gebhart/patrepeval huggingface dataset:
Abstract 1559: TLR7/8 immune-stimulating antibody conjugates elicit robust myeloid activation leading to enhanced effector function and anti-tumor immunity in pre-clinical models (2019)

Abstract Deficient anti-tumor immunity often results from an immunosuppressive tumor microenvironment (TME) that renders antigen presenting cells (APCs) unable to effectively stimulate T cells. Recent studies indicate that local delivery of immunostimulatory adjuvants can activate tumor resident APCs, driving uptake, processing and presentation of tumor neoantigens to T cells that mediate anti-tumor immunity. To overcome challenges associated with intratumoral delivery of such adjuvants, we developed a novel class of TLR immune-stimulating antibody conjugates (TAC) that comprise a TLR7/8 agonist conjugated to tumor-targeting monoclonal antibodies. In vitro co-cultures with human cancer cell lines and leukocytes revealed that TACs potently activate primary APCs, leading to increased co-stimulatory molecule expression (e.g. CD40, CD86) and secretion of pro-inflammatory cytokines (e.g. TNFα). The TACs also enhanced antibody-mediated effector functions such as ADCC and ADCP. Surprisingly, these constructs also induced dendritic cell (DC) differentiation from monocytes, as measured by changes in cellular morphology and DC surface markers (e.g. CD14 downregulation). CyTOF-based analysis of intracellular signaling in human leukocytes revealed a unique signaling signature of the conjugate compared to a mixture of its components, suggesting a novel biological mechanism by which the conjugate stimulates APCs. Finally, we demonstrated in vivo efficacy in syngeneic tumor models in which TAC treatment led to tumor clearance and development of immunologic memory. These results provide a strong rationale for this technology as a platform for cancer immunotherapy. Citation Format: Shelley E. Ackerman, Joseph C. Gonzalez, Josh D. Gregorio, Jason C. Paik, Felix J. Hartmann, Justin A. Kenkel, Arthur Lee, Angela Luo, Cecelia I. Pearson, Murray L. Nguyen, Benjamin Ackerman, Lauren Y. Sheu, Richard P. Laura, Steven J. Chapin, Brian S. Safina, Sean C. Bendall, David Dornan, Edgar G. Engleman, Michael N. Alonso. TLR7/8 immune-stimulating antibody conjugates elicit robust myeloid activation leading to enhanced effector function and anti-tumor immunity in pre-clinical models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1559.
Antibiotics: opportunities for genetic manipulation (1989)

New antibiotics can still be discovered by the development of novel screening procedures. Notable successes over the last few years include the monobactams, beta-lactamase inhibitors (clavulanic acid) and new glycopeptides in the antibacterial field; antiparasitic agents such as avermectins; and herbicidal antibiotics like bialaphos. In the future we can expect the engineering of genes from 'difficult' pathogens, including mycobacteria and fungi, and cancer cells, to provide increasingly useful in vitro targets for the screening of antibiotics that can kill pathogens and tumours. There will also be a greater awareness of the need to reveal the full potential for antibiotic production on the part of microorganisms by the physiological and/or genetic awakening of 'silent' genes. Nevertheless, the supply of natural antibiotics for direct use or chemical modification is not infinite and there will be increasing scope for widening the range of available antibiotics by genetic engineering. 'Hybrid' antibiotics have been shown to be generated by the transfer of genes on suitable vectors between strains producing chemically related compounds. More exciting is the possibility of generating novelty by the genetic engineering of the synthases that determine the basic structure of antibiotics belonging to such classes as the beta-lactams and polyketides. Research in this area will certainly yield knowledge of considerable scientific interest and probably also of potential applicability. In the improvement of antibiotic titre in actinomycetes, protoplast fusion between divergent selection lines has taken a place alongside random mutation and screening. In some cases the cloning of genes controlling metabolic 'bottlenecks' in fungi and actinomycetes will give an immediate benefit in the conversion of accumulated biosynthetic intermediates to the desired end product. However, the main impact of genetic engineering in titre improvement will probably come only after a further use of this technology to understand and manipulate the regulation of antibiotic biosynthesis as a facet of the general challenge of understanding differential gene expression. Streptomyces offers a particularly fertile field for such research, following the isolation of DNA segments that carry groups of closely linked operons for the biosynthesis of and resistance to particular antibiotics, and of genes with pleiotropic effects on morphological differentiation and secondary metabolite formation.
Ultralarge and Thermally Stable Electro‐optic Activities from Diels–Alder Crosslinkable Polymers Containing Binary Chromophore Systems (2006)

The dispersion of an efficient secondary chromophore into in situ crosslinked nonlinear optical polymer networks is described. The secondary chromophore leads to both enhanced electro-optical (EO) activity (> 260 pm V–1 at 1.31 μm) and alignment stability at 85 °C. Analysis of the EO properties shows exceptional poling efficiency of these binary systems at high chromophore loading levels, in contrast to experimental results obtained from single-chromophore polymers.
The 4-1BB Costimulation Augments the Proliferation of CD4+CD25+ Regulatory T Cells (2004)

The thymus-derived CD4(+)CD25(+) T cells belong to a subset of regulatory T cells potentially capable of suppressing the proliferation of pathogenic effector T cells. Intriguingly, these suppressor cells are themselves anergic, proliferating poorly to mitogenic stimulation in culture. In this study, we find that the 4-1BB costimulator receptor, best known for promoting the proliferation and survival of CD8(+) T cells, also induces the proliferation of the CD4(+)CD25(+) regulatory T cells both in culture and in vivo. The proliferating CD4(+)CD25(+) T cells produce no detectable IL-2, suggesting that 4-1BB costimulation of these cells does not involve IL-2 production. The 4-1BB-expanded CD4(+)CD25(+) T cells are functional, as they remain suppressive to other T cells in coculture. These results support the notion that the peripheral expansion of the CD4(+)CD25(+) T cells is controlled in part by costimulation.
Self-Assembly of Alkanethiol Molecules onto Platinum and Platinum Oxide Surfaces (2003)

We studied the self-assembly of n-alkanethiols CH3(CH2)mSH (m = 5, 7, 9, 11, 13, 15, 17, 19, 21) onto platinum thin films with two different surface properties: metallic and oxide. Water contact angle, ellipsometry, and reflection−absorption infrared spectroscopy (RAIRS) measurements suggested that well-organized, methyl-terminated monolayer films formed on the metallic platinum surface. On the other hand, the molecular films formed with the alkanethiol molecules on platinum oxide surfaces were loosely packed and poorly ordered. For the monolayer films formed with alkanethiols of different chain lengths on metallic Pt surfaces, a transition from slightly disordered to crystalline-like structure was observed with increasing chain length. Based on the intensities of the methylene and methyl C−H vibration modes in the RAIRS, the tilt angle of the alkyl chain in the monolayers on Pt surfaces was estimated to be less than 15° with respect to the surface normal. X-ray photoelectron spectroscopy revealed the formation of metal−thiolate bonding of the thiol headgroups in the alkanethiol molecules with Pt atoms on the surfaces.
Malondialdehyde alteration of low density lipoproteins leads to cholesteryl ester accumulation in human monocyte-macrophages (1980)

Glutaraldehyde treatment of (125)I-labeled low density lipoprotein ((125)I-native-LDL) produced a modified LDL ((125)I-glut-LDL) with a molecular weight of 10 x 10(6) or more. Malondialdehyde treatment of (125)I-native-LDL produced a product ((125)I-MDA-LDL) with a molecular weight not appreciably different from that of the original lipoprotein. However, the electrophoretic mobility of MDA-LDL indicated a more negative charge than native-LDL. (125)I-MDA-LDL was degraded by two processes: a high-affinity saturable process with maximal velocity at 10-15 mug of protein per ml and a slower, nonsaturable process. The degradation of (125)I-MDA-LDL was readily inhibited by increasing concentrations of nonradioactive MDA-LDL but was not inhibited by acetylated LDL or native-LDL even at concentrations as high as 1600 mug of protein per ml. After exposure of native-LDL to blood platelet aggregation and release in vitro, 1.73 +/- 0.19 nmol of malondialdehyde per mg of LDL protein was bound to the platelet-modified-LDL. No detectable malondialdehyde was recovered from native-LDL that had been treated identically except that the platelets were omitted from the reaction mixture. After incubation with glut-LDL, MDA-LDL, or platelet-modified-LDL for 3 days, human monocyte-macrophages showed a dramatic increase in cholesteryl ester content whereas the cholesteryl ester content of cells incubated with the same concentration of native-LDL did not. Based on these experiments we propose that modification of native-LDL may be a prerequisite to the accumulation of cholesteryl esters within the cells of the atherosclerotic reaction. We further hypothesize that one modification of LDL in vivo may result from malondialdehyde which is released from blood platelets or is produced by lipid peroxidation at the site of arterial injury.
The role of NHERF‐1 in the regulation of renal proximal tubule sodium–hydrogen exchanger 3 and sodium‐dependent phosphate cotransporter 2a (2005)

Adaptor proteins containing PDZ interactive domains have been recently identified to regulate the trafficking and activity of ion transporters and channels in epithelial tissue. In the renal proximal tubule, three PDZ adaptor proteins, namely NHERF-1, NHERF-2 and PDZK1, are expressed in the apical membrane, heterodimerize with one another, and, at least in vitro, are capable of binding to NHE3 and Npt2a, two major regulated renal proximal tubule apical membrane transporters. Studies using NHERF-1 null mice have begun to provide insights into the organization of these adaptor proteins and their specific interactions with NHE3 and Npt2a. Experiments using brush border membranes and cultured renal proximal tubule cells indicate a specific requirement for NHERF-1 for cAMP-mediated phosphorylation and inhibition of NHE3. NHERF-1 null mice demonstrate increased urinary excretion of phosphate associated with mistargeting of Npt2a to the apical membrane of renal proximal tubule cells. NHERF-1 null animals challenged with a low phosphate diet and proximal tubule cells from these animals cultured in a low phosphate media fail to adapt as well as wild-type mice. These studies indicate a unique requirement for NHERF-1 in cAMP regulation of NHE3 and in the trafficking of Npt2a.
Characterization of a monoclonal antibody (5E9) that defines a human cell surface antigen of cell activation. (1981)

This study describes the monoclonal antibody 5E9 and the cell surface antigen it defines. The hybridoma cell line T3-5E9 was derived from fusion of P3 X 63/Ag8 myeloma cells and spleen cells from BALB/c mice immunized with HSB-2 cells, a human T cell line. Although binding to only 1 to 5% of peripheral blood (PB) and spleen mononuclear cells, 5E9 antibody bound to 40 to 80% of Con A-, PHA-, or PWM-activated PB cells. Moreover, 5E9 antibody bound to variable numbers of Sezary, acute myelogenous leukemia, and ALL PB leukemia cells. 5E9 antibody bound to all hematopoietic and nonhematopoietic cell lines tested, to 11 +/- 1% of thymocytes, and 40% of nucleated bone marrow cells. Under reducing conditions, immunoprecipitation studies using 5E9 antibody demonstrated 5E9 antigen to be an 90,000 m.w. glycoprotein. Under nonreducing conditions, antigen 5E9 is a disulfide-linked dimer of approximately 190,000 daltons. Sequential precipitation experiments using antibody 5E9, alpha OD heteroantiserum (raised against T ALL cells), and monoclonal antibody OKT9 demonstrated that the 3 antibody preparations recognized the same 90,000 m.w. glycoprotein. Thus, antibody 5E9 defines an 90,000 m.w. human cell surface antigen that is absent on the majority of PB mononuclear cells and is expressed on rapidly dividing normal and malignant human cells. This monoclonal antibody should be a useful marker of human cell activation.
Palmitate decreases proton pumping of liver‐type cytochrome c oxidase (2001)

The H+/e- stoichiometry of reconstituted cytochrome c oxidase from bovine kidney, containing subunit VIaL (liver type), is 0.5 under standard conditions but 1.0 on addition of 1% cardiolipin to the lipid mixture (asolectin). Low concentrations of palmitate (half-maximal effect at 0.5 microm), but not laurate, myristate, stearate, oleate, 1-hexadecanol, palmitoyl glycerol and palmitoyl CoA, decreased the H+/e- ratio in the presence of cardiolipin from 1.0 to 0.5, accompanied by an increase of coupled, but not of uncoupled respiration of proteoliposomes. Cardiolipin and palmitate did not influence the H+/e- stoichiometry and respiration of reconstituted cytochrome c oxidase from bovine heart, containing subunit VIaH (heart-type). The H+/e- stoichiometry of the heart enzyme, however, is decreased from 1.0 to 0.5 by 5 mm intraliposomal ATP (instead of 5 mm ADP). It is assumed that palmitate binds to subunit VIaL. The partial uncoupling of proton pumping in cytochrome c oxidase is suggested to participate in mammalian thermogenesis.
Do nonsteroidal anti-inflammatory drugs decrease the risk for Alzheimer's disease? (1995)

Based on reports that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the risk for Alzheimer's disease (AD), we studied the cross-sectional relation between NSAID use and the risk for AD in a population-based study of disease and disability in older people. After controlling for age, education, gender, and use of benzodiazepines, we found a relative risk (RR) for AD of 0.38 (0.15 to 0.95) when comparing NSAID users (n = 365) to NSAID non-users (n = 5,893). To address confounding by indication or contraindication, we compared NSAID users with a subset of NSAID non-users who were using topical medication for ear, eye, or dermatologic conditions (n = 365). In this comparison, the adjusted RR for AD was 0.54 (0.16 to 1.78). These findings are compatible with a possible protective effect of NSAIDs on the risk for AD.
Positron-Emission Tomography and Assessment of Cancer Therapy (2006)

Positron-emission tomography (PET) is a noninvasive imaging technique that exploits the unique decay physics of positron-emitting isotopes. The isotopes of oxygen, carbon, nitrogen, and fluorine have been used in the development of diagnostically useful biologic compounds that are available for PET imaging in order to provide a functional or metabolic assessment of normal tissues or disease conditions.The past few years have seen a tremendous expansion of clinical applications of PET, particularly in oncology, mostly with the use of 18F-fluorodeoxyglucose (18F-FDG) as the PET tracer. PET with 18F-FDG is now being used in the evaluation of several neoplasms, both . . .
Accurate linear technique for camera calibration considering lens distortion by solving an eigenvalue problem (1993)

A new technique for calibrating a camera with high accuracy and low computational cost is proposed. The geometric camera parameters considered include camera position, orientation, focal length, radial lens distortion, pixel size, and optical axis piercing point. With this method, the camera parameters to be estimated are divided into two parts: the radial lens distortion coefficient κ and a composite parameter vector <b>c</b> composed of all the above-mentioned geometric camera parameters other than κ. Instead of using nonlinear optimization techniques, the estimation of κ is transformed into an eigenvalue problem of an 8 x 8 matrix. The method is fast because it requires only linear computation; it is accurate because the effect of the lens distortion is considered and because all the information contained in the calibration points is used. Computer simulations and real experiments show that the calibration method can achieve an accuracy of 1 part in 10,000 in 3-D measurement, which is better than that of the well-known method proposed by R. Y. Tsai.
A Highly Efficient, Practical, and General Route for the Synthesis of (R3P)2Pd(0): Structural Evidence on the Reduction Mechanism of Pd(II) to Pd(0) (2010)

A highly efficient, practical, and general method was developed to synthesize a family of (R(3)P)(2)Pd(0) complexes, using a stoichiometric amount of phosphine ligands and readily available Pd(II) precursors. The stepwise pathway of reducing Pd(II) to Pd(0) was established by isolating two key intermediates. Both [t-Bu(2)(4-Me(2)NC(6)H(4))P](2)Pd and (t-Bu(2)NpP)(2)Pd are new compounds. Preliminary studies on [t-Bu(2)(4-Me(2)NC(6)H(4))P](2)Pd have indicated that it is a very active catalyst (84-95% isolated yield) in the Cu-free Sonogashira coupling involving aryl and heteroaryl chlorides at 0.5 mol % catalyst loading.
N4-Hexanoylspermidine, a New Polyamine-Related Compound That Accumulates during Ovary and Petal Senescence in Pea (1996)

A previously unknown polyamine conjugate that accumulates in senescing ovaries of pea (Pisum sativum L.) was shown by mass spectrometry, nuclear magnetic resonance, and chemical synthesis to be N4-hexanoylspermidine (hexanoyl-spd) This structure was indicated by analysis of the dansylated polyamine using fast atom bombardment mass spectrometry, following purification by high-performance liquid chromatography. Furthermore, acid hydrolysis of the compound yielded spermidine and hexanoic acid. 1H-nuclear magnetic resonance suggested that spermidine was substituted at N4 in the conjugate. Hexanoyl-spd was synthesized, and its didansyl derivative was shown to have an identical mass spectrum and high-performance liquid chromatography retention time as the derivatized natural compound. Further confirmation of its structure was obtained by comparison of the synthetic and natural polyamines as trifluoroacetyl derivatives using gas chromatography-mass spectrometry. This new polyamine conjugate is present in pea ovaries at low levels at anthesis and its concentration remains low in developing seeded fruit or in parthenocarpic fruit that have been induced by application of growth regulators to emasculated flowers or by topping the plant. Conjugate levels are also low in parthenocarpic fruit induced naturally in the slender (la crys) mutant. However, levels of hexanoyl-spd increase progressively in senescing petals and ovaries, beginning at anthesis or 2 d later, respectively.
Comparison of the pharmacokinetic profiles of two locally administered doxycycline gels in crevicular fluid and saliva (2004)

Both doxycycline gels showed pharmacokinetics of controlled-release delivery systems.
Microbial biotechnology: fundamentals of applied microbiology (2008)

Knowledge in microbiology is growing exponentially through the determination of genomic sequences of hundreds of microorganisms and the invention of new technologies such as genomics, transcriptomics, and proteomics, to deal with this avalanche of information. These genomic data are now exploited in thousands of applications, ranging from those in medicine, agriculture, organic chemistry, public health, biomass conversion, to biomining. Microbial Biotechnology. Fundamentals of Applied Microbiology focuses on uses of major societal importance, enabling an in-depth analysis of these critically important applications. Some, such as wastewater treatment, have changed only modestly over time, others, such as directed molecular evolution, or 'green' chemistry, are as current as today's headlines. This fully revised second edition provides an exciting interdisciplinary journey through the rapidly changing landscape of discovery in microbial biotechnology. An ideal text for courses in applied microbiology and biotechnology courses, this book will also serve as an invaluable overview of recent advances in this field for professional life scientists and for the diverse community of other professionals with interests in biotechnology.
Discovery of a Piperidine-4-carboxamide CCR5 Antagonist (TAK-220) with Highly Potent Anti-HIV-1 Activity (2006)

We incorporated various polar groups into previously described piperidine-4-carboxamide CCR5 antagonists to improve their metabolic stability in human hepatic microsomes. Introducing a carbamoyl group into the phenyl ring of the 4-benzylpiperidine moiety afforded the less lipophilic compound 5f, which possessed both high metabolic stability and good inhibitory activity of HIV-1 envelope-mediated membrane fusion (IC(50) = 5.8 nM). Further optimization to increase potency led to the discovery of 1-acetyl-N-{3-[4-(4-carbamoylbenzyl)piperidin-1-yl]propyl}-N-(3-chloro-4-methylphenyl)piperidine-4-carboxamide (5m, TAK-220), which showed high CCR5 binding affinity (IC(50) = 3.5 nM) and potent inhibition of membrane fusion (IC(50) = 0.42 nM), as well as good metabolic stability. Compound 5m strongly inhibited the replication of CCR5-using HIV-1 clinical isolates in human peripheral blood mononuclear cells (mean EC(50) = 1.1 nM, EC(90) = 13 nM) and exhibited a good pharmacokinetic profile in monkeys (BA = 29%). This compound has been chosen as a clinical candidate for further development.
Size-tunable infrared (1000–1600 nm) electroluminescence from PbS quantum-dot nanocrystals in a semiconducting polymer (2003)

Nanocomposites consisting of PbS nanocrystals in a conjugated polymer matrix were fabricated. We report results of photo- and electroluminescence across the range of 1000 to 1600 nm with tunability obtained via the quantum-size effect. The intensity of electroluminescence reached values corresponding to an internal quantum efficiency up to 1.2%. We discuss the impact of using different-length capping ligands on the transfer of excitations from polymer matrix to nanocrystals.
Nausea and Vomiting (2017)

Mechanisms of Nausea and Emesis: Introduction and Retrospective (Alan D. Miller and John Kucharczyk). Motion-Induced Nausea and Vomiting (Alan D. Miller). The Stomach - Both a Target and Potential Contributor in Space Sickness (Pascal Berry). Humoral Factors in Nausea and Emesis (John Kucharczyk and Kent Harding). The Central Connections of Area Postrema Define the Paraventricular System Involved in Anti-Noxious Behaviors (I.N.C. Lawes). Postirradiation Emesis (Gregory L. King and Milan T. Makale). Nausea and Vomiting in the Clinical Practices of Radiology and Anesthesia (M. Riding, D.S. Litz, and A. Gerber). Vomiting in Neurological Disorders (H. Hugenholtz). Nausea and Vomiting in Cancer Patients (D. J. Stewart). Antiemetics and Cancer Chemotherapy (M. Brigden and J. Barnett). ISBN 0-8493-6781-6.