gebhart/patrepeval huggingface dataset:
A Sequential Four-drug Chemotherapy and Biotherapy with Interferon Alpha and GM-CSF - An Innovative Protocol for the Treatment of Metastatic Melanoma (1998)

We present the results of our chemo-biotherapy protocol for patients with metastatic melanoma. The rationale for the design of the combined therapy was induction of systemic anti-tumor immunity by: (a) priming with IFN-alpha for enhancement of tumor and histocompatibility antigen expression, (b) therapy by the 4-drug regimen (BCNU, DTIC, cisplatin and tamoxifen) for maximal tumor destruction, followed by (c) an immunomodulatory, low dose of GM-CSF. Treatment was given in cycles of three weeks: first IFN-alpha (3 x 10(6) U/day on days 1, 3, and 5); then the 4-drug regimen given according to Del Prete et al., (4); followed by GM-CSF (20 micrograms/m2/day on days 15 to 21). All patients were previously untreated by chemotherapy, and had a performance status of ECOG 0-2. Treatment was discontinued upon severe toxicity or disease progression. In responding patients--once maximal response was achieved-IFN alpha treatment (3 x 10(6) U/day, three times weekly) was continued for a period of two years or until disease progression. All 40 patients (28 males and 12 females) who received the above program were evaluable for response and toxicity and received at least two cycles of therapy. At a median follow-up of one year, 50% had achieved an objective response, with 22.5% complete responses (CR), and 27.5% partial remissions (PR). Median duration of response is 11 months (12 for CR and 9 for PR patients). Median survival for all patients is 14 months (range, 7-21), increasing to 22 months (range, 15-29) in responding patients. Activation of patients' peripheral blood Macrophages and Dendritic Cells was observed following GM-CSF treatment. The chemo-biotherapy protocol presented above--while associated with acceptable toxicity--resulted in a relatively high response rate with an increase in the number of durable responses in patients with metastatic melanoma.
Role of surface ligands in optical properties of colloidal CdSe/CdS quantum dots (2011)

In order to study the role of surface ligands in determining optical properties of colloidal quantum dots (QDs), we have selectively fabricated and studied CdSe/CdS core-shell QDs with strongly confined electron and hole states attached with commonly used surface ligands. Optical properties, viz. absorption and fluorescence of these QDs, are characterized from which salient changes have been observed for different ligand substitutions which, through theoretical analysis, can be associated with electronic structure properties of the QD-ligand composite systems, in particular localization of wave functions of electrons and holes in the QDs and the band matching of the HOMO-LUMO gap of the ligands. The findings can be utilized to facilitate the understanding and optimization of properties of QD biomarkers with functionalizing surface ligands for targeting cellular objects.
Surface‐enhanced Raman scattering (SERS) of random silver or gold particle arrays on aminodextran‐coated polystyrene beads (2005)

Abstract Citrate and/or chemically modified aminodextran (Amdex) SERS bands were detected from silver particle‐Amdex‐polystyrene (PS) beads either as singlets or small clusters, prepared by reaction between aqueous silver nitrate, Amdex‐coated PS beads, and aqueous sodium citrate solution. However, citrate on individual silver or gold particles of the same size was not detected with 633‐nm excitation. SERS of dyes such as rhodamine 6 G was readily observed on individual silver particles or on the gold beads. Three distinct modes of citrate/modified‐Amdex binding to the silver particle‐Amdex‐PS beads were characterized: (1) exchangeable citrate bound through one or more carboxylate groups—citrate could be washed away with H 2 O or D 2 O; displaced by successively greater concentrations of R6G; or squeezed out mechanically by applying the pressure of a second coverslip on top of a droplet of bead suspension; (2) nonexchangeable Amdex bound to silver via a primary alcoholate ion of oxidized, glutaraldehyde‐cross‐linked Amdex; and (3) nonexchangeable oxidized Amdex bound to silver via carboxylate group(s) but with H/D exchangeable alcohol hydrogen atom. That oxidation of the glucopyranose residues of Amdex on PS beads had taken place by Ag(I) as silver nitrate in aqueous solution to split out carboxylate groups was first identified from their characteristic vibrational modes in the SERS spectra of colloidal silver suspensions. Minimum amplification factors for (R6G on Ag)/(R6G on Au) with 633‐nm excitation were estimated as 1 × 10 15 /1 × 10 11 . An extra SERS enhancement of about 1000‐fold due to multiplicity of metal particles per bead was included. Copyright © 2005 John Wiley &amp; Sons, Ltd.
Speculative Security Checks in Sandboxing Systems (2005)

Sandboxing systems are extremely useful for secure execution of untrusted applications. Many of the sandboxing systems proposed so far provide security by intercepting system calls invoked by an application and controlling their execution. However, a problem in existing sandboxing systems is the amount of overhead required for security checks performed after system call interceptions. In this paper, we propose a sandboxing system that executes speculative security checks. The proposed system predicts the behavior of a sandboxed application and executes speculative security checks in parallel with the application, thus reducing the overhead. Behavior is predicted based on system call profiles in past executions of the application. We implemented the system on Linux and made a preliminary evaluation.
Acute Respiratory Distress Syndrome in a Welder Exposed to Metal Fumes (1999)

A 43-year-old man began having malaise, chills, and fever 12 hours after cutting a galvanized steel grating with an acetylene torch at work. Over the next 72 hours, his symptoms persisted and became worse with progressive shortness of breath. He was admitted to the hospital and begun on antibiotics and steroids. The next day his condition had deteriorated to the point that he had to be intubated. Chest x-ray film and computed tomography showed patchy and interstitial infiltration bilaterally, consistent with acute respiratory distress syndrome. Open lung biopsy showed focal mild interstitial pneumonia. Multiple laboratory studies were negative for an infectious or an immune process. The patient remained on mechanical ventilation for 10 days and was discharged from the hospital 2 days after extubation. He continued to improve, with minimal symptoms and a return to normal activity levels several months after the incident with no continued treatment. Re-creation of his exposure was done under controlled circumstances, with air sampling revealing elevated air levels for cadmium and zinc and borderline levels of arsenic, manganese, lead, and iron.
Functional studies on the ligand-binding domain of Ultraspiracle from Drosophila melanogaster (2004)

The functional insect ecdysteroid receptor is comprised of the ecdysone receptor (EcR) and Ultraspiracle (USP). The ligand-binding domain (LBD) of USP was fused to the GAL4 DNA-binding domain (GAL4-DBD) and characterized by analyzing the effect of site-directed mutations in the LBD. Normal and mutant proteins were tested for ligand and DNA binding, dimerization, and their ability to induce gene expression. The presence of helix 12 proved to be essential for DNA binding and was necessary to confer efficient ecdysteroid binding to the heterodimer with the EcR (LBD), but did not influence dimerization. The antagonistic position of helix 12 is indispensible for interaction between the fusion protein and DNA, whereas hormone binding to the EcR (LBD) was only partially reduced if fixation of helix 12 was disturbed. The mutation of amino acids, which presumably bind to a fatty acid evoked a profound negative influence on transactivation ability, although enhanced transactivation potency and ligand binding to the ecdysteroid receptor was impaired to varying degrees by mutation of these residues. Mutations of one fatty acid-binding residue within the ligand-binding pocket, 1323, however, evoked enhanced transactivation. The results confirmed that the LBD of Ultraspiracle modifies ecdysteroid receptor function through intermolecular interactions and demonstrated that the ligand-binding pocket of USP modifies the DNA-binding and transactivation abilities of the fusion protein.
The Role of JAK-3 in Regulating TLR-Mediated Inflammatory Cytokine Production in Innate Immune Cells (2013)

The role of JAK-3 in TLR-mediated innate immune responses is poorly understood, although the suppressive function of JAK3 inhibition in adaptive immune response has been well studied. In this study, we found that JAK3 inhibition enhanced TLR-mediated immune responses by differentially regulating pro- and anti- inflammatory cytokine production in innate immune cells. Specifically, JAK3 inhibition by pharmacological inhibitors or specific small interfering RNA or JAK3 gene knockout resulted in an increase in TLR-mediated production of proinflammatory cytokines while concurrently decreasing the production of IL-10. Inhibition of JAK3 suppressed phosphorylation of PI3K downstream effectors including Akt, mammalian target of rapamycin complex 1, glycogen synthase kinase 3β (GSK3β), and CREB. Constitutive activation of Akt or inhibition of GSK3β abrogated the capability of JAK3 inhibition to enhance proinflammatory cytokines and suppress IL-10 production. In contrast, inhibition of PI3K enhanced this regulatory ability of JAK3 in LPS-stimulated monocytes. At the transcriptional level, JAK3 knockout lead to the increased phosphorylation of STATs that could be attenuated by neutralization of de novo inflammatory cytokines. JAK3 inhibition exhibited a GSK3 activity-dependent ability to enhance phosphorylation levels and DNA binding of NF-κB p65. Moreover, JAK3 inhibition correlated with an increased CD4(+) T cell response. Additionally, higher neutrophil infiltration, IL-17 expression, and intestinal epithelium erosion were observed in JAK3 knockout mice. These findings demonstrate the negative regulatory function of JAK3 and elucidate the signaling pathway by which JAK3 differentially regulates TLR-mediated inflammatory cytokine production in innate immune cells.
The chemokine receptor CXCR3 is expressed in a subset of B-cell lymphomas and is a marker of B-cell chronic lymphocytic leukemia (2000)

Chemotaxis in leukocytes is mediated through binding of soluble chemokines to transmembrane G-protein coupled receptors. The chemokine receptor CXCR3 has been previously shown to be widely expressed on activated T cells and to mediate T-cell chemotaxis on binding to various ligands, including Mig, IP-10, and ITAC. By using immunohistochemical and flow cytometric analysis, we report that CXCR3 is also expressed on a subset of peripheral blood B cells and in distinct subtypes of B-cell lymphoma. CXCR3 immunohistochemical or flow cytometric expression was seen in 37 of 39 cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (diffusely positive in 33 cases), whereas mantle cell lymphoma (30 cases), follicular lymphoma (27 cases), and small noncleaved cell lymphoma (8 cases) were negative in all but 2 cases. Strong CXCR3 expression was also seen in splenic marginal zone lymphoma (14 of 14 cases) and in the monocytoid and plasmacytic cells in extranodal marginal zone lymphoma (15 of 16 cases). This differential expression of CXCR3 in B-cell tumors contrasts with that of another B-cell-associated chemokine receptor, BLR1/CXCR5, which we show here is expressed on all types of B-cell lymphoma tested. We also report that the CXCR3 ligand, Mig, is coexpressed on tumor cells in many cases of CLL/SLL (10 of 13 cases examined) with Mig expression less frequently seen in other B-cell lymphoma subtypes. Coexpression of CXCR3 and its ligand, Mig, may be an important functional interaction in B-CLL, as well as a useful diagnostic marker for the differential diagnosis of small cell lymphomas. (Blood. 2000;95:627-632)
Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles (2005)

Although genomewide RNA expression analysis has become a routine tool in biomedical research, extracting biological insight from such information remains a major challenge. Here, we describe a powerful analytical method called Gene Set Enrichment Analysis (GSEA) for interpreting gene expression data. The method derives its power by focusing on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation. We demonstrate how GSEA yields insights into several cancer-related data sets, including leukemia and lung cancer. Notably, where single-gene analysis finds little similarity between two independent studies of patient survival in lung cancer, GSEA reveals many biological pathways in common. The GSEA method is embodied in a freely available software package, together with an initial database of 1,325 biologically defined gene sets.
Trial Watch (2012)

Toll-like receptors (TLRs) are prototypic pattern recognition receptors (PRRs) best known for their ability to activate the innate immune system in response to conserved microbial components such as lipopolysaccharide and double-stranded RNA. Accumulating evidence indicates that the function of TLRs is not restricted to the elicitation of innate immune responses against invading pathogens. TLRs have indeed been shown to participate in tissue repair and injury-induced regeneration as well as in adaptive immune responses against cancer. In particular, TLR4 signaling appears to be required for the efficient processing and cross-presentation of cell-associated tumor antigens by dendritic cells, which de facto underlie optimal therapeutic responses to some anticancer drugs. Thus, TLRs constitute prominent therapeutic targets for the activation/intensification of anticancer immune responses. In line with this notion, long-used preparations such as the Coley toxin (a mixture of killed Streptococcus pyogenes and Serratia marcescens bacteria) and the bacillus Calmette-Guérin (BCG, an attenuated strain of Mycobacterium bovis originally developed as a vaccine against tuberculosis), both of which have been associated with consistent anticancer responses, potently activate TLR2 and TLR4 signaling. Today, besides BCG, only one TLR agonist is FDA-approved for therapeutic use in cancer patients: imiquimod. In this Trial Watch, we will briefly present the role of TLRs in innate and cognate immunity and discuss the progress of clinical studies evaluating the safety and efficacy of experimental TLR agonists as immunostimulatory agents for oncological indications.
Interleukin‐1βconverting enzyme: A novel cysteine protease required for IL‐1β production and implicated in programmed cell death (1995)

Interleukin-1 beta converting enzyme is the first member of a new class of cysteine proteases. The most distinguishing feature of this family is a nearly absolute specificity for cleavage at aspartic acid. This enzyme has been the subject of intense research because of its role in the production of IL-1 beta, a key mediator of inflammation. These studies have culminated in the design of potent inhibitors and determination of its crystal structure. The structure secures the relationship of the enzyme to CED-3, the product of a gene required for programmed cell death in Caenorhabditis elegans, suggesting that members of this family function in cell death in vertebrates.
Weight Loss and Other Damage to Developing Worker Honeybees from Infestation withVarroa Jacobsoni (1982)

SummaryThe type and degree of damage to adult workers of Apis mellifera from infestation with the parasitic mite Varroa jacobsoni during development was investigated. Mean weights of infested bees upon emergence as adults were 6·3% to 25% less than for healthy bees. Mean % weight loss was correlated at a high level of significance with the number of mites in the cell. Only 6% of infested bees showed obvious physical deformation in the form of wing damage.
Biogenesis of glycosomes of Trypanosoma brucei: an in vitro model of 3-phosphoglycerate kinase import. (1988)

Glycosomes are intracellular, membrane-bound microbody organelles of trypanosomes and leishmania. Nine glycolytic enzymes are the major protein components of the glycosomes of Trypanosoma brucei long-slender bloodstream forms. Glycosomal proteins are believed to be synthesized in the cytoplasm and inserted across the glycosomal membrane posttranslationally. We have developed an in vitro protein import assay for the study of glycosomal biogenesis in T. brucei. All nine glycosomal glycolytic enzymes were detectable by immunoprecipitation and gel analysis of radiolabeled products derived from in vitro translation of total mRNA. Radiolabeled translational products were incubated with purified glycosomes isolated from bloodstream forms and digested with protease to remove proteins not imported into glycosomes. Gel analysis of reisolated glycosomes revealed that glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12) and 3-phosphoglycerate kinase (PGK) (EC 2.7.2.3) were apparently imported intact into the glycosome. Specificity of the protein import assay was verified by using translational products derived from cloned genes encoding T. brucei glycosomal PGK and its 95% homologous cytosolic isozyme. Glycosomal PGK was inserted into the glycosome in vitro with a 27.6% efficiency, but no imported cytosolic PGK was detectable. Preliminary data suggest that certain sequences between the N terminus and residue 123 may be important for import of glycosomal PGK. Our assay, combined with the potential use of genetically altered substrate proteins, may provide the opportunity to explore the recognition systems involved in glycosome biogenesis.
Conversion of guanosine into its N 2-methyl derivative (1977)

N 2 -Methylguanosine (1c) may be prepared in satisfactory yield by treating the protected guanosine derivative (5a) with diazomethane and then removing the protecting groups; (5a), which readily reacts with dimethylamine to give (5c), may be prepared from (4a) in good yield.
Effect of Different Bile Salts on the Relative Hypoglycemia of Witepsol W35 Suppositories Containing Insulin in Diabetic Beagle Dogs (2001)

Insulin suppositories were formulated using Witepsol W35 as a base to investigate the effect of various bile salts/acids on the plasma glucose concentration of diabetic beagle dogs. Comparison of the effect of these formulations was made with that produced by insulin subcutaneous injections. Of the bile salts/acids studied, incorporation of 100 mg of deoxycholic acid (DCA), sodium cholate (NaC), or sodium deoxycholate (NaDC) with insulin (10 U/Kg) showed that suppositories containing NaDC produced the highest area under the curve (AUC) and relative hypoglycemia (RH) of 290 +/- 83 mg%h and 28% +/- 8.1%, respectively. To study the optimum amount of NaDC in insulin suppositories to produce the highest RH, 50-200 mg/suppository were used, and we found that 150 mg NaDC produced 35% +/- 13% RH. We also studied the influence of different doses of insulin (5-20 U/kg) in the presence of NaDC (100 mg). It was found that increase of the insulin dose was accompanied by an increase in AUC and maximum reduction in plasma glucose level Cmax. A combination of NaDC (100 mg) and NaC (50 mg) produced an AUC of 252 +/- 13mg%h and an RH of 49% +/- 2.6%, which were higher than produced by either of its individual components (NaC 50 mg or NaDC 100 mg) when used alone or when compared with an equivalent amount of NaDC (150 mg). When the effect of sodium taurocholate (NaTC) and sodium taurodeoxycholate (NaTDC) was studied, it was found that an insulin suppository containing 100 mg of either NaTC or NaTDC produced an RH equivalent to that produced previouslY with a mixture of NaDC (100 mg) and NaC (50 mg). On the other hand, NaC (50 mg) did not improve the hypoglycemic effect of NaTC any further. In conclusion, a relative hYpoglycemia of about 50% can be reached using insulin suppositories containing Witepsol W35 as a base and NaDC plus NaC (100 mg plus 50 mg, respectively), NaTDC (100mg), or NaTC (100 mg) as rectal absorption enhancers of insulin. A desirable hypoglycemia, expressed as Cmax, and/or AUC can be reached by adjusting the insulin dose in the formulation according to the degree of hyperglycemia.
A decision support expert system for correction of manufacturing process problems (1990)

As computer-integrated manufacturing technology replaces human operators with robots and automated equipment, the thinking and reasoning abilities of the operators are also removed. Unexpected events in a manufacturing operation are an everyday occurrence, so the loss of the operator's reasoning abilities in solving process problems can be devastating. In order to keep complex equipment functioning efficiently, a decision support expert system prototype for correcting machining process problems is presented in this paper. The development and the long range goal of using the expert system for correcting process problems are also discussed.
Interferometric Near-Infrared Spectroscopy (iNIRS) for determination of optical and dynamical properties of turbid media (2016)

We introduce and implement interferometric near-infrared spectroscopy (iNIRS), which simultaneously extracts optical and dynamical properties of turbid media through analysis of a spectral interference fringe pattern. The spectral interference fringe pattern is measured using a Mach-Zehnder interferometer with a frequency-swept narrow linewidth laser. Fourier analysis of the detected signal is used to determine time-of-flight (TOF)-resolved intensity, which is then analyzed over time to yield TOF-resolved intensity autocorrelations. This approach enables quantification of optical properties, which is not possible in conventional, continuous-wave near-infrared spectroscopy (NIRS). Furthermore, iNIRS quantifies scatterer motion based on TOF-resolved autocorrelations, which is a feature inaccessible by well-established diffuse correlation spectroscopy (DCS) techniques. We prove this by determining TOF-resolved intensity and temporal autocorrelations for light transmitted through diffusive fluid phantoms with optical thicknesses of up to 55 reduced mean free paths (approximately 120 scattering events). The TOF-resolved intensity is used to determine optical properties with time-resolved diffusion theory, while the TOF-resolved intensity autocorrelations are used to determine dynamics with diffusing wave spectroscopy. iNIRS advances the capabilities of diffuse optical methods and is suitable for in vivo tissue characterization. Moreover, iNIRS combines NIRS and DCS capabilities into a single modality.
Invasive and non-invasive diagnosis ofHelicobacter pylori-associated atrophic gastritis: A comparative study (2005)

A strong reverse correlation was found between histologic/ endoscopic antral atrophy and serum G-17 levels, and between corpus atrophy and serum PG1 levels.