gebhart/patrepeval huggingface dataset:
Synthesis and Evaluation of Multivalent Branched HPMA Copolymer−Fab′ Conjugates Targeted to the B-Cell Antigen CD20 (2008)

Several drug delivery designs combine synthetic drug carriers with covalently conjugated targeting moieties. Such modifications of monoclonal antibodies (mAb), or their Fab' fragments, inevitably result in diminished affinity for their targeted tissue. In an attempt to overcome this limitation, high molecular weight, branched N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers were synthesized and conjugated with Fab' fragments of the anti-CD20 antibody, 1F5. This produced multivalent conjugates with varying valency (amount of Fab' per macromolecule) targeted to the B-cell antigen CD20. Evaluation of a multivalent effect was done by determining the apparent K(D) at low concentrations of conjugates, the Sips heterogeneity factor, a, and the binding enhancement factors of each construct. The results clearly indicated that multivalency could improve the affinity of the HPMA copolymer-Fab' conjugates to that of unconjugated mAb.
Intrahippocampal Infusions of K-ATP Channel Modulators Influence Spontaneous Alternation Performance: Relationships to Acetylcholine Release in the Hippocampus (2001)

One mechanism by which administration of glucose enhances cognitive functions may be by modulating central ATP-sensitive potassium (K-ATP) channels. K-ATP channels appear to couple glucose metabolism and neuronal excitability, with channel blockade increasing the likelihood of neurosecretion. The present experiment examined the effects of glucose and the direct K-ATP channel modulators glibenclamide and lemakalim on spontaneous alternation performance and hippocampal ACh release. Rats received either artificial CSF vehicle or vehicle plus drug for two consecutive 12 min periods via microdialysis probes (3 mm; flow rate of 2.1 microliter/min) implanted in the left hippocampus. During the second 12 min period, rats were tested for spontaneous alternation performance. Dialysate was simultaneously collected for later analysis of ACh content. Both glucose (6.6 mm) and glibenclamide (100 micrometer) significantly increased alternation scores compared with those of controls. Conversely, lemakalim (200 micrometer) significantly reduced alternation scores relative to those of controls. Simultaneous administration of lemakalim with either glucose or glibenclamide resulted in alternation scores not significantly different from control values. All drug treatments enhanced hippocampal ACh output relative to control values. The results demonstrate that K-ATP channel modulators influence behavior when administered directly into the hippocampus, with channel blockers enhancing and openers impairing spontaneous alternation performance, thus supporting the hypothesis that glucose enhances memory via action at central K-ATP channels. That lemakalim, as well as glibenclamide and glucose, increased hippocampal ACh output suggests a dissociation between the effects of K-ATP channel modulators on behavior and hippocampal ACh release.
Photoaffinity labeling of avermectin binding sites from Caenorhabditis elegans and Drosophila melanogaster. (1992)

An azido-avermectin analog [4'' alpha-(4-azidosalicylamido-epsilon-caproylamido-beta-alan ylamido)-4''-deoxyavermectin B1a; azido-AVM] was synthesized and used to photoaffinity label avermectin binding sites present in the membranes of Caenorhabditis elegans and Drosophila melanogaster. Azido-AVM was biologically active and behaved like a competitive inhibitor of [3H]ivermectin binding to C. elegans membranes (Ki = 0.2 nM). Radiolabeled azido-AVM bound specifically and with high affinity to C. elegans membranes (Kd = 0.14 nM) and, upon photoactivation, became covalently linked to three C. elegans polypeptides of 53, 47, and 8 kDa. Photoaffinity labeling of a membrane preparation from D. melanogaster heads resulted in labeling of a single major polypeptide of approximately 47 kDa. The proteins that were covalently tagged in these experiments are believed to be associated with avermectin-sensitive chloride channels present in the neuromuscular systems of C. elegans and D. melanogaster. Azido-AVM did not bind to rat brain membranes and therefore was selective for the nematode and insect receptors.
Is sialic acid in milk food for the brain? (2006)

Abstract The rapid brain growth of infants places exceptionally high demands on the supply of nutrients from the diet. Human milk is the best source of food for brain growth and cognition. One of nature's richest sources of sialic acid, a vital component of brain gangliosides and the building block of polysialic acid (PSA) on neural cell adhesion molecule (NCAM), is found in human breast milk. However, infant formulas contain very little amounts. Gangliosides and polysialylated NCAM in the brain have an important role in cell-to-cell interactions, neuronal outgrowth, modifying synaptic connectivity, and memory formation. An exogenous source of sialic acid may be critical under conditions of extremely rapid brain growth, particularly during the first months after birth. Here we review the major differences in sialic acid concentration between human milk and infant formulas, and how sialic acid-bearing nutrients are metabolized. The role of this essential micronutrient in the developing brain is examined, particularly with respect to PSA, which has a major effect on brain plasticity.
Evaluation of corticosterone secretion-inducing activities of ginsenosides and their prosapogenins and sapogenins. (1983)

Ginsenosides Rb1, Rb2, Rc, Rd, Re and Rg1 (GRb1, GRb2 and so on) isolated from the roots of Panax ginseng C.A. MEYER, and their 20S- and 20R-prosapogenins (S-PS and R-PS), 20S- and 20R-protopanaxadiols (S-PPD and R-PPD), and a mixture of 20S- and 20R-panaxadiols (SR-PD) at various doses were administered to rats intraperitoneally. Plasma corticosterone and glucose levels at 30 min after the administration were determined, and ED50 values for corticosterone level were estimated. The ED50 values of GRd, GRb2, GRc and GRb1 were 7.1, 20, 44 and 112μmol/kg, respectively. ED50 of S-PS, the genuine prosapogenin of GRb1, GRb2, GRc and GRd, which has no sugar residue attached to the C-20 position, was 28μmol/kg, and the artifact prosapogenin R-PS also showed nearly the same activity, 26μmol/kg. The ED50 values of genuine and artifact sapogenins S- and R-PPD were 42 and 32μmol/kg, respectively, but an epimeric mixture of two artifact sapogenins SR-PD showed no activity at a dose of 80μmol/kg. The ED50 values of GRe and GRg1, glycosides of 20S-protopanaxatriol, were 107 and >160μmol/kg, respectively. Most of these 11 compounds did not significantly affect the plasma glucose level at 30 min after the treatment.
Long-Term Adult Feline Liver Organoid Cultures for Disease Modeling of Hepatic Steatosis (2017)

Hepatic steatosis is a highly prevalent liver disease, yet research is hampered by the lack of tractable cellular and animal models. Steatosis also occurs in cats, where it can cause severe hepatic failure. Previous studies demonstrate the potential of liver organoids for modeling genetic diseases. To examine the possibility of using organoids to model steatosis, we established a long-term feline liver organoid culture with adult liver stem cell characteristics and differentiation potential toward hepatocyte-like cells. Next, organoids from mouse, human, dog, and cat liver were provided with fatty acids. Lipid accumulation was observed in all organoids and interestingly, feline liver organoids accumulated more lipid droplets than human organoids. Finally, we demonstrate effects of interference with β-oxidation on lipid accumulation in feline liver organoids. In conclusion, feline liver organoids can be successfully cultured and display a predisposition for lipid accumulation, making them an interesting model in hepatic steatosis research.
Epigallocatechin-3-Gallate Enhances CD8+ T Cell–Mediated Antitumor Immunity Induced by DNA Vaccination (2007)

Immunotherapy and chemotherapy are generally effective against small tumors in animal models of cancer. However, these treatment regimens are generally ineffective against large, bulky tumors. We have found that a multimodality treatment regimen using DNA vaccination in combination with chemotherapeutic agent epigallocatechin-3-gallate (EGCG), a compound found in green tea, is effective in inhibiting large tumor growth. EGCG was found to induce tumor cellular apoptosis in a dose-dependent manner. The combination of EGCG and DNA vaccination led to an enhanced tumor-specific T-cell immune response and enhanced antitumor effects, resulting in a higher cure rate than either immunotherapy or EGCG alone. In addition, combined DNA vaccination and oral EGCG treatment provided long-term antitumor protection in cured mice. Cured animals rejected a challenge of E7-expressing tumors, such as TC-1 and B16E7, but not a challenge of B16 7 weeks after the combined treatment, showing antigen-specific immune responses. These results suggest that multimodality treatment strategies, such as combining immunotherapy with a tumor-killing cancer drug, may be a more effective anticancer strategy than single-modality treatments.
Controlled and living polymerizations : methods and materials (2009)

ANIONIC VINYL POLYMERIZATION Introduction Structure of Carbanions Initiation Mechanism of Styrene and Diene Polymerization Mechanism of Anionic Polymerization of Acrylic Monomers Some Applications of Anionic Polymerization Conclusions and Outlook CARBOCATIONIC POLYMERIZATION Introduction Mechanistic and Kinetic Details of Living Cationic Polymerization Living Cationic Polymerization Functional Polymers by Living Cationic Polymerization Telechelic Polymers Macromonomers Linear Diblock Copolymers Linear Triblock Copolymers Block Copolymers with Nonlinear Architecture Branched and Hyperbranched Polymers Surface Initiated Polymerization - Polymer Brushes Conclusions RADICAL POLYMERIZATION Introduction Typical Features of Radical Polymerization Controlled Reversible-Deactivation Radical Polymerization SFRP: NMP and OMRP Systems - Examples and Peculiarities ATRP - Examples and Peculiarities Degenerative Transfer Processes and RAFT Relative Advantages and Limitations of SFRP, ATRP, and DT Processes Controlled Polymer Architectures by CRP: Topology Chain Composition Functional Polymers Applications of Materials Prepared by CRP Outlook LIVING TRANSITION METAL-CATALYZED ALKENE PUOLYMERIZATION: POLYOLEFIN SYNTHESIS AND NEW POLYMER ARCHITECTURES Introduction Living Alpha-Olefin Polymerization Living Propylene Polymerization Living Polymerization of Ethylene Living Nonconjugated Diene Polymerization Living Homo- and Copolymerization of Cyclic Olefins Random Copolymers Block Copolymers Outlook and Summary LIVING RING-OPENING POLYMERIZATION OF HETEROCYCLIC MONOMERS Introduction Anionic and Coordination Living Ring-Opening Polymerization (LROP) Cationic CROP and LROP CROP and LROP Conducted in Dispersions Conclusions LIVING RING-OPENING METATHESIS POLYMERIZATION Overview of Ring-Opening Metathesis Polymerization (ROMP) Initiators for Living ROMP Applications of Polymers Synthesized using ROMP: From Novel Materials to Commerical Products Challenges and Perspectives for the Future Conclusion MACROMOLECULAR ARCHITECTURES BY LIVING AND CONTROLLED/ LIVING POLYMERIZATIONS Introduction Star Polymers Comb Polymers Cyclic Polymers Dendritic Polymers Complex Macromolecular Architectures Applications Conclusions SYNTHESIS OF BLOCK AND GRAFT COPOLYMERS Introduction Principles of Block Copolymerization ABA Triblock Copolymers (AB)n Linear Multiblock Copolymers ABC Triblock Terpolymers Synthesis of ABCA Tetra- and ABCBA Pentablock Terpolymers Synthesis of ABCD Quaterpolymers Applications Concluding Remarks MORPHOLOGIES IN BLOCK COPOLYMERS Introduction Block Copolymers in Bulk State Block Copolymer Thin Films Block Copolymer Micelles Applications Summary and Outlook INDUSTRIAL APPLICATIONS Introduction Synthesis of Anionic Styrenic Block Copolymers Adhesives and Sealants Compounding Applications Polymer Modification Cross-Linked Systems Bitumen Modification Footwear Viscosity Modification and Other Highly Diluted SBC Applications Emerging Technology in Block Copolymers
High efficiency optical reconstruction of binary phase-only filters using the Hughes liquid crystal light valve (1987)

The Hughes liquid crystal light valve (LCLV) has been evaluated for its applicability in writing and reading binary phase-only filters (BPOFs) in optical correlators. Experimental measurements of relevant performance characteristics of the LCLV as well as experimental results demonstrating its use for reconstructing BPOF's are reported. We also find that this device allows a significant optical system throughput. In addition, we discuss generation of the BPOF with a MacIntosh computer system.
Analysis of Receptor Binding by the Channel-forming Toxin Aerolysin Using Surface Plasmon Resonance (1999)

Aerolysin is a channel-forming bacterial toxin that binds to glycosylphosphatidylinositol (GPI) anchors on host cell-surface structures. The nature of the receptors and the location of the receptor-binding sites on the toxin molecule were investigated using surface plasmon resonance. Aerolysin bound to the GPI-anchored proteins Thy-1, variant surface glycoprotein, and contactin with similar rate constants and affinities. Enzymatic removal of N-linked sugars from Thy-1 did not affect toxin binding, indicating that these sugars are not involved in the high affinity interaction with aerolysin. Aerolysin is a bilobal protein, and both lobes were shown to be required for optimal binding. The large lobe by itself bound Thy-1 with an affinity that was at least 10-fold weaker than that of the whole toxin, whereas the small lobe bound the GPI-anchored protein at least 1000-fold more weakly than the intact toxin. Mutation analyses provided further evidence that both lobes were involved in GPI anchor binding, with certain single amino acid substitutions in either domain leading to reductions in affinity of as much as 100-fold. A variant with single amino acid substitutions in both lobes of the protein was completely unable to bind the receptor. The membrane protein glycophorin, which is heavily glycosylated but not GPI-anchored, bound weakly to immobilized proaerolysin, suggesting that interactions with cell-surface carbohydrate structures other than GPI anchors may partially mediate toxin binding to host cells.
Experimental optimization of probe length to increase the sequence specificity of high-density oligonucleotide microarrays (2007)

Our study suggests that the optimal probe length for specificity is 19-21-mer. This conclusion will assist in improvement of microarray design for both transcriptome analysis and mutation screening.
Extended Protection against Phlebovirus Infection Conferred by Recombinant Adenovirus Expressing Consensus Interferon (DEF201) (2012)

Punta Toro virus (PTV; Bunyaviridae, Phlebovirus) is related to Rift Valley fever virus (RVFV), a pathogenic agent which causes severe disease in humans and livestock primarily in the sub-Saharan region of Africa. The recent range expansion of RVFV and the potential for its intentional release into naïve populations pose a significant threat to public health and agriculture. Studies modeling disease in rodents and nonhuman primates have shown that PTV and RVFV are highly sensitive to the antiviral effects of alpha interferon (IFN-α), an important component of the innate antiviral host response. While recombinant IFN-α has high therapeutic value, its utility for the treatment of neglected tropical diseases is hindered by its short in vivo half-life and costly production of longer-lasting pegylated IFNs. Here, we demonstrate extended preexposure protection against lethal PTV challenge following a single intranasal administration of DEF201, which is a replication-deficient human adenovirus type 5 vector engineered to constitutively express consensus IFN-α (cIFN-α) from transduced host cells. DEF201 was also efficacious when administered within 24 h as a postexposure countermeasure. Serum concentrations of cIFN-α could be detected as early as 8 h following treatment and persisted for more than 1 week. The prolonged antiphlebovirus prophylactic effect, low production costs, and ease of administration make DEF201 a promising agent for intervention during natural disease outbreaks and for countering possible bioterrorist acts.
The Promoter for C4-type Mitochondrial Aspartate Aminotransferase Does not Direct Bundle Sheath-specific Expression in Transgenic Rice Plants (2005)

For NAD-malic enzyme (NAD-ME)-type C4 photosynthesis, two types of aspartate aminotransferase (AAT) are involved. We examined the expression pattern of the Panicum miliaceum mitochondrial Aat gene (PmAat) and P. miliaceum cytosolic Aat gene (PcAat) in transgenic rice plants, which were specifically expressed in bundle sheath cells (BSCs) and mesophyll cells (MCs), respectively. Expression of a beta-glucuronidase (GUS) reporter gene under the control of the PcAat promoter was regulated in an organ-preferential and light-dependent manner in the transgenic rice plants. However, the PmAat promoter drove the GUS expression in all organs we tested without light dependency, and this non-preferential expression pattern was also observed in transgenic rice with introduction of the intact PmAat gene. The expression patterns of the rice counterpart Aat genes to PmAat or PcAat showed that the rice mitochondrial Aat (RmAat1) gene was expressed in all organs tested in a light-independent manner, while expression of the rice cytosolic Aat (RcAat1) gene showed an organ-preferential and light-dependent pattern. Taking these results together, we can generalize that the regulatory system of BSC-specific or light-dependent expression of mitochondrial Aat is not shared between P. miliaceum (C4) and rice (C3) and that the expression of the C4 genes introduced into rice mimics that of their counterpart genes in rice.
Blockage of the vascular endothelial growth factor stress response increases the antitumor effects of ionizing radiation. (1999)

The family of vascular endothelial growth factor (VEGF) proteins include potent and specific mitogens for vascular endothelial cells that function in the lation of angiogenesis Inhibition of VEGF-induced angiogenesis either by neutralizing antibodies or dominant-negative soluble receptor, blocks the growth of primary and metastatic experimental tumors Here we report that VEGF expression is induced in Lewis lung carcinomas (LLCs) both in vitro and vivo after exposure to ionizing radiation (IR) and in human tumor cell lines (Seg-1 esophageal adenocarcinoma, SQ20B squamous cell carcinoma, T98 and U87 glioblastomas, and U1 melanoma) in vitro. The biological significance of IR-induced VEGF production is supported by our finding that treatment of tumor-bearing mice (LLC, Seg-1, SQ20B, and U87) with a neutralizing antibody to VEGF-165 before irradiation is associated with a greater than additive antitumor effect. In vitro, the addition of VEGF decreases IR-induced killing of human umbilical vein endothelial cells, and the anti-VEGF treatment potentiates IR-induced lethality of human umbilical vein endothelial cells. Neither recombinant VEGF protein nor neutralizing antibody to VEGF affects the radiosensitivity of tumor cells These findings support a model in which induction of VEGF by IR contributes to the protection of tumor blood vessels from radiation-mediated cytotoxicity and thereby to tumor radioresistance.
Long-term survival of AT-1 cardiomyocyte grafts in syngeneic myocardium (1993)

The long-term viability of cardiomyocyte grafts in the adult myocardium was tested. AT-1 cardiomyocytes, a differentiated tumor line derived from transgenic mice expressing an atrial natriuretic factor-simian virus 40 T antigen fusion gene, were grafted directly into the myocardium of syngeneic animals. Viable grafts were detected as long as 4 mo postimplantation. Thymidine uptake studies suggested that the grafted cardiomyocytes retained mitotic activity. The presence of AT-1 cardiomyocyte grafts and the associated myocardial remodeling were not accompanied by overt cardiac arrhythmia. Electron microscopic analyses showed that the majority of the grafts were juxtaposed directly to the host myocardium and were not encapsulated. This study indicates that the myocardium can serve as a stable platform for cells that have been manipulated in vitro and suggests that cardiomyocyte grafts may provide a useful means for the local delivery of recombinant molecules to the heart. The long-term survival of the AT-1 cardiomyocytes in the heart also raises the possibility that similar grafting approaches may be used to replace diseased myocardium.
UCSF ChimeraX: Structure visualization for researchers, educators, and developers (2020)

UCSF ChimeraX is the next-generation interactive visualization program from the Resource for Biocomputing, Visualization, and Informatics (RBVI), following UCSF Chimera. ChimeraX brings (a) significant performance and graphics enhancements; (b) new implementations of Chimera's most highly used tools, many with further improvements; (c) several entirely new analysis features; (d) support for new areas such as virtual reality, light-sheet microscopy, and medical imaging data; (e) major ease-of-use advances, including toolbars with icons to perform actions with a single click, basic "undo" capabilities, and more logical and consistent commands; and (f) an app store for researchers to contribute new tools. ChimeraX includes full user documentation and is free for noncommercial use, with downloads available for Windows, Linux, and macOS from https://www.rbvi.ucsf.edu/chimerax.
SHELL-BASED EXPERT SYSTEMS IN BUSINESS: A RETURN ON INVESTMENT PERSPECTIVE (1988)

This paper examines an important issue emerging in information systems management--the decision to proceed with an expert system application in a business setting. The focus is knowledge based systems at the lower end of the complexity spectrum--small, very focused systems that can be implemented by the use of shell-based development environments. This group represents the majority of expert systems that are currently being implemented and has some characteristics quite different from the larger systems. A classification scheme is suggested to differentiate three levels of ES development, from multi-million dollar life cycle cost ES environments to those that are in the low five figure range. The Low End segment of the range, the focus of this paper, is characterized by lower unit costs, powerful development tools and a large number of small, successful applications. The important role of Low End systems is discussed, with particular emphasis on their relatively high yield in standalone applications. Such systems do not meet the AI demands of moderately or very complex problems but there is a surprising breadth in their use. A group of key success factors for Low End systems is proposed, based on a synthesis of the applications literature. To operationalize these factors, three actual cases using Low End technology--from marketing, government and agribusiness-- are briefly described. Low End systems are not all gain. Their low unit costs can often mask the risks of proceeding headlong into an application without careful examination of the variables that can predict successful results. An agenda for action is offered for specific management policies for the planning of knowledge-based applications.