gebhart/patrepeval huggingface dataset:
Promoting Patient Safety by Preventing Medical Error (1998)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Immuno-Hybridization Chain Reaction for Enhancing Detection of Individual Cytokine-Secreting Human Peripheral Mononuclear Cells (2011)

We present here a new method to enhance the detection of secreted cytokines and chemokines from single human mononuclear cells. The technique uses a hybridization chain reaction (HCR) to amplify signals resulting from sandwich immunoassays. This immuno-HCR employs oligonucleotide-based initiators covalently linked to antibodies to propagate a chain reaction of hybridization events involving a pair of complementary hairpin oligomers bearing fluorescent labels. Integrating this strategy for signal amplification with microengraving (a soft lithographic method for printing arrays of secreted proteins from thousands of single cells) improves both the limits of detection and sensitivity for cytokines and chemokines captured from individual cells by an average of 200-fold relative to methods for direct detection by fluoresence. This approach should enhance the utility of microengraving for defining the immunological signatures of diseases and responses to interventional therapies based on multiplexed single-cell analysis.
Gut-enriched Kruppel-like factor represses cyclin D1 promoter activity through Sp1 motif (2000)

Cancer cells differ from normal cells in many characteristics including loss of differentiation and uninhibited cell proliferation. Recent studies have focused on the identification of factors contributing to cell growth and differentiation. Gut-enriched Krüppel-like factor (GKLF or KLF4) is a newly identified eukaryotic transcription factor and has been shown to play a role in regulating growth arrest. We have previously shown that GKLF mRNA levels were significantly decreased in colon cancer tissues, and that over-expression of GKLF in colonic adenocarcinoma cells (HT-29) resulted in reduction of cyclin D1 (CD1) mRNA and protein levels. The current study was undertaken to determine the mechanisms by which GKLF inhibited CD1 expression. In a transient transfection system, GKLF suppressed CD1 promoter activity by 55%. Sequential deletion and site-directed mutation analysis of the CD1 promoter have identified the sequence between -141 and -66, a region containing an Sp1 response element, to be essential for GKLF function. By electrophoretic mobility gel shift assay, recombinant GKLF and nuclear extracts from HT-29 cells were found to bind to the Sp1 motif on the CD1 promoter. The inhibitory effect of GKLF on the CD1 promoter activity was completely abolished by excessive amount of Sp1 DNA and GKLF significantly reduced the stimulatory function of Sp1 suggesting that GKLF and Sp1 may compete for the same binding site on the CD1 promoter. These results indicate that GKLF is a transcriptional repressor of the CD1 gene and that the inhibitory effect of GKLF is, in part, mediated by interaction with the Sp1 binding domain on its promoter.
The Outstanding Biological Stability ofβ- andγ-Peptides toward Proteolytic Enzymes: An In Vitro Investigation with Fifteen Peptidases (2001)

A series of 36 linear and cyclic beta- and gamma-peptides consisting of as few as two, and as many as 15 residues, was offered as substrates to 15 commercially available proteases of bacterial, fungal, and eukaryotic origin, including a beta-lactamase and amidases, as well as most vigorous, nonspecific proteases, such as the 20S proteasome from human erythrocytes. For comparison, an alpha-eicosapeptide and standard substrates of the proteolytic enzymes were included in the investigation. Under conditions of complete cleavage of the alpha-peptide within 15 min the beta- and gamma-peptides were stable for at least 48 h. Inhibition studies with seven beta- and gamma-peptides and alpha-chymotrypsin show that the residual enzyme activity toward succinyl-Ala-Ala-Pro-Phe-p-nitroanilide is unchanged within experimental error after incubation for 15 min with the peptide analogues. Thus, beta- and gamma-peptides with proteinogenic side chains, that is, consisting of the singly or doubly homologated natural alpha-amino acids (one or two CH(2) groups inserted in the backbone of each residue), are completely stable to common proteases, without inhibiting their normal activity (as demonstrated for alpha-chymotrypsin). This proteolytic stability of peptides built of homologated amino acids is a prerequisite for their potential use as drugs.
Selective Inhibition of Kindling Development by Intraventricular Administration of TrkB Receptor Body (1999)

Recent work has shown that neurotrophin gene expression is increased after seizures evoked in the kindling model of epilepsy, but whether neurotrophins regulate kindling development is as yet unclear. In this study, we attempted to block selectively the activation of distinct neurotrophin receptors throughout kindling development in the rat via chronic intracerebroventricular administration of trk receptor bodies. The efficacy and selectivity of the trk receptor bodies were established by inhibition of neurotrophin-induced trk receptor phosphorylation in pheochromocytoma (PC12) cells and primary cultures of cortical neurons. The intracerebroventricular infusion of trkB receptor body (trkB-Fc) inhibited development of kindling in comparison with that seen with saline or human IgG controls, trkA-Fc, or trkC-Fc. These results imply that activation of trkB receptors contributes to the development of kindling, a form of activity-dependent behavioral plasticity in the adult mammalian brain.
Identification of a novel antiapoptotic protein, GAM-1, encoded by the CELO adenovirus (1997)

We have developed a simple screening method to identify genes that mimic bcl-2 or adenovirus E1B 19K in enhancing cell survival after transfection and have used this method to identify such a gene in the avian adenovirus CELO. The gene encodes a novel 30-kDa nuclear protein, which we have named GAM-1, that functions comparably to Bcl-2 and adenovirus E1B 19K in blocking apoptosis. However, GAM-1 has no sequence homology to Bcl-2, E1B 19K, or any other known antiapoptotic proteins and thus defines a novel antiapoptotic function.
Systemic Delivery of Liposomal Short-Chain Ceramide Limits Solid Tumor Growth in Murine Models of Breast Adenocarcinoma (2005)

Abstract In vitro tumor cell culture models have illuminated the potential therapeutic utility of elevating the intracellular concentration of the antimitogenic and proapoptotic sphingolipid, ceramide. However, although cell-permeable, short-chain ceramide is an effective apoptotic agent in vitro, its use as an in vivo, systemically delivered therapeutic is limited by its inherent lipid hydrophobicity and physicochemical properties. Here, we report that the systemic i.v. delivery of C6-ceramide (C6) in a pegylated liposomal formulation significantly limited the growth of solid tumors in a syngeneic BALB/c mouse tumor model of breast adenocarcinoma. Over a 3-week treatment period, a well-tolerated dose of 36 mg/kg liposomal-C6 elicited a &amp;gt;6-fold reduction in tumor size compared with empty ghost liposomes. Histologic analyses of solid tumors from liposomal-C6-treated mice showed a marked increase in the presence of apoptotic cells, with a coincident decrease in cellular proliferation and in the development of a microvessel network. Liposomal-C6 accumulated within caveolae and mitochondria, suggesting putative mechanisms by which ceramide induces selective cancer cell cytotoxicity. A pharmacokinetic analysis of systemic liposomal-C6 delivery showed that the pegylated liposomal formulation follows first-order kinetics in the blood and achieves a steady-state concentration in tumor tissue. Confirming the therapeutic utility of i.v. liposomal-C6 administration, we also shown diminution of solid tumor growth in a human xenograft model of breast cancer. Together, these results indicate that bioactive ceramide analogues can be incorporated into pegylated liposomal vehicles for improved solubility, drug delivery, and antineoplastic efficacy.
Rac Affects Invasion of Human Renal Cell Carcinomas by Up-regulating Tissue Inhibitor of Metalloproteinases (TIMP)-1 and TIMP-2 Expression (2001)

Rho-like GTPases, including Cdc42, Rac1, and RhoA, regulate distinct actin cytoskeleton changes required for adhesion, migration, and invasion of cells. Tiam1 specifically activates Rac, and earlier studies have demonstrated that Tiam1-Rac signaling affects migration and invasion in a cell type- and cell substrate-specific manner. In the present study, we examined the role of Tiam1-Rac signaling in migration and invasion of human renal cell carcinomas. Stable overexpression of Tiam1 or constitutively active V12-Rac1 in a human renal cell carcinoma cell line (clearCa-28) strongly inhibited cell migration by promoting E-cadherin-mediated cell-cell adhesion. Blocking E-cadherin-mediated adhesion by E-cadherin-specific HAV peptides allowed cells to migrate, but was not sufficient to antagonize Tiam1- and V12-Rac1-induced inhibition of Matrigel invasion, suggesting that Rac may influence invasion also through other mechanisms. Indeed, Tiam1-mediated Rac activation induced transcriptional up-regulation of tissue inhibitor of metalloproteinases-1 (TIMP-1) and post-transcriptional up-regulation of TIMP-2, whereas secretion and activity levels of their counterparts, matrix metalloproteinase-9 and matrix metalloproteinase-2, respectively, were not affected. Application of recombinant TIMP-1 and TIMP-2 proteins significantly inhibited invasion of mock-transfected clearCa-28 cells, supporting a role of TIMPs in Rac-mediated inhibition of invasion. To our knowledge, this is the first evidence that increased Rac signaling may inhibit invasion of epithelial tumor cells by up-regulation of TIMP-1 and TIMP-2.
Compact, configurable inertial gesture recognition (2001)

We describe an inertial gesture recognition framework composed of three parts. The first is a compact, six-axis inertial measurement unit to fully measure human motion. The data from this unit is then analyzed by a gesture recognition algorithm which considers data on an axis-by-axis basis and categorizes them as simple motions (line, twist, etc.) with magnitude and duration. An application designer can then combine these atoms together both concurrently and consecutively to create composite gestures which can be tied to output routines. The framework was implemented on a Palm III to demonstrate its light-weight nature and to evoke devices which possess both a sense of their own motion and the ability to respond to it
Surface modification and characterization of some commonly used catheter materials. II. Friction characterization (1983)

The effects of the modification of polystyrene (PS), polyethylene (PE), poly(vinyl chloride) (PVC), silicone rubber (SR), and fluorinated ethylene propylene (FEP) copolymer by radio frequency glow discharge in a helium environment were presented in part I. The hydrated polymer surfaces were characterized by XPS, SEM, visual microscopy, and by contact angle measurements. In general, exposure of the polymers to RFGD produced an oxidized hydrophilic surface, yet the roughness of the surface was unaltered by the relatively mild plasma conditions used. In this article, the frictional behavior of oxidized and unoxidized SR, PE, and FEP in distilled water, isotonic saline, and blood plasma environments is examined experimentally. The results are discussed in relation to the properties generally believed to affect frictional phenomena and to the surface properties as determined in part I. Results indicate that RFGD-treated SR generates less friction than untreated SR when dragged across all untreated and treated polymer surfaces, whether the medium is distilled water or an isotonic saline solution. Friction is consistently lower in a blood plasma medium between all surfaces investigated, most probably because of the presence of adsorbed proteins at the polymer interfaces.
Synthesis of hydroxyl‐terminated poly(ether ether ketone) with pendenttert‐butyl groups and its use as a toughener for epoxy resins (2005)

Abstract Hydroxyl‐terminated poly(ether ether ketone) with pendent tert ‐butyl groups (PEEKTOH) was synthesized by the nucleophilic substitution reaction of 4,4′‐difluorobenzophenone with tert ‐butyl hydroquinone with potassium carbonate as a catalyst and N ‐methyl‐2‐pyrrolidone as a solvent. Diglycidyl ether of bisphenol A epoxy resin was toughened with PEEKTOHs having different molecular weights. The melt‐mixed binary blends were homogeneous and showed a single composition‐dependent glass‐transition temperature ( T g ). Kelley–Bueche and Gordon–Taylor equations gave good correlation with the experimental T g . Scanning electron microscopy studies of the cured blends revealed a two‐phase morphology. A sea‐island morphology in which the thermoplastic was dispersed in a continuous matrix of epoxy resin was observed. Phase separation occurred by a nucleation and growth mechanism. The dynamic mechanical spectrum of the blends gave two peaks corresponding to epoxy‐rich and thermoplastic‐rich phases. The T g of the epoxy‐rich phase was lower than that of the unmodified epoxy resin, indicating the presence of dissolved PEEKTOH in the epoxy matrix. There was an increase in the tensile strength with the addition of PEEKTOH. The fracture toughness increased by 135% with the addition of high‐molecular‐weight PEEKTOH. The improvement in the fracture toughness was dependent on the molecular weight and concentration of the oligomers present in the blend. Fracture mechanisms such as crack path deflection, ductile tearing of the thermoplastic, and local plastic deformation of the matrix occurred in the blends. The thermal stability of the blends was not affected by blending with PEEKTOH. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 541–556, 2006
On-chip spectrophotometry for bioanalysis using microring resonators (2011)

We measure optical absorption in color-producing enzymatic reactions for biochemical analysis with a microscale optofluidic device. Cavity-enhanced laser spectrophotometry is performed on analytes within a microfluidic channel at visible wavelengths with silicon nitride microring resonators of 100 µm radius and quality factor of ~180,000. The resonator transmission spectrum is analyzed to determine optical absorption with a detection limit of 0.12 cm(-1). The device can be used to detect the activity of individual enzymes in a few minutes within a 100 fL sensing volume. The high sensitivity, small footprint, and low analyte consumption make absorption-based microring resonators attractive for lab-on-a-chip applications.
Photolithographic Route to the Fabrication of Micro/Nanowires of III–V Semiconductors (2004)

Abstract Nano/microwires of semiconducting materials (e.g., GaAs and InP) with triangular cross‐sections can be fabricated by “top–down” approaches that combine lithography of high‐quality bulk wafers (using either traditional photolithography or phase‐shift optical lithography) with anisotropic chemical etching. This method gives good control over the lateral dimensions, lengths, and morphologies of free‐standing wires. The behaviors of many different resist layers and etching chemistries are presented. It is shown how wire arrays with highly ordered alignments can be transfer printed onto plastic substrates. This “top–down” approach provides a simple, effective, and versatile way of generating high‐quality single‐crystalline wires of various compound semiconductors. The resultant wires and wire arrays have potential applications in electronics, optics, optoelectronics, and sensing.
Evaluating analytic gradients on quantum hardware (2019)

An important application for near-term quantum computing lies in optimization tasks, with applications ranging from quantum chemistry and drug discovery to machine learning. In many settings, most prominently in so-called parametrized or variational algorithms, the objective function is a result of hybrid quantum-classical processing. To optimize the objective, it is useful to have access to exact gradients of quantum circuits with respect to gate parameters. This paper shows how gradients of expectation values of quantum measurements can be estimated using the same, or almost the same, architecture that executes the original circuit. It generalizes previous results for qubit-based platforms, and proposes recipes for the computation of gradients of continuous-variable circuits. Interestingly, in many important instances it is sufficient to run the original quantum circuit twice while shifting a single gate parameter to obtain the corresponding component of the gradient. More general cases can be solved by conditioning a single gate on an ancilla.
Boar Acrosin (1973)

Acrosin, a proteolytic enzyme located in the acrosome of sperm, exhibits amidase, esterase, and proteinase activity on synthetic and natural substrates containing arginyl and lysyl residues.
Antibody response of infants to cell surface-exposed outer membrane proteins of Haemophilus influenzae type b after systemic Haemophilus disease (1982)

The immune response of nine infants with Haemophilus influenzae type b meningitis was examined by using a radioimmunoprecipitation procedure designed to detect antibodies directed against cell surface-exposed outer membrane proteins of this pathogen. Using intrinsically or extrinsically radiolabeled intact H. influenzae type b cells with acute- and convalescent-phase human sera in this radioimmunoprecipitation system, we found that all of the infants produced an antibody response directed against several different H. influenzae type b outer membrane proteins. Anti-H. influenzae type b outer membrane protein antibodies present in convalescent sera, but not found in acute sera, were directed against cell surface-exposed H. influenzae type b outer membrane proteins. In contrast, both acute and convalescent sera contained antibody activity directed against numerous H. influenzae type b outer membrane proteins whose antigenic determinants were apparently inaccessible to antibody on intact H. influenzae type b cells. The ability of infants to develop an antibody response to cell surface-exposed, antibody-accessible H. influenzae type b outer membrane proteins indicates that these proteins may have vaccinogenic potential.
Dexamethasone induction of osteoblast mRNAs in rat marrow stromal cell cultures (1991)

We have examined the ability of dexamethasone, retinoic acid, and vitamin D3 to induce osteogenic differentiation in rat marrow stromal cell cultures by measuring the expression of mRNAs associated with the differentiated osteoblast phenotype as well as analyzing collagen secretion and alkaline phosphatase activity. Marrow cells were cultured for 8 days in primary culture and 8 days in secondary culture, with and without 10 nM dexamethasone or 1 microM retinoic acid. Under all conditions, cultures produced high levels of osteonectin mRNA. Cells grown with dexamethasone in both primary and secondary culture contained elevated alkaline phosphatase mRNA and significant amounts of type I collagen and osteopontin mRNA. Addition of 1,25-dihydroxyvitamin D3 to these dexamethasone-treated cultures induced expression of osteocalcin mRNA and increased osteopontin mRNA. The levels of alkaline phosphatase, osteopontin, and osteocalcin mRNAs in Dex/Dex/VitD3 cultures were comparable to those of 1,25-dihydroxyvitamin D3-treated ROS 17/2.8 osteosarcoma cells. Omitting dexamethasone from either primary or secondary culture resulted in significantly less alkaline phosphatase mRNA, little osteopontin mRNA, and no osteocalcin mRNA. Retinoic acid increased alkaline phosphatase activity to a greater extent than did dexamethasone but did not have a parallel effect on the expression of alkaline phosphatase mRNA and induced neither osteopontin or osteocalcin mRNAs. In all conditions, marrow stromal cells synthesized and secreted a mixture of type I and III collagens. However, dexamethasone-treated cells also synthesized an additional collagen type, provisionally identified as type V. The synthesis and secretion of collagens type I and III was decreased by both dexamethasone and retinoic acid. Neither dexamethasone nor retinoic acid induced mRNAs associated with the chondrogenic phenotype. We conclude that dexamethasone, but not retinoic acid, promotes the expression of markers of the osteoblast phenotype in cultures of rat marrow stromal fibroblasts.
Homologous Human and Murine Antisense Oligonucleotides Targeting Stat6 : Functional Effects on Germline C ε Transcript (1999)

Interleukin (IL)-4 and (IL)-13 induce immunoglobulin (Ig)E synthesis via activation of the transcription factor signal transducer and activator of transcription (Stat)6. The present study describes the identification and characterization of antisense oligonucleotides to Stat6 as an approach to interrupt IL-4 and IL-13 signaling and thereby to attenuate germline Cepsilon transcription, a prerequisite to IgE synthesis. A limited gene-walk was performed with chemically modified oligonucleotides to identify sequences capable of downregulating both human and murine Stat6. A chimeric oligonucleotide (9b, base sequence GTGAGGTCCTGTTCAGTGGG) demonstrated high levels of antisense activity in both species. Further characterization of 9b showed a dose-dependent Stat6 messenger RNA (mRNA) and protein downregulation (concentration that produces 50% inhibition of effect = 168 and 215 nM, respectively) through a ribonuclease H-dependent antisense mechanism with no effect on closely related members of the Stat family. Further, pretreatment of DND39 cells (human Burkitt lymphoma cell line) with oligonucleotide 9b before IL-4 stimulation successfully downregulated germline Cepsilon transcription. Because Stat6 represents an attractive but technically challenging drug discovery target, antisense oligonucleotides may provide an alternative approach to low molecular-weight compounds for inhibiting IL-4 and IL-13 signaling.