correction assume the ideal case in which Friedel mates in the scattered wave have contributed pairs of Fourier components that overlap with one another in the image plane. This&quot;ideal&quot; situation may be only poorly satisfied, or not satisfied at all, as the particle size gets smaller, the defocus value gets larger, and the resolution gets higher. We have therefore investigated whether currently used methods of CTF correction are also effective in restoring the single-sideband image information that becomes displaced (delocalized) by half (or more) the diameter of a particle of finite size. Computer simulations are used to show that restoration either by&quot;phase flipping&quot; or by multiplying by the CTF recovers only about half of the delocalized information. The other half of the delocalized information goes into a doubly defocused&quot;twin&quot; image of the type produced during optical reconstruction of an in-line hologram. Restoration with a Wiener filter is effective in recovering the delocalized information only when the signal-to-noise ratio (S/N) is orders of magnitude higher than that which exists in low-dose images of biological specimens, in which case the Wiener filter approaches division by the CTF (i.e. the formal inverse). For realistic values of the S/N, however, the&quot;twin image&quot; problem seenwith a Wiener filter is very similar to that seen when either phase flipping or multiplying by the CTF are used for restoration. The results of these simulations suggest that CTF correction is a poor alternative to using a Zernike-type phase plate when imaging biological specimens, in ...
Date: March 28, 2008
Creator: Downing, Kenneth H. & Glaeser, Robert M.
Partner: UNT Libraries Government Documents Department

RNA Helicase DDX5 Regulates MicroRNA Expression and Contributes to Cytoskeletal Reorganization in Basal Breast Cancer Cells

Description: RNA helicase DDX5 (also p68) is involved in all aspects of RNA metabolism and serves as a transcriptional co-regulator, but its functional role in breast cancer remains elusive. Here, we report an integrative biology study of DDX5 in breast cancer, encompassing quantitative proteomics, global MicroRNA profiling, and detailed biochemical characterization of cell lines and human tissues. We showed that protein expression of DDX5 increased progressively from the luminal to basal breast cancer cell lines, and correlated positively with that of CD44 in the basal subtypes. Through immunohistochemistry analyses of tissue microarrays containing over 200 invasive human ductal carcinomas, we observed that DDX5 was upregulated in the majority of malignant tissues, and its expression correlated strongly with those of Ki67 and EGFR in the triple-negative tumors. We demonstrated that DDX5 regulated a subset of MicroRNAs including miR-21 and miR-182 in basal breast cancer cells. Knockdown of DDX5 resulted in reorganization of actin cytoskeleton and reduction of cellular proliferation. The effects were accompanied by upregulation of tumor suppressor PDCD4 (a known miR-21 target); as well as upregulation of cofilin and profilin, two key proteins involved in actin polymerization and cytoskeleton maintenance, as a consequence of miR-182 downregulation. Treatment with miR-182 inhibitors resulted in morphologic phenotypes resembling those induced by DDX5 knockdown. Using bioinformatics tools for pathway and network analyses, we confirmed that the network for regulation of actin cytoskeleton was predominantly enriched for the predicted downstream targets of miR-182. Our results reveal a new functional role of DDX5 in breast cancer via the DDX5→miR-182→actin cytoskeleton pathway, and suggest the potential clinical utility of DDX5 and its downstream MicroRNAs in the theranostics of breast cancer.
Date: November 15, 2011
Creator: Wang, Daojing; Huang, Jing & Hu, Zhi
Partner: UNT Libraries Government Documents Department

Communication Between the Cell Membrane and the Nucleus: Role of Protein Compartmentalization

Description: Understanding how the information is conveyed from outside to inside the cell is a critical challenge for all biologists involved in signal transduction. The flow of information initiated by cell-cell and cell-extracellular matrix contacts is mediated by the formation of adhesion complexes involving multiple proteins. Inside adhesion complexes, connective membrane skeleton (CMS) proteins are signal transducers that bind to adhesion molecules, organize the cytoskeleton, and initiate biochemical cascades. Adhesion complex-mediated signal transduction ultimately directs the formation of supramolecular structures in the cell nucleus, as illustrated by the establishment of multi complexes of DNA-bound transcription factors, and the redistribution of nuclear structural proteins to form nuclear subdomains. Recently, several CMS proteins have been observed to travel to the cell nucleus, suggesting a distinctive role for these proteins in signal transduction. This review focuses on the nuclear translocation of structural signal transducers of the membrane skeleton and also extends our analysis to possible translocation of resident nuclear proteins to the membrane skeleton. This leads us to envision the communication between spatially distant cellular compartments (i.e., membrane skeleton and cell nucleus) as a bidirectional flow of information (a dynamic reciprocity) based on subtle multilevel structural and biochemical equilibria. At one level, it is mediated by the interaction between structural signal transducers and their binding partners, at another level it may be mediated by the balance and integration of signal transducers in different cellular compartments.
Date: October 21, 1998
Creator: Lelievre, Sophie A & Bissell, Mina J
Partner: UNT Libraries Government Documents Department

Gene Expression in the Third Dimension: The ECM-nucleus Connection

Description: Decades ago, we and others proposed that the dynamic interplay between a cell and its surrounding environment dictates cell phenotype and tissue structure. Whereas much has been discovered about the effects of extracellular matrix molecules on cell growth and tissue specific gene expression, the nuclear mechanisms through which these molecules promote these physiological events remain unknown. Using mammary epithelial cells as a model, the purpose of this review is to discuss how the extracellular matrix influences nuclear structure and function in a three-dimensional context to promote epithelial morphogenesis and function in the mammary gland.
Date: October 1, 2009
Creator: Spencer, Virginia A; Xu, Ren & Bissell, Mina
Partner: UNT Libraries Government Documents Department

Reprogramming stem cells is a microenvironmental task

Description: That tumor cells for all practical purposes are unstable and plastic could be expected. However, the astonishing ability of the nuclei from cells of normal adult tissues to be reprogrammed - given the right embryonic context - found its final truth even for mammals in the experiments that allowed engineering Dolly (1). The landmark experiments showed that nuclei originating from cells of frozen mammary tissues were capable of being reprogrammed by the embryonic cytoplasm and its microenvironment to produce a normal sheep. The rest is history. However, whether microenvironments other than those of the embryos can also reprogram adult cells of different tissue origins still containing their cytoplasm is of obvious interest. In this issue of PNAS, the laboratory of Gilbert Smith (2) reports on how the mammary gland microenvironment can reprogram both embryonic and adult stem neuronal cells. The work is a follow-up to their previous report on testis stem cells that were reprogrammed by the mammary microenvironment (3). They demonstrated that cells isolated from the seminiferous tubules of the mature testis, mixed with normal mammary epithelial cells, contributed a sizable number of epithelial progeny to normal mammary outgrowths in transplanted mammary fat pads. However, in those experiments they were unable to distinguish which subpopulation of the testis cells contributed progeny to the mammary epithelial tree. The current work adds new, compelling, and provocative information to our understanding of stem cell plasticity. Booth et al. (2) use neuronal stem cells (NSCs) isolated from WAP-cre/R26R mice combined with unlabeled mammary epithelial cells that subsequently are implanted in cleared mammary fat pads. In this new microenvironment, the NSCs that are incorporated into the branching mammary tree make chimeric glands (Fig. 1) that remarkably can also express the milk protein {beta}-casein, progesterone receptor, and estrogen receptor {alpha}. Remarkably, the primary transplants are ...
Date: October 14, 2008
Creator: Bissell, Mina J & Inman, Jamie
Partner: UNT Libraries Government Documents Department

Apical polarity in three-dimensional culture systems: where to now?

Description: Delineation of the mechanisms that establish and maintain the polarity of epithelial tissues is essential to understanding morphogenesis, tissue specificity and cancer. Three-dimensional culture assays provide a useful platform for dissecting these processes but, as discussed in a recent study in BMC Biology on the culture of mammary gland epithelial cells, multiple parameters that influence the model must be taken into account.
Date: January 21, 2010
Creator: Inman, J. L. & Bissell, Mina
Partner: UNT Libraries Government Documents Department

Involvement of extracellular matrix constituents in breast cancer

Description: It has recently been established that the extracellular matrix is required for normal functional differentiation of mammary epithelia not only in culture, but also in vivo. The mechanisms by which extracellular matrix affects differentiation, as well as the nature of extracellular matrix constituents which have major impacts on mammary gland function, have only now begun to be dissected. The intricate variety of extracellular matrix-mediated events and the remarkable degree of plasticity of extracellular matrix structure and composition at virtually all times during ontogeny, make such studies difficult. Similarly, during carcinogenesis, the extracellular matrix undergoes gross alterations, the consequences of which are not yet precisely understood. Nevertheless, an increasing amount of data suggests that the extracellular matrix and extracellular matrix-receptors might participate in the control of most, if not all, of the successive stages of breast tumors, from appearance to progression and metastasis.
Date: June 1, 1995
Creator: Lochter, Andre & Bissell, Mina J
Partner: UNT Libraries Government Documents Department

Mechanism of Excretion of a Bacterial Proteinase: Factors Controlling Accumulation of the Extracellular Proteinase of a Sarcina Strain (Coccus P)

Description: It has been known that the extracellular proteinase of Coccus P is found only in cultures grown in the presence of Ca{sup 2+}. It is now shown that this cation is required neither for synthesis, excretion, or activation of a zymogen nor as a prosthetic factor necessary for enzymatic activity. The only function of Ca{sup 2+} is to stabilize the active structure of the enzyme molecule, presumably by substituting for absence of S-S bridges. In the absence of Ca{sup 2+} , the excreted proteinase undergoes rapid autodigestion and, instead of the active protein, its hydrolytic products are accumulated in the culture fluid. In minimal medium and under conditions of enzyme stability [presence of Ca{sup 2+} and Ficoll (Pharmacia)], Coccus P accumulates the proteinase at a gradually reduced speed although the rate of cultural growth remains constant. It is shown that this decline in rate of accumulation is caused by the excreted proteinase itself, possibly acting on its own precursor emerging from the cell in a form susceptible to proteolytic attack and not amenable to Ca{sup 2+} protection. A proteinase precursor is actually demonstrable in a calciumless culture at the onset of the enzyme accumulation which follows Ca{sup 2+} addition. It is suggested that excreted proteins require an unfolded (or incompletely folded) structure to cross the cell envelope. The proteinase excreted by a Sarcina strain (Coccus P) is found only in cultures containing Ca{sup 2+} ions (1), a feature common to proteinases of other bacteria (4, 12, 18) and to other excreted enzymes (14). Among the nontoxic divalent cations, Ca{sup 2+} is rather specific in this effect. Other ions such as Mn{sup 2+} or Mg{sup 2+}, the latter being present in all media as an indispensible growth factor, are ineffective. Addition of Ca{sup 2+} to the proteolytically inactive supernatant fluid of ...
Date: June 29, 1970
Partner: UNT Libraries Government Documents Department


Description: Iodoacetamide has been shown by others to be a radiation sensitizer for bacteria and for certain mammalian cells tested in vitro. This work describes an examination of the effectiveness of iodoacetamide used in vivo. Survival of ascites tumor cells maintained in the peritoneal cavity of mice was used as an indicator of sensitization. Survival was assessed using TD{sub 50} and total tumor cell population determination methods. A comparison of results obtained by these methods is made. The effects of oxygen tension and radiation dose rate upon results was examined. Iodoacetamide was found to be effective as a radiation sensitizer under all conditions although to a lesser degree than that reported by others for in vitro experiments with bacteria. Radioactive tracer studies indicate that iodoacetamide has rapid and total access to most if not all tissues of the body. This fact coupled with the observation of a sensitization in an in vivo system where the anoxia so prevalent in well developed tumors was present, suggests the possibility of clinical usefulness of iodoacetamide in cancer radiation therapy. Certain observations are reported on the effect of various cell and host treatment procedures upon cell population growth kinetics seen subsequent to inoculation of hosts with the cells. A hypothesis is presented which can account for the observations made by the author and also for those made by some others who report that large inocula, i.e., greater than 10 cells, are required to give rise to a lethal tumor in isologous hosts of the strain of tumor origin. The hypothesis may also account for what is known in the literature as the 'Hybrid Effect.'
Date: October 1, 1970
Creator: Richards, F. Robert & Kelly, Lola S.
Partner: UNT Libraries Government Documents Department

Suppression of Apoptosis by Basement Membrane Requires three-dimensional Tissue Organization and Withdrawal from the Cell Cycle

Description: The basement membrane (BM) extracellular matrix induces differentiation and suppresses apoptosis in mammary epithelial cells, whereas cells lacking BM lose their differentiated phenotype and undergo apoptosis. Addition of purified BM components, which are known to induce {beta}-casein expression, did not prevent apoptosis, indicating that a more complex BM was necessary. A comparison of culture conditions where apoptosis would or would not occur allowed us to relate inhibition of apoptosis to a complete withdrawal from the cell cycle, which was observed only when cells acquired a three-dimensional alveolar structure in response to BM. In the absence of this morphology, both the G1 cyclin kinase inhibitor p21/WAF-I and positive proliferative signals including c-myc and cyclin Dl were expressed and the retinoblastoma protein (Rb) continued to be hyperphosphorylated. When we overexpressed either c-myc in quiescent cells or p21 when cells were still cycling, apoptosis was induced. In the absence of three-dimensional alveolar structures, mammary epithelial cells secrete a number of factors including transforming growth factor a and tenascin, which when added exogenously to quiescent cells induced expression of c-myc and interleukin-{beta}1-converting enzyme (ICE) mRNA and led to apoptosis. These experiments demonstrate that a correct tissue architecture is crucial for long-range homeostasis, suppression of apoptosis, and maintenance of differentiated phenotype.
Date: December 28, 1995
Creator: Boudreau, N.; Werb, Z. & Bissell, M.J.
Partner: UNT Libraries Government Documents Department

DNA repair efficiency in germ cells and early mouse embryos and consequences for radiation-induced transgenerational genomic damage

Description: Exposure to ionizing radiation and other environmental agents can affect the genomic integrity of germ cells and induce adverse health effects in the progeny. Efficient DNA repair during gametogenesis and the early embryonic cycles after fertilization is critical for preventing transmission of DNA damage to the progeny and relies on maternal factors stored in the egg before fertilization. The ability of the maternal repair machinery to repair DNA damage in both parental genomes in the fertilizing egg is especially crucial for the fertilizing male genome that has not experienced a DNA repair-competent cellular environment for several weeks prior to fertilization. During the DNA repair-deficient period of spermatogenesis, DNA lesions may accumulate in sperm and be carried into the egg where, if not properly repaired, could result in the formation of heritable chromosomal aberrations or mutations and associated birth defects. Studies with female mice deficient in specific DNA repair genes have shown that: (i) cell cycle checkpoints are activated in the fertilized egg by DNA damage carried by the sperm; and (ii) the maternal genotype plays a major role in determining the efficiency of repairing genomic lesions in the fertilizing sperm and directly affect the risk for abnormal reproductive outcomes. There is also growing evidence that implicates DNA damage carried by the fertilizing gamete as a mediator of postfertilization processes that contribute to genomic instability in subsequent generations. Transgenerational genomic instability most likely involves epigenetic mechanisms or error-prone DNA repair processes in the early embryo. Maternal and embryonic DNA repair processes during the early phases of mammalian embryonic development can have far reaching consequences for the genomic integrity and health of subsequent generations.
Date: January 18, 2009
Creator: Marchetti, Francesco & Wyrobek, Andrew J.
Partner: UNT Libraries Government Documents Department

Protein Kinase CK2 Regulates Cytoskeletal Reorganization during Ionizing Radiation-Induced Senescence of Human Mesenchymal Stem Cells

Description: Human mesenchymal stem cells (hMSC) are critical for tissue regeneration. How hMSC respond to genotoxic stresses and potentially contribute to aging and cancer remain underexplored. We demonstrated that ionizing radiation induced cellular senescence of hMSC over a period of 10 days, showing a critical transition between day 3 and day 6. This was confirmed by senescence-associated beta-galactosidase (SA-{beta}-gal) staining, protein expression profiles of key cell cycle regulators (retinoblastoma (Rb) protein, p53, p21{sup waf1/Cip1}, and p16{sup INK4A}), and senescence-associated secretory phenotypes (SASPs) (IL-8, IL-12, GRO, and MDC). We observed dramatic cytoskeletal reorganization of hMSC through reduction of myosin-10, redistribution of myosin-9, and secretion of profilin-1. Using a SILAC-based phosphoproteomics method, we detected significant reduction of myosin-9 phosphorylation at Ser1943, coinciding with its redistribution. Importantly, through treatment with cell permeable inhibitors (4,5,6,7-tetrabromo-1H-benzotriazole (TBB) and 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT)), and gene knockdown using RNA interference, we identified CK2, a kinase responsible for myosin-9 phosphorylation at Ser1943, as a key factor contributing to the radiation-induced senescence of hMSC. We showed that individual knockdown of CK2 catalytic subunits CK2{alpha} and CK2{alpha}{prime} induced hMSC senescence. However, only knockdown of CK2{alpha} resulted in morphological phenotypes resembling those of radiation-induced senescence. These results suggest that CK2{alpha} and CK2{alpha}{prime} play differential roles in hMSC senescence progression, and their relative expression might represent a novel regulatory mechanism for CK2 activity.
Date: August 21, 2009
Creator: Wang, Daojing & Jang, Deok-Jin
Partner: UNT Libraries Government Documents Department

Prototype Vector Machine for Large Scale Semi-Supervised Learning

Description: Practicaldataminingrarelyfalls exactlyinto the supervisedlearning scenario. Rather, the growing amount of unlabeled data poses a big challenge to large-scale semi-supervised learning (SSL). We note that the computationalintensivenessofgraph-based SSLarises largely from the manifold or graph regularization, which in turn lead to large models that are dificult to handle. To alleviate this, we proposed the prototype vector machine (PVM), a highlyscalable,graph-based algorithm for large-scale SSL. Our key innovation is the use of&quot;prototypes vectors&quot; for effcient approximation on both the graph-based regularizer and model representation. The choice of prototypes are grounded upon two important criteria: they not only perform effective low-rank approximation of the kernel matrix, but also span a model suffering the minimum information loss compared with the complete model. We demonstrate encouraging performance and appealing scaling properties of the PVM on a number of machine learning benchmark data sets.
Date: April 29, 2009
Creator: Zhang, Kai; Kwok, James T. & Parvin, Bahram
Partner: UNT Libraries Government Documents Department


Description: Biological images have the potential to reveal complex signatures that may not be amenable to morphological modeling in terms of shape, location, texture, and color. An effective analytical method is to characterize the composition of a specimen based on user-defined patterns of texture and contrast formation. However, such a simple requirement demands an improved model for stability and robustness. Here, an interactive computational model is introduced for learning patterns of interest by example. The learned patterns bound an active contour model in which the traditional gradient descent optimization is replaced by the more efficient optimization of the graph cut methods. First, the energy function is defined according to the curve evolution. Next, a graph is constructed with weighted edges on the energy function and is optimized with the graph cut algorithm. As a result, the method combines the advantages of the level set method and graph cut algorithm, i.e.,&quot;topological&quot; invariance and computational efficiency. The technique is extended to the multi-phase segmentation problem; the method is validated on synthetic images and then applied to specimens imaged by transmission electron microscopy(TEM).
Date: May 8, 2009
Creator: Chang, Hang; Auer, Manfred & Parvin, Bahram
Partner: UNT Libraries Government Documents Department