gebhart/patrepeval huggingface dataset:
Conditionally replicative adenoviruses for ovarian cancer therapy. (2002)

The purpose of this review article is to present a logical rationale for the investigation of conditionally replicative adenoviral vectors for the treatment of ovarian carcinoma. A medline database search was performed to identify relevant articles in the English language for the years 1966 to present. The key words used included replicative adenovirus, conditionally replicative adenovirus, transcriptional targeting, replication selective adenovirus, and "ONYX." A total of 89 references were identified and reviewed. Each reference was reviewed for relevance to clinical translation of conditionally replicative adenoviral vector therapy for ovarian cancer. Data from current clinical trials would suggest that potential obstacles for effective replicative viral therapy of ovarian carcinoma include efficient tumor cell infection, restrictions of the cell surface coxsackie and adenovirus receptor, rapid clearance of vector in the ascites environment, tumor cells specificity, and limitations of current findings of clinical trials. The articles were, therefore, evaluated and included if they addressed these shortcomings. Current data would suggest that advanced generation conditionally replicative adenoviral vectors will soon be available for clinical trials in ovarian cancer. Ovarian cancer, because of expression of targetable receptors, transducible cells, and containment within the i.p. cavity, represents a solid tumor suited uniquely for investigation with advanced generation conditionally replicative adenoviral vectors.
Perfluoroalkyl Acid Uptake in Lettuce (Lactuca sativa) and Strawberry (Fragaria ananassa) Irrigated with Reclaimed Water (2014)

Using reclaimed water to irrigate food crops presents an exposure pathway for persistent organic contaminants such as perfluoroalkyl acids (PFAAs) to enter the human food chain. This greenhouse study used reclaimed water augmented with varying concentrations (0.2-40 μg/L) of PFAAs, including perfluorocarboxylates (C3F7COO(-) to C8F17COO(-)) and perfluorosulfonates (C4F9SO2O(-), C6F13SO2O(-), C8F17SO2O(-)), to investigate potential uptake and concentration-response trends in lettuce (Lactuca sativa) and strawberry (Fragaria ananassa). In addition, studies were conducted to evaluate the role of soil organic carbon concentrations on plant uptake of PFAAs. PFAA concentrations in lettuce leaves and strawberry fruit were measured for each aqueous PFAA concentration applied. PFAA plant concentrations increased linearly with the aqueous concentration for all PFAAs, with PFCAs bioaccumulating to a greater degree than PFSAs in the edible portions of the tested plants. Chain-length-dependency trends were evident in both lettuce shoot and strawberry fruit, with decreasing concentrations associated with increasing chain length. Perfluorobutanoate (PFBA) and perfluoropentanoate (PFPeA), both short-chain PFAAs (<8 carbon chain length), accumulated the most compared with other PFAAs tested in the edible parts of both lettuce and strawberry. PFAA concentrations in strawberry root and shoot were also measured at selected PFAA aqueous concentrations (0.4, 4, and 40 μg/L). Short-chain perfluorocarboxylates were the dominant fraction in the strawberry fruit and shoot compartments, whereas a more even distribution of all PFAAs appeared in the root compartment. Lettuce grown in soils with varying organic carbon contents (0.4%, 2%, 6%) was used to assess the impact of organic carbon sorption on PFAA bioaccumulation. The lettuce grown in soil with the 6% organic carbon content had the lowest bioaccumulation of PFAAs. Bioaccumulation factors for lettuce were correlated to carbon chain length of PFAAs, showing approximately a 0.4 to 0.6 log decrease per CF2 group. This study confirms that PFAAs can enter and bioaccumulate in food crops irrigated with reclaimed water. Bioaccumulation potential depends on analyte functional group and chain length, concentration in the reclaimed water, and organic carbon content of the soil.
Characterization of Molecular Interactions of Mytilus edulis Foot Proteins on Model Hydrated Surfaces (2001)

Abstract : The sea mussel Mytilus edulis adheres tenaciously to surfaces that exhibit a wide range of properties in seawater. A study was conducted to gain a better understanding of the interactions between two of the mussel foot proteins found in the adhesive plaque (Mefp-1 and Mefp-2) and several substrata with different surface properties (germanium, polystyrene and poly (octadecyl methacrylate). Mefp-1 excludes Mefp-2 from a germanium surface until the L-dopa residues of Mefp-1 are converted to the quinone form, suggesting that Mefp-1 is a hi-functional primer that requires activation by a catechol oxidase. However, Mefp-2 adsorbs to germanium, polystyrene and poly (octadecyl methacrylate) at least as strongly as Mefp-1,indicating that Mefp-1 does not possess unique properties that allows it to out-perform other mussel foot proteins in forming an adhesive bond with the substratum. We also tested the hypothesis that nucleophilic addition of the epsilon-amino groups of lysine residues into the oxidized catechol functionality (quinone) of the L-dopa residues in Mefp-1 is a cross-linking reaction in the plaque. Experimental results did not support this hypothesis. The plaque-forming reactions responsible for mussel adhesion to surfaces remain elusive.
C-Glycosylation of Substituted Heterocycles Under Friedel-Crafts Conditions (II): Ribosylation of Multi-Functionalized Thiophenes and Furans for the Synthesis of Purine-Like C-Nucleosides (1990)

Abstract In our continuing studies of the Friedel-Crafts glycosylation of preformed heterocycles, we have observed that while the SnCl4 catalyzed glycosylation of methyl 4-(formylamino)thiophene-3-carboxylate (5) gives readily the C-nucleosides 7b and 7a, the corresponding Et2AlCl catalyzed reaction gives exclusively the N-nucleoside 11. These nucleosides can be further elaborated into the bicyclic thieno[3,4-d]-pyrimidine system. Similarly, methyl 4-(formylamino)furan-3-carboxylate (19) gave the expected C-nucleosides 2Ob and 2Oa upon glycosylation in the presence of SnCl4. However, these nucleosides could not be converted into the furo[3,4-d]pyrimidine system. Interestingly, several of the N-formamido compounds exhibit pronounced rotational isomerism, which was demonstrated by 1H NMR spectroscopy
A transferrin-like GPI-linked iron-binding protein in detergent-insoluble noncaveolar microdomains at the apical surface of fetal intestinal epithelial cells. (1995)

A GPI-anchored 80-kD protein was found to be the major component of detergent-insoluble complexes, prepared from fetal porcine small intestine, constituting about 25% of the total amount of protein. An antibody was raised to the 80-kD protein, and by immunogold electron microscopy of ultracryosections of mucosal tissue, the protein was localized to the apical surface of the enterocytes, whereas it was absent from the basolateral plasma membrane. Interestingly, it was mainly found in patches of flat or invaginated apical membrane domains rather than at the surface of microvilli. Caveolae were not found in association with these labeled microdomains. In addition, the 80-kD protein was seen in apical endocytic vacuoles and in tubulo-vesicular structures, suggesting that the apical microdomains are involved in endocytosis of the 80-kD protein. By its NH2-terminal amino acid sequence, iron-binding capacity and partial immunological cross-reactivity with serum transferrin, the 80-kD protein was shown to belong to the transferrin family, and it is probably homologous to melanotransferrin, a human melanoma-associated antigen. The 80-kD iron-binding protein was fully detergent-soluble immediately after synthesis and only became insoluble after gaining resistance to endo H, supporting a mechanism for exocytic delivery to the apical cell surface by way of detergent-insoluble glycolipid "rafts" that fuse with the plasmalemma at restricted sites devoid of microvilli.
Simple Estimates of the Electron Transport Properties of Molecules (2002)

We discuss how the complex bandstructure describes tunneling within a molecule, and how it can be used to understand single molecule conduction. Simple estimates of the conduction properties of some molecules can be obtained with minimal (or no) computational effort. Examples considered include tunneling current through SiO2, transistor action of biphenyl-dithiol, the effect of benzene ring rotation on tunneling through polyphenyl chains, and a “designed” molecule which – according to the form of its complex bandstructure – may function as a p-channel transistor.
8–37h‐CGRP antagonizes actions of amylin on carbohydrate metabolism in vitro and in vivo (1991)

8-37hCGRP is a potent antagonist at calcitonin gene-related peptide (CGRP) liver membrane receptors; it also blocks vasodilator actions of CGRP and the related peptide, amylin, in intact rats. We now report that 8-37hCGRP antagonizes amylin inhibition of insulin-stimulated labelled glucose uptake into isolated rat soleus muscle, and inhibits amylin-evoked elevation of plasma lactate and glucose in fasted anaesthetized rats. The different relative potencies of the 3 ligands (amylin, CGRP, 8-37hCGRP) on the liver receptor and on the soleus muscle point to distinct CGRP receptors in liver membranes and amylin receptors on muscle cells.
Geldanamycin induces degradation of hypoxia-inducible factor 1alpha protein via the proteosome pathway in prostate cancer cells. (2002)

Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor composed of alpha and beta subunits. HIF-1 is critically involved in cellular responses to hypoxia, glycolysis, and angiogenesis. Here, we show that treatment of prostate cancer PC-3 and LNCaP cells with the benzoquinone ansamycin geldanamycin, an Hsp90-specific inhibitor, induced degradation of HIF-1alpha protein in a dose- and time-dependent manner under both normoxia and hypoxia. This inhibition was also shown in other common cancer types tested. Rapid degradation of nuclear HIF-1alpha protein levels was accompanied by respective inhibition in HIF-1alpha functional transcription activity of VEGF. No difference between HIF-1alpha mRNA levels before or after geldanamycin treatment was found. Moreover, [35S]methionine pulse-chase analysis revealed that HIF-1alpha protein half-life was markedly decreased in the presence of geldanamycin compared with that in control. The geldanamycin-induced degradation of HIF-1alpha was reversed by proteosome inhibitors lactacystin and MG-132. We conclude that geldanamycin induces reduction of HIF-1alpha levels and its downstream transcriptional activity by accelerating protein degradation independent of O2 tension. Thus, benzoquinone ansamycin drugs and their derivatives, such as 17-allyl-aminogeldanamycin, are excellent candidates as small molecule drug inhibitors of HIF-1 overexpression in cancer cells.
CFTR gene transfer with AAV improves early cystic fibrosis pig phenotypes (2016)

The physiological components that contribute to cystic fibrosis (CF) lung disease are steadily being elucidated. Gene therapy could potentially correct these defects. <i>CFTR</i>-null pigs provide a relevant model to test gene therapy vectors. Using an in vivo selection strategy that amplifies successful capsids by replicating their genomes with helper adenovirus coinfection, we selected an adeno-associated virus (AAV) with tropism for pig airway epithelia. The evolved capsid, termed AAV2H22, is based on AAV2 with 5 point mutations that result in a 240-fold increased infection efficiency. In contrast to AAV2, AAV2H22 binds specifically to pig airway epithelia and is less reliant on heparan sulfate for transduction. We administer AAV2H22-CFTR expressing the CF transmembrane conductance regulator (<i>CFTR</i>) cDNA to the airways of CF pigs. The transduced airways expressed CFTR on ciliated and nonciliated cells, induced anion transport, and improved the airway surface liquid pH and bacterial killing. Most gene therapy studies to date focus solely on Cl<sup>-</sup> transport as the primary metric of phenotypic correction. Here, we describe a gene therapy experiment where we not only correct defective anion transport, but also restore bacterial killing in <i>CFTR</i>-null pig airways.
Lipoplatin Formulation Review Article (2011)

Patented platform technologies have been used for the liposomal encapsulation of cisplatin (Lipoplatin) into tumor-targeted 110 nm (in diameter) nanoparticles. The molecular mechanisms, preclinical and clinical data concerning lipoplatin, are reviewed here. Lipoplatin has been successfully administered in three randomized Phase II and III clinical trials. The clinical data mainly include non-small-cell lung cancer but also pancreatic, breast, and head and neck cancers. It is anticipated that lipoplatin will replace cisplatin as well as increase its potential applications. For the first time, a platinum drug has shown superiority to cisplatin, at least in non-squamous non-small-cell lung cancer as reported in a Phase III study which documented a simultaneous lowering of all of the side effects of cisplatin.
Targeting IL-12/IL-23 by Employing a p40 Peptide-Based Vaccine Ameliorates TNBS-Induced Acute and Chronic Murine Colitis (2011)

Interleukin (IL)-12 and IL-23 both share the p40 subunit and are key cytokines in the pathogenesis of Crohn's disease. Previously, we have developed and identified three mouse p40 peptide-based and virus-like particle vaccines. Here, we evaluated the effects and immune mechanisms of the optimal vaccine in downregulating intestinal inflammation in murine acute and chronic colitis, induced by intrarectal administrations of trinitrobenzene sulfonic acid (TNBS). Mice were injected subcutaneously with vaccine, vaccine carrier or saline three times, and then intrarectally administered TNBS weekly for 2 wks (acute colitis) or 7 wks (chronic colitis). The severity of colitis was evaluated by body weight, histology and collagen and cytokine levels in colon tissue. Th1 and Th17 cells in mesenteric lymph nodes (MLN) were determined. Our results showed the vaccine induced high level and long-lasting specific IgG antibodies to p40, IL-12 and IL-23. After administrations of TNBS, vaccinated mice had significantly less body weight loss and a significant decrease of inflammatory scores, collagen deposition and expression of p40, IL-12, IL-23, IL-17, TNF, iNOS and Bcl-2 in colon tissues, compared with carrier and saline groups. Moreover, vaccinated mice exhibited a trend to lower percentages of Th1 cells in acute colitis and of Th17 cells in chronic colitis in MLN than in controls. In summary, administration of the vaccine induced specific antibodies to IL-12 and IL-23, which was associated with improvement of intestinal inflammation and fibrosis. This suggests that the vaccine may provide a potential approach for the long-term treatment of Crohn's disease.
Barrier-to-autointegration factor (BAF) bridges DNA in a discrete, higher-order nucleoprotein complex (2000)

Barrier-to-autointegration factor (BAF) is a highly conserved cellular protein that was identified by its activity in protecting retroviral DNA against autointegration. We show that BAF has the property of bridging double-stranded DNA in a highly ordered nucleoprotein complex. Whereas BAF protein alone is a dimer in solution, upon binding DNA, BAF forms a dodecamer with DNA bound at multiple discrete sites in the complex. The interactions between BAF and DNA are entirely nonspecific with respect to DNA sequence. The dual interaction of BAF with DNA and LAP2, a protein associated with the nuclear lamina, suggests a role for LAP2 in chromosome organization. Consistent with this idea, RNA interference experiments with Caenorhabditis elegans reveal a defect in mitosis.
Human squamous cell lung cancers express increased epidermal growth factor receptors. (1984)

Epidermal growth factor (EGF) promotes the growth of cultured benign and malignant cells. Recent studies have demonstrated that the amount of EGF receptor is elevated in squamous cell carcinoma cells in tissue culture when compared with normal epidermal cells. This study demonstrates that elevated levels of EGF receptor are detected in biopsy specimens of human squamous cell carcinomas of the lung with a murine monoclonal antibody, EGF-R1, which binds specifically to the receptor. The increased receptor ranged from 2.5- to 5-fold that of normal skin. These findings have been observed in 11 of 11 squamous carcinomas and two of two epidermoid head and neck cancers. Seven of eight adenocarcinomas, two of two small cell, and four of eight undifferentiated lung cancers had negligible amounts of EGF receptor. The EGF receptor antibody did not bind significantly to normal lung tissues and 35 nonepidermoid tumors. Therefore, EGF receptor may be an excellent marker for epidermoid malignancies.
<title>Silicon Liquid Crystal Light Valves: Status And Issues</title> (1983)

The structure, operation and performance of the silicon-based liquid crystal light valves: the photoactivated, CCD-addressed and visible-to-IR converter are described. The performance limitations of the readout structure, in particular, those affecting resolution, sensitivity, contrast ratio and speed, are discussed.
B lymphocyte stimulator levels in systemic lupus erythematosus: Higher circulating levels in African American patients and increased production after influenza vaccination in patients with low baseline levels (2011)

Our findings indicate that African American patients with SLE have higher BLyS levels regardless of disease activity. Humoral response to influenza vaccination is not correlated with baseline BLyS levels in SLE patients, and only those patients with low baseline BLyS levels demonstrate an increased BLyS response after vaccination.
Cell–cell contact between marrow stromal cells and myeloma cells via VCAM-1 and α4β1-integrin enhances production of osteoclast-stimulating activity (2000)

Abstract Myeloma is a unique hematologic malignancy that exclusively homes in the bone marrow and induces massive osteoclastic bone destruction presumably by producing cytokines that promote the differentiation of the hematopoietic progenitors to osteoclasts (osteoclastogenesis). It is recognized that neighboring bone marrow stromal cells influence the expression of the malignant phenotype in myeloma cells. This study examined the role of the interactions between myeloma cells and neighboring stromal cells in the production of osteoclastogenic factors to elucidate the mechanism underlying extensive osteoclastic bone destruction. A murine myeloma cell line 5TGM1, which causes severe osteolysis, expresses α4β1-integrin and tightly adheres to the mouse marrow stromal cell line ST2, which expresses the vascular cell adhesion molecule-1 (VCAM-1), a ligand for α4β1-integrin. Co-cultures of 5TGM1 with primary bone marrow cells generated tartrate-resistant acid phosphatase-positive multinucleated bone-resorbing osteoclasts. Co-cultures of 5TGM1 with ST2 showed increased production of bone-resorbing activity and neutralizing antibodies against VCAM-1 or α4β1-integrin inhibited this. The 5TGM1 cells contacting recombinant VCAM-1 produced increased osteoclastogenic and bone-resorbing activity. The activity was not blocked by the neutralizing antibody to known osteoclastogenic cytokines including interleukin (IL)-1, IL-6, tumor necrosis factor, or parathyroid hormone-related peptide. These data suggest that myeloma cells are responsible for producing osteoclastogenic activity and that establishment of direct contact with marrow stromal cells via α4β1-integrin/VCAM-1 increases the production of this activity by myeloma cells. They also suggest that the presence of stromal cells may provide a microenvironment that allows exclusive colonization of myeloma cells in the bone marrow.
Improvement in contractile recovery of isolated rat heart after cardioplegic ischaemic arrest with endogenous phosphocreatine: involvement of antiperoxidative effect? (1991)

PCr decreases the vulnerability of myocardium to oxidative stress and ischaemic damage. These effects cannot be explained by PCr induced shifts in Ca2+ concentration. Protective effects of PCr and tocopherol are quantitatively additive, most probably due to their different mechanisms of action, and tocopherol may be effective in extending the ability of PCr to stabilise cell membrane structure.
Changes in the Proteome Associated with the Action of Bcr-Abl Tyrosine Kinase Are Not Related to Transcriptional Regulation (2002)

Chronic myeloid leukemia (CML) is a hematopoietic stem cell disease, the hallmark of which is the Bcr-Abl protein tyrosine kinase (PTK). Without intervention the disease progresses from a benign chronic phase to a rapidly fatal blast crisis. To identify the molecular mechanisms underlying disease progression we used two-dimensional gel electrophoresis on a model we have previously described using the expression of a conditional mutant of Bcr-Abl PTK in a multipotent stem cell line, FDCP-Mix. Long term exposure of FDCP-Mix cells to Bcr-Abl mimics disease progression in CML. Four major differences were observed as a consequence of long term exposure to the Bcr-Abl PTK compared with cells exposed short term. The proteins were identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry-generated peptide mass fingerprint data and liquid chromatography-tandem mass spectrometry-generated sequence information. Leukotriene A4 hydrolase, an enzyme known to be deregulated in CML, was found to be up-regulated. Annexin VI, vacuolar ATP synthase catalytic subunit A, and mortalin were found to be down-regulated. Poly(A) PCR cDNA analysis showed there was no correlation between the protein expression changes and mRNA levels. Western blot analysis also indicated no change in the levels of mortalin or leukotriene A4 hydrolase, indicating that post-translational events may modify protein content of the specific spots. Leukotriene B4 levels (product of leukotriene A4 hydrolase) were, however, reduced in cells exposed long term to Bcr-Abl activity. This study demonstrates the potential of proteomic analysis to define novel effects of oncogenes.
The Role of Edema in Diffuse Sclerosis and Other Leukoencephalopathies (1978)

The pathologic changes associated with broad zones of demyelination of the cerebral white matter, the diffuse sclerosis group, are analyzed with respect to the contribution of cerebral edema to their pathogenesis. The characteristics of cerebral edema in general are reviewed, and the interpretation offered that only one type of cerebral edema, that characterized by an extracellular accumulation of fluid, occurs in man. In the diffuse sclerosis group, edema is most readily recognized by the tendency for the arcuate zone of the white matter to be spared when the deeper white matter is severely degenerated. Edema is demonstrated in metachromatic leukodystrophy, globoid cell leukodystrophy, adrenoleukodystrophy, disorders of amino acid metabolism, trauma, hypertensive disease, radiation effect, diffuse hypoxia with acidosis, and other conditions, i.e., both in disorders of myelin metabolism and in conditions in which normal myelin is injured by extrinsic influences. These groups cannot be consistently distinguished morphologically, in part because the injury by edema often obscures any primary morphologic change which may have been present. A familial tendency does not necessarily denote a metabolic abnormality specifically related to the chemistry of a myelin constituent, since the lesions might result from edema induced by some other type of familial process. Such familial processes might be metabolic, but are not specifically related to myelin formation or catabolism, as might be true of diseases like phenylketonuria or maple syrup urine disease. Edema may also occur in instances in which a familial disease induces diffuse hypoxia and acidosis, as exemplified by two instances of severe white matter degeneration in subacute necrotizing encephalomyelopathy; one of these is an additional instance of apparent "crib death" by this cause.