gebhart/patrepeval huggingface dataset:
Modeling TTL-based Internet caches (2004)

This paper presents a way of modeling the hit rates of caches that use a time-to-live (TTL)-based consistency policy. TTL-based consistency, as exemplified by DNS and Web caches, is a policy in which a data item, once retrieved, remains valid for a period known as the "time-to-live". Cache systems using large TTL periods are known to have high hit rates and scale well, but the effects of using shorter TTL periods are not well understood. We model hit rate as a function of request arrival times and the choice of TTL, enabling us to better understand cache behavior for shorter TTL periods. Our formula for the hit rate is closed form and relies upon a simplifying assumption about the interarrival times of requests for the data item in question: that these requests can be modeled as a sequence of independent and identically distributed random variables. Analyzing extensive DNS traces, we find that the results of the formula match observed statistics surprisingly well; in particular, the analysis is able to adequately explain the somewhat counterintuitive empirical finding of Jung et al. that the cache hit rate for DNS accesses rapidly increases as a function of TTL, exceeding 80% for a TTL of 15 minutes.
Association of the T1799A BRAF mutation with tumor extrathyroidal invasion, higher peripheral platelet counts, and over-expression of platelet-derived growth factor-B in papillary thyroid cancer (2008)

The relationship among BRAF mutation, platelet counts, and platelet-derived growth factor (PDGF) with respect to clinicopathological outcomes of papillary thyroid cancer (PTC) may play a role in PTC pathogenesis but remains undefined. We examined the T1799A BRAF mutation by direct genomic DNA sequencing in 108 primary PTC samples from a Chinese cohort and analyzed its relationship with clinicopathological, hematological, and other laboratory results as well as the levels of expression of PDGF in tumors. We found that the BRAF mutation was significantly associated with extrathyroidal invasion and advanced tumor stages III and IV. Specifically, extrathyroidal invasion was seen in 30/54 (56%) PTC with BRAF mutation versus 18/54 (33%) PTC without the mutation (P=0.02). Tumor stages III and IV were seen in 16/54 (30%) PTC with BRAF mutation versus 7/54 (13%) PTC without the mutation (P=0.04). The BRAF mutation was also significantly associated with a higher platelet count, with 249.28+/-53.76 x 10(9)/l in the group of patients with BRAF mutation versus 207.79+/-58.98 x 10(9)/l in the group without the mutation (P=0.001). An association of higher platelet accounts with extrathyroidal invasion was also seen, with 242.66+/-51.85 x 10(9)/l in patients with extrathyroidal invasion versus 218.49+/-59.10 x 10(9)/l in patients without extrathyroidal invasion (P=0.03). The BRAF T1799A-positive PTC tissues harbored a significantly higher level of PDGF-B than BRAF T1799A-negative PTC tissues. The data suggest that the BRAF T1799A mutation is associated with aggressive pathological outcomes of PTC in which high platelet counts and increased PDGF production may play a role.
Assembly and Immunological Properties of Newcastle Disease Virus-Like Particles Containing the Respiratory Syncytial Virus F and G Proteins (2010)

Human respiratory syncytial virus (RSV) is a serious respiratory pathogen in infants and young children as well as elderly and immunocompromised populations. However, no RSV vaccines are available. We have explored the potential of virus-like particles (VLPs) as an RSV vaccine candidate. VLPs composed entirely of RSV proteins were produced at levels inadequate for their preparation as immunogens. However, VLPs composed of the Newcastle disease virus (NDV) nucleocapsid and membrane proteins and chimera proteins containing the ectodomains of RSV F and G proteins fused to the transmembrane and cytoplasmic domains of NDV F and HN proteins, respectively, were quantitatively prepared from avian cells. Immunization of mice with these VLPs, without adjuvant, stimulated robust, anti-RSV F and G protein antibody responses. IgG2a/IgG1 ratios were very high, suggesting predominantly T(H)1 responses. In contrast to infectious RSV immunization, neutralization antibody titers were robust and stable for 4 months. Immunization with a single dose of VLPs resulted in the complete protection of mice from RSV replication in lungs. Upon RSV intranasal challenge of VLP-immunized mice, no enhanced lung pathology was observed, in contrast to the pathology observed in mice immunized with formalin-inactivated RSV. These results suggest that these VLPs are effective RSV vaccines in mice, in contrast to other nonreplicating RSV vaccine candidates.
A Feedback Model for Automated Real Estate Assessment (1977)

Pressing changes are needed in the administration of real estate taxation that will not only ensure that all properties be assessed accurately and equitably, but will enable taxpayers to perceive that they are being treated fairly. In this paper, we examine what properties an automated mass appraisal system should exhibit so as to meet efficacy, equity and public acceptability criteria. A new automated system designed on the basis of these properties which utilizes feedback control and pattern recognition concepts is presented. Results of an empirical study using Pittsburgh data supports the feasibility of the proposed system.
Super in vitro synergy between inhibitors of dihydrofolate reductase and inhibitors of other folate-requiring enzymes: the critical role of polyglutamylation. (1998)

The combined action among polyglutamylatable and nonpolyglutamylatable antifolates, directed against dihydrofolate reductase (DHFR), glycinamide ribonucleotide formyltransferase (GARFT), 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase (AICARFT), and thymidylate synthase (TS), in human ileocecal HCT-8 cells was examined in a 96-well plate growth inhibition assay (96-h continuous drug exposure). An interaction parameter, alpha, was estimated for each of 95 experiments by fitting a seven-parameter model to data with weighted nonlinear regression. In a representative experiment, raising the folic acid concentration in the medium dramatically increased the Loewe synergy for the combination of trimetrexate (TMTX) and the GARFT inhibitor AG2034 (from a mean alpha +/- SE of 1.50 +/- 0.25 at 2.3 microM folic acid to 146 +/- 20 at 78 microM folic acid). Enhancements were also found for combinations of TMTX with the GARFT inhibitors AG2032, Lometrexol, and LY309887, the AICARFT inhibitor AG2009, and the TS inhibitors LY231514 and Tomudex but not with the GARFT inhibitor LL95509 or with the TS inhibitors AG337, ZD9331, and BW1843U89. Replacing TMTX with methotrexate in two-drug mixtures decreased the intensity of Loewe synergy. Examination of isobolograms at different effect levels revealed informative reproducible changes in isobol patterns. No two-drug combinations among inhibitors of GARFT, AICARFT, and TS exhibited Loewe synergy at either 2.3 or 78 microM folic acid. Thus, the ideal requirement for the folic acid-enhanced synergy is that a nonpolyglutamylatable DHFR inhibitor be combined with a polyglutamylatable inhibitor of another folate-requiring enzyme. A hypothesis to explain this general phenomenon involves the critical role of folylpoly-gamma-glutamate synthetase and the effect of the DHFR inhibitor in decreasing the protection by folic acid of cells to the other antifolates.
Endogenous Opioids: Biology and Function (1984)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Epitope mapping of monoclonal antibodies by mass spectrometry: Identification of protein antigens in complex biological systems (1998)

We describe the application of immunoaffinity extraction and mass spectrometry to the analysis of Ty1 Gag protein in lysates of Saccharomyces cerevisiae. A magnetic bead-conjugated monoclonal antibody was used to achieve selective extraction, the specificity of which was established by matrix-assisted laser desorption/ionization mass spectrometric (MS) analysis of an extract of the lysate of cells overexpressing the Ty1 Gag protein. MS analysis of similar extracts of lysates following tryptic hydrolysis confirmed selective extraction of the epitope-containing peptide fragment. Sufficient sensitivity was achieved to allow the application of this approach to the analysis of lysates of wild-type cells. Furthermore, the sequence of the epitope-containing peptide was confirmed by electrospray-tandem MS. To our knowledge, this constitutes the first report of the application of immunoaffinity extraction and tandem MS analysis to the characterization of an antigen recovered from a complex cellular system.
3D flexible multichannel neural probe array (2003)

A 3D flexible multichannel microprobe array was designed, fabricated and tested. Since each probe had several recording pads, the probe array could be used to measure neural activity at various depths in the brain. They were batch fabricated with interconnections, using a specific folding process to fold the planar probe structures. This flexible probe array was inserted into a rat's brain without fracturing and was successfully used to measure neural signals.
Coinfection with Multiple Tick-Borne Pathogens in a Walker Hound Kennel in North Carolina (1999)

Both dogs and humans can be coinfected with various Ehrlichia, Bartonella, Rickettsia, and Babesia species. We investigated a kennel of sick Walker Hounds and their owners in southeastern North Carolina for evidence of tick-borne infections and associated risk factors. A high degree of coinfection was documented in the dog population. Of the 27 dogs, 26 were seroreactive to an Ehrlichia sp., 16 to Babesia canis, and 25 to Bartonella vinsonii, and 22 seroconverted to Rickettsia rickettsii antigens. According to PCR results, 15 dogs were infected with Ehrlichia canis, 9 with Ehrlichia chaffeensis, 8 with Ehrlichia ewingii, 3 with Ehrlichia equi, 9 with Ehrlichia platys, 20 with a Rickettsia species, 16 with a Bartonella species, and 7 with B. canis. The detection of DNA from any Ehrlichia species was associated with clinical illness and with concurrent B. canis infection (by PCR). Both E. canis and an uncharacterized Rickettsia species appeared to result in chronic or recurrent infection. Death in the dog population was associated with living in a dirt lot rather than the concrete kennel. Of 23 people on whom serologic testing was conducted, eight were seroreactive to Bartonella henselae, one to E. chaffeensis, and one to R. rickettsii antigen; however, none had clinical or hematologic abnormalities consistent with illness caused by these organisms. We conclude that kennel dogs with heavy tick exposure can be infected at a high rate with multiple, potentially zoonotic, tick-borne pathogens. In addition, our findings further illustrate the utility of PCR for documenting coinfection with tick-transmitted pathogens.
Quantitation of human in vitro megakaryocytopoiesis by radioimmunoassay (1987)

The isolation and characterization of human megakaryocyte growth factors has been hampered because evaluation of megakaryocyte growth in semisolid medium requires both lengthy incubation and visual quantitation. In addition, colony formation requires cell division, while most regulation of platelet production may involve individual, nonproliferating differentiating megakaryocytes. We have developed a radioimmunoassay (RIA) that makes use of an iodinated murine monoclonal antibody (MoAb) specific for platelet/megakaryocyte glycoprotein IIb/IIIa (GPIIb/IIIa) to measure megakaryocyte production in liquid marrow culture. This assay is sensitive to 3 X 10(3) platelets (roughly 30 megakaryocytes) and linear up to 1 X 10(6) platelets, and thus it provides a useful range for quantitating megakaryocyte production in in vitro marrow culture. Significant differences (threefold to fivefold) in megakaryocyte/platelet-specific GPIIb/IIIa complex are detected between stimulated and unstimulated marrow cultures by day 7, although antigen accrual in stimulated cultures continues through at least day 16. Conditions that promote megakaryocyte growth in semisolid medium (ie, aplastic plasma and PHA-LCM) have also been facilitory in liquid culture. This rapid and sensitive assay for cell-bound GPIIb/IIIa should facilitate recognition and isolation of megakaryocyte and platelet growth factors.
Immune-Correlates Analysis of an HIV-1 Vaccine Efficacy Trial (2012)

This immune-correlates study generated the hypotheses that V1V2 antibodies may have contributed to protection against HIV-1 infection, whereas high levels of Env-specific IgA antibodies may have mitigated the effects of protective antibodies. Vaccines that are designed to induce higher levels of V1V2 antibodies and lower levels of Env-specific IgA antibodies than are induced by the RV144 vaccine may have improved efficacy against HIV-1 infection.
A local search mechanism for peer-to-peer networks (2002)

One important problem in peer-to-peer (P2P) networks is searching and retrieving the correct information. However, existing searching mechanisms in pure peer-to-peer networks are inefficient due to the decentralized nature of such networks. We propose two mechanisms for information retrieval in pure peer-to-peer networks. The first, the modified Breadth-First Search (BFS) mechanism, is an extension of the current Gnuttela protocol, allows searching with keywords, and is designed to minimize the number of messages that are needed to search the network. The second, the Intelligent Search mechanism, uses the past behavior of the P2P network to further improve the scalability of the search procedure. In this algorithm, each peer autonomously decides which of its peers are most likely to answer a given query. The algorithm is entirely distributed, and therefore scales well with the size of the network. We implemented our mechanisms as middleware platforms. To show the advantages of our mechanisms we present experimental results using the middleware implementation.
Preparation of Long-Acting Superoxide Dismutase Using High Molecular Weight Polyethylene Glycol (41,000-72,000 Daltons) (1991)

Superoxide dismutase (SOD) has demonstrated therapeutic potential for treating a variety of conditions including radiation injury, oxygen toxicity, reperfusion injury, and inflammation, especially arthritis. However, the native enzyme's short half-life in plasma (6 minutes in mice, 25 minutes in man) limits the enzyme's effectiveness in many applications, or requires infusion of large doses. High doses of SOD derived from either natural or rDNA sources may increase the potential for immunologic sensitization. One effective use of native SOD is intra-articular administration for treatment of arthritis, where injection of SOD into joints retards elimination (15 hour terminal half-life), allowing the effective use of lower doses. To overcome the limitations resulting from rapid clearance, various researchers have increased the persistence of SOD by cross-linking SOD or by attaching polymeric substances, including dextrans, albumin, Ficoll, polyvinyl alcohol or polyethylene glycol (PEG). PEG is relatively safe; however, the amount of modification by PEG, is the MW range 1,900-5,000 daltons, which is necessary to optimally increase serum persistence and reduce immunogenicity, results in the loss of much of the enzymatic activity. In this report we describe the preparation of SOD adducts containing 1 to 4 strands of high MW PEG (41,000-72,000 daltons). The MW range of these adducts, measured by steric exclusion HPLC based on protein standards, is 200,000 to over 1,000,000 daltons. The number of PEG strands attached per SOD dimer (32,000 daltons) was measured by HPLC. Because of the low degree of protein modification required to produce very high MW products, these PEG-SODs retain 90%-100% of the SOD activity of the native enzyme. Additionally, these very large adducts demonstrate longer persistence and lower immunogenicity and antigenicity compared to the more highly modified PEG-SODs containing low MW PEG (i.e., 7-16 strands of 5,000 dalton methoxy-PEG).
Genetic variation at the interleukin-1 locus is a determinant of changes in soluble endothelial factors in patients with acute coronary syndromes (2002)

Acute coronary syndromes (ACSs) are associated with both systemic inflammatory activation and endothelial cell activation, and both of these are linked to patient outcome. Genetic variation at the interleukin-1 (IL-1) locus influences the clinical patterns of inflammatory disease. We therefore examined the association between IL-1 gene polymorphisms and levels of systemic inflammatory activation markers [C-reactive protein (CRP) and IL-1 receptor antagonist (IL-1ra)] and of soluble endothelial activation markers [von Willebrand factor (vWF) and E-selectin], in a cohort of 63 patients presenting with non-ST-elevation ACS. The IL-1 locus did not significantly influence any of the markers studied at 24 h after presentation. Associations of IL-1 polymorphisms with the changes (Delta) in CRP, IL-1ra, E-selectin and vWF levels between 24 and 48 h were examined in later studies. Delta CRP and Delta IL-1ra showed no significant association with any of the polymorphisms studied. There was a strong association between carriage of the rare allele (allele 2) of the intron 2 variable number of tandem repeats polymorphism of IL-1RN (designated IL-1RN*2) and Delta E-selectin levels: [carriage of *2, 3.03 ng/ml [95% confidence interval (CI) 6.26 to 1.51 ng/ml]; non-carriage of *2, 0.12 ng/ml (95% CI 1.07 to -1.76 ng/ml); P=0.0016], and also between carriage of IL-1RN*2 and Delta vWF levels [carriage of *2, 0.78 i.u./ml (95% CI 0.96 to 0.44 i.u./ml); non-carriage of *2, 0.1 i.u./ml (95% CI 0.19 to -0.1 i.u./ml); P=0.0003]. A composite analysis consisting of carriage of IL-1RN*2 and the genotype at position -511 in the IL-1B gene suggests the existence of haplotypes that influence Delta vWF and Delta E-selectin in patients with ACS. Carriage of IL-1RN*2 was also associated with a 2-fold increased likelihood of a troponin-positive status compared with non-carriage (P=0.0385). These data indicate that, in the setting of non-ST-elevation ACS, genetic variation at the IL-1 gene locus contributes to the changes in soluble markers of endothelial inflammation.
[TiPHOS(Rh)]+:  A Fortuitous Coordination Mode and an Effective Hydrosilylation Bimetallic Catalyst (2005)

The reaction of the titanocene diphosphine {(η5-C5H5)[η5-C5Me3-1,2-(PPh2)2]TiCl2} (TiPHOS; 1) with [Rh(COD)2](OTf) led to the new early−late heterobimetallic complex [(TiPHOS)Rh(COD)](OTf) (2), whose structure has been determined by X-ray diffraction analysis and by dynamic NMR studies. A weak bonding interaction between one of the two chloride atoms of the TiPHOS ligand and the rhodium center has been observed. The bimetallic complex 2 has been tested in parallel with the monometallic complex [(o-dppbe)Rh(COD)](OTf) (3) and has proved to be a very effective catalyst for the hydrosilylation of aromatic ketones.
Kinetic modeling of hardwood prehydrolysis. Part II. Xylan removal by dilute hydrochloric acid prehydrolysis (1985)

Knowledge of prehydrolysis kinetics has applicability to the design, development, and modeling of processes to separate wood into its basic chemical constituents (i.e., cellulose, hemicellulose, and lignin).The kinetics of xylan hemicellulose removal with 0.10 M HC1 at 120 C from quaking aspen, paper birch, American elm, red maple, and southern red oak was studied.The mathematical model developed in Part I to describe the kinetics of xylan removal by water prehydrolysis of these species could be used to model xylan removal with dilute hydrochloric acid.Xylan removal could thus be modeled as the sum of two parallel first-order reactions-one fast and one slow.However, unlike the case with water prehydrolysis where the rate constants for the fast (kf) and slow (kJ reaction processes could be correlated with each other, they could not be correlated for HCl prehydrolysis.Instead the kf and k, values determined for each species clustered about average k, and k, values for all the species as a whole.A single set of parameters determined from a nonlinear least squares fit of the experimental prehydrolysis data for all the species as a whole to the model could be used to reasonably describe the course of xylan removal from all the species.The fact that one set of parameters could be used suggests that the same reactions are taking place on prehydrolysis and that the chemical structure and physical morphology of the xylan hemicellulose were essentially the same in the species studied and probably in all temperate hardwood species.The model thus provides a good approximation of xylan removal from any temperate hardwood with dilute hydrochloric acid at the reaction conditions studied.
The potential of adeno-associated viral vectors for gene delivery to muscle tissue (2014)

Delivering therapeutic genes to large muscle mass in humans is arguably the most urgent unmet demand in treating diseases affecting muscle tissues throughout the whole body. Muscle-directed, rAAV-mediated gene transfer for expressing antibodies is a promising strategy to combat deadly infectious diseases. Developing strategies to circumvent the immune response following rAAV administration in humans will facilitate clinical application.
Charged residues are major determinants of the transmembrane orientation of a signal-anchor sequence. (1991)

Uncleaved signal-anchor sequences of membrane proteins inserted into the endoplasmic reticulum initiate the translocation of either the amino-terminal or the carboxyl-terminal polypeptide segment across the bilayer. Which topology is acquired is not determined by the apolar segment of the signal but rather by the hydrophilic sequences flanking it. To study the role of charged residues in determining the membrane topology, the insertion of mutants of the asialoglycoprotein receptor H1, a single-spanning protein with a cytoplasmic amino terminus, was analyzed in transfected COS-7 cells. When the charged amino acids flanking the hydrophobic signal were mutated to residues of opposite charge, half the polypeptides inserted with the inverted orientation. When, in addition, the amino-terminal domain of the mutant protein was truncated, approximately 90% of the polypeptides acquired the inverted topology. The transmembrane orientation appears to be primarily determined by the charges flanking the signal sequence but is modulated by the domains to be translocated.
Mechanisms of DNA uptake by mammalian cells: fate of exogenously added DNA monitored by the use of fluorescent dyes. (1982)

Coprecipitation of DNA with calcium phosphate is a commonly used method of gene transfer in mammalian cells. We have found that DNA forms a tight complex with Ca Pi and that DNA in this complex is resistant to nucleases present in serum or added externally. Under optimal conditions, virtually all of the recipient mouse Ltk- Aprt- cells take up Ca Pi--DNA complexes, as determined by fluorescent dyes specific for DNA (4',6-diaminilo-2-phenylindol dihydrochloride) or for calcium salts (chlorotetracycline). However, only a small proportion of the cells have detectable CA Pi--DNA complexes in the nucleus. Uptake of the Ca Pi--DNA complexes was highly dependent upon the pH at which the Ca Pi--DNA complexes was formed and upon the concentration of DNA in the complex.