gebhart/patrepeval huggingface dataset:
Determination of Epitope Specificities of a Large Number of Monoclonal Antibodies by Solid-Phase Mutual Inhibition Assays Using Biotinylated Antigen (1992)

A generally applicable method for the determination of the epitope specificities of a large number of monoclonal antibodies (MAbs) is presented. The method is based on the solid-phase mutual inhibition assay using 96-well plates coated with the respective MAbs, competitor MAbs, biotinylated antigen and avidin-peroxidase conjugate. Using carcinoembryonic antigen (CEA) as a model antigen the method was applied to the determination of epitope specificities of anti-CEA MAbs. A constant amount of biotinylated CEA was incubated with a given MAb immobilized on wells of 96-well plates in the presence of increasing amounts of soluble competitor MAbs. The biotinylated CEA bound to the immobilized antibody were then reacted with avidin-peroxidase conjugate and the activity of the bound peroxidase was determined by the use of o-phenylenediamine and hydrogen peroxidase. The method used here alleviates the laborious procedures of labeling all antibodies to be tested and the confusion caused by differential labeling among different MAbs, and is convenient for mapping analysis of many MAbs if the corresponding purified antigen is available.
Thrombin, a mediator of cerebrovascular inflammation in AD and hypoxia (2013)

Considerable evidence implicates hypoxia and vascular inflammation in Alzheimer's disease (AD). Thrombin, a multifunctional inflammatory mediator, is demonstrable in the brains of AD patients both in the vessel walls and senile plaques. Hypoxia-inducible factor 1α (HIF-1α), a key regulator of the cellular response to hypoxia, is also upregulated in the vasculature of human AD brains. The objective of this study is to investigate inflammatory protein expression in the cerebrovasculature of transgenic AD mice and to explore the role of thrombin as a mediator of cerebrovascular inflammation and oxidative stress in AD and in hypoxia-induced changes in brain endothelial cells. Immunofluorescent analysis of the cerebrovasculature in AD mice demonstrates significant (p < 0.01-0.001) increases in thrombin, HIF-1α, interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinases (MMPs), and reactive oxygen species (ROS) compared to controls. Administration of the thrombin inhibitor dabigatran (100 mg/kg) to AD mice for 34 weeks significantly decreases expression of inflammatory proteins and ROS. Exposure of cultured brain endothelial cells to hypoxia for 6 h causes an upregulation of thrombin, HIF-1α, MCP-1, IL-6, and MMP2 and ROS. Treatment of endothelial cells with the dabigatran (1 nM) reduces ROS generation and inflammatory protein expression (p < 0.01-0.001). The data demonstrate that inhibition of thrombin in culture blocks the increase in inflammatory protein expression and ROS generation evoked by hypoxia. Also, administration of dabigatran to transgenic AD mice diminishes ROS levels in brain and reduces cerebrovascular expression of inflammatory proteins. Taken together, these results suggest that inhibiting thrombin generation could have therapeutic value in AD and other disorders where hypoxia, inflammation, and oxidative stress are involved.
Adsorption-induced surface stress and its effects on resonance frequency of microcantilevers (1995)

It is well known that bimetallic microcantilevers can exhibit static deflection as a result of thermal effects, including exothermic adsorption of chemicals on their surfaces. It is shown here that the resonance frequency of a cantilever can change due to a combination of mass loading and change of spring constant resulting from adsorption of chemicals on the surface. Cantilevers also undergo static bending that is induced by differential surface stress. The magnitude of these effects depends upon the chemical properties of the surface and upon the amount of material adsorbed. Hence cantilever deflection as well as resonance frequency change can be used as the basis for development of novel chemical sensors.
In Vivo Quantification of Carotid Artery Wall Dimensions (2009)

The study data for carotid MRI and ultrasound IMT showed strong agreement, indicating that both modalities measure the thickness of the intima and media. The advantage of MRI over ultrasound is that the measurement variability is smaller, enabling smaller sample sizes and potentially shorter study duration in cardiovascular prevention trials.
Prediction of solvent-induced morphological changes of polyelectrolyte diblock copolymer micelles (2015)

Self-assembly processes of polyelectrolyte block copolymers are ubiquitous in industrial and biological processes; understanding their physical properties can also provide insights into the design of polyelectrolyte materials with novel and tailored properties. Here, we report systematic analysis on how the ionic strength of the solvent and the length of the polyelectrolyte block affect the self-assembly and morphology of the polyelectrolyte block copolymer materials by constructing a salt-dependent morphological phase diagram using an implicit solvent ionic strength (ISIS) method for dissipative particle dynamics (DPD) simulations. This diagram permits the determination of the conditions for the morphological transition into a specific shape, namely vesicles or lamellar aggregates, wormlike/cylindrical micelles, and spherical micelles. The scaling behavior for the size of spherical micelles is predicted, in terms of radius of gyration (R(g,m)) and thickness of corona (Hcorona), as a function of solvent ionic strength (c(s)) and polyelectrolyte length (NA), which are R(g,m) ∼ c(s)(-0.06)N(A)(0.54) and Hcorona ∼ c(s)(-0.11)N(A)(0.75). The simulation results were corroborated through AFM and static light scattering measurements on the example of the self-assembly of monodisperse, single-stranded DNA block-copolynucleotides (polyT50-b-F-dUTP). Overall, we were able to predict the salt-responsive morphology of polyelectrolyte materials in aqueous solution and show that a spherical-cylindrical-lamellar change in morphology can be obtained through an increase in solvent ionic strength or a decrease of polyelectrolyte length.
Compound prism design principles, I (2011)

Prisms have been needlessly neglected as components used in modern optical design. In optical throughput, stray light, flexibility, and in their ability to be used in direct-view geometry, they excel over gratings. Here we show that even their well-known weak dispersion relative to gratings has been overrated by designing doublet and double Amici direct-vision compound prisms that have 14° and 23° of dispersion across the visible spectrum, equivalent to 800 and 1300 lines/mm gratings. By taking advantage of the multiple degrees of freedom available in a compound prism design, we also show prisms whose angular dispersion shows improved linearity in wavelength. In order to achieve these designs, we exploit the well-behaved nature of prism design space to write customized algorithms that optimize directly in the nonlinear design space. Using these algorithms, we showcase a number of prism designs that illustrate a performance and flexibility that goes beyond what has often been considered possible with prisms.
Autophagy-Dependent Viral Recognition by Plasmacytoid Dendritic Cells (2007)

Plasmacytoid dendritic cells (pDCs) detect viruses in the acidified endosomes by means of Toll-like receptors (TLRs). Yet, pDC responses to certain single-stranded RNA (ssRNA) viruses occur only after live viral infection. We present evidence here that the recognition of such viruses by TLR7 requires transport of cytosolic viral replication intermediates into the lysosome by the process of autophagy. In addition, autophagy was found to be required for the production of interferon-alpha by pDCs. These results support a key role for autophagy in mediating ssRNA virus detection and interferon-alpha secretion by pDCs and suggest that cytosolic replication intermediates of viruses serve as pathogen signatures recognized by TLR7.
Sarizotan as a treatment for dyskinesias in Parkinson's disease: A double‐blind placebo‐controlled trial (2006)

The objective of this study is to conduct a dose-finding study of sarizotan in Parkinson's disease (PD) patients with dyskinesia to identify a safe dose and to identify a sensitive dyskinesia rating measure. Sarizotan is a novel compound with full 5-HT(1A) agonist properties and additional high affinity for D(3) and D(4) receptors. An open label study documented improvements in PD patients with levodopa-induced dyskinesia. There is no precedent for study designs or outcome measures in pivotal trials of antidyskinesia therapies. The approach used here was a multicenter, randomized, placebo-controlled, double-blind, parallel study. Included were PD patients optimized to levodopa and dopaminergic drugs with moderately disabling dyskinesias present greater than or equal to 25% of the waking day. Interventions included sarizotan 2, 4, or 10 mg/day or matching placebo, given in two doses. There were two outcome measures: the primary measure was change from baseline in diary-based on time without dyskinesia; the secondary measures were change from baseline in scores on the Abnormal Involuntary Movement Scale (AIMS), the composite score of Unified Parkinson's Disease Rating Scale (UPDRS) Items 32+33 (dyskinesia duration and disability) and total UPDRS. A total of 398 subjects were randomized, with 381 included in the intention-to-treat population. No significant changes occurred on sarizotan compared to placebo on any diary-based measure of dyskinesia or the AIMS score. The composite score of UPDRS Items 32+33 was significantly improved with 2 mg/day sarizotan, with a trend at 10 mg/day. Adverse events were not significantly different in sarizotan- and placebo-treated patients, but off time significantly increased with sarizotan 10 mg/day. Sarizotan 2 mg/day is a safe agent in PD patients with dyskinesia. To test its role in abating dyskinesia, future studies should focus on this dose and will use the composite score of UPDRS Items 32+33 as the primary outcome.
Biological and Clinical Significance of Cathepsin D in Breast Cancer Metastasis (1996)

Cathepsin D (cath-D) is an aspartyl lysosomal protease expressed in all tissues. Most metastatic breast cancer cell lines, unlike normal cells, secrete high levels of pro-cath-D. This abnormal secretion is due to both overexpression of the cath-D gene and to an altered processing of the precursor protein. Cath-D gene transcription is increased by estrogen and growth factors in estrogen-receptor-positive breast cancer cells and by an unknown mechanism in estrogen-receptor-negative cells. A large number of independent clinical studies associated high cath-D concentrations in the cytosol of primary breast cancers with increased risk of subsequent metastasis. The amino acid sequence of cath-D analyzed in two breast cancer cell lines is normal, but glycosylation appears to be different with more acidic isoforms. To assess the potential role of this protease in cancer metastasis, we transfected a human cDNA cath-D expression vector in 3Y1-Ad12 embryonic rat tumorigenic cells which did not secrete the proenzyme. A moderate overexpression of human cath-D was sufficient to increase the metastatic potential of these cells in nude mice. The mechanism of cath-D-induced metastasis seems to require maturation of the proenzyme, in endosomes and in large acidic compartments identified as phagosomes. Rather than increase cancer cell escape from the primary tumor through basement membrane degradation as proposed for neutral proteinases, cath-D appears to facilitate cell growth at distant sites. The mechanism of this indirect mitogenic effect is discussed from results obtained in different models. Different cath-D substrates (growth inhibitors, precursors of growth factors, etc.) are proposed to mediate this activity.
Multiple functions of p27Kip1 and its alterations in tumor cells: a review (2000)

Cyclin-dependent kinases (CDKs), together with cyclins, their regulatory subunits, govern cell-cycle progression in eukaryotic cells. p27(Kip1) is a member of a family of CDK inhibitors (CDIs) that bind to cyclin/CDK complexes and arrest cell division. There is considerable evidence that p27(Kip1) plays an important role in multiple fundamental cellular processes, including cell proliferation, cell differentiation, and apoptosis. Moreover, p27(Kip1) is a putative tumor-suppressor gene that appears to play a critical role in the pathogenesis of several human malignancies and its reduced expression has been shown to correlate with poor prognosis in cancer patients. This study reviews current information on the functions of p27(Kip1), its abnormalities found in human tumors, and the possible clinical implications of these findings with respect to the management of cancer patients.
Inclusion of Anionic Guests inside a Molecular Cage with Palladium(II) Centers as Electrostatic Anchors (2009)

Anchors away! Four banana-shaped ligands and two PdII ions assemble quantitatively to form a ball-shaped object with four large portals (see picture). The two PdII ions form stable, square-planar complexes with the pyridyl donors of the ligands, but can undergo further interactions with anions. Their positioning in a confined distance by the rigid ligands make them act as electrostatic anchors for dianionic guests of a certain size.
Fast wavelength-parallel polarimeter for broadband optical networks (2004)

We describe a novel wavelength-parallel polarimeter operating in the light-wave band that measures the complete state of polarization of 256 wavelengths in parallel within 20 ms (software-limited), with the potential for submillisecond operation. By use of fast switching ferroelectric liquid crystals in conjunction with an InGaAs arrayed detector, selection and wavelength-parallel detection of individual polarization components can be achieved within approximately 150 microseconds. This instrument offers unprecedented sensing capability that is relevant to the compensation of polarization-related impairments in high-speed light-wave communications.
Nitrogen Bridgehead Compounds Part 90. An Efficient Versatile Synthesis of 1-Methyl-2-substituted 1,2,3,4-Tetrahydro-6H-pyrazino[2,1-b]quinazoline-3,6-diones (1998)

A versatile synthesis of 2-substituted I-methyl-and 1,4-dimethyl-1,2,3,4-tetrahydro-6H-pyrazino[2,l-b]quiuazoline-3,6-diones is presented, starting from 2-(I-hromoethy1)quinazolin-4(3H)-one.The key step of the reaction sequence is the diastereoselective cyclization of 2-{[I-(N-2-haloacyl-N-substituted amino]ethyl}quinazolin-4(3H)-ones.Usually 1,4-dimethyl derivatives are obtained as pure racemic cis-compounds (2-alkyl and 2-benzyl derivatives), or a mixture of diastereomers, containing the 4-methyl group in quasiaxial position.TNTRODUCTION The diverse biological activities of heterocondensed quinazolines have contributed to extensive efforts directed towards syntheses of novel members of these ring system^.^.^ Pyrazino[2,1-b]quinazoline-3,6diones are known to exhibit sedative, hypnotic and tranquilizing activities.'They are formally anthranoylcyclodipeptides having conformationally restricted structures, which as rigid spacers became a focus of increased attention in studies of stabilization of specific backbone conformation^.^Recently several alkaloids containing pyrazino[2,I-b]quiuazoline-3,6-dione structural moiety have been isolated from Aspergillus species.'.They have received increasing interest due to their biological activity.Among them valuable pharmacons are found: spiroquinazolooe alkaloid of Aspergill~sf[avi~es,~ the structurally related alkaloid fumiquinazolone (isolated from marine fungus Aspergillus fumigatus9) having Substance P inhibitory activity1' on human neurokinin-1 receptors, and furthermore a new hexacyclic alkaloid metabolite of Aspergillus jsherii, which has been claimed as antineoplastic enhancer."Synthesis of pyrazino[2,1-b]quinazolines was achieved by oxidative cyclization of o-aminobenzylpiperazinelz and 1-(0-azidobenzoyl)-2,5-piperazinediones,'~ by deprotection of 2-@eptidoamino)benzophenones,'4 their derivatives,'' and N-substituted anthranilic acids.162-Methyl-l,2,3,4-tetrahydro-6Hpyazino[2,1-blquinazoline-3,6-diones and other 2-substituted derivatives were prepared by cyclocondensation of anthranilic acid with 5-ethoxy-l-methyl-l,2,3,6-tetrahydropirazin-2-ones,'78 and by cyclization of 2-[~-(2-chloroacet~l)-~-arylamino]meth~l~uinazo1-4(3-ones,'~ respectively.-~~ ~~ .~~ .
Clinical update for the diagnosis and treatment ofClostridium difficileinfection (2014)

Clostridium difficile infection (CDI) presents a rapidly evolving challenge in the battle against hospital-acquired infections. Recent advances in CDI diagnosis and management include rapid changes in diagnostic approach with the introduction of newer tests, such as detection of glutamate dehydrogenase in stool and polymerase chain reaction to detect the gene for toxin production, which will soon revolutionize the diagnostic approach to CDI. New medications and multiple medical society guidelines have introduced changing concepts in the definitions of severity of CDI and the choice of therapeutic agents, while rapid expansion of data on the efficacy of fecal microbiota transplantation heralds a revolutionary change in the management of patients suffering multiple relapses of CDI. Through a comprehensive review of current medical literature, this article aims to offer an intensive review of the current state of CDI diagnosis, discuss the strengths and limitations of available laboratory tests, compare both current and future treatments options and offer recommendations for best practice strategies.
Cytokine profiling and in vitro studies of murine bone growth using biological fluids from children with juvenile idiopathic arthritis (2007)

SF and serum JIA samples can impair bone growth at the growth plate. In synovial fluid, the effect is variable but resistant to treatment with IL-1beta, IL-6 and TNF-alpha specific antibodies and IGF-1, suggesting that other factors in this biological fluid may also have an effect on longitudinal growth through IGF-1-independent mechanisms.
Adsorption of catechol and comparative solutes on hydroxyapatite (2003)

Contemporary medical and dental adhesives often have difficulty sticking to wet surfaces or weaken with long-term exposure to water. Substantial research has been dedicated to finding a means of achieving adhesion in an aqueous environment. A study evaluates the adsorption of catechol relative to other chemical groups as means of gauging how effective they may be as adsorptive groups in adhesives. Contact angle and surface-tension measurements of solutions of catechols and other chemical groups were used to determine their works of adhesion. Adsorption isotherms were also constructed to ascertain Langmuir constants. Solutes containing catechol groups were compared to solutes containing other polar groups to see how well catechol adsorbs to hydroxyapatite, the mineral component of bones and teeth, relative to other chemical groups found in adhesives. The results of this study show that catechol and molecules containing catechol groups have higher rates and energies of adsorption to hydroxyapatite than do groups such as alcohols, amines, and carboxylic acids.
Latency and reactivation of human cytomegalovirus (2006)

Human cytomegalovirus (HCMV) persists as a subclinical, lifelong infection in the normal human host, maintained at least in part by its carriage in the absence of detectable infectious virus--the hallmark of latent infection. Reactivation from latency in immunocompromised individuals, in contrast, often results in serious disease. Latency and reactivation are defining characteristics of the herpesviruses and key to understanding their biology. However, the precise cellular sites in which HCMV is carried and the mechanisms regulating its latency and reactivation during natural infection remain poorly understood. This review will detail our current knowledge of where HCMV is carried in healthy individuals, which viral genes are expressed upon carriage of the virus and what effect this has on cellular gene expression. It will also address the accumulating evidence suggesting that reactivation of HCMV from latency appears to be linked intrinsically to the differentiation status of the myeloid cell, and how the cellular mechanisms that normally control host gene expression play a critical role in the differential regulation of viral gene expression during latency and reactivation.
The Shank Family of Postsynaptic Density Proteins Interacts with and Promotes Synaptic Accumulation of the βPIX Guanine Nucleotide Exchange Factor for Rac1 and Cdc42 (2003)

The Shank/ProSAP family of multidomain proteins is known to play an important role in organizing synaptic multiprotein complexes. Here we report a novel interaction between Shank and beta PIX, a guanine nucleotide exchange factor for the Rac1 and Cdc42 small GTPases. This interaction is mediated by the PDZ domain of Shank and the C-terminal leucine zipper domain and the PDZ domain-binding motif at the extreme C terminus of beta PIX. Shank colocalizes with beta PIX at excitatory synaptic sites in cultured neurons. In brain, Shank forms a complex with beta PIX and beta PIX-associated signaling molecules including p21-associated kinase (PAK), an effector kinase of Rac1/Cdc42. Importantly, overexpression of Shank in cultured neurons promotes synaptic accumulation of beta PIX and PAK. Considering the involvement of Rac1 and PAK in spine dynamics, these results suggest that Shank recruits beta PIX and PAK to spines for the regulation of postsynaptic structure.
Inhibitors of 15-Prostaglandin Dehydrogenase To Potentiate Tissue Repair (2017)

The enzyme 15-prostaglandin dehydrogenase (15-PGDH) catalyzes the first step in the degradation of prostaglandins including PGE2. It is a negative regulator of tissue repair and regeneration in multiple organs. Accordingly, inhibitors of 15-PGDH are anticipated to elevate in vivo levels of PGE2 and to promote healing and tissue regeneration. The small molecule SW033291 (1) inhibits 15-PGDH with K<sub>i</sub> = 0.1 nM in vitro, doubles PGE2 levels in vivo, and shows efficacy in mouse models of recovery from bone marrow transplantation, ulcerative colitis, and partial hepatectomy. Here we describe optimized variants of 1 with improved solubility, druglike properties, and in vivo activity.
In Vitro and In Vivo Effects of Tetrakisphosphonates on Bone Resorption, Tumor Osteolysis, Ectopic Calcification, and Macrophages (1997)

The biological effects of bisphosphonates in calcium-related disorders are attributed to the incorporation of the bisphosphonates in bone, enabling direct interaction with osteoclasts and/or osteoblasts. The high accumulation of bisphosphonates in bone, due to their high affinity to hydroxyapatite (HAP), is essential for mediating in vitro and in vivo activity. In this study we examined the activity of tetrakisphosphonates, molecules containing two P-C-P type bisphosphonate moieties connected by a carbon chain. The novel compounds were examined in a battery of in vitro and in vivo models including HAP formation and dissolution, ectopic calcification, bone resorption, tumor osteolysis, and of macrophage-like cells (anti- or pro-inflammatory properties). The inhibition of ectopic calcification was ranked as follows: geminal bisphosphonates > bisacylphosphonates > tetrakisphosphonates. Pamidronate, but not the tetrakisphosphonates, was an effective antiosteolytic agent. Neither DNTP (tetrasodium 1,9-dihydroxynonane 1,1,9,9-tetrakisphosphonate) nor the bisacylphosphonate, PiBP (pimeloylbisphosphonate) seem to possess strong macrophage suppressive or inductive effects and can be considered to be relatively inactive in terms of anti- or pro-inflammatory action. A significant anticalcification effect was caused by various phosphonates, such as the tetrakisphosphonates, but DNTP, a tetrakisphosphonate, was found toxic as it impeded somatic growth and bone development.