gebhart/patrepeval huggingface dataset:
An agent-based approach to dialogue management in personal assistants (2005)

Personal assistants need to allow the user to interact with the system in a flexible and adaptive way such as through spoken language dialogue. In this research we focus on an application in which the user can use a variety of devices to interact with a collection of personal assistants each specializing in a task domain such as email or calendar management, information seeking, etc. We propose an agent-based approach for developing the dialogue manager that acts as the central point maintaining continuous user-system interaction and coordinating the activities of the assistants. In addition, this approach enables development of multi-modal interfaces. We describe our initial implementation which contains an email management agent that the user can interact with through a spoken dialogue and an interface on PDAs. The dialogue manager was implemented by extending a BDI agent architecture.
Series on pharmacology in practice. 10. Antithrombotic therapy: role of platelet-inhibitor drugs. III. Management of arterial thromboembolic and atherosclerotic disease (third of three parts). (1981)

As already mentioned in the first two parts of this series, the evidence that platelets play an important role in arterial thromboembolic and atherosclerotic disease has led to numerous studies designed to test the possible efficacy of platelet-inhibiting drugs in various cardiovascular conditions in animals and in humans. Although the number of such published studies today probably exceeds 500, for practicality we comment only on those large prospective trials in humans that have followed the strict criteria of drug trials. We specifically refer to patients with valvular heart disease and prosthetic heart valves, patients with cerebrovascular disease, and patients with coronary artery disease.
Plasma Myeloperoxidase Predicts Incident Cardiovascular Risks in Stable Patients Undergoing Medical Management for Coronary Artery Disease (2010)

Plasma MPO concentrations provide independent prognostic value for the prediction of long-term incident MACEs in a stable, medically managed patient population with coronary artery disease. In individuals with increased hsCRP concentrations, we observed lower risk of incident MACEs when concomitant MPO concentrations were low vs when MPO concentrations were high.
Comparison of daptomycin, vancomycin, and ampicillin-gentamicin for treatment of experimental endocarditis caused by penicillin-resistant enterococci (1992)

Infections with enterococci that are resistant to multiple antibiotics are an emerging clinical problem. We evaluated the antibiotic treatment of experimental enterococcal endocarditis caused by two strains with different mechanisms of penicillin resistance. Enterococcus faecalis HH-22 is resistant to aminoglycosides and penicillin on the basis of plasmid-mediated modifying enzymes; Enterococcus raffinosus SF-195 is susceptible to aminoglycosides but is resistant to penicillin on the basis of low-affinity penicillin-binding proteins. Animals infected with strain HH-22 received 5 days of treatment with the following: no treatment; daptomycin (20 mg/kg of body weight twice daily [b.i.d.], intramuscularly [i.m.]), vancomycin (20 mg/kg b.i.d., intravenously), or ampicillin (100 mg/kg three times daily, i.m.) plus gentamicin (2.5 mg/kg b.i.d. i.m.). Although vancomycin was superior to ampicillin-gentamicin (P less than 0.01), daptomycin was significantly better than all other treatment regimens (P less than 0.01) in reducing intravegetation enterococcal densities, although no vegetations were rendered culture negative by this agent. Animals infected with strain SF-195 received 5 days of no therapy, ampicillin, ampicillin-gentamicin, vancomycin, or daptomycin (all at the dosage regimens described above). Daptomycin, vancomycin, and ampicillin-gentamicin each lowered intravegetation enterococcal densities significantly better than did ampicillin monotherapy or no treatment (P less than 0.01); moreover, these three treatment regimens rendered significantly more vegetations culture negative than did ampicillin monotherapy or no treatment (P less than 0.05). Serum daptomycin levels remained above the MICs and MBCs for both enterococcal strains throughout the 12-h dosing interval used in the study. Daptomycin and vancomycin were both active in vivo in these models of experimental enterococcal endocarditis caused by penicillin-resistant strains, irrespective of the mechanism of resistance. This activity correlated with the unique cell wall sites of action of these agents (binding to lipoteichoic acid and pentapeptide precursor, respectively) compared with the sites of action of beta-lactams (penicillin-binding proteins). Beta-Lactamase production by strain HH-22 precluded in vivo efficacy with ampicillin-gentamicin combinations. In contrast, this combination was active in vivo against strain SF-195, which exhibited intermediate-level penicillin resistance (MIC, 32 micrograms/ml), likely reflecting the ability of high-dose ampicillin to achieve enough binding to low-affinity penicillin-binding proteins to cause augmented aminoglycoside uptake.
Helix-Stabilizing Agent, CC-1065, Enhances Suppression of Translation by an Antisense Oligodeoxynucleotide (1995)

The antitumor antibiotic CC-1065 is known to bind at selected sequences in the minor groove of duplex nucleic acids and to hyperstabilize the duplexes against thermal melting. These properties suggested that CC-1065 may enhance translation inhibition by antisense oligonucleotides directed against a specific mRNA. A 585 bp mRNA transcript containing the equine infectious anemia virus (EIAV) S2 gene and a portion of the env gene was prepared. Also, a complementary 20 mer antisense oligodeoxynucleotide (5'-TGTTGGGTAATAGG-GGTTGA-3') was prepared against a target sequence in the mRNA located near the translational initiation sites of the overlapping S2 and env genes. The center of the target sequence had an expected CC-1065 recognition sequence (5'-UAUUA-3'). Translation in the presence of CC-1065 and antisense was markedly suppressed compared with that of antisense alone. Addition of a sense 20 mer strand, with or without CC-1065, had little or no effect on translation. CC-1065 and related compounds may be useful as ligands for enhancing the stability of sense-antisense duplexes and for promoting the inhibition of translation by antisense oligonucleotides.
The economics of behavioral health carve‐outs (1998)

Abstract Behavioral health care carve‐outs provide efficiencies of specialization; direct payer carve‐outs also eliminate risk selection.
The inverse electron demand Diels–Alder click reaction in radiochemistry (2013)

The inverse electron-demand Diels-Alder (IEDDA) cycloaddition between 1,2,4,5-tetrazines and strained alkene dienophiles is an emergent variety of catalyst-free 'click' chemistry that has the potential to have a transformational impact on the synthesis and development of radiopharmaceuticals. The ligation is selective, rapid, high-yielding, clean, and bioorthogonal and, since its advent in 2008, has been employed in a wide variety of chemical settings. In radiochemistry, the reaction has proven particularly useful with (18) F and has already been utilized to create a number of (18) F-labeled agents, including the PARP1-targeting small molecule (18) F-AZD2281, the αv β3 integrin-targeting peptide (18) F-RGD, and the GLP-1-targeting peptide (18) F-exendin. The inherent flexibility of the ligation has also been applied to the construction of radiometal-based probes, specifically the development of a modular strategy for the synthesis of radioimmunoconjugates that effectively eliminates variability in the construction of these agents. Further, the exceptional speed and biorthogonality of the reaction have made it especially promising in the realm of in vivo pretargeted imaging and therapy, and pretargeted imaging strategies based on the isotopes (111) In, (18) F, and (64) Cu have already proven capable of producing images with high tumor contrast and low levels of uptake in background, nontarget organs. Ultimately, the characteristics of inverse electron-demand Diels-Alder click chemistry make it almost uniquely well-suited for radiochemistry, and although the field is young, this ligation has the potential to make a tremendous impact on the synthesis, development, and study of novel radiopharmaceuticals.
Anti-integrin (LFA-1, VLA-4, and Mac-1) antibody treatment and acute cardiac graft rejection in the rat (1996)

Abstract Cell adhesion molecules mediate interactions with other cells and extracellular matrix, control cell infiltration in sites of inflammation, and regulate cell activation. Previous studies have shown that treatment of rat cardiac transplant recipients with a combination of antibodies against the T-cell integrins LFA-1 and VLA-4 gave a modest prolongation of graft survival. Current experiments were designed to examine the effect of blocking Mac-1, an im portant monocyte adhesion receptor and mediator of monocyte migration, together with anti-LFA-1 and anti-VLA-4 antibodies on cardiac graft survival and on the graft rejection pattern. The anti-Mac-1, CDllb-specific antibody OX-42 did not affect graft survival time al though it did decrease the graft in filtration by rounded, ED-2-positive macrophages.
The Insulin Receptor (1972)

Studies with bulky and insoluble insulin derivatives indicate that this hormone can activate various metabolic processes by interaction with cell surface structures. A definition of “receptor” is offered which is operationally useful in studies directed to the identification and purification of receptor structures. Studies are described which measure the specific binding of insulin to intact fat cells and liver and fat cell membranes. The properties of these interactions and the correlation with metabolic events indicate that biologically significant receptors are being studied. The possible contribution of membrane carbohydrates, proteins and lipids to the environment and function of the receptor is considered. Studies pertinent to the extraction and purification of the insulin receptor are discussed.
Inhibition of Amyloid Fibril Formation and Cytotoxicity by Hydroxyindole Derivatives (2006)

Gaining insight into the mechanism of amyloid fibril formation, the hallmark of multiple degenerative syndromes of unrelated origin, and exploring novel directions of inhibition are crucial for preventing disease development. Specific interactions between aromatic moieties were suggested to have a key role in the recognition and self-assembly processes leading to the formation of amyloid fibrils by several amyloidogenic polypeptides, including the beta-amyloid polypeptide associated with Alzheimer's disease. Our finding of the high-affinity molecular recognition and intense amyloidogenic potential of tryptophan-containing peptide fragments led to the hypothesis that screening for indole derivatives might lead to the identification of potential inhibitors of amyloid formation. Such inhibitors could mediate specific recognition processes without allowing further growth of the well-ordered amyloid chain. Using fluorescence spectroscopy, atomic force microscopy, and electron microscopy to screen 29 indole derivatives, we identified three potent inhibitors: indole-3-carbinol (I3C), 3-hydroxyindole (3HI), and 4-hydroxyindole (4HI). The latter, a simple low-molecular weight aromatic compound, was the most effective, completely abrogating not only the formation of aggregated structures by Abeta but also the cytotoxic activity of aggregated Abeta toward cultured cells. The results of this study provide further experimental support for the paradigm of amyloid inhibition by heteroaromatic interaction and point to indole derivatives as a simple molecular platform for the development of novel fibrillization inhibitors.
Cytotoxic activity of epidermal growth factor-genistein against breast cancer cells. (1998)

The receptor (R) for epidermal growth factor (EGF) is expressed at high levels on human breast cancer cells and associates with ErbB2, ErbB3, and Src proto-oncogene family protein tyrosine kinases (PTKs) to form membrane-associated PTK complexes with pivotal signaling functions. Recombinant human EGF was conjugated to the soybean-derived PTK inhibitor genistein (Gen) to construct an EGF-R-directed cytotoxic agent with PTK inhibitory activity. The EGF-Gen conjugate was capable of binding to and entering EGF-R-positive MDA-MB-231 and BT-20 breast cancer cells (but not EGF-R-negative NALM-6 or HL-60 leukemia cells) via its EGF moiety, and it effectively competed with unconjugated EGF for target EGF-R molecules in ligand binding assays. EGF-Gen inhibited the EGF-R tyrosine kinase in breast cancer cells at nanomolar concentrations, whereas the IC50 for unconjugated Gen was >10 microM. Notably, EGF-Gen triggered a rapid apoptotic cell death in MDA-MB-231 as well as BT-20 breast cancer cells at nanomolar concentrations. The EGF-Gen-induced apoptosis was EGF-R-specific because cells treated with the control granulocyte-colony stimulating factor-Gen conjugate did not become apoptotic. Apoptosis was dependent both on the PTK inhibitory function of Gen and the targeting function of EGF, because cells treated with unconjugated Gen plus unconjugated EGF did not undergo apoptosis. The IC50s of EGF-Gen versus unconjugated Gen against MDA-MB-231 and BT-20 cells in clonogenic assays were 30 +/- 3 nM versus 120 +/- 18 microM (P < 0.001) and 30 +/- 10 nM versus 112 +/- 17 microM (P < 0.001), respectively. Thus, the EGF-Gen conjugate is a >100-fold more potent inhibitor of EGF-R tyrosine kinase activity in intact breast cancer cells than unconjugated Gen and a >100-fold more potent cytotoxic agent against EGF-R+ human breast cancer cells than unconjugated Gen. Taken together, these results indicate that the EGF-R-associated PTK complexes have vital antiapoptotic functions in human breast cancer cells and may therefore be used as therapeutic targets.
THE ROLE OF CD4+ HELPER T CELLS IN THE DESTRUCTION OF MICROENCAPSULATED ISLET XENOGRAFTS IN NOD MICE (1990)

Islet transplants for large numbers of patients with diabetes will require xenografts. Microencapsulation is an appealing method for islet xenografting. However, graft function has been limited by a cellular reaction, particularly intense in spontaneously diabetic, NOD mice. The purpose of this study was to elucidate the mechanism of this reaction. Poly-1-lysine-alginate microcapsules containing 4000-12,000 dog or 1800-2000 rat islets were xenografted intraperitoneally into streptozotocin (SZN)-diabetic C57BL/6J and NOD mice, with or without recipient treatment with GK 1.5 (anti-CD4 monoclonal antibody) (20-30 microliters i.p. every 5 days, begun on day -7. Grafts were considered technically successful if random blood glucose (BG) was normalized (less than 150 mg/dl) within 36 hr. Graft failure was defined as BG greater than 250 mg/dl. Dog and rat islets in microcapsules normalized BG in both SZN and NOD mice within 24 hr routinely. Empty microcapsules and GK 1.5 treatments alone did not affect BG. NODs destroyed both microencapsulated dog and rat islets more rapidly than did SZN-diabetic mice (P less than .01). Graft biopsies showed an intense cellular reaction, composed of lymphocytes, macrophages and giant cells, and no viable islets. GK 1.5 treatment significantly prolonged both dog-to-NOD and rat-to-NOD grafts (P less than 0.01). Biopsies of long-term functioning grafts (on days 65-85) demonstrated viable islets and no cellular reaction around microcapsules; 1/4 rat and 1/8 dog islet xenografts continued to function indefinitely in NOD recipients, even after cessation of GK 1.5 therapy. Prediabetic NODs receiving encapsulated dog or rat islets mounted a moderate cellular reaction to grafts. Empty microcapsules excited no cellular reaction in diabetic or prediabetic NODs. We conclude that the NOD reaction to microencapsulated xenogeneic islets is helper T cell-dependent, and that the target of this reaction is not the microcapsule itself, but the donor cells within.
THE INFLUENCE OF LACTIC CULTURES ON GROUND BEEF QUALITY (1970)

SUMMARY– The effects of adding 5 and 10% lactic culture (Streptococcus lactis and Leuconostoc citrovorum) grown in skim milk; 2.5, 5, 10, and 20% lactic cultures grown in 20% milk solids; 1 and 2% frozen concentrated lactic cultures; lactic acid to pH 5.0 and 4.5; and 2.5, 5, and 10% skim milk to ground beef stored at refrigeration temperature (7°C) were studied in the 6 preliminary trials. Results obtained were used to formulate the principal investigation. The influence of 10% lactic culture and 10% lactic culture plus 450 ppm of ascorbic acid were tested in 5 replicate trials for the principal investigation. Cultures used in the replicate trials were grown in 20% milk solids. CVT (crystal violet tetrazolium) counts for gram‐negative bacteria, pH, VNC (volatile nitrogen content), and organoleptic observations were evaluated. Data from the preliminary study indicated a profound inhibitory action of the lactic cultures on the growth of the inherent gram‐negative bacteria in ground beef. The addition of 10% lactic culture grown in 20% milk solids was effective in preventing aerobic growth. The addition of pure lactic acid inhibited microbial growth, but caused an undesirable color and aroma. Frozen concentrated cultures required 1% lactose to inhibit the growth. The CVT count in the uncultured meat significantly increased (P &lt; .01) as the storage time progressed. Cultured meat did not exhibit a significant increase in CVT count until 7 days of storage. The pH of the cultured meat significantly declined (P &lt;.01) whereas the uncultured meat indicated a significant increase in pH (P &lt; .01) during storage. VNC in the uncultured meat was significantly higher (P &lt;.01) than in the cultured meat. Cultured meat with 450 ppm of ascorbic acid was consistently preferred for flavor, aroma, and when color was compared with the uncultured meat and the meat with culture alone.
Isolation of Vitamin B12-binding Proteins Using Affinity Chromatography (1972)

TranscobalaminII has been isolated from Cohn Fraction III derived from 1,400 liters of pooled human plasma, using affinity chromatography on vitamin B+Sepharose and several conventional purification techniques.The final preparation was purified 2 million-fold relative to human plasma with a yield of 12.8% and was homogeneous based on polyacrylamide disc gel electrophoresis, sedimentation equilibrium ultracentrifugation, and chromatography on Sephadex G-150.Transcobalamin II binds 28.6 pg of vitamin Blz per mg of protein and contains one vitamin Bla-binding site per 59,500 g of protein as determined by amino acid analysis.The molecular weight determined by sedimentation equilibrium ultracentrifugation was 53,900 and by gel filtration on Sephadex G-150 was 60,000.Sodium dodecyl sulfate polyacrylamide gel electrophoresis disclosed two peptides with molecular weight values of 38,000 and 25,000 which suggests that transcobalamin II contains 2 subunits.When vitamin Blz binds to transcobalamin II there is a shift in the peak of vitamin Blz absorption from 361 nm to 364 nm.Analysis of transcobalamin II for carbohydrate content using gas-liquid chromatography and amino sugar analysis by the amino acid analyzer suggest that this trace plasma protein is not a glycoprotein.
Differential staining of cartilage and bone in whole mouse fetuses by alcian blue and alizarin red S (1980)

The procedure described by Inouye ('76) for the staining of full-term mouse fetal skeletons has been adapted for use with mouse embryos and fetuses of days 14-18 of gestation. The main adaptations for younger specimens involve a longer time in acetone, in lieu of skinning, and omission of the aqueous KOH step. These adaptations require more time but result in consistently good staining of intact specimens.
Mitochondrial Transformation in Yeast by Bombardment with Microprojectiles (1988)

The genetic transformation of mitochondria and chloroplasts has been an intractable problem. The newly developed "biolistic" (biological ballistic) process was used to deliver DNA into yeast cells to stably transform their mitochondria. A nonreverting strain, which is respiratory deficient because of a deletion in the mitochondrial oxi3 gene, was bombarded with tungsten microprojectiles coated with DNA bearing sequences that could correct the oxi3 deletion. Respiratory-competent transformants were obtained in which the introduced oxi3 DNA is integrated at the homologous site in the mitochondrial genome. Organelle genomes can now be manipulated by molecular genetic techniques in the same way as nuclear genomes.
Inverse Electrostatic Effect:  Electrostatic Repulsion in the Unfolded State Stabilizes a Leucine Zipper, (2004)

The pH-dependent stability of a protein is strongly affected by electrostatic interactions between ionizable residues in the folded as well as unfolded state. Here we characterize the individual contributions of charged Glu and His residues to stability and determine the NMR structure of the designed, heterodimeric leucine zipper AB consisting of an acidic A chain and a basic B chain. Thermodynamic parameters are compared with those of the homologous leucine zipper AB(SS) in which the A and B chains are disulfide-linked. NMR structures of AB based on (1)H NMR data collected at 600 MHz converge, and formation of the same six interchain salt bridges found previously in disulfide-linked AB(SS) [Marti, D. N., and Bosshard, H. R. (2003) J. Mol. Biol. 330, 621-637] is indicated. While the structures of AB and AB(SS) are very similar, their pH-dependent relative stabilities are strikingly different. The stability of AB peaks at pH approximately 4.5 and is higher at pH 8 than at pH 2. In contrast, AB(SS) is most stable at acidic pH where no interhelical salt bridges are formed. The different energetic contributions of charged Glu and His residues to stability of the two coiled coil structures were evaluated from pK(a) shifts induced by folding. The six charged Glu residues involved in salt bridges stabilize leucine zipper AB by 4.5 kJ/mol yet destabilize disulfide-linked AB(SS) by -1.1 kJ/mol. Two non-ion-paired Glu charges destabilize AB by only -1.8 kJ/mol but AB(SS) by -5.6 kJ/mol. The higher relative stability of AB at neutral pH is not caused by more favorable electrostatic interactions in the folded leucine zipper. It is due mainly to unfavorable electrostatic interactions in the unfolded A and B chains and may therefore be called an inverse electrostatic effect. This study illustrates the importance of residual interactions in the unfolded state and how the energetics of the unfolded state affect the stability of the folded protein.
High volumetric uptake of ammonia using Cu-MOF-74/Cu-CPO-27 (2015)

Cu-MOF-74 (also known as Cu-CPO-27) was identified as a sorbent having one of the highest densities of Cu(ii) sites per unit volume. Given that Cu(ii) in the framework can be thermally activated to yield a five-coordinate Cu(ii) species, we identified this MOF as a potential candidate for maximal volumetric uptake of ammonia. To that end, the kinetic breakthrough of ammonia in Cu-MOF-74/Cu-CPO-27 was examined under both dry and humid conditions. Under dry conditions the MOF exhibited a respectable performance (2.6 vs. 2.9 NH3 per nm(3) for the current record holder HKUST-1), and under 80% relative humidity, the MOF outperformed HKUST-1 (5.9 vs. 3.9 NH3 per nm(3), respectively).