gebhart/patrepeval huggingface dataset:
Identifying Cancer Stem Cells in Solid Tumors: Case Not Proven (2006)

Building on studies of leukemia, a number of recent articles have reported data suggesting that cancer stem cells could be isolated from solid human cancers. Some of these reports have speculated that the isolation of these cells will allow the identification of the specific molecular properties that can be targeted for therapeutic purposes. Although previous work with animal model systems also suggests the presence of stem cells in solid tumors, there remain many uncertainties, both theoretical and technical, about the interpretation of the current results. The case that a small proportion of cells in solid tumors are specific cancer stem cells and that these cells can be successfully identified and isolated has not yet been proven.
Overexpression of 20-Oxidase Confers a Gibberellin-Overproduction Phenotype in Arabidopsis (1998)

In the gibberellin (GA) biosynthesis pathway, 20-oxidase catalyzes the oxidation and elimination of carbon-20 to give rise to C19-GAs. All bioactive GAs are C19-GAs. We have overexpressed a cDNA encoding 20-oxidase isolated from Arabidopsis seedlings in transgenic Arabidopsis plants. These transgenic plants display a phenotype that may be attributed to the overproduction of GA. The phenotype includes a longer hypocotyl, lighter-green leaves, increased stem elongation, earlier flowering, and decreased seed dormancy. However, the fertility of the transgenic plants is not affected. Increased levels of endogenous GA1, GA9, and GA20 were detected in seedlings of the transgenic line examined. GA4, which is thought to be the predominantly active GA in Arabidopsis, was not present at increased levels in this line. These results suggest that the overexpression of this 20-oxidase increases the levels of some endogenous GAs in transgenic seedlings, which causes the GA-overproduction phenotype.
Self-Assembled Polymeric Micellar Nanoparticles as Nanocarriers for Poorly Soluble Anticancer Drug Ethaselen (2009)

A series of monomethoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA) diblock copolymers were synthesized, and mPEG-PLA micelle was fabricated and used as a nanocarrier for solubilization and delivery of a promising anticancer drug ethaselen. Ethaselen was efficiently encapsulated into the micelles by the dialysis method, and the solubility of ethaselen in water was remarkably increased up to 82 μg/mL before freeze-drying. The mean diameter of ethaselen-loaded micelles ranged from 51 to 98 nm with a narrow size distribution and depended on the length of PLA block. In vitro hemolysis study indicated that mPEG-PLA copolymers and ethaselen-loaded polymeric micelles had no hemolytic effect on the erythrocyte. The enhanced antitumor efficacy and reduced toxic effect of ethaselen-loaded polymeric micelle when compared with ethaselen-HP-β-CD inclusion were observed at the same dose in H22human liver cancer cell bearing mouse models. These suggested that mPEG-PLA polymeric micelle nanoparticles had great potential as nanocarriers for effective solubilization of poorly soluble ethaselen and further reducing side effects and toxicities of the drug.
UNDERSTANDING GENE AND ALLELE FUNCTION WITH TWO-HYBRID METHODS (1997)

Two-hybrid schemes for detecting protein-protein interactions have deepened our understanding of biology by allowing scientists to identify individual important proteins. Recent developments will allow biologists to chart regulatory networks and to rapidly generate hypotheses for the function of genes, allelic variants, and the connections between proteins that make up these networks. Future developments will allow biologists to test inferences about the function of network elements, and allow global approaches to questions of biological function.
Multiple cadherin extracellular repeats mediate homophilic binding and adhesion (2001)

The extracellular homophilic-binding domain of the cadherins consists of 5 cadherin repeats (EC1-EC5). Studies on cadherin specificity have implicated the NH(2)-terminal EC1 domain in the homophilic binding interaction, but the roles of the other extracellular cadherin (EC) domains have not been evaluated. We have undertaken a systematic analysis of the binding properties of the entire cadherin extracellular domain and the contributions of the other EC domains to homophilic binding. Lateral (cis) dimerization of the extracellular domain is thought to be required for adhesive function. Sedimentation analysis of the soluble extracellular segment of C-cadherin revealed that it exists in a monomer-dimer equilibrium with an affinity constant of approximately 64 microm. No higher order oligomers were detected, indicating that homophilic binding between cis-dimers is of significantly lower affinity. The homophilic binding properties of a series of deletion constructs, lacking successive or individual EC domains fused at the COOH terminus to an Fc domain, were analyzed using a bead aggregation assay and a cell attachment-based adhesion assay. A protein with only the first two NH(2)-terminal EC domains (CEC1-2Fc) exhibited very low activity compared with the entire extracellular domain (CEC1-5Fc), demonstrating that EC1 alone is not sufficient for effective homophilic binding. CEC1-3Fc exhibited high activity, but not as much as CEC1-4Fc or CEC1-5Fc. EC3 is not required for homophilic binding, however, since CEC1-2-4Fc and CEC1-2-4-5Fc exhibited high activity in both assays. These and experiments using additional EC combinations show that many, if not all, the EC domains contribute to the formation of the cadherin homophilic bond, and specific one-to-one interaction between particular EC domains may not be required. These conclusions are consistent with a previous study on direct molecular force measurements between cadherin ectodomains demonstrating multiple adhesive interactions (Sivasankar, S., W. Brieher, N. Lavrik, B. Gumbiner, and D. Leckband. 1999. PROC: Natl. Acad. Sci. USA. 96:11820-11824; Sivasankar, S., B. Gumbiner, and D. Leckband. 2001. Biophys J. 80:1758-68). We propose new models for how the cadherin extracellular repeats may contribute to adhesive specificity and function.
Efforts toward elucidating Thalidomide’s molecular target: an expedient synthesis of the first Thalidomide biotin analogue (2010)

Herein we describe the synthesis of the first Thalidomide-biotin analogue in order to initiate investigations into the unknown molecular mode of action of Thalidomide. In this manner we describe the attachment of biotin tether through the Huisgen 1,3-dipolar cycloaddition or "click" synthetic methodology.
Disruption of Rosetting in Plasmodium falciparum Malaria with Chemically Modified Heparin and Low Molecular Weight Derivatives Possessing Reduced Anticoagulant and Other Serine Protease Inhibition Activities (2008)

Severe malaria has been, in part, associated with the ability of parasite infected red blood cells to aggregate together with uninfected erythrocytes to form rosettes via the parasite protein PfEMP-1. In this study, inhibitors of rosetting by the Plasmodium falciparum strain R-29, based on chemically modified heparin polysaccharides (IC 50 = 1.97 x 10 (-2) and 3.05 x 10 (-3) mg.mL (-1)) and their depolymerized, low molecular weight derivatives were identified with reduced anticoagulant and protease (renin, pepsin, and cathepsin-D) activities. Low molecular weight derivatives of the two most effective inhibitors were shown to have distinct minimum size and strain-specific structural requirements for rosette disruption. These also formed distinct complexes in solution when bound to platelet-factor IV.
The McGill Quality of Life Questionnaire: a measure of quality of life appropriate for people with advanced disease. A preliminary study of validity and acceptability (1995)

This is the first report on the McGill Quality of Life Questionnaire (MQOL), a questionnaire relevant to all phases of the disease trajectory for people with a life-threatening illness. This questionnaire differs from most others in three ways: the existential domain is measured; the physical domain is important but not predominant; positive contributions to quality of life are measured. This study was conducted in a palliative care setting. Principal components analysis suggests four subscales: physical symptoms, psychological symptoms, outlook on life, and meaningful existence. Construct validity of the subscales is demonstrated through the pattern of correlations with the items from the Spitzer Quality of Life Index. The importance of measuring the existential domain is highlighted by the finding that, of all the MQOL subscales and Spitzer items, only the meaningful existence subscale correlated significantly with a single item scale rating overall quality of life.
Fabrication of Ultrathin Silicon Nanoporous Membranes and Their Application in Filtering Industrially Important Biomolecules (2013)

Ultrathin silicon nanoporous membranes with multiple pores were fabricated using batch processes involving chemical vapor deposition and rapid thermal annealing. Transmission electron microscope images showed the existence of nanopores with an average pore size of 13 nm. Measurement of ionic conduction of electrolytes with varying conductivity across the membranes confirmed the existence of pores and the repeatability of the process. The functional diameter of the pores was determined by analyzing the permeability of several industrially and medically important globular biomolecules of varying sizes such as α-amylase, bovine serum albumin, catalase and xanthine oxidase. Biomolecules with hydrodynamic diameters up to 8 nm passed through the nanopores, whereas the passage of the larger molecules was hindered. The surface charges on the molecules determine the functional diameter of the pores, and hence the permeability, as substantiated by varying the pH of the buffer solution. The filtered proteins were found to be uncleaved from sodium dodecyl sulfate polyacrylamide gel electrophoresis, and the enzyme assay of the filtered amylase showed that the activity remained unchanged.
Facile fabrication of large-grain CH3NH3PbI3−xBrx films for high-efficiency solar cells via CH3NH3Br-selective Ostwald ripening (2016)

Organometallic halide perovskite solar cells (PSCs) have shown great promise as a low-cost, high-efficiency photovoltaic technology. Structural and electro-optical properties of the perovskite absorber layer are most critical to device operation characteristics. Here we present a facile fabrication of high-efficiency PSCs based on compact, large-grain, pinhole-free CH3NH3PbI3-xBrx (MAPbI3-xBrx) thin films with high reproducibility. A simple methylammonium bromide (MABr) treatment via spin-coating with a proper MABr concentration converts MAPbI3 thin films with different initial film qualities (for example, grain size and pinholes) to high-quality MAPbI3-xBrx thin films following an Ostwald ripening process, which is strongly affected by MABr concentration and is ineffective when replacing MABr with methylammonium iodide. A higher MABr concentration enhances I-Br anion exchange reaction, yielding poorer device performance. This MABr-selective Ostwald ripening process improves cell efficiency but also enhances device stability and thus represents a simple, promising strategy for further improving PSC performance with higher reproducibility and reliability.
Stimulation of Phosphorylation of Mitogen-Activated Protein Kinase by 1α,25-Dihydroxyvitamin D3 in Promyelocytic NB4 Leukemia Cells: A Structure-Function Study* (1998)

Recent studies have shown that 1alpha,25-dihydroxyvitamin D3 [1alpha,25-(OH)2D3] actions in cell growth and differentiation are mediated by both its nuclear receptor (VDRnuc) and its rapid membrane-related effects. In the present study, we investigated the effect of 1alpha,25-(OH)2D3 on p42mapk phosphorylation using human acute promyelocytic leukemia cells (NB4). 1Alpha,25-(OH)2D3 (10[-8] M) significantly increased p42mapk phosphorylation in a time- and dose-dependent manner, with the earliest response detectable at 30 sec. Because 1alpha,25-(OH)2D3 is a conformationally flexible molecule, we have used a series of conformationally locked (6-s-cis vs. 6-s-trans) analogs to evaluate which shape is optimal for activation. Four 6-s-cis-locked analogs (HF, JM, JN, and JP) and two 6-s-trans-locked analog (JB and JD) were studied. HF, JM, JN, and JP all increased p42mapk phosphorylation at 1 and 5 min (10[-8] M), but JB and JD had little effect. Analog HL [1beta,25-(OH)2D3], a specific antagonist for only the rapid effects of 1alpha,25-(OH)2D3, attenuated 1alpha,25-(OH)2D3-induced p42mapk phosphorylation 65-90%. To assess the potential involvement of the VDRnuc in mediating the analog's action, the relative abilities of the analogs to compete with [3H]1alpha,25-(OH)2D3 for binding in vitro to the VDRnuc of NB4 cells was measured. All 6-s-cis analogs bound poorly to VDRnuc (relative competitive index, 0.5-2%) compared with 1alpha,25-(OH)2D3 (relative competitive index, 100%). The present studies demonstrate for the first time that in NB4 cells 1alpha,25-(OH)2D3 rapidly activates the p42mapk pathway, and that this effect can be selectively mediated by analogs that can assume a 6-s-cis conformation.
Progressive Vaccinia Associated With Combined Variable Immunodeficiency (1983)

Progressive vaccinia developed in a previously healthy woman following smallpox vaccination and was successfully treated with vaccinia immune human globulin and methisazone. Immunologic evaluation over the next 4 1/2 years revealed evidence for combined variable immunodeficiency with increased numbers of circulating OKT 8 positive (suppressor-cytotoxic T) cells and the virtual absence of OKT 4 positive (helper-inducer T) cells.
Pulse radiolysis study on the reactivity of Trolox C phenoxyl radical with superoxide anion (1989)

The reaction between the phenoxyl radical of Trolox C, a water-soluble vitamin E analogue, and superoxide anion radical was examined by using the pulse radiolysis technique. The results indicate that the Trolox C phenoxyl radical may undergo a rapid one-electron transfer from superoxide radical [k = (4.5 +/- 0.5) x 10(8) M-1.S-1] to its reduced form. This finding indicates that superoxide radical might play a role in the repair of vitamin e phenoxyl radical.
A compact broadband, six-bit MMIC phasor with integrated digital drivers (2002)

Digital and microwave technologies have been successfully combined on a single chip to realize a broadband, 6-b monolithic microwave IC (MMIC) phase shifter. It exhibits low insertion loss, good voltage standing wave ratio (VSWR), and exceptional phase performance with less than 3 degrees RMS phase error for all 64 phase states over the entire 7.2-10.2 GHz band. Compared to previous designs, the number of required control lines has been reduced by a factor of two due to the integration of the digital drive circuitry. Phase shifter and digital driver design, fabrication, and performance are described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Atomic Layer Deposition of PbI2 Thin Films (2019)

Atomic layer deposition (ALD) enables the deposition of numerous materials in thin film form, yet there are no ALD processes for metal iodides. Herein, we demonstrate an ALD process for PbI2, a metal iodide with a two-dimensional (2D) structure that has applications in areas such as photo-detection and photovoltaics. This process uses lead silylamide Pb(btsa)(2) and SnI4 as precursors and works at temperatures below 90 degrees C, on a variety of starting surfaces and substrates such as polymers, metals, metal sulfides, and oxides. The starting surface defines the crystalline texture and morphology of the PbI2 films. Rough substrates yield porous PbI2 films with randomly oriented 2D layers, whereas smooth substrates yield dense films with 2D layers parallel to the substrate surface. Exposure to light increases conductivity of the ALD PbI2 films which enables their use in photodetectors. The films can be converted into a CH3NH3PbI3 halide perovskite, an important solar cell absorber material. For various applications, ALD offers advantages such as ability to uniformly coat large areas and simple means to control film thickness. We anticipate that the chemistry exploited in the PbI2 ALD process is also applicable for ALD of other metal halides.
HER2/neu-derived peptides are shared antigens among human non-small cell lung cancer and ovarian cancer. (1994)

Previously, we have reported a correlation between the expression of HER2/neu and sensitivity to HLA-A2-restricted cytotoxic T-cells (CTL) in ovarian cancer. To investigate the role of HER2/neu in human non-small cell lung cancer (NSCLC), we established autologous tumor-specific CTL from tumor-infiltrating lymphocytes of HLA-A2+ HER2/neu+ NSCLC patients. These CTL lines specifically recognized HLA-A2+ HER2/neu+ autologous and allogeneic NSCLC cell lines as well as HLA-A2+ HER2/neu+ heterologous ovarian cancer cell lines. Furthermore, these CTL recognized an overexpressed, HER2/neu-derived peptide. From these results, we conclude that HLA-A2 serves as a restriction element in NSCLC. More importantly, at least one HER2/neu-derived peptide is a tumor-associated antigen in NSCLC and ovarian cancer.
Bottlenecks for metabolic engineering of isoflavone glycoconjugates inArabidopsis (2002)

In view of their perceived chemopreventive activities against hormone-dependent cancers, cardiovascular disease, and postmenopausal ailments, there is considerable interest in engineering plants to contain isoflavone phytoestrogens. However, attempts to date have only resulted in low levels of isoflavone accumulation in non-legumes. Introducing soybean isoflavone synthase (IFS) into Arabidopsis thaliana leads to accumulation of low levels of genistein glycosides. Leaves of wild-type A. thaliana contain high levels of similar conjugates of the flavonols quercetin and kaempferol, which could be increased by threefold on introduction of an alfalfa chalcone isomerase transgene. Levels of genistein were not increased by expressing both IFS and alfalfa chalcone isomerase, but levels of flavonol conjugates were reduced to a greater extent than could be accounted for by flux into isoflavone. Introduction of IFS into the tt6 / tt3 double mutant blocked in flavonol, and anthocyanin synthesis resulted in high levels of genistein. The bottleneck for constitutive isoflavone production in Arabidopsis is, therefore, competition for flavanone between IFS and endogenous flavonol synthesis, and the flavonol pathway is reciprocally but disproportionately affected by IFS.
Implant-induced high-resistivity regions in InP and InGaAs (1989)

We have investigated the effects of ion bombardment on the electrical properties of intentionally doped InP and InGaAs grown by metalorganic molecular-beam epitaxy. The sheet resistivity and mobility of n+InP (Sn) and n+InGaAs (Sn) or p+InGaAs (Be) epilayers grown on semi-insulating InP substrates were measured as a function of ion species (O, B, H, or Fe), ion dose (1012–1015 cm−2), and post-implant annealing temperature (100–600 °C). In n+InP, the resistivity after bombardment goes through a maximum with annealing temperature, reaching a value of ∼106 Ω/⧠ for 0.5-μm-thick films after implantation with H or O and annealing at 200–300 °C. The as-grown resistivity is restored by annealing above 500 °C. Ion doses below 1012 cm−2 actually lead to a decrease in resistivity through the creation of shallow donor levels. By contrast, the implantation of Fe above a critical dose where the Fe density exceeds the dopant concentration leads to the formation of thermally stable, high-resistivity (&amp;gt;106 Ω/⧠) material. The temperature dependence of the resistivity shows an activation energy of 0.67 eV, which corresponds to the acceptor level of substitutional Fe in InP. Both n+InGaAs and p+InGaAs show somewhat similar behavior after implantation with maximum resistivities of ∼105 Ω/⧠ regardless of implant species. Once again for relatively low doses of O or H (below ∼1013 cm−2 in this case) there is creation of shallow defect levels that lower the resistivity of the material. The formation of these levels in InP has been investigated in more detail by measuring the depth-dependent carrier profile in implanted high-resistivity InP. The profile of the damage-induced centers is in close correlation with the nuclear energy deposition profile of the implanted ion in some cases, and with the profiles of stoichiometric excess due to unequal recoil of the lattice constituents in other cases.
A Nanoparticle-Based Model Delivery System To Guide the Rational Design of Gene Delivery to the Liver. 1. Synthesis and Characterization (2005)

Nonviral gene delivery systems are amenable to forming colloidal particles with a wide range of physicochemical properties that include size, surface charge, and density and type of ligand presented. However, it is not known how to best design these particles without having a set of physicochemical design constraints that have been optimized for the intended gene delivery application. Here, a nanoparticle-based model delivery system is developed that can mimic the surface properties of nonviral gene delivery particles, and this model system is used to define design constraints that should be applied to next generation gene delivery particles. As a test case, a well-defined nanoparticle-based system is developed to guide the rational design of gene delivery to hepatocytes in the liver. The synthetic scheme utilizes monodisperse polystyrene particles and provides for variation of mean particle size and particle size distribution through variation in reaction conditions. The nanoparticles are PEGylated to provide stability in serum and also incorporate targeting ligands, e.g., galactose, at tunable densities. Four nanoparticles are synthesized from uniformly sized polystyrene beads specifically for the purpose of identifying design constraints to guide next generation gene delivery to the liver. These four nanoparticles are Gal-50 and Gal-140, that are galactosylated 50 and 140 nm nanoparticles, and MeO-50 and MeO-140, that are methoxy-terminated 50 and 140 nm nanoparticles. All four particles have the same surface charge, and Gal-50 and Gal-140 have the same surface galactose density. The availability of galactose ligands to receptor binding is demonstrated here by agglutination with RCA120.
Discovery of 1,5-Disubstituted Pyridones: A New Class of Positive Allosteric Modulators of the Metabotropic Glutamate 2 Receptor (2010)

A series of 1,5-disubstituted pyridones was identified as positive allosteric modulators (PAMs) of the metabotropic glutamate receptor 2 (mGluR2) via high throughput screening (HTS). Subsequent SAR exploration led to the identification of several compounds with improved in vitro activity. Lead compound 8 was further profiled and found to attenuate the increase in PCP induced locomotor activity in mice.
Isolation and identification of a bovine adenovirus type 3 with an adenovirus-associated virus. (1978)

A bovine adenovirus with agglutinating activity was isolated from feedlot calves and classified as serotype 3. The agglutinating activity was shown to be the property of an adenovirus-associated virus (AAV). The AAV was isolated from the bovine adenovirus by isopycnic centrifugation in CsCl; the AAV had a density of 1.4 g/cm2. This AAV is serologically related to bovine AAV-TR-15, but is distinct from bovine parvovirus-1 and primate AAV types 1 to 4, using counterimmunoelectrophoresis and hemagglutination-inhibition.