gebhart/patrepeval huggingface dataset:
Comparative Morphology and Biochemistry of Pancreatic Tissue Fragments Transplanted into the Anterior Eye Chamber and Subcutaneous Regions of the Rat (2001)

The present study was designed to compare the morphological changes occurring in pancreatic tissue fragments transplanted into the anterior eye chamber (AEC) and the subcutaneous (SC) regions of the rat. Pancreatic tissue segments were removed from the tail end of the pancreas of neonatal rats and transplanted into the AEC and SC region of the neck of homologous rats. Five weeks after transplantation, the grafts were removed and processed for light microscopy, immunohistochemistry and radioimmunoassay. In both pancreatic tissue grafts, the acinar cells degenerated completely after transplantation. In contrast to this, insulin-, glucagon-, somatostatin- and pancreatic polypeptide-positive cells and pancreatic ducts survived equally well in both the AEC and SC grafts. The pattern and percentage distribution of insulin-, glucagon-, somatostatin- and PP-producing cells in the AEC and SC grafts was similar to that observed in normal pancreas. However, the percentage distribution of glucagon- and PP-containing cells was significantly (p < 0.03) lower in SC grafts when compared to normal. Radioimmunoassay showed that the AEC and SC pancreatic tissue grafts contained large quantities of insulin and glucagon. However, the insulin content of AEC was slightly but not significantly higher than that of SC grafts. The protein content of pancreatic tissue grafts in these transplantation sites was still significantly (p < 0.05) lower compared to normal. Lymphatic infiltration was also more conspicuous in SC grafts compared to AEC grafts. This infiltration by lymphatic cells was confined only to the endocrine portion of the graft. In conclusion, pancreatic tissue grafts survived in both the AEC and SC regions of rats but the AEC appears to be more conducive to graft survival than the SC region.
The mechanism of action of decay-accelerating factor (DAF). DAF inhibits the assembly of C3 convertases by dissociating C2a and Bb. (1987)

DAF is a 70,000-Mr membrane protein that inhibits the amplification of the complement cascade on the cell surface, and protects cells from damage by complement. The precise mechanism of action of DAF is not entirely clear. Purified DAF was incorporated into the membrane of EAC4b cells. EAC4b2 and EDAF AC4b2 cells were prepared with radiolabeled C2. The same amount of labeled C2 bound to both cells, showing that DAF does not prevent the binding of C2 zymogen to C4b. After adding Cl, the radioactivity of bound C2 dissociated more rapidly from EDAF AC4b cells than from EAC4b cells. In EAC4b cells, bound C2 was converted to C2a, which gradually dissociated into the supernatants. In the DAF-treated cells, on the other hand, a large amount of C2a rapidly appeared in the supernatants and only a small amount of C2a remained on the cells. In a similar experiment using EhuAC4b, DAF on human erythrocyte membrane also dissociated the C2a from the cells. These results were confirmed by hemolytic assay and the accelerated decay of C2a caused the rapid depletion of C2 from the fluid phase. In addition, we found that DAF functions on the alternative pathway C3 convertase, C3bBb in the same manner. Thus, DAF, which associates with C4b and C3b in the membrane, acts on C2a and Bb, but not on intact C2 and B, and dissociates them rapidly from the binding sites, thereby preventing the assembly of the classical and alternative pathways C3 convertases.
Comparison of estrogen receptor DNA binding in untreated and acquired antiestrogen-resistant human breast tumors. (1997)

Preliminary studies have suggested that measuring the ability of immunoreactive 67-kDa estrogen receptor (ER) to bind DNA and form in vitro complexes with its cognate estrogen response element (ERE) might serve to identify breast tumors most likely to respond to antiestrogens like tamoxifen. Data from two different surveys of untreated primary breast tumors confirmed that only 67% (74 of 111) of ER-positive tumors express a receptor capable of forming ER-ERE complexes by gel-shift assay, with tumors of lower ER content having significantly reduced ER DNA-binding frequency (56%) relative to those of higher ER content (82%; P = 0.007). In contrast to these untreated tumors, a panel of 41 receptor-positive breast tumors excised after acquiring clinical resistance to tamoxifen during either primary (n = 26) or adjuvant therapy (n = 15) showed a significantly greater ER DNA-binding frequency, with nearly 90% capable of forming ER-ERE complexes (P < 0.02). To assess experimentally whether ER DNA-binding function is altered during the development of antiestrogen resistance, nude mouse MCF-7 tumor xenografts were analyzed before and after the acquisition of in vivo resistance to either tamoxifen or a pure steroidal antiestrogen, ICI 182,780. Tamoxifen-resistant MCF-7 tumors retained full expression of 67-kDa DNA-binding ER, and despite a markedly reduced ER content in the ICI 182,780-treated tumors, the expressed ER in these antiestrogen-resistant tumors exhibited full ability to form ER-ERE complexes. These findings indicate that breast tumors with acquired antiestrogen resistance continue to express ER of normal size and DNA-binding ability and suggest that the failure of antiestrogens to arrest tumor growth during emergence of clinical resistance results from an altered gene-regulatory mechanism(s) other than ER-ERE complex formation.
Network Structure and Strong Microphase Separation for High Ion Conductivity in Polymerized Ionic Liquid Block Copolymers (2013)

A series of strongly microphase-separated polymerized ionic liquid (PIL) diblock copolymers, poly(styrene-b-1-((2-acryloyloxy)ethyl)-3-butylimidazolium bis(trifluoromethanesulfonyl)imide) (poly(S-b-AEBIm-TFSI)), were synthesized to explore relationships between morphology and ionic conductivity. Using small-angle X-ray scattering and transmission electron microscopy, a variety of self-assembled nanostructures including hexagonally packed cylinders, lamellae, and coexisting lamellae and network morphologies were observed by varying PIL composition (6.6–23.6 PIL mol %). At comparable PIL composition, this acrylate-based PIL block copolymer with strong microphase separation exhibited ∼1.5–2 orders of magnitude higher ionic conductivity than a methacrylate-based PIL block copolymer with weak microphase separation. Remarkably, we achieved high ionic conductivity (0.88 mS cm–1 at 150 °C) and a morphology factor (normalized ionic conductivity, f) of ∼1 through the morphological transition from lamellar to a coexistence of lamellar and three-dimensional network morphologies with increasing PIL composition in anhydrous single-ion conducting PIL block copolymers, which highlights a good agreement with the model predictions. In addition to strong microphase separation and the connectivity of conducting microdomains, the orientation of conducting microdomains and the compatibility between polymer backbone and IL moiety of PIL also significantly affect the ionic conductivity. This study provides avenues to controlling the extent of microphase separation, morphology, and ion transport properties in PIL block copolymers for energy conversion and storage applications.
Tumor Microenvironment and Differential Responses to Therapy (2017)

Cancer evolution plays a key role in both the development of tumors and their response to therapy. Like all evolutionary processes, tumor evolution is shaped by the environment. In tumors, this consists of a complex mixture of nontransformed cell types and extracellular matrix. Chemotherapy or radiotherapy imposes further strong selective pressures on cancer cells during cancer treatment. Here, we review how different components of the tumor microenvironment can modulate the response to chemo- and radiotherapy. We further describe how therapeutic strategies directly alter the composition, or function, of the tumor microenvironment, thereby further altering the selective pressures to which cancer cells are exposed. Last, we explore the consequences of these interactions for therapy outcomes and how to exploit our increasing understanding of the tumor microenvironment for therapeutic benefit.
Cyclophosphamide and dimethyl dioctadecyl ammonium bromide immunopotentiate the delayed-type hypersensitivity response to inactivated enveloped viruses. (1986)

Immunization of BALB/c mice with measles virus inactivated with beta-propiolactone and mixed with 100 micrograms of the cationic surface-active lipid dimethyl dioctadecyl ammonium bromide (DDA) primes for a strong virus-specific delayed-type hypersensitivity (DTH) response that peaks 1 week later. Optimal immunization and challenge doses were found to be 8 and 4 micrograms/mouse, respectively, and pretreatment with 200 mg of cyclophosphamide/kg 2 days prior to immunization significantly enhanced the DTH response. When compared to Freund's complete and incomplete adjuvants, DDA was superior for induction of DTH to inactivated purified measles virus. As DDA could be administered to animals at a site different from the measles virus antigens, or 1 day previously, and still significantly enhance the DTH response, DDA is probably acting more as an immune modulator than as a simple adjuvant. The conditions for an optimal DTH response to measles virus were also shown to be applicable to other enveloped viruses, for example, a strong DTH response was similarly generated to inactivated purified influenza PR8 virus and to herpes simplex virus type I antigens present in plasma membranes isolated from infected Vero cells.
Techniques for conic splines (1985)

A number of techniques are presented for making conic splines more effective for 2D computer graphics. We give a brief account of the theory of conic splines oriented to computer graphics. We make Pitteway's algorithm exact, and repair an "aliasing" problem that has plagued the algorithm since its introduction in 1967. The curvature-matching problem for conics is solved by way of a simple formula for curvature at an endpoint which permits curvature to be matched exactly at non-inflectior points and more closely than was previously realized possible at points of inflection. A formula for minimum-curvature-variation of conic splines is given. These techniques provide additional support for Pavlidis' position [6] that conics can often be very effective as splines.The work was motivated by, and provides much of the foundation for, an implementation of conic splines at Sun Microsystems as part of Sun's Pixrect graphics package, the lowest layer of Sun's graphics support.
A Theory of Intensity Distribution in Band Systems (1926)

A theory of the relative intensity of the various bands in a system of electronic bands is developed by an extension of an idea used by Franck in discussing the dissociation of molecules by light absorption. The theory predicts the existence of two especially favored values of the change in the vibrational quantum numbers, in accord with the empirical facts as discussed by Birge.A means of calculating the intensity distribution from the known constants of the molecule is presented and shown to be in semi-quantitative agreement with the facts in the case of the following band systems: SiN, AlO, CO (fourth positive group of carbon), ${\mathrm{I}}_{2}$ (absorption), ${\mathrm{O}}_{2}$ (Schumann-Runge system), CN (violet system), CO (first negative group of carbon), ${\mathrm{N}}_{2}$ (second positive group of nitrogen), and ${\mathrm{N}}_{2}$ (first negative group of nitrogen).In the case of ${\mathrm{I}}_{2}$ there is a discrepancy, if Loomis' assignment of ${n}^{\ensuremath{'}\ensuremath{'}}$ values is used, which does not appear if Mecke's original assignment is used. It is suggested that at least some of the lower levels postulated by Mecke are real but that absorption from them always results in dissociation of the molecule and so they are not represented in the quantized absorption spectrum.
A Critical Look at Growth Factors and Epithelial-to-Mesenchymal Transition in the Adult Kidney (2006)

In the adult kidney, the cellular phenotypes are maintained by a strict balance of growth factors. Epithelial-to-mesenchymal transition (EMT) is a program whereby injured epithelial cells that function as ion and fluid transporters become matrix remodelling mesenchymal cells. This process requires either transcriptional repression of genes that maintain the epithelial phenotype and transcriptional activation, or relieved repression of genes needed for functional myofibroblasts. The transcriptional regulators are controlled by several integrated signalling pathways which are triggered by growth factors. Emerging evidence indicates that the growth factors TGFbeta/CTGF and BMP-7/HGF are the main determinants that maintain the two cellular phenotypes. Both TGFbeta and BMP-7 counteract the activity of each other by cross-inducing their respective inhibitory Smads. Both growth factors may also induce the expression of other factors that can change the cellular environment and enhance their function. Chronic kidney diseases (regardless of the aetiology of the disease) are associated with increased TGFbeta and CTGF expression levels which, in turn, have an inverse effect on the activity level of BMP-7 and HGF, leading to an EMT of injured tubular epithelial cells and a progression of the disease. A detailed understanding of the complex interrelationship between these growth factors may lead to the development of novel drugs.
Transcriptional regulation of the aconitase genes (acnA and acnB) of Escherichia coli (1997)

Escherichia coli contains two differentially regulated aconitase genes, acnA and acnB. Two acnA promoters transcribing from start points located 407 bp (P1acnA) and 50 bp (P2acnA) upstream of the acnA coding region, and one acnB promoter (PacnB) with a start point 95 bp upstream of the acnB coding region, were identified by primer extension analysis. A 2.8 kb acnA monocistronic transcript was detected by Northern blot hybridization, but only in redox-stressed (methyl-viologen-treated) cultures, and a 2.5 kb acnB monocistronic transcript was detected in exponential- but not stationary-phase cultures. These findings are consistent with previous observations that acnA is specifically subject to SoxRS-mediated activation, whereas acnB encodes the major aconitase that is synthesized earlier in the growth cycle than AcnA. Further studies with acn-lacZ gene fusions and a wider range of transcription regulators indicated that acnA expression is initiated by sigma 38 from P1acnA, and from P2acnA it is activated directly or indirectly by CRP, FruR, Fur and SoxRS, and repressed by ArcA and FNR. In contrast, acnB expression is activated by CRP and repressed by ArcA, FruR and Fis from PacnB. Comparable studies with fum-lacZ fusions indicated that transcription of fumC, but not of fumA or fumB, is initiated by RNA polymerase containing sigma 38. It is concluded that AcnB is the major citric acid cycle enzyme, whereas AcnA is an aerobic stationary-phase enzyme that is specifically induced by iron and redox-stress.
Approval Summary: Sunitinib for the Treatment of Imatinib Refractory or Intolerant Gastrointestinal Stromal Tumors and Advanced Renal Cell Carcinoma (2007)

On January 26, 2006, the FDA approved sunitinib for the treatment of patients with imatinib refractory or intolerant GIST. Accelerated approval was granted for the treatment of advanced renal cell carcinoma.
The gene that encodes the human CD20 (B1) differentiation antigen is located on chromosome 11 near the t(11;14)(q13;q32) translocation site. (1989)

The human CD20 gene (B1) encodes a B lymphocyte-specific, cell-surface molecule that is involved in B cell activation and differentiation. We report that the CD20 gene is located on human chromosome 11 at position q12-q13. The location of CD20 was determined by in situ hybridization and was further confirmed by Southern blot analysis of DNA from rodent/human hybrids that contained only portions of human chromosome 11. This localization places the CD20 gene near the site of the t(11;14)(q13;q32) translocation that is found in a subgroup of B cell-lineage malignancies. The site of this translocation has been previously identified by DNA cloning and termed bcl-1. The CD20 gene was found to lie on the centromeric side of bcl-1 on chromosome 11 and to be separated from bcl-1 by at least 50 kb of DNA. These results raise the possibility that alterations in the expression of the CD20 gene may result after the t(11;14) chromosomal alteration.
Mitotic checkpoint genes in budding yeast and the dependence of mitosis on DNA replication and repair. (1994)

In eukaryotes a cell-cycle control termed a checkpoint causes arrest in the S or G2 phases when chromosomes are incompletely replicated or damaged. Previously, we showed in budding yeast that RAD9 and RAD17 are checkpoint genes required for arrest in the G2 phase after DNA damage. Here, we describe a genetic strategy that identified four additional checkpoint genes that act in two pathways. Both classes of genes are required for arrest in the G2 phase after DNA damage, and one class of genes is also required for arrest in S phase when DNA replication is incomplete. The G2-specific genes include MEC3 (for mitosis entry checkpoint), RAD9, RAD17, and RAD24. The genes common to both S phase and G2 phase pathways are MEC1 and MEC2. The MEC2 gene proves to be identical to the RAD53 gene. Checkpoint mutants were identified by their interactions with a temperature-sensitive allele of the cell division cycle gene CDC13; cdc13 mutants arrested in G2 and survived at the restrictive temperature, whereas all cdc13 checkpoint double mutants failed to arrest in G2 and died rapidly at the restrictive temperature. The cell-cycle roles of the RAD and MEC genes were examined by combination of rad and mec mutant alleles with 10 cdc mutant alleles that arrest in different stages of the cell cycle at the restrictive temperature and by the response of rad and mec mutant alleles to DNA damaging agents and to hydroxyurea, a drug that inhibits DNA replication. We conclude that the checkpoint in budding yeast consists of overlapping S-phase and G2-phase pathways that respond to incomplete DNA replication and/or DNA damage and cause arret of cells before mitosis.
Radioimmunoassay for Human Follicle-Stimulating Hormone1 (1967)

Journal Article Radioimmunoassay for Human Follicle-Stimulating Hormone Get access A. REES MIDGLEY A. REES MIDGLEY 1Department of Pathology, The University of Michigan Ann Arbor, Michigan 48104 Search for other works by this author on: Oxford Academic Google Scholar The Journal of Clinical Endocrinology & Metabolism, Volume 27, Issue 2, 1 February 1967, Pages 295–299, https://doi.org/10.1210/jcem-27-2-295 Published: 01 February 1967 Article history Received: 26 September 1966 Accepted: 10 November 1966 Published: 01 February 1967
Structural Determinants in the Platelet-derived Growth Factor α-Receptor Implicated in Modulation of Chemotaxis (1996)

Activation of the platelet-derived growth factor (PDGF) beta-receptor leads to cell growth and chemotaxis. The PDGF alpha-receptor also mediates a mitogenic signal, but fails to induce cell migration in certain cell types. To examine this difference in signal transduction, a series of point-mutated PDGF alpha-receptors were analyzed. Porcine aortic endothelial cells expressing mutant PDGF alpha-receptors, in which tyrosine residues 768, 993, or 1018 were changed to phenylalanine residues migrated toward PDGF, whereas wild-type alpha-receptors and mutant alpha-receptors changed at tyrosine residues 720, 944, or 988 failed to migrate. All mutant receptors were mitogenically active and their capacity to activate phosphatidylinositol 3'-kinase and phospholipase C-gamma was not different from that of the wild-type receptor. Tyr-768 was found to be phosphorylated in PDGF-stimulated cells; in the Y768F mutant, there was a considerable increase in phosphorylation of Ser-767. Tyr-993 was not phosphorylated, but mutation of this tyrosine residue to a phenylalanine residue resulted in increased efficiency of phosphorylation on Tyr-988. Tyr-1018 is known to be an autophosphorylation site. Phosphorylated Tyr-768 and Tyr-1018 may bind signal transduction molecules involved in negative modulation of the chemotactic signaling capacity, whereas phosphorylated Tyr-988 may mediate increased chemotaxis. Thus our data indicate that the PDGF alpha-receptor has an intrinsic ability to transduce a chemotactic signal, and that this signal is counteracted by overriding negative signals.
Spatiotemporal control of gene expression with pulse-generating networks (2004)

One of the important challenges in the emerging field of synthetic biology is designing artificial networks that achieve coordinated behavior in cell communities. Here we present a synthetic multicellular bacterial system where receiver cells exhibit transient gene expression in response to a long-lasting signal from neighboring sender cells. The engineered sender cells synthesize an inducer, an acyl-homoserine lactone (AHL), which freely diffuses to spatially proximate receiver cells. The receiver cells contain a pulse-generator circuit that incorporates a feed-forward regulatory motif. The circuit responds to a long-lasting increase in the level of AHL by transiently activating, and then repressing, the expression of a GFP. Based on simulation models, we engineered variants of the pulse-generator circuit that exhibit different quantitative responses such as increased duration and intensity of the pulse. As shown by our models and experiments, the maximum amplitude and timing of the pulse depend not only on the final inducer concentration, but also on its rate of increase. The ability to differentiate between various rates of increase in inducer concentrations affords the system a unique spatiotemporal behavior for cells grown on solid media. Specifically, receiver cells can respond to communication from nearby sender cells while completely ignoring communication from senders cells further away, despite the fact that AHL concentrations eventually reach high levels everywhere. Because of the resemblance to naturally occurring feed-forward motifs, the pulse generator can serve as a model to improve our understanding of such systems.
Small interfering RNA targeting Fas protects mice against renal ischemia-reperfusion injury (2004)

Fas-mediated apoptosis has been suggested to contribute to tubular cell death after renal ischemia-reperfusion injury. Here we investigate whether small interfering RNA (siRNA) duplexes targeting Fas protect mice from acute renal failure after clamping of the renal artery. Renal ischemia-reperfusion injury was induced by clamping the renal vein and artery for 15 or 35 min. Mice were treated before or after ischemia with siRNA targeting Fas or a control gene, administered by hydrodynamic injection, low-volume renal vein injection, or both. Treated mice were evaluated for renal Fas protein and mRNA expression, tissue histopathology, and apoptosis by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) staining. Blood urea nitrogen and survival were monitored in mice in which the contralateral kidney had been removed. A single hydrodynamic injection of Fas siRNA reduced Fas mRNA and protein expression in the kidney 4-fold. Kidneys from mice that received Fas siRNA two days earlier had substantially less renal tubular apoptosis by TUNEL staining and less tubular atrophy and hyaline damage. Whereas 90% of mice pretreated with saline or GFP siRNA died, only 20% of Fas-siRNA-pretreated animals died. The same survival advantage was provided by a single low-volume Fas siRNA injection into the renal vein. Moreover, postischemic injection through the renal vein protected 38% of mice from death. This study confirms the importance of Fas-mediated apoptosis in renal ischemia-reperfusion injury. Silencing Fas by systemic or local catheterization holds therapeutic promise to limit ischemia-reperfusion injury.