gebhart/patrepeval huggingface dataset:
Comparative Performance of High-Density Oligonucleotide Sequencing and Dideoxynucleotide Sequencing of HIV Type 1 pol from Clinical Samples (1998)

The performance of the high-density oligonucleotide array methodology (GeneChip) in detecting drug resistance mutations in HIV-1 pol was compared with that of automated dideoxynucleotide sequencing (ABI) of clinical samples, viral stocks, and plasmid-derived NL4-3 clones. Sequences from 29 clinical samples (plasma RNA, n = 17; lymph node RNA, n = 5; lymph node DNA, n = 7) from 12 patients, from 6 viral stock RNA samples, and from 13 NL4-3 clones were generated by both methods. Editing was done independently by a different investigator for each method before comparing the sequences. In addition, NL4-3 wild type (WT) and mutants were mixed in varying concentrations and sequenced by both methods. Overall, a concordance of 99.1% was found for a total of 30,865 bases compared. The comparison of clinical samples (plasma RNA and lymph node RNA and DNA) showed a slightly lower match of base calls, 98.8% for 19,831 nucleotides compared (protease region, 99.5%, n = 8272; RT region, 98.3%, n = 11,316), than for viral stocks and NL4-3 clones (protease region, 99.8%; RT region, 99.5%). Artificial mixing experiments showed a bias toward calling wild-type bases by GeneChip. Discordant base calls are most likely due to differential detection of mixtures. The concordance between GeneChip and ABI was high and appeared dependent on the nature of the templates (directly amplified versus cloned) and the complexity of mixes.
GENERATION OF CYTOTOXIC T LYMPHOCYTES IN VITRO (1974)

Mouse cytotoxic T lymphocytes (CTL) were generated in mixed leukocyte cultures (MLC) using spleen cells as responding cells and irradiated allogeneic spleen cells as stimulating cells. Cytotoxicity was assessed by a quantitative 51Cr assay system and the relative frequency of CTL in individual cell populations was estimated from dose-response curves. Inclusion of 2-mercaptoethanol in the MLC medium resulted in a 20–40-fold increase in the relative number of CTL generated at the peak of the response. Under these culture conditions, cell-mediated cytotoxic activity was detectable in MLC populations as early as 48 h after the onset of the cultures. When spleen cells from mice immunized with allogeneic tumor cells 2–4 mo previously were cultured with irradiated spleen cells of the same alloantigenic specificity (MLC-Imm), it was found that the cell-mediated cytotoxic response was detectable earlier and reached higher levels than that observed in a primary MLC. At the peak of the response, MLC-Imm populations were observed to lyse up to 50% of the target cells within 3 h at a lymphocyte: target cell ratio of 0.3:1. Immunological and physical characterization of the effector cells generated in MLC-Imm indicated that they were medium to large-sized T lymphocytes. Altogether, these studies suggested the existence of an anamnestic cell-mediated cytotoxic response in MLC-Imm.
CM101 treatment overrides tumor-induced immunoprivilege leading to apoptosis. (2000)

CM101, a bacterial polysaccharide exotoxin produced by group B Streptococcus (GBS), also referred to as GBS toxin, has been shown to target pathological neovasculature and activate complement (C3), thereby inducing neovascularitis, infiltration of inflammatory cells, inhibition of tumor growth, and apoptosis in murine tumor models. Data from refractory cancer patients in a Phase I clinical trial with CM101 indicated a similar mechanism of tumor-targeted inflammation. To further our understanding of the mechanism of action of CM101 as an antitumor agent, we examined the role of the inflammatory response in inducing tumor apoptosis in a normal mouse and tumor-bearing mouse model. The i.v. infusion of CM101 into B16BL-6 melanoma tumor-bearing mice elevated p53 mRNA in circulating leukocytes as measured by reverse transcription-PCR, and immunohistochemistry demonstrated infiltration and sequestration of leukocytes. Whole tumor lysates from excised tumors exhibited an increase in binding to the murine p21(Waf1/Cip1) derived p53 DNA binding sequence compared with control whole tumor lysates, in which minimal or no DNA binding was observed. CM101 infusion led to elevated levels of Fas protein within the tumors as well as a decrease in the expression of fas ligand (fasL). Furthermore, tumors were apoptotic as determined by terminal deoxynucleotidyl transferase-mediated nick end labeling and DNA fragmentation assays. Collectively, these data suggest that CM101 up-regulates p53 in tumor-infiltrating leukocytes, initiating a loss of tumor immunoprivilege and consequently rendering the tumor sensitive to Fas/fasL-mediated apoptosis. CM101 induced loss of tumor immunoprivilege through changes in the expression of leukocyte p53, tumor Fas and fasL coupled with neovascularitis and leukocyte infiltration, constitutes a plausible molecular pathway for tumor reduction observed in cancer patients.
Lethal graft-vs-host disease across major histocompatibility barriers: requirement for leucyl-leucine methyl ester sensitive cytotoxic T cells. (1987)

L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) is selectively toxic for human natural killer (NK) cells and cytotoxic T lymphocytes (CTL) at both the precursor and effector stage of differentiation. The present studies explored the effects of Leu-Leu-OMe on murine spleen cell function. Leu-Leu-OMe exposure removed NK function from murine spleen cells but spared their capacity to proliferate in response to lipopolysaccharide and Con A. The capacity to generate CTL from both L3T4 (+) and Lyt-2 (+) precursors was lost after Leu-Leu-OMe treatment, whereas alloantigen-induced proliferation and interleukin 2 (IL 2) production by L3T4 (+) T helper cells remained intact. Lethal graft vs host disease (GVHD), which developed in irradiated (C57BL/6 X DBA/2)F1 recipients of C57BL/6 bone marrow and spleen cells was completely prevented by Leu-Leu-OMe treatment of donor cells. In contrast depletion of Lyt-2 positive cells from the donor inoculum did not prevent acute GVHD in this fully major histo-compatibility complex (MHC) incompatible strain combination. However, Leu-Leu-OMe treatment of the Lyt-2 depleted inoculum completely prevented lethal GVHD, although the treated cells retained the capacity to proliferate and secrete IL 2 normally after in vitro stimulation with (C57BL/6 X DFA/2)F1 spleen cells. These findings indicate that L3T4 (+) T helper cells alone are unable to initiate lethal GVHD in this H-2 incompatible strain combination. Rather, lethal GVHD requires the transfer of a Leu-Leu-OMe sensitive T cell subset, likely to be thymus educated pre-CTL. Leu-Leu-OMe treatment should provide a useful way to delineate subpopulations of cells involved in the production of lethal GVHD and an approach to preventing this complication of bone marrow transplantation.
Practical path planning and obstacle avoidance for autonomous mowing (2006)

There is a need for systems which can autonomously perform coverage tasks on large outdoor areas. Unfortunately, the state-of-the-art is to use GPS based localization, which is not suitable for precise operations near trees and other obstructions. In this paper we present a robotic platform for autonomous coverage tasks. The system architecture integrates laser based localization and mapping using the Atlas Framework with Rapidly-Exploring Random Trees path planning and Virtual Force Field obstacle avoidance. We demonstrate the performance of the system in simulation as well as with real world experiments.
Cell/Tissue Culture and In Vitro Manipulation (1988)

Cell and tissue culture techniques for corn are rapidly approaching the full spectrum of culture systems possible in plants. Regenerable tissue cultures of elite corn inbreds are required for the rapid incorporation of traits modified by in vitro genetic manipulations into breeding lines. Black Mexican Sweet corn suspension cultures, for example, display a mitotic index of about 4% unless special methods are employed to increase the accumulation of mitotic figures. Because of the low mitotic index, relatively little is known about chromosomal variation in the cultures themselves. In addition to cytological alterations, the spontaneous mutation rate among tissue culture cells is sufficiently high to generate extensive genetic variation among regenerated plants and their first or second generation progeny. A variety of cellular level selections have been conducted including selections for disease, herbicide, and antibiotic tolerances and for altered levels of free amino acids.
Molecular evolution and domain structure of plasminogen‐related growth factors (HGF/SF and HGF1/MSP) (1994)

Plasminogen-related growth factors, a new family of polypeptide growth factors with the basic domain organization and mechanism of activation of the blood proteinase plasminogen, include hepatocyte growth factor/scatter factor (HGF/SF), a potent effector of the growth, movement, and differentiation of epithelia and endothelia, and hepatocyte growth factor-like/macrophage stimulating protein (HGF1/MSP), an effector of macrophage chemotaxis and phagocytosis. Phylogeny of the serine proteinase domains and analysis of intron-exon boundaries and kringle sequences indicate that HGF/SF, HGF1/MSP, plasminogen, and apolipoprotein (a) have evolved from a common ancestral gene that consisted of an N-terminal domain corresponding to plasminogen activation peptide (PAP), 3 copies of the kringle domain, and a serine proteinase domain. Models of the N domains of HGF/SF, HGF1/MSP, and plasminogen, characterized by the presence of 4 conserved Cys residues forming a loop in a loop, have been modeled based on disulfide-bond constraints. There is a distinct pattern of charged and hydrophobic residues in the helix-strand-helix motif proposed for the PAP domain of HGF/SF; these may be important for receptor interaction. Three-dimensional structures of the 4 kringle and the serine proteinase domains of HGF/SF were constructed by comparative modeling using the suite of programs COMPOSER and were energy minimized. Docking of a lysine analogue indicates a putative lysine-binding pocket within kringle 2 (and possibly another in kringle 4). The models suggest a mechanism for the formation of a noncovalent HGF/SF homodimer that may be responsible for the activation of the Met receptor. These data provide evidence for the divergent evolution and structural similarity of plasminogen, HGF/SF, and HGF1/MSP, and highlight a new strategy for growth factor evolution, namely the adaptation of a proteolytic enzyme to a role in receptor activation.
Zero-Shot Learning With Transferred Samples (2017)

By transferring knowledge from the abundant labeled samples of known source classes, zero-shot learning (ZSL) makes it possible to train recognition models for novel target classes that have no labeled samples. Conventional ZSL approaches usually adopt a two-step recognition strategy, in which the test sample is projected into an intermediary space in the first step, and then the recognition is carried out by considering the similarity between the sample and target classes in the intermediary space. Due to this redundant intermediate transformation, information loss is unavoidable, thus degrading the performance of overall system. Rather than adopting this two-step strategy, in this paper, we propose a novel one-step recognition framework that is able to perform recognition in the original feature space by using directly trained classifiers. To address the lack of labeled samples for training supervised classifiers for the target classes, we propose to transfer samples from source classes with pseudo labels assigned, in which the transferred samples are selected based on their transferability and diversity. Moreover, to account for the unreliability of pseudo labels of transferred samples, we modify the standard support vector machine formulation such that the unreliable positive samples can be recognized and suppressed in the training phase. The entire framework is fairly general with the possibility of further extensions to several common ZSL settings. Extensive experiments on four benchmark data sets demonstrate the superiority of the proposed framework, compared with the state-of-the-art approaches, in various settings.
Encapsulation of Organic Molecules and Enzymes in Sol—Gel Glasses (1992)

The ability to trap organic and bioorganic molecules in inorganic oxides through the sol-gel process, first introduced in 1984, opened the road for a whole new class of materials and to intensive activity in many laboratories. The types of materials and their applications are reviewed. These include photocatalysts for redox reactions; photochromic materials and other information recording materials; filters and light-guides; fluorescent, phosphorescent and dye-laser materials; a variety of chemical sensors; and bioactive (enzymatic) glasses.
Plasma vitamin A and beta-carotene in retinitis pigmentosa. (1975)

Plasma levels of vitamin A and beta-carotene were measured by spectrophotometry in 39 patients with genetically determined retinitis pigmentosa, No difference was found between the levels in these patients and the levels in a control group.
Constitution of Colloidal Particles Formed from a Solid Dispersion System. (1997)

Colloidal particles, produced upon the dispersion into water of a solid dispersion system composed of (R)-1-[2, 3-dihydro-1-(2'-methylphenacyl)-2-oxo-5-phenyl-1H-1, 4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea (YM022), hydroxypropylmethylcellulose 2910 (TC-5E) and polyoxyethylene hydrogenated castor oil 60 (HCO-60) at a weight ratio of 1 : 3.5 : 0.5, were characterized with respect to their physicohemical properties. From the IR absorption spectroscopic analysis, it was found that the colloidal particles, composed of YM022, TC-5E and HCO-60, have a combined weight ratio of 1 : 0.2 : 0.3. Although colloidal particles were prepared form solid dispersion systems with various weright ratios of YM022/TC-5E/HCO-60, they showed a similarity in combined ratio, suggesting the presence of specific interactions among the components. Particle diameter seemed to be affected by the composition of colloidal particles. Smaller particles contained less TC-5E which was related to the large portion of YM022 in colloidal particles. The amount of HCO-60 incorporated into colloidal particles was not affected by the particle diameter and correlated with the amount of YM022 at a fixed ratio (1.0 : 0.3). This suggested that TC-5E might function as a 3-dimensional framework for solid dispersion, while HCO-60 might interact with YM022 resulting in a fixed weight ratio between YM022/HCO-60 in colloidal particles.
Molecular recognition specificity of Bacillus globigii spore antibodies (2000)

Western blotting methods have been used to assess the specificity of polyclonal antibodies raised against Bacillus globigii spore and vegetative cell preparations. None of the antibodies studied were completely species-specific in their recognition of spore surface epitopes. One polyclonal serum recognized several spore surface epitopes and demonstrated limited cross-reaction with the spore surface of the near-neighbour species B. subtilis. A second polyclonal serum, raised against aged spore antigens, recognized damaged spore epitopes primarily. Both of these antibodies also cross-reacted with vegetative cell epitopes present in all four Bacillus species (B. globigii, B. subtilis, B. cereus and B. anthracis) studied.
Protein and Fat Metabolism in Hibernating Bears (1981)

Hibernation in the bear (Ursus americanus) is unique in that it is continuous for 3 to 7 months and occurs at near normal body temperature, yet the bear does not eat, drink, urinate, or defecate. During hibernation there is no loss of lean body mass because amino acids enter protein synthetic pathways at increased rates producing reciprocal decreases in entry into the urea cycle. The urea that is formed is hydrolyzed and the nitrogen released is combined with glycerol to form amino acids, which reenter protein synthetic pathways. Body fat supplies the substrate for metabolism (400 kilocalories/day). Ketosis does not occur. Metabolic water is sufficient to maintain normal hydration. About 100 ml of urine is filtered daily by the kidneys but the baldder wall transports water and solute back into blood at a rate about equal to their entry into the bladder. The bear cannot duplicate its winter adaptation in summer when housed in the cold and dark. During hibernation the bear shows hypothalamic hypothyroidism and increased testosterone production. These changes appear necessary for developing the selective states of anabolism and catabolism found in the hibernating bear.
Curcumin Inhibits Tumor Growth and Angiogenesis in Ovarian Carcinoma by Targeting the Nuclear Factor-κB Pathway (2007)

Based on significant efficacy in preclinical models, curcumin-based therapies may be attractive in patients with ovarian carcinoma.
The Helicase and RNaseIIIa Domains of Arabidopsis Dicer-Like1 Modulate Catalytic Parameters during MicroRNA Biogenesis (2012)

Dicer-Like1 (DCL1), an RNaseIII endonuclease, and Hyponastic Leaves1 (HYL1), a double-stranded RNA-binding protein, are core components of the plant microRNA (miRNA) biogenesis machinery. hyl1 null mutants accumulate low levels of miRNAs and display pleiotropic developmental phenotypes. We report the identification of five new hyl1 suppressor mutants, all of which are alleles of DCL1. These new alleles affect either the helicase or the RNaseIIIa domains of DCL1, highlighting the critical functions of these domains. Biochemical analysis of the DCL1 suppressor variants reveals that they process the primary transcript (pri-miRNA) more efficiently than wild-type DCL1, with both higher K(cat) and lower K(m) values. The DCL1 variants largely rescue wild-type miRNA accumulation levels in vivo, but do not rescue the MIRNA processing precision defects of the hyl1 null mutant. In vitro, the helicase domain confers ATP dependence on DCL1-catalyzed MIRNA processing, attenuates DCL1 cleavage activity, and is required for precise MIRNA processing of some substrates.
Comparative genomic hybridization analysis of breast tumors with predetermined profiles of DNA amplification. (1997)

In a separate study (F. Courjal et al., Cancer Res., 57: 4360-4367, 1997), we have analyzed by Southern blotting the relationship between DNA amplification and clinicopathological features of breast cancer. Six regions of recurrent amplifications were tested (8p12, 8q24, 11q13, 12q13, 17q12, and 20q13), and the results suggested that there was a relationship between DNA amplification profiles and breast tumor phenotype. We had delineated three subgroups of tumors showing distinct DNA amplification profiles and clinicopathological characteristics: group A, tumors showing amplification at 11q13 and/or 8p12 and/or 20q13; group B, tumors amplified at ERBB2 and/or MYC and/or MDM2/SAS; and group C, tumors with no detectable amplification. The aim of the present work was to characterize extensively the amplification profiles in the different subgroups of tumors. Sixty-one breast tumors distributed in all three subgroups were studied by comparative genomic hybridization (CGH). There was an overall good agreement between Southern blotting results and CGH data. As expected, CGH revealed gains undetected by Southern blotting. Most of these gains occurred in regions for which no adapted probes were available but also revealed nondetected amplifications at 8q24 or 20q13. Tumors showed multiple aberrations with a medium number of 5.6 copy number variations/tumor, whereas, according to Southern blotting results, 38% of the tumors analyzed were devoid of any amplification. This proportion fell to 6.5% after CGH analysis. Recurrent gains were observed in tumors from all three subgroups, albeit at varying incidences, and involved 1q, 8q, 17q23-q24, and 20q13. Gains covered large regions of DNA and could possibly include several cores of amplification. Some events, such as gains at 16p11-p12 and 14q or losses at 22q, showed more restricted distributions, suggesting the existence of additional sets of preferential coamplifications. The complexity of genetic profiles revealed by CGH indicates that breast cancer development depends on a large (yet undetermined) number of genetic events. The description of molecular phenotypes in breast cancer may therefore prove to be complex, and it should be interesting to see how many breast tumor subtypes will be defined in the end.
Vanadium as a modulator of cellular regulatory cascades and oncogene expression (1993)

Vanadium, a trace metal in the environment and in biological systems, influences the behavior of enzymes, mimics and regulates growth factor activity, is a potential mutagenic and carcinogenic agent, and regulates gene expression. The diverse biological actions of vanadium result from its capacity to function as an oxyanion, oxycation, or prooxidant. Vanadium is found in water, rocks, and soils in low concentration and in relatively high concentrations in coal and oil deposits. Vanadium compounds at much higher concentrations than are typically ingested are being considered in the treatment of diabetes mellitus. The actions of insulin and vanadium on the insulin receptor are similar, but the mechanisms are not identical. Vanadium modulates growth-factor-mediated signal transduction pathways. Vanadium promotes cell transformation and diminishes cell adhesion. Consistent with its mitogenic action and its capacity to mimic mitogenic growth factors, vanadium stimulates expression of protooncogenes. In particular, oxygen-derived active species are involved in the expression of the jun protooncogene in the presence of vanadium. The unique cellular activity of vanadium makes it a tool of unparalleled potential for studying mechanisms of cell growth, differentiation, and metabolism.
Interferon-Induced Ifit Proteins: Their Role in Viral Pathogenesis (2014)

A major component of the protective antiviral host defense is contributed by the intracellular actions of the proteins encoded by interferon-stimulated genes (ISGs); among these are the interferon-induced proteins with tetratricopeptide repeats (IFITs), consisting of four members in human and three in mouse. IFIT proteins do not have any known enzyme activity. Instead, they inhibit virus replication by binding and regulating the functions of cellular and viral proteins and RNAs. Although all IFITs are comprised of multiple copies of the degenerate tetratricopeptide repeats, their distinct tertiary structures enable them to bind different partners and affect host-virus interactions differently. The recent use of Ifit knockout mouse models has revealed novel antiviral functions of these proteins and new insights into the specificities of ISG actions. This article focuses on human and murine IFIT1 and IFIT2 by reviewing their mechanisms of action, their critical roles in protecting mice from viral pathogenesis, and viral strategies to evade IFIT action.