gebhart/patrepeval huggingface dataset:
Developing synthetic multivalent cellular effectors (2017)

I have designed bioconjugates that can elicit desired cellular responses – cellular effectors. Using multivalent interactions, involving the simultaneous binding of multiple receptors to multiple ligands, I have designed cellular effectors to use as vaccines and to direct stem cell fate. I have developed multivalent scaffolds to be used as a “universal” influenza vaccine, vaccine constructs for Respiratory Syncytial Virus (RSV) that do not present the variable antigenic site Ø, developed a novel strategy for nanopatterning protein antigens to guide the immune response toward and away from desired epitopes, and generated polypeptide-based scaffolds that can explicitly control the valency of multivalent conjugates as well as the inter-ligand spacing and used these to direct stem cell fate. All of these systems have shown that by controlling the nanoscale presentation of ligands, the system response can be altered and directed toward a desired behavior. The scaffolds that I have developed can be used in other vaccine design and stem cell proliferation studies. The general application of nanopatterning protein antigens has already been applied to several other systems in our lab and we hypothesize that it will be broadly applicable in future antigen design studies. Thus, the work presented in this thesis will stand as a foundation for future studies in vaccine design and cell signaling studies.
Heat sensitivity, thermotolerance, and profile of heat shock protein synthesis of human myelogenous leukemias. (1989)

In anticipation of using single or fractionated hyperthermia treatment in ex vivo purging of leukemic bone marrow in the clinic, we have compared the hyperthermic sensitivity, kinetics of thermotolerance, and heat-shock protein synthesis in three human myelogenous leukemic cell lines. In terms of heat sensitivity, the chronic myelogenous leukemic cell line K562 was found to be the most resistant. The Dos of the 43, 44, and 45 degrees C heat survival curves were 22, 13, and 6 min, respectively. HL-60 and KG-1, both acute myelogenous leukemic lines, however, were found to be several fold more sensitive to the cytotoxic effects of heat. The Dos of the 43, 44, and 45 degrees C heat survival curves for HL-60 were 7.6, 5.6, and 2 min and for KG-1 were 5.7, 4.5, and 1.7 min, respectively. All cell lines developed thermotolerance. However, K562 developed more tolerance which lasted for longer times. For K562 cells at priming heat doses of 45 degrees C/10 min, 42 degrees C/2 h, or 41 degrees C/2 h thermotolerance was maximum at 4 to 6 h and began to decay at 24 h. HL-60 and KG-1 cells showed some thermotolerance at the priming doses of 45 degrees C/5 min or 42 degrees C/30 min and had fully decayed by 24 h. K562 cells synthesized Mr 70,000 heat shock protein for over 24 h following the 45 degrees C/10 min heat shock, while HL-60 and KG-1 synthesized Mr 70,000 heat shock protein for 2-4 h for the same amount of cell kill. These studies suggest that most human leukemias may be extremely sensitive to the cytotoxic effects of heat, and in vitro purging of leukemias from bone marrow specimens by heat needs to be further studied both by in vitro and in vivo model systems.
Genetic changes in sweat gland carcinomas (2000)

The molecular pathogenesis of malignant appendageal tumors is poorly understood. Immunohistochemical staining, polymerase chain reaction (PCR)-based loss of heterozygosity (LOH) and sequencing analyses were performed in a mixed group of 21 sweat gland carcinomas. LOH was mostly confined to the chromosome arm 17p. None of the remaining 17 tumors showed LOH at any loci. Nuclear accumulation of p53 protein was observed in 3 tumors, all of which also showed LOH of 17p. One eccrine gland adenocarcinoma showed allelic loss of 17p and a Cys 176 Arg mutation in the p53 gene. The other three tumors that showed LOH of 17p, however, had wild-type p53 genes. A clear transition from benign eccrine poroma to porocarcinoma that was associated with p53 protein stabilization and allelic loss was observed in one tumor. One eccrine porocarcinoma/undifferentiated adnexal carcinoma showed prominent microsatellite instability, probably reflecting an underlying defect in DNA mismatch repair. Overexpression of erbB-2 was observed in three tumors. The low frequencies of LOH and p53 alterations in sweat gland carcinomas contrasted with the multiple genetic defects normally observed in cutaneous squamous cell carcinomas, and may be partly explained by the relative protection of cutaneous appendages from ultraviolet light and other environmental mutagens.
Lyra: A New Approach to Geometric Layout Rule Checking (1982)

Lyra is a layout rule checking program for Manhattan VLSI circuits. In Lyra, rules are specified in terms of constraints that must hold at certain corners in the design. The corner-based mechanism permits a wide variety of rules to be specified easily, including rules involving asymmetric constructs such as transistor overhangs. Lyra's mechanism also has locality, which can be exploited to construct incremental and/or hierarchical checkers. A rule compiler translates symbolic rules into efficient code for checking those rules, and permits the system to be retargeted for different processes.
High epitope density in a single protein molecule significantly enhances antigenicity as well as immunogenicity: a novel strategy for modern vaccine development and a preliminary investigation about B cell discrimination of monomeric proteins (2005)

Although early studies have shown a close correlation between epitope density and epitope-specific humoral immune responses, few attempts have been made to quantitatively compare the antigenic and immunogenic differences between protein molecules bearing low or high degrees of epitope density, nor have studies quantitatively investigated the mechanism of B cell discrimination of monomeric antigens. In this study, we prepared glutathione S-transferase (GST) fusion proteins bearing various copies of the M2e epitope from the influenza virus M2 protein [GST-(M2e)8, GST-(M2e)4 and GST-(M2e)1], which were used to detect and compare the real-time kinetic binding with M2e-specific mAb by surface plasma resonance. Our data show clearly that fusion proteins bearing higher M2e epitope density resulted in higher average avidity for M2e-specific mAb. Furthermore, it was observed that fusion proteins bearing high M2e epitope density could induce polyclonal antibodies (pAb) with enhanced an average affinity constant (KA) for M2e epitope peptide compared to fusion proteins bearing low epitope density. The average KA of pAb induced by GST-(M2e)8 (3.08 x 10(8) M(-1) or 9.96 x 10(8) M(-1)) was up to two orders of magnitude greater than the average KA of pAb induced by GST-(M2e)1 (2.00 x 10(6) M(-1) or 3.43 x 10(6) M(-1)). Thus, the data presented here demonstrate that high epitope density in a single protein molecule significantly enhances antigenicity and immunogenicity. These findings enrich our knowledge of how epitope density might relate to the recognition, activation and antibody production processes of epitope-specific immature B cells.
NORTH AMERICAN STONEFLIES (PLECOPTERA): SYSTEMATICS, DISTRIBUTION, AND TAXONOMIC REFERENCES (1986)

(Uploaded by Plazi from the Biodiversity Heritage Library) No abstract provided.
Effects of Controlled-Release Metoprolol on Total Mortality, Hospitalizations, and Well-being in Patients With Heart Failure (2000)

In this study of patients with symptomatic heartfailure, metoprolol CR/XL improved survival, reduced the need for hospitalizations due to worsening heart failure, improved NYHA functional class, and had beneficial effects on patient well-being.
Recombinant human bone morphogenetic protein‐9 potently induces osteogenic differentiation of human periodontal ligament fibroblasts (2016)

To accomplish effective periodontal regeneration for periodontal defects, several regenerative methods using growth and differentiation factors, including bone morphogenetic proteins (BMPs), have been developed. Bone morphogenetic protein-9 exhibits the most potent osteogenic activity of this growth factor family. However, it is unclear whether exogenous BMP-9 can induce osteogenic differentiation in human periodontal ligament (PDL) fibroblasts. Here, we examined the effects of recombinant human (rh) BMP-9 on osteoblastic differentiation in human PDL fibroblasts in vitro, compared with rhBMP-2. Recombinant human BMP-9 potently induced alkaline phosphatase (ALP) activity, mineralization, and increased expression of runt-related transcription factor-2/core binding factor alpha 1 (RUNX2/CBFA1), osterix, inhibitor of DNA binding/differentiation-1 (ID1), osteopontin, and bone sialoprotein genes, compared with rhBMP-2. The levels of rhBMP-9-induced osterix and ALP mRNA were significantly reduced in activin receptor-like kinase-1 and -2 small interfering RNA (siRNA)-transfected human PDL fibroblasts. Recombinant human BMP-9-induced ALP activity was not inhibited by noggin, in contrast to rhBMP-2 induced ALP activity, which was. Phosphorylation of SMAD1/5/8 in human PDL fibroblasts was induced by addition of rhBMP-9. Recombinant human BMP-9-induced ALP activity was suppressed by SB203580, SP600125, and U0126, which are inhibitors of p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase 1/2 (ERK1/2), respectively. Our data suggest that rhBMP-9 is a potent inducer of the differentiation of human PDL fibroblasts into osteoblast-like cells and that this may be mediated by the SMAD and mitogen-activated protein kinase (p38, ERK1/2, and JNK) pathways.
FCH domain only-2 organizes clathrin-coated structures and interacts with Disabled-2 for low-density lipoprotein receptor endocytosis (2012)

Clathrin-mediated endocytosis regulates the internalization of many nutrient and signaling receptors. Clathrin and endocytic accessory proteins are recruited to receptors by specific adaptors. The adaptor Disabled-2 (Dab2) recruits its cargoes, including the low-density lipoprotein receptor (LDLR), and mediates endocytosis, even when the major adaptor protein AP2 is depleted. We hypothesized that the accessory proteins normally recruited by AP2 may be recruited by Dab2 if AP2 is absent. We identified one such accessory protein, the F-BAR protein FCH domain only-2 (FCHO2), as a major Dab2-interacting protein. The μ-homology domain (μHD) of FCHO2 binds directly to DPF sequences in Dab2 that also bind AP2. Disrupting the Dab2-FCHO2 interaction inhibited Dab2-mediated LDLR endocytosis in AP2-depleted cells. Depleting FCHO2 reduced the number but increased the size of clathrin structures on the adherent surface of HeLa cells and inhibited LDLR and transferrin receptor clustering. However, LDLR was internalized efficiently by FCHO2-deficient cells when additional time was provided for LDLR to enter the enlarged structures before budding, suggesting that later steps of endocytosis are normal under these conditions. These results indicate FCHO2 regulates the size of clathrin structures, and its interaction with Dab2 is needed for LDLR endocytosis under conditions of low AP2.
The IL-6R α chain controls lung CD4+CD25+ Treg development and function during allergic airway inflammation in vivo (2005)

The cytokine IL-6 acts via a specific receptor complex that consists of the membrane-bound IL-6 receptor (mIL-6R) or the soluble IL-6 receptor (sIL-6R) and glycoprotein 130 (gp130). In this study, we investigated the role of IL-6R components in asthma. We observed increased levels of sIL-6R in the airways of patients with allergic asthma as compared to those in controls. In addition, local blockade of the sIL-6R in a murine model of late-phase asthma after OVA sensitization by gp130-fraction constant led to suppression of Th2 cells in the lung. By contrast, blockade of mIL-6R induced local expansion of Foxp3-positive CD4+CD25+ Tregs with increased immunosuppressive capacities. CD4+CD25+ but not CD4+CD25- lung T cells selectively expressed the IL-6R alpha chain and showed IL-6-dependent STAT-3 phosphorylation. Finally, in an in vivo transfer model of asthma in immunodeficient Rag1 mice, CD4+CD25+ T cells isolated from anti-IL-6R antibody-treated mice exhibited marked immunosuppressive and antiinflammatory functions. IL-6 signaling therefore controls the balance between effector cells and Tregs in the lung by means of different receptor components. Furthermore, inhibition of IL-6 signaling emerges as a novel molecular approach for the treatment of allergic asthma.
Mechanism of photoinactivation and re-activation in the bioluminescence system of the ctenophore Mnemiopsis (1984)

The bioluminescence of the ctenophore Mnemiopsis takes place when the photoprotein mnemiopsin in the photocytes reacts with Ca2+. The luminescence is inhibited in sunlight and this photoinhibition is reversible by keeping the live specimens in the dark. The extracts of mnemiopsin are similarly photoinhibited, but the photoinhibition cannot be reversed in the dark. We have found that photo-inhibited mnemiopsin can be re-activated in the dark by incubation with coelenterazine and O2 only in solutions having a pH very close to 9.0. The re-activation in vivo probably takes place in the same manner, using the coelenterazine that is supplied from its abundant storage form. Various lines of experimental evidence suggest that the photoinactivation of mnemiopsin results in the dissociation of coelenterazine and oxygen from the molecule of photoprotein; the dissociated form of the former molecule is an inactive form of coelenterazine, not free coelenterazine.
Water-Soluble Poly(acrylic acid) Grafted Luminescent Silicon Nanoparticles and Their Use as Fluorescent Biological Staining Labels (2004)

UV-induced graft polymerization of acrylic acid (AAc) on the surface of silicon nanoparticles was used to prepare a stable aqueous luminescent silicon nanoparticle solution. By grafting a water-soluble polymer on the particle surface, the dispersions in water of the silicon nanoparticles became very stable and clear aqueous solutions could be obtained. XPS and NMR spectroscopy confirmed that PAAc was covalently grafted to the silicon nanoparticles. The grafted PAAc on silicon particles increased not only the dispersibility but also improved the photoluminescence stability of the silicon nanoparticles against degradation by water. The surface-modified nanoparticles were used as biological labels for cell imaging. The Si quantum dot labels exihibited bright fluorescence images and provided higher resistance to photobleaching than the commonly used organic dyes.
The Liver as a Source of Extrarenal Erythropoietin Production (1972)

Abstract Nephrectomized rats exposed to intense hypoxia produce sufficient erythropoietin (Ep) to detectably increase their plasma Ep titers. Extrarenal Ep production is no longer detectable if nephrectomized rats are also subjected to 80% hepatectomy prior to being made hypoxic at 0.465 atmos and is barely detectable but significantly lower than in nephrectomized rats when exposed to 0.435 atmos. These results suggest that the liver plays an important role in the production of extrarenal erythropoietin.
Highly parallel oligonucleotide purification and functionalization using reversible chemistry (2011)

We have developed a cost-effective, highly parallel method for purification and functionalization of 5'-labeled oligonucleotides. The approach is based on 5'-hexa-His phase tag purification, followed by exchange of the hexa-His tag for a functional group using reversible reaction chemistry. These methods are suitable for large-scale (micromole to millimole) production of oligonucleotides and are amenable to highly parallel processing of many oligonucleotides individually or in high complexity pools. Examples of the preparation of 5'-biotin, 95-mer, oligonucleotide pools of >40K complexity at micromole scale are shown. These pools are prepared in up to ~16% yield and 90-99% purity. Approaches for using this method in other applications are also discussed.
Chemosensitivity testing of human tumors using a microplate adenosine triphosphate luminescence assay: clinical correlation for cisplatin resistance of ovarian carcinoma. (1995)

An ATP luminescence assay (TCA 100) was used to measure chemotherapeutic drug sensitivity and resistance of dissociated tumor cells cultured for 6 days in serum-free medium and 96-well polypropylene microplates. Studies were performed with surgical, needle biopsy, pleural, or ascitic fluid specimens using 10,000-20,000 cells/well. ATP measurements were used to determine tumor growth inhibition. Single agent and drug combinations were evaluated using the area under the curve and 50% inhibitory concentration (IC50) results for a series of test drug concentrations. The ATP luminometry method had high sensitivity, linearity, and precision for measuring the activity of single agents and drug combinations. Assay reproducibility was high with intraassay and interassay coefficients of variation of 10-15% for percentage of tumor growth inhibition, 5-10% for area under curve, and 15-20% for IC50 results. Good correlation (r = 0.93) between the area under the curve, and IC50 results was observed. Cytological studies with 124 specimens demonstrated selective growth of malignant cells in the serum-free culture system. Studies with malignant and benign specimens also showed selective growth of malignant cells in the serum-free medium used for assay. The assay had a success rate of 87% based on criteria for specimen histopathology, magnitude of cell growth, and dose-response drug activity. Cisplatin results for ovarian carcinoma are presented for 81 specimens from 70 untreated patients and 33 specimens from 30 refractory patients. A model for interpretation of these results based on the correlation of clinical response with the area under the curve and IC50 results indicates that the assay has > 90% accuracy for cisplatin resistance of ovarian carcinoma. Additional studies are in progress to evaluate the clinical efficacy of this assay.
Naturally occurring antibodies to an epitope on Plasmodium falciparum gametes detected by monoclonal antibody-based competitive enzyme-linked immunosorbent assay (1988)

The antibody response to an epitope on gamete antigens of Plasmodium falciparum in persons naturally exposed to malaria has been investigated by competitive enzyme-linked immunosorbent assay. The assay detects antibodies to an epitope on the 48/45-kilodalton (kDa) gamete surface antigen by competition with horseradish peroxidase-labeled monoclonal antibody IIC5-B10. Five sera previously shown to immunoprecipitate the 230- and 48/45-kDa antigens significantly inhibited IIC5-B10 binding to an average of 24.2% of control. The one serum which precipitated only the 48/45-kDa antigen did not inhibit IIC5-B10 binding. For 26 sera which were negative by immunoprecipitation, mean binding in the assay was 112.7% of control (pooled London nonimmune sera). Recognition of both 230-kDa and 48/45-kDa antigens was associated with a titer of 1:9 or greater (reciprocal geometric mean titer, 27.6) for inhibition to more than 2 standard deviations from the mean of the negative sera. The results show that the IIC5-B10 binding site is a naturally immunogenic epitope recognized by the majority of persons who had antibodies to the 48/45-kDa protein. An additional finding was enhancement of binding of IIC5-B10 to an average of 154.4% of control by five sera which recognized only the 230-kDa antigen, presumably due to conformational alteration of the gamete antigen complex.
A Phosphatidylcholine-Specific Phospholipase C Regulates Activation of p42/44 Mitogen-Activated Protein Kinases in Lipopolysaccharide-Stimulated Human Alveolar Macrophages (1999)

This study uses human alveolar macrophages to determine whether activation of a phosphatidylcholine (PC)-specific phospholipase C (PC-PLC) is linked to activation of the p42/44 (ERK) kinases by LPS. LPS-induced ERK kinase activation was inhibited by tricyclodecan-9-yl xanthogenate (D609), a relatively specific inhibitor of PC-PLC. LPS also increased amounts of diacylglycerol (DAG), and this increase in DAG was inhibited by D609. LPS induction of DAG was, at least in part, derived from PC hydrolysis. Ceramide was also increased in LPS-treated alveolar macrophages, and this increase in ceramide was inhibited by D609. Addition of exogenous C2 ceramide or bacterial-derived sphingomyelinase to alveolar macrophages increased ERK kinase activity. LPS also activated PKC zeta, and this activation was inhibited by D609. LPS-activated PKC zeta phosphorylated MAP kinase kinase, the kinase directly upstream of the ERK kinases. LPS-induced cytokine production (RNA and protein) was also inhibited by D609. As an aggregate, these studies support the hypothesis that one way by which LPS activates the ERK kinases is via activation of PC-PLC and that activation of a PC-PLC is an important component of macrophage activation by LPS.
Addition of colchicine-tubulin complex to microtubule ends: The mechanism of substoichiometric colchicine poisoning (1977)

Colchicine blocks microtubule polymerization by an unusual substoichiometric poisoning mechanism. We have investigated the mechanism by which this poisoning occurs with several experimental approaches, and have found that colchicine acts by addition to microtubule ends as a colchicine-tubulin complex.
Self-Directed Assembly of Photoactive Hybrid Silicates Derived from an Azobenzene-Bridged Silsesquioxane (2002)

Hybrid silicate materials derived from organo-bridged silsesquioxane precursors, RO3-Si-R'-Si-OR3, where R and R' are organic ligands, represent a remarkably diverse class of nanocomposites capable of forming both Si-O-Si and Si-C-Si bonds with molecular scale homogeneity. Recently, in an effort to better control their structure and function, surfactant-directed self-assembly or self-directed assembly has been used to synthesize hierarchical organo-bridged polysilsesquioxanes that exhibit order over multiple length scales. Here we report the synthesis and self-directed assembly of an optically active azobenzene-bridged silsesquioxane, 4,4'-bis(3-triethoxysilylpropylureido)azobenzene 1. Hydrogen-bonding interactions between the three active centers of the bis-ureide groups (-NH-CO-NH) combined with pi-pi interactions between the azobenzene groups serve to self-assemble 1 into a highly ordered lamellar mesostructure in which the d-spacing is optically controlled through photoisomerization of the azobenzene moiety before or after assembly.
Murine thymic CD4+ T cell subsets: a subset (Thy0) that secretes diverse cytokines and overexpresses the V beta 8 T cell receptor gene family. (1992)

We demonstrate here the presence of a distinct mature CD4+8- T cell subset in mouse thymus. This subset, termed "Thy0," is delineated by the absence of 3G11 expression from about half of the 6C10-/HSAlow/- fraction of CD4+8- thymic cells. Thy0 is detectable from the neonatal period and largely contributes the Th0-type diverse cytokine production previously reported for the HSAlow/-CD4+ thymic population. Further, cells expressing the T cell receptor V beta 8 gene family are found at increasing frequency in Thy0 with age, comprising 40-60% of Thy0 in adult BALB/c mice. This alteration of V beta 8+ cell frequency is unique to Thy0, since no other CD4+ subset in thymus or spleen shows such V beta 8 overusage. All functional CD4+ T cell subsets, including Thy0, show appropriate V beta clonal deletion associated with endogenous superantigens. Thus, it appears that Thy0 is an intrathymically generated secondary cell subset produced after CD4+ T cell selection.