gebhart/patrepeval huggingface dataset:
The ELISPOT Assay: An Easily Transferable Method for Measuring Cellular Responses and Identifying T Cell Epitopes (2002)

Characterization of human leukocyte antigen (HLA) class I restricted epitopes derived from viral pathogens is imperative for formulating therapeutic interventions, as well as for vaccine design and monitoring. Sensitive, easy and cost-effective assays that measure the frequency of antigen-specific T lymphocytes are crucial for evaluating and improving vaccines and therapies. This paper reviews the ELISPOT technique that allows for quantifying HIV-specific T lymphocytes at the single cell level from peripheral blood by detection of antigen-induced cytokine secretion. The assay can be used successfully to quantify T cell immune responses in humans infected with different pathogens and to assess T cell immunogenicity of vaccines in phase I/II and III clinical trials. This review focuses on the ELISPOT methodology and discusses how it can be standardized and potentially used by multiple international laboratories attached to clinical trial sites.
Cell migration into scaffolds under co-culture conditions in a microfluidic platform (2008)

Capillary morphogenesis is a complex cellular process that occurs in response to external stimuli. A number of assays have been used to study critical regulators of the process, but those assays are typically limited by the inability to control biochemical gradients and to obtain images on the single cell level. We have recently developed a new microfluidic platform that has the capability to control the biochemical and biomechanical forces within a three dimensional scaffold coupled with accessible image acquisition. Here, the developed platform is used to evaluate and quantify capillary growth and endothelial cell migration from an intact cell monolayer. We also evaluate the endothelial cell response when placed in co-culture with physiologically relevant cell types, including cancer cells and smooth muscle cells. This resulted in the following observations: cancer cells can either attract (MTLn3 cancer cell line) endothelial cells and induce capillary formation or have minimal effect (U87MG cancer cell line) while smooth muscle cells (10T 1/2) suppress endothelial activity. Results presented demonstrate the capabilities of this platform to study cellular morphogenesis both qualitatively and quantitatively while having the advantage of enhanced imaging and internal biological controls. Finally, the platform has numerous applications in the study of angiogenesis, or migration of other cell types including tumor cells, into a three-dimensional scaffold or across an endothelial layer under precisely controlled conditions of mechanical, biochemical and co-culture environments.
Coagulation and Bleeding Disorders: Review and Update (2000)

Hemostasis is initiated by injury to the vascular wall, leading to the deposition of platelets adhering to components of the subendothelium. Platelet adhesion requires the presence of von Willebrand factor and platelet receptors (IIb/IIIa and Ib/IX). Additional platelets are recruited to the site of injury by release of platelet granular contents, including ADP. The "platelet plug" is stabilized by interaction with fibrinogen. In this review, I consider laboratory tests used to evaluate coagulation, including prothrombin time, activated partial thromboplastin time, thrombin time, and platelet count. I discuss hereditary disorders of platelets and/or coagulation proteins that lead to clinical bleeding as well as acquired disorders, including disseminated intravascular coagulation and acquired circulating anticoagulants.
Electron transfer at semiconductor electrode-liquid electrolyte interfaces (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectron transfer at semiconductor electrode-liquid electrolyte interfacesCarl A. Koval and Jason N. HowardCite this: Chem. Rev. 1992, 92, 3, 411–433Publication Date (Print):May 1, 1992Publication History Published online1 May 2002Published inissue 1 May 1992https://pubs.acs.org/doi/10.1021/cr00011a004https://doi.org/10.1021/cr00011a004research-articleACS PublicationsRequest reuse permissionsArticle Views3246Altmetric-Citations155LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Use of Interphase Fluorescence In Situ Hybridization as a Powerful Diagnostic Tool in Cytology (2002)

Interphase fluorescence in situ hybridization (I-FISH) using labeled nucleic acid probes detects chromosomal and genetic aberrations at a cellular level. I-FISH is a relatively fast and sensitive technique for evaluating a large number of cells and revealing more specific information than other techniques. It has been proven to be an invaluable molecular test in cytologic analyses for the detection of subtle genetic alterations that correlate with disease progression. In this postgenomic era, with the draft of the human genome available and expansion of the knowledge of tumor-specific genetic changes, the application of I-FISH probes in cytologic analysis should be of great value in the early detection, risk assessment, and monitoring of therapy efficacy in cancer. Here, we outline the principle of the I-FISH procedure, present suggestions to efficiently analyze cytologic materials, provide examples of practical applications, and discuss new aspects of the technique.
Controlling adsorbate vibrational lifetimes using superlattices (2000)

We propose using short-period superlattices as substrates to control the vibrational relaxation dynamics of adsorbate overlayers. The mass modulation of superlattices creates both band gaps and large spectral enhancements in the phonon density of states. These modifications can dramatically alter the coupling between vibrational modes of the adsorbate overlayer and the substrate lattice, thereby significantly affecting the lifetime of adsorbate modes.
A novel proteoliposomal vaccine elicits potent antitumor immunity in mice (2007)

Therapeutic vaccination against idiotype is a promising strategy for immunotherapy of B-cell malignancies. Its feasibility, however, is limited by the requirement for a patient-specific product. Here we describe a novel vaccine formulation prepared by simply extracting cell-membrane proteins from lymphoma cells and incorporating them together with IL-2 into proteoliposomes. The vaccine was produced in 24 hours, compared with more labor-intensive and time-consuming hybridoma or recombinant DNA methods. The vaccine elicited T-cell immunity in vivo, as demonstrated by secretion of type 1 cytokines. It protected against tumor challenge at doses of tumor antigen 50 to 100 times lower than that previously observed using either liposomes formulated with IL-2 and secreted lymphoma immunoglobulin or a prototype vaccine consisting of lymphoma immunoglobulin conjugated to keyhole limpet hemocyanin. The increased potency justifies testing similar patient-specific human vaccines prepared using extracts from primary tumor samples.
Guanine Nucleotide Exchange Factors Regulate Specificity of Downstream Signaling from Rac and Cdc42 (1998)

The Rac and Cdc42 GTPases regulate diverse cellular behaviors involving the actin cytoskeleton, gene transcription, and the activity of multiple protein and lipid kinases. All of these pathways can potentially become activated when GTP-Rac or GTP-Cdc42 is formed in response to external cell signals, yet it is evident that each activity must also be able to be controlled individually. The mechanisms by which such specificity of GTPase signaling in response to upstream stimuli is achieved remains unclear. We investigated the action of several well characterized guanine nucleotide exchange factors (GEFRho) to activate Rac- and/or Cdc42-dependent kinase pathways. Coexpression studies in COS-7 cells revealed that the ability of individual guanine nucleotide exchange factors (GEFs) to activate the p21-activated kinase PAK1 could be dissociated from activation of c-Jun amino-terminal kinase, even though activation of both pathways requires the action of the GEFs on Rac and/or Cdc42. In contrast, expression of constitutively active forms of Rac or Cdc42 effectively stimulated both downstream kinases. We conclude that GEFs can be important determinants of downstream signaling specificity for members of the Rho GTPase family.
Chronic Pain and Emotional Distress in Children and Adolescents (1996)

Pediatric chronic pain continues to be relatively underinvestigated and undertreated. The objective of the present cross-sectional study was to investigate the emotional distress hypothesized to be concurrently associated with the chronic pain experience in children and adolescents. One hundred and sixty children and adolescents with chronic pain and their parents completed standardized assessment instruments measuring pain intensity, depressive symptoms, state anxiety, trait anxiety, general self-esteem, and internalizing and externalizing behavior problems. Consistent with the a priori Biobehavioral Model of Pediatric Pain, higher patient-perceived pain intensity was associated with higher depressive and anxious symptoms, lower general self-esteem, and higher behavior problems. The results are discussed in regard to preventing and treating pain and suffering in children and adolescents with chronic pain.
A phase I study of anti-CD123 monoclonal antibody (mAb) CSL360 targeting leukemia stem cells (LSC) in AML. (2010)

e13012 Background: Eradication of LSC is a goal of anti-leukemic therapy. AML LSC found in CD34+CD38- cell fractions express high levels of IL-3Rα (CD123), unlike CD34+CD38- cells from normal samples. CSL360 is a recombinant, chimeric IgG1, anti-CD123 mAb that neutralizes IL-3 and has anti-leukemic activity preclinically in vitro and in vivo. Methods: A phase I, escalating-dose study of CSL360 assessed safety, PK, immunogenicity, and bioactivity. Relapsed, refractory, or high-risk AML patients (pt) received 12 weekly, iv infusions, unless withdrawn early due to treatment-related toxicity or progressive disease (PD). Pts who achieved clinical response could receive additional doses. Blast counts in blood and marrow, % LSC in marrow, CD123 levels, extent of receptor binding, and ex vivo signaling of blast cells were measured. Results: In total 304 iv infusions were administered to 40 pts across 5 dose levels (0.1-10 mg/kg). Reasons for discontinuation were: PD (20), completed 12 doses (11), SAE (3), withdrew consent or investigator decision (6). Complete, sustained saturation and down-regulation of CD123 occurred at ≥ 3 mg/kg and abolished ex vivo proliferative responsiveness of blasts to IL-3, indicating abolition of IL-3 signaling. Treatments were safe; MTD was not reached. AEs and SAEs did not increase with increasing dose level; 5/62 (8%) SAEs were related/possibly related to treatment. AUC and Cmax increased proportionally (linear kinetics); T ½ was 4.1 days. Immunogenicity was detected in lower dose level cohorts only. Changes from baseline in % LSC in marrow were inconsistent and minor except for a large increase in one pt. One other pt (relapsed after 2 allo-SCT, including 1 double cord SCT) became leukemia-free after 3 doses, achieved CR after 12 doses, withdrew after 17 doses (SAE) and remained in CR at last follow up. No other pt had objective response or definitive clinical benefit. Conclusions: CSL360 bound CD123 specifically and safely but without clear anti-leukemic activity in high risk AML pts, suggesting blockade of IL-3 signaling is an insufficient therapeutic strategy. Improving ADCC by enhancing Fc- mediated effector function of an anti-CD123 mAb could be efficacious against AML LSC and blasts. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration CSL Ltd.
N-Benzoylpyrazoles Are Novel Small-Molecule Inhibitors of Human Neutrophil Elastase (2007)

Human neutrophil elastase (NE) plays an important role in the pathogenesis of pulmonary disease. Using high-throughput chemolibrary screening, we identified 10 N-benzoylpyrazole derivatives that were potent NE inhibitors. Nine additional NE inhibitors were identified through further screening of N-benzoylpyrazole analogues. Evaluation of inhibitory activity against a range of proteases showed high specificity for NE, although several derivatives were also potent inhibitors of chymotrypsin. Analysis of reaction kinetics and inhibitor stability revealed that N-benzoylpyrazoles were pseudoirreversible competitive inhibitors of NE. Structure-activity relationship (SAR) analysis demonstrated that modification of N-benzoylpyrazole ring substituents modulated enzyme selectivity and potency. Furthermore, molecular modeling of the binding of selected active and inactive compounds to the NE active site revealed that active compounds fit well into the catalytic site, whereas inactive derivatives contained substituents or conformations that hindered binding or accessibility to the catalytic residues. Thus, N-benzoylpyrazole derivatives represent novel structural templates that can be utilized for further development of efficacious NE inhibitors.
Synthesis of Seven‐Arm Poly(vinyl pyrrolidone) Star Polymers with Lysozyme Core Prepared by MADIX/RAFT Polymerization (2008)

Abstract A poly(vinyl pyrrolidone) (PVP) seven‐arms star polymer with lysozyme core was synthesized by conjugating linear N ‐succinimidyl ester terminated PVP polymer to lysozyme. Reactive PVP polymers were synthesized using a MADIX/RAFT agent functionalized with N ‐succinimidyl ester. The polymerization of N ‐vinyl pyrrolidone proceeded in a living fashion up to more than 90% conversion reaching molecular weight of up to 33 000 g · mol −1 with narrow molecular weight distributions. The PVP polymer was conjugated to lysozyme resulting in the attachment of seven PVP polymers to one lysozyme core. While the reaction was found to be complete when using low‐molecular weight PVP, some by‐products with less than seven arms were observed when using PVP with a molecular weight of 33 000 g · mol −1 . magnified image
Increased renal production of C-type natriuretic peptide (CNP) in patients with cirrhosis and functional renal failure (2000)

Increased urinary CNP in cirrhotic patients in the absence of renal arteriovenous concentration gradients suggests enhanced renal CNP production in cirrhosis. Furthermore, an inverse relation between urinary CNP and urinary sodium excretion suggests a role for this peptide in renal sodium handling in patients with cirrhosis.
Characteristics of solubilized human-somatotropin-binding protein from the liver of pregnant rabbits (1980)

A specific binding site for somatotropin was solubilized by 1% (v/v) Triton X-100 from a crude particulate membrane fraction of pregnant rabbit liver, partially purified and characterized. The solubilized binding site retained many of the characteristics observed in the original particulate fraction, indicating that extraction of the binding site with Triton X-100 does not cause any major changes in its properties. The binding of human 125I-labelled-somatotropin to the solubilized binding site is a saturable and reversible process, depending on temperature, incubation time, pH and ionic environment. Analysis of the kinetic data revealed a finite number of binding sites with an affinity constant of 0.32 x 10(10)M-1. The binding activity for human 125I-labelled-somatotropin was adsorbed to a concanavalin-A-Sepharose column and was dissociated from the column with alpha-methyl-D-glucoside, suggesting that the binding protein may be a glycoprotein. Using affinity chromatography on concanavalin-A-Sepharose, ion-exchange chromatography on DEAE-cellulose and gel filtration on Sepharose 6B, the binding protein was purified 1000-4000-fold from the original liver homogenate. When the partially purified preparation was chromatographed on Sepharose 6B, the binding protein eluted as a molecule with an apparent molecular weight of 200000, with a Stokes' radius of 4.9 nm. Sucrose-density-gradient centrifugation of the preparation showed that the sedimentation coefficient of the binding protein was 7.2S. Isoelectric focusing experiments revealed that a major part of the protein has an acidic pI (4.2-4.5). Exposure of the protein to trypsin decreased the binding activity for human 125I-labelled-somatotropin or bovine 125I-labelled-somatotropin, whereas ribonuclease, deoxyribonuclease, phospholipase C or neuraminidase had little or no effect.
Direct Measurement of the Forces Between Complementary Strands of DNA (1994)

Interaction forces between single strands of DNA were measured with the atomic force microscope by a procedure in which DNA oligonucleotides were covalently attached to a spherical probe and surface. Adhesive forces measured between complementary 20-base strands fell into three distinct distributions centered at 1.52, 1.11, and 0.83 nano-newtons, which are associated with the rupture of the interchain interaction between a single pair of molecules involving 20, 16, and 12 base pairs, respectively. When a third long DNA molecule was coupled between complementary surfaces, both intra- and interchain forces were observed. The intrachain interaction resulting from the molecule's elasticity manifested itself as a long-range cohesive force.
Anomaly detection from hyperspectral imagery (2002)

We develop anomaly detectors, i.e., detectors that do not presuppose a signature model of one or more dimensions, for three clutter models: the local normal model, the global normal mixture model, and the global linear mixture model. The local normal model treats the neighborhood of a pixel as having a normal probability distribution. The normal mixture model considers the observation from each pixel as arising from one of several possible classes such that each class has a normal probability distribution. The linear mixture model considers each observation to be a linear combination of fixed spectra, known as endmembers, that are, or may be, associated with materials in the scene, and the coefficients, interpreted as fractional abundance, are constrained to be nonnegative and sum to one. We show how the generalized likelihood ratio test (GLRT) may be used to derive anomaly detectors for the local normal and global normal mixture models. The anomaly detector applied with the linear mixture approach proceeds by identifying target like endmembers based on properties of the histogram of the abundance estimates and employing a matched filter in the space of abundance estimates. To overcome the limitations of the individual models, we develop a joint decision logic, based on a maximum entropy probability model and the GLRT, that utilizes multiple decision statistics, and we apply this approach using the detection statistics derived from the three clutter models. Examples demonstrate that the joint decision logic can improve detection performance in comparison with the individual anomaly detectors. We also describe the application of linear prediction filters to repeated images of the same area to detect changes that occur within the scene over time.
Preliminary toxicity studies with the DNA-binding antibiotic, CC-1065. (1984)

It was previously shown that the potent new DNA-binding antibiotic, CC-1065, prolonged life span, but was not curative, when administered to mice bearing a variety of transplantable tumors. In this paper we show results of preliminary studies indicating that CC-1065 caused lethal delayed hepatotoxicity at therapeutic antineoplastic doses. In non-tumor-bearing mice toxic deaths were delayed ca 50 days after a single iv dose of 12.5 micrograms/kg and as much as 70 days after 10 micrograms/kg was given ip. Intravenous mouse LD50's were 9 micrograms/kg, single dose, and 0.3 microgram/kg/day, five daily doses. Intraperitoneal LD50's were 0.53 approximately 6.90 micrograms/kg, single dose, and 0.14 microgram/kg/day, five daily doses. Mice treated with high doses iv died within 12 days with frank hepatic necrosis, whereas delayed deaths at lower doses were associated with changes in hepatic mitochondrial morphology. This suggested that separate mechanisms of hepatotoxicity were operative at high and low dose ranges. Attempts to prevent the delayed toxicity of CC-1065 in the mouse by treatment with WR-2721, N-acetylcysteine, phenobarbital, Aroclor 1254, and 3-methylcholanthrene were unsuccessful; no effect on the LD50 or the times of death was observed. Lethal doses in the rabbit were similar on a body surface area basis to those in the mouse; evidence of hepatotoxicity was also observed in the rabbit.
Mac-1 (CD11b/CD18) mediates adherence-dependent hydrogen peroxide production by human and canine neutrophils. (1990)

Human neutrophils exposed to protein-coated polystyrene or cultured endothelial monolayers produce large quantities of H2O2 in response to soluble stimuli that elicit little or no secretion of reactive oxygen species from cells in suspension. To characterize the mechanisms involved in this adherence-dependent respiratory burst, we have investigated the possible role of one integrin known to participate in the adhesion of neutrophils to endothelial cells, CD11b/CD18 (Mac-1). H2O2 production was examined with chemotactic factor-stimulated human and canine neutrophils exposed to protein-coated surfaces and cultured human and canine endothelial cells. The two protein-coated surfaces used were type I collagen-coated glass or plastic, a surface to which neither human nor canine neutrophils adhered, and keyhole limpet hemocyanin (KLH)-coated glass or plastic, a surface to which human and canine neutrophils adhered only after chemotactic stimulation. FMLP-stimulated human neutrophils and platelet activating factor-stimulated canine neutrophils failed to produce detectable H2O2 when in contact with type I collagen, but secreted large amounts of H2O2 when adherent to KLH or endothelial cell monolayers. FMLP-stimulated neutrophils from patients with CD18-deficiency failed to adhere to any of these surfaces and failed to produce H2O2 under these conditions. mAb reactive with CD18 and CD11b were equally effective in markedly inhibiting the adhesion of normal human neutrophils to these surfaces and markedly inhibited the production of H2O2. A mAb reactive with CD18 blocked adhesion of stimulated canine neutrophils, and mAb directed against both CD18 and CD11b blocked H2O2 production by canine neutrophils on KLH and endothelium. A nonbinding mAb and a mAb reactive with CD11a did not inhibit H2O2 production of human cells on KLH or endothelial monolayers, and nonbinding and binding control mAb did not inhibit H2O2 production by canine neutrophils. These results indicate that Mac-1 (CD11b/CD18) can mediate adhesion-dependent H2O2 production by human and canine neutrophils exposed to chemotactic factors.