gebhart/patrepeval huggingface dataset:
Immunotargeting of liposomes to activated vascular endothelial cells: A strategy for site-selective delivery in the cardiovascular system (1997)

Endothelial-selective delivery of therapeutic agents, such as drugs or genes, would provide a useful tool for modifying vascular function in various disease states. A potential molecular target for such delivery is E-selectin, an endothelial-specific cell surface molecule expressed at sites of activation in vivo and inducible in cultured human umbilical vein endothelial cells (HUVEC) by treatment with cytokines such as recombinant human interleukin 1beta (IL-1beta). Liposomes of various types (classical, sterically stabilized, cationic, pH-sensitive), each conjugated with mAb H18/7, a murine monoclonal antibody that recognizes the extracellular domain of E-selectin, bound selectively and specifically to IL-1beta-activated HUVEC at levels up to 275-fold higher than to unactivated HUVEC. E-selectin-targeted immunoliposomes appeared in acidic, perinuclear vesicles 2-4 hr after binding to the cell surface, consistent with internalization via the endosome/lysosome pathway. Activated HUVEC incubated with E-selectin-targeted immunoliposomes, loaded with the cytotoxic agent doxorubicin, exhibited significantly decreased cell survival, whereas unactivated HUVEC were unaffected by such treatment. These results demonstrate the feasibility of exploiting cell surface activation markers for the endothelial-selective delivery of biologically active agents via immunoliposomes. Application of this targeting approach in vivo may lead to novel therapeutic strategies in the treatment of cardiovascular disease.
p16INK4A and CDH13 hypermethylation in tumor and serum of non‐small cell lung cancer patients (2005)

Aberrant promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the etiopathogenesis of lung cancer and is a promising tool for cancer detection. In the present study, promoter hypermethylation of p16INK4A and CDH13 genes was investigated in tumor tissue and in matched serum from 61 patients with histologically confirmed non-small cell lung cancer. Using a fluorescence-based method of methylation-specific PCR (F-MSP), methylation of p16INK4A and CDH13 was detected in 79% and 66% of tumors, respectively, and was not significantly related to conventional clinicopathological characteristics of patients or tumors. Methylation of both genes was observed in 52% of tumors and of at least one gene in 92% of lesions. In matched serum, hypermethylation of p16INK4A and CDH13 was observed in 26% and 23% of patients, respectively, but as they were not associated, the methylation of at least one gene was detected in 39% of patients. In conclusion, the frequency of p16INK4A or CDH13 hypermethylation in patient serum, together with evidence of their early occurrence in lung cancerogenesis and the total lack of methylation in serum from healthy individuals, offer a promising tool for non invasive early detection of lung cancer.
Cell-based screen for antimitotic agents and identification of analogues of rhizoxin, eleutherobin, and paclitaxel in natural extracts. (2000)

We describe a cell-based assay for antimitotic compounds that is suitable for drug discovery and for quantitative determination of antimitotic activity. In the assay, cells arrested in mitosis as a result of exposure to antimitotic agents in pure form or in crude natural extracts are detected by ELISA using the monoclonal antibody TG-3. The assay was used to screen >24,000 extracts of marine microorganisms and invertebrates and terrestrial plants and to guide the purification of active compounds from 5 of 119 positive extracts. A new rhizoxin analogue was found in a Pseudomonas species, six new eleutherobin analogues were identified from the octocoral Erythropodium caribaeorum, and two paclitaxel analogues were found in the stem bark of the tree Ilex macrophylla. The assay was also used for quantitative comparison of the antimitotic activity of different analogues. It revealed the importance of the C-11 to C-13 segment of the diterpene core of eleutherobin for its antimitotic activity. The identification of antimitotic compounds in very low abundance and their high (0.5%) occurrence in natural extracts indicates that drug discovery efforts using this cell-based assay may lead to the identification of structurally novel antimitotic agents.
Construction and Functional Evaluation of a Single-Chain Antibody Fusion Protein With Fibrin Targeting and Thrombin Inhibition After Activation by Factor Xa (2000)

A fusion protein was constructed that binds to a fibrin-specific epitope and inhibits thrombin after its activation by factor Xa. This recombinant anticoagulant effectively inhibits appositional clot growth in vitro. Its efficient and fast production at low cost should facilitate a large-scale evaluation to determine whether an effective localized antithrombin activity can be achieved without systemic bleeding complications.
Primordial germ cell development in cultures of dispersed central disks of stage X chick blastoderms (1989)

Central disk fragments cut from stage X chick blastoderms were dispersed and cultured on glass coverslips. After 48 hr of incubation the cultures showed various degrees of organization into three-layered aggregates in which no axis development was observed. Primordial germ cells (PGCs) were detected in all cultures. The number of PGCs was found to be correlated to the initial cell concentration in the suspension. By regression analysis it was found that in cultures initiated from 10 central disks or more, the mean number of PGCs per fragment was constant and matched the number of PGCs found for intact control central disks incubated for the same length of time. It appears that in cultures of stage X, the morphologic expression of PGCs is related to the level of differentiation and organization of the somatic cells in the culture, which, in turn, is dependent on the initial concentration of cells in the culture.
Structure, characterization, and expression of the gene encoding the mouse Mel1a melatonin receptor. (1996)

Recently, a distinct family of G protein-coupled receptors has been cloned that mediates the biological effects of melatonin. Of two sub-types cloned from mammals (Mel1a and Mel1b), the Mel1a receptor appears to mediate the circadian and reproductive effects of the hormone. We now report the cloning, characterization, and expression of the gene encoding the Mel1a receptor in mice. The receptor gene is composed of two exons, separated by an intron of greater than 13 kilobases. Exon 1 encodes the entire 5'-untranslated region and the coding region through the first cytoplasmic loop. Exon 2 encodes the rest of the coding region and the entire 3'-untranslated region. 5'-Rapid amplification of complementary DNA ends and ribonuclease protection analyses show that the major transcription start site is 103 nucleotides upstream of the translation start codon. Sequence analysis of 1.1 kilobases of the 5'-flanking region reveals that it does not contain TATA or CAAT boxes. The 5'-flanking region drives luciferase expression 114-fold over basal levels in a murine retinal cell line that endogenously expresses the Mel1a receptor. The mouse receptor binds 2-[125]iodomelatonin with high affinity (K(d) = 55.6 pM) when expressed transiently in COS-7 cells. In situ hybridization studies establish that Mel1a receptor messenger RNA is expressed in the hypothalamic suprachiasmatic nuclei and hypophyseal pars tuberalis, presumed sites of the circadian and some of reproductive actions of melatonin, respectively. These results provide information on Mel1a receptor gene structure essential for designing transgenic and gene knock-out studies and analyzing the transcriptional regulation of receptor gene expression.
Synthesis of azido polymers as potential energetic propellant binders (2006)

Composite propellants are considered as major sources of chemical energy for rocket propellants. In the preparation of composite propellant energetic formulations, the propellant binder plays a vital role. Various energetic polymeric binders were developed during last five decades to satisfy safety, high energy and processing conditions. In this review, we discuss the various synthetic routes for of preparation of high energetic polymeric binders, including glycidyl azide polymers (GAP)s, GAP co-polymers, oxetane polymers, oxirane polymers, azido polyesters, N, N′-bonded epoxy binders, aliphatic vinyl azide polymers and poly(allyl azide) (PAAz).
Suppressive subtractive hybridization as a tool for identifying genetic diversity in an environmental metagenome: the rumen as a model (2004)

Molecular techniques previously used for genome comparisons of closely related bacterial species could prove extremely valuable for comparisons of complex microbial communities, or metagenomes. Our study aimed to determine the breadth and value of suppressive subtractive hybridization (SSH) in a pilot-scale analysis of metagenomic DNA from communities of microorganisms in the rumen. Suppressive subtractive hybridization was performed using total genomic DNA isolated from rumen fluid samples of two hay-fed steers, arbitrarily designated as tester or driver. Ninety-six subtraction DNA fragments from the tester metagenome were amplified, cloned and the DNA sequences were determined. Verification of the isolation of DNA fragments unique to the tester metagenome was accomplished through dot blot and Southern blot hybridizations. Tester-specific SSH fragments were found in 95 of 96 randomly selected clones. DNA sequences of subtraction fragments were analysed by computer assisted DNA and amino acid comparisons. Putative translations of 26 (32.1%) subtractive hybridization fragments exhibited significant similarity to Bacterial proteins, whereas 15 (18.5%) distinctive subtracted fragments had significant similarity to proteins from Archaea. The remainder of the subtractive hybridization fragments displayed no similarity to GenBank sequences. This metagenomic approach has exposed an unexpectedly large difference in Archaeal community structure between the rumen microbial populations of two steers fed identical diets and housed together. 16S rRNA dot blot hybridizations revealed similar proportions of Bacteria and Archaea in both rumen samples and suggest that the differences uncovered by SSH are the result of varying community structural composition. Our study demonstrates a novel approach to comparative analyses of environmental microbial communities through the use of SSH.
A Bandwidth Enhancement Technique for Mobile Handset Antennas Using Wavetraps (2006)

A novel technique for enhancing the impedance bandwidth of wireless terminal antennas is presented. By introducing resonant short circuit transmission lines to the long sides of the chassis edges, an effective electrical shortening of the terminal ground plane is achieved. This effect has been used to realize terminal ground planes with resonant lengths at high frequencies, such as GSM 1800/1900 MHz or UMTS 2 GHz, thereby extending the impedance bandwidth. The proposed technique has been validated by simulations and measurements. Three typical applications are presented where the introduction of wavetraps improves the bandwidth and/or in-band performance
Chili Pepper Fruits: Presumed Precursors of Fatty Acids Characteristic for Capsaicinoids (2008)

Capsaicin is a molecule unique to fruits from the genus Capsicum. It is responsible for the pungent sensation and displays valuable pharmacological properties. Despite the fruits' economic importance and decades of research, the regulation of the content of capsaicinoids in individual fruits is not completely elucidated, and no agricultural cultivation of chili of defined pungency is assured. Precursor candidates of the fatty acid moiety of the capsaicinoids, especially for the unique 8-methyl- trans-6-nonenoic acid, were examined. Thioesters, acyl-ACP and acyl-CoA, were isolated from the placenta of Capsicum fruits by means of DEAE-Sepharose chromatography, selectively converted to the corresponding N-butylamides, and analyzed by GC-MS. Fatty acid moieties characteristic for capsaicinoids were identified. In two different varieties ( Capsicum chinense var. Habanero orange and Capsicum annuum var. Jalapeno) it was shown that the fatty acid pattern corresponds to the distribution pattern of the capsaicinoids formed up to this time. The acyl-thioester fractions contained already the 8-methyl- trans-6-nonenoic acid.
A granulocyte reactive monoclonal antibody, 1G10, identifies the Gal beta 1-4 (Fuc alpha 1-3)GlcNAc (X determinant) expressed in HL-60 cells on both glycolipid and glycoprotein molecules (1983)

1G10, a monoclonal IgM antibody that identifies a differentiation antigen on human granulocytes and a subpopulation of monocytes, was found to react specifically with glycosphingolipids bearing the Gal beta 1–4(Fuc alpha 1–3)GlcNAc hapten (X determinant). This carbohydrate determinant was found on both glycolipid and glycoprotein molecules isolated from HL-60 cells (a promyelocytic leukemia cell line). Thus, this highly conserved carbohydrate-defined determinant previously described on mouse embryonic and mouse and human carcinoma cells is also expressed as a tissue-specific differentiation antigen on normal human granulocytes.
Large-Scale Identification of Single-Feature Polymorphisms in Complex Genomes (2003)

We have developed a high-throughput genotyping platform by hybridizing genomic DNA from Arabidopsis thaliana accessions to an RNA expression GeneChip (AtGenome1). Using newly developed analytical tools, a large number of single-feature polymorphisms (SFPs) were identified. A comparison of two accessions, the reference strain Columbia (Col) and the strain Landsberg erecta (Ler), identified nearly 4000 SFPs, which could be reliably scored at a 5% error rate. Ler sequence was used to confirm 117 of 121 SFPs and to determine the sensitivity of array hybridization. Features containing sequence repeats, as well as those from high copy genes, showed greater polymorphism rates. A linear clustering algorithm was developed to identify clusters of SFPs representing potential deletions in 111 genes at a 5% false discovery rate (FDR). Among the potential deletions were transposons, disease resistance genes, and genes involved in secondary metabolism. The applicability of this technique was demonstrated by genotyping a recombinant inbred line. Recombination break points could be clearly defined, and in one case delimited to an interval of 29 kb. We further demonstrate that array hybridization can be combined with bulk segregant analysis to quickly map mutations. The extension of these tools to organisms with complex genomes, such as Arabidopsis, will greatly increase our ability to map and clone quantitative trait loci (QTL).
Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected. Interim guidance (2020)

T his is the second edition (version 1.2) of this document, which was originally adapted from Clinical management of severe acute respiratory infection when MERS-CoV infection is suspected (WHO, 2019).
Combination Chemotherapy and IL-15 Administration Induce Permanent Tumor Regression in a Mouse Lung Tumor Model: NK and T Cell-Mediated Effects Antagonized by B Cells (1998)

Previous studies have demonstrated that IL-15 administration after cyclophosphamide (CY) injection of C57BL/6J mice bearing the i.m. 76-9 rhabdomyosarcoma resulted in a significant prolongation of life. In the present study, we investigated the immune response against the 76-9 experimental lung metastases after CY + IL-15 therapy. Administration of CY + IL-15, but not IL-15 alone, induced prolongation of life and cures in 32% of mice bearing established experimental pulmonary metastases of 76-9 tumor. The CY + IL-15 therapy resulted in increased levels of NK1.1+/LGL-1+ cells, and CD8+/CD44+ T cells in PBL. In vitro cytotoxic assay of PBL indicated the induction of lymphokine-activated killer cell activity, but no evident tumor-specific class I-restricted lytic activity. Survival studies showed that the presence of NK and T lymphocytes is necessary for successful CY + IL-15 therapy. Experiments using knockout mice implied that either alphabeta or gammadelta T cells were required for an antitumor effect induced by CY + IL-15 therapy. However, mice lacking in both alphabeta and gammadelta T cells failed to respond to combination therapy. Cured B6 and alphabeta or gammadelta T cell-deficient mice were immune to rechallenge with 76-9, but not B16LM tumor. B cell-deficient mice showed a significant improvement in the survival rate both after CY and combination CY + IL-15 therapy compared with normal B6 mice. Overall, the data suggest that the interaction of NK cells with tumor-specific alphabeta or gammadelta T lymphocytes is necessary for successful therapy, while B cells appear to suppress the antitumor effects of CY + IL-15 therapy.
Long-Lasting Results with Hydroxylapatite (Radiesse) Facial Filler (2006)

Radiesse was shown to be a highly effective, long-lasting material for facial soft-tissue augmentation. The safe and well-tolerated compound drew high marks in patient satisfaction. A precise injection technique helped minimize potential effects such as nodule formation and helped avoid persistent overcorrection, livid coloring, and asymmetry. Radiesse can be considered a very good option for an aesthetic soft-tissue facial filler when real volumetric augmentation is needed.
Cytosolic phospholipase A2 in hypoxic pulmonary vasoconstriction (2002)

Cytosolic phospholipase A2 (cPLA2) releases arachidonic acid (AA) from phospholipids in cell membranes. To assess the role of cPLA2 in hypoxic pulmonary vasoconstriction (HPV), we measured the increase in left lung pulmonary vascular resistance (LPVR) before and during hypoxia produced by left main stem bronchus occlusion (LMBO) in mice with and without a targeted deletion of the PLA2g4a gene that encodes cPLA2α. LMBO increased LPVR in cPLA2α+/+ mice but not in cPLA2α–/– mice. cPLA2α+/+ mice were better able to maintain systemic oxygenation during LMBO than were cPLA2α–/– mice. Administration of a cPLA2 inhibitor, arachidonyl trifluoromethyl ketone, blocked the LMBO-induced increase in LPVR in wild-type mice, while exogenous AA restored HPV in cPLA2α–/– mice. Intravenous angiotensin II infusion increased PVR similarly in cPLA2α+/+ and cPLA2α–/– mice. Inhibitors of cyclooxygenase or nitric oxide synthase restored HPV in cPLA2α–/– mice. Breathing 10% oxygen for 3 weeks produced less right ventricular hypertrophy in cPLA2α–/– than in cPLA2α+/+ mice, but restored HPV in cPLA2α–/– mice despite the continued absence of cPLA2 activity. These results indicate that cPLA2 contributes to the murine pulmonary vasoconstrictor response to hypoxia. Augmenting pulmonary vascular tone restores HPV in the absence of cPLA2 activity.
Prevention of solely estrogen-induced mammary tumors in female aci rats by tamoxifen: evidence for estrogen receptor mediation (2002)

There is increasing evidence that both endogenous and exogenously ingested estrogens play a primary role in sporadic breast cancer causation. To establish further that solely estrogen-induced mammary oncogenesis in female ACI rats is an estrogen receptor (ERalpha)-driven process, we show for the first time that concomitant treatment with the antiestrogen, tamoxifen citrate (TAMc), completely prevents the induction of 17beta-estradiol (E(2))-induced mammary gland tumors (MGTs). This finding is also supported by the reduced mammary gland (MG) lobulo-alveolar development and proliferative activity observed in TAMc+E(2)-treated animals compared with MGs from animals treated with E(2) alone. These data also correlated with a marked decrease in the number of MG cells expressing ERalpha and progesterone receptor (PR) in immunostained MG tissue sections from TAMc+E(2)-treated animals. Additionally, a marked decline in the level of expression of ERalpha 47, 56 and 66 kDa forms, and PR-A and PR-B was seen in TAMc+E(2)-treated MGs, compared with MGs treated solely with E(2). Thus, both ERalpha and PR MG profiles in TAMc+E(2)-treated rats essentially revert to their respective receptor profiles seen in untreated control and TAMc-alone-treated rats. The presence of 56 and 54 kDa isoforms in chronically E(2)-treated MGs and in MGTs respectively may contribute to fostering the enhanced E(2)-dependent growth response of both precursor and frank MGT epithelial cells. These findings are consistent with an ERalpha/PR-mediated mg cell proliferation, a prerequisite for generating the high frequency of chromosomal instability seen in E(2)-induced ductal carcinomas in situ and primary MGTs in female ACI rats reported by us previously.
A Versatile Set of Aminooxy Amino Acids for the Synthesis of Neoglycopeptides. (2004)

Four &lt;i&gt;N&lt;/i&gt;-alkylaminooxy amino acids have been synthesized in 22−56% overall yield from readily\navailable amino acid precursors. Each amino acid can be efficiently incorporated into peptides using\nBoc-chemistry-based solid-phase peptide synthesis, and in three of the four cases the resulting\npeptides can be chemoselectively glycosylated at the aminooxy side chains to generate neoglycopeptides. The range of &lt;i&gt;N&lt;/i&gt;-alkylaminooxy amino acids prepared allows attachment of sugars at two-,\nthree-, or four-atom distances from the peptide backbone, and each ensures that attached sugars\nadopt cyclic conformations. These derivatives provide convenient access to arrays of biologically\nrelevant neoglycopeptides that may be used to probe the influence of attached sugars on the\nstructure and function of peptides and proteins.
Picture retrieval by content description (1992)

The tundamental problem of modelling data effec tively in the context of still pictures is addressed, which marks a significant departure from the conventional means of imple menting pictorial databases. In using the entity-attribute-rela tionship model, the main semantic concepts of entity. at tribute and relationship can be represented in a simple man ner which correspond very closely to the noun, adjective and verb which are the essential components of a simple descrip tion of a picture. Such a system has the advantage over traditional ways of representing the data in an automated system in that it allows, inter aha, the concept of relationships between two (or more) objects to be successfully represented in the database. Our basic starting point is man-machine cooperation in which the pattern processing capability of the human eye is fully exploited As a result, it should provide a much better degree of flexibility in the identification of com plex patterns. Evaluation experiments carried out on a proto type system based on this approach are able to yield precision and recall performances of over 62% and 88% respectively.