gebhart/patrepeval huggingface dataset:
Antibody-Mediated Delivery of Anti– KRAS -siRNA In Vivo Overcomes Therapy Resistance in Colon Cancer (2015)

The coupling of siRNA against KRAS to anti-EGFR antibodies provides a novel therapy approach for KRAS-mutated EGFR-positive cancer cells in vitro and in vivo. These findings provide an innovative approach for cancer-specific siRNA application and for enhanced therapeutic potential of monoclonal antibody therapy and personalized treatment of cancer entities.
New generation QuIC assays for prion seeding activity (2012)

The ability of abnormal TSE-associated forms of PrP to seed the formation of amyloid fibrils from recombinant PrP(Sen) has served as the basis for several relatively rapid and highly sensitive tests for prion diseases. These tests include rPrP-PMCA (rPMCA), standard quaking-induced conversion (S-QuIC), amyloid seeding assay (ASA), real-time QuIC (RT-QuIC) and enhanced QuIC (eQuIC). Here, we summarize recent improvements in the RT-QuIC-based assays that enhance the practicality, sensitivity and quantitative attributes of assays QuIC and promote the detection of prion seeding activity in dilute, inhibitor-laden fluids such as blood plasma.
Functional insulin and insulin-like growth factor-1 receptors are preferentially expressed in multiple myeloma cell lines as compared to B-lymphoblastoid cell lines. (1994)

While IGF-1 plays a role in early B-cell development, little is known of insulin and insulin-like growth factor-1 (IGF-1) action in post-marrow B-cells. Recently, our laboratory demonstrated that mouse and human multiple myeloma (MM) cell lines possess functional insulin receptors (IRs) and IGF-1 receptors (IGF-1Rs). In this study, we show that responsiveness to insulin and IGF-1 is more developed in human MM cell lines than in human B-lymphoblastoid cell lines. Two human MM cell lines (U266 and RPMI 8226) were compared to three B-lymphoblastoid cell lines [Epstein-Barr virus immortalized B-cells (EBV), a Burkitt lymphoma cell line (Ramos), and a non-EBV lymphoblastoid cell line (HS Sultan)]. Surface IR and IGF-1R expression, measured by flow cytometry, demonstrated that the MM cell lines expressed more IRs and IGF-1Rs than did the EBV, Ramos, or HS Sultan cell lines. In vitro receptor kinase activity of affinity-purified receptors showed that the MM cells had more phosphorylated receptors than did the EBV, Ramos, or HS Sultan cells. Intracellular receptor signaling was also markedly different between the two cell groups. Whole cell phosphorylation studies showed that MM cells possessed not only hormone-dependent receptor autophosphorylation (M(r) 97,000) but also substrate phosphorylation (M(r) 185,000; 60,000). The lymphoblastoid cells, while demonstrating receptor autophosphorylation (IR autophosphorylation in the EBV cell line at 200 nM hormone was similar to MM receptor phosphorylation at 2 nM), lacked hormone-responsive substrates. The MM cell lines contained significantly more hormone-stimulated phosphatidylinositol 3-kinase (PI 3-kinase) activity than the B-lymphoblastoid cell lines. In the MM cells, PI 3-kinase was activated by at least 10-fold, but, in the B-lymphoblastoid cell lines, it was activated by no more than 2-fold. Hormone-responsive glucose metabolism was also greater in the MM cell lines. In the U266 cells, insulin increased lactate production 62 +/- 9 and 101 +/- 12% (mean +/- SE) at concentrations of 2 nM and 200 nM, respectively. IGF-1 produced 72 +/- 9 and 99 +/- 13% increases at similar concentrations. In the 8226 cells, insulin increased lactate production 4 +/- 4 and 36 +/- 15% at 2 and 200 nM, respectively. IGF-1 produced a 13 +/- 6 and 70 +/- 18% increase. In the EBV and Ramos cells, neither hormone increased lactate production by more than 10 +/- 3%.(ABSTRACT TRUNCATED AT 400 WORDS)
RecA-Catalyzed, Sequence-Specific Alkylation of DNA by Cross-Linking Oligonucleotides. Effects of Length and Nonhomologous Base Substitutions (1996)

Oligodeoxyribonucleotides (ODNs) bearing the reactive nitrogen mustard chlorambucil have been used as sequence-directed affinity labeling reagents to investigate the length and homology requirements for RecA-catalyzed alkylation of double-stranded DNA. The cross-linkage reaction, which takes place at the N-7 position of a targeted complementary strand guanine following strand exchange, was highly sequence specific with both a 272 bp DNA fragment and a linearized plasmid. Alkylation required the ODN to be at least 26 nucleotides long and to possess homology to the target in the vicinity of the modification site. The extent of alkylation was improved by using longer ODNs, with a 50-mer giving over 50% reaction. Mismatches inhibited alkylation when they perturbed the structure of the strand exchange product near the targeted guanine. Longer heterology also inhibited alkylation when it prevented strand exchange. Our inability to detect cross-linkage in stable synaptic complexes unable to undergo complete strand exchange is best explained by a model for homologous alignment in which the presynaptic filament approaches from the minor groove of the duplex. Since the N-7 position of guanine is in the major groove, it is inaccessible to the tethered chlorambucil group of the ODN during the search for homology. The reaction specificity of chlorambucil-bearing ODNs suggests that they may have general use as recombinase-mediated DNA targeting agents.
The multidrug resistance phenotype: 31P nuclear magnetic resonance characterization and 2-deoxyglucose toxicity. (1991)

In order to identify changes in 31P nuclear magnetic resonance (NMR) spectra associated with multiple drug resistance (MDR), a number of wild type and drug-resistant cancer cell lines were studied. The resistant cells included cells selected with various drugs, mainly Adriamycin, as well as cells transfected with the human multidrug resistance gene (MDR1 gene), which encodes P-glycoprotein. In most cases, 31P NMR spectra were significantly different from those of parental, drug-sensitive lines. The spectra of resistant cells generally indicated increased levels of ATP and phosphocreatine in the cytoplasm. These changes are compatible with the increased glucose utilization rate previously described for resistant cells. Major changes were also observed in the levels of glycerophosphocholine and glycerophosphoethanolamine. Changes in cellular metabolism reflected by 31P NMR spectra depend on the drug used to select the cells for MDR. The direction of these changes was not consistent for all cell lines studied and could not be directly attributed to expression of P-glycoprotein, suggesting that the changes may be related to alterations in metabolism and membrane function associated with other mechanisms of MDR. The results demonstrate the suitability of 31P NMR for studies of biochemical changes associated with MDR. The toxicity of 2-deoxyglucose, a glucose antimetabolite, was investigated in addition to the NMR studies and was found to be consistently higher in multidrug-resistant cells than in the parental drug-sensitive lines. For MCF-7 breast cancer cells, where several sublines with different levels of resistance were available, the toxicity was highest for the most resistant lines.
High quality glottal LPC-vocoding (2005)

This paper presents an analysis procedure for a parametric coder, capable of coding speech at 2-3 kbit/s. The production model used is essentially that of the LPC-vocoder, however augmented with a variable glottal pulse model for voiced excitation. Starting with formulating a suitable error criterion, a scheme is discussed in detail for extracting close to optimal synthesis parameters. The error measure is in the time-domain essentially defined as for waveform coders. A medium size data base has been used to evaluate the coder. For high quality input speech the resulting speech quality is far above that of standard vocoders. For most of the data base, even trained listeners cannot tell the coded signal from the original signal when listening over loudspeakers.
Avidity and bactericidal activity of antibody elicited by different Haemophilus influenzae type b conjugate vaccines. The Vaccine Study Group (1992)

<h3>Objective.</h3> —Antibody avidity is a measure of the functional affinity of serum antibody to bind to antigen. In this study, we compared the avidity of antibodies elicited by vaccination with three<i>Haemophilus influenzae</i>type b (Hib) conjugate vaccines and investigated the relationship between antibody avidity and the ability of antibody to activate complement-mediated bactericidal activity. <h3>Design.</h3> —A convenience sample of 171 postvaccination serum samples with more than 0.5 μg/mL of anticapsular antibody, the minimum concentration required for measurement of avidity. The serum samples were obtained from infants participating in immunogenicity trials with Hib capsular polysaccharide (PRP) conjugated to meningococcal outer membrane protein complex (PRP-OMPC) or to tetanus toxoid (PRP-T), or PRP oligomers conjugated to a nontoxic mutant diphtheria toxin, CRM<sub>197</sub>(Oligo-CRM). <h3>Patients.</h3> —Healthy infants recruited in private practices. <h3>Primary Outcome Measures.</h3> —Avidity of vaccine-induced serum anticapsular antibody and serum bactericidal titers. <h3>Results.</h3> —In infants vaccinated at 2, 4, and 6 months of age, Oligo-CRM evoked antibody of higher avidity than PRP-OMPC (<i>P</i>&lt;.001). The mean avidity of antibody elicited by PRP-T was intermediate, being lower than Oligo-CRM (<i>P</i>&lt;.02) but higher than PRP-OMPC (<i>P</i>=.001). Also, after one dose, 18-month-old infants given Oligo-CRM had higher avidity antibodies compared with those given PRP-OMPC (<i>P</i>&lt;.001). Half of the infants in both age groups who were given Oligo-CRM developed antibody avidity of 2.50 nM<sup>-1</sup>or greater, whereas more than two thirds of the infants given PRP-OMPC had avidity values of 1.25 nM<sup>-1</sup>or less. Antibodies with avidity of 1.25 nM<sup>-1</sup>or less were, on average, 6.6-fold less active in assays of complement-mediated bactericidal activity than antibodies with avidity of 2.50 nM<sup>-1</sup>or greater (<i>P</i>&lt;.001). <h3>Conclusions.</h3> —Oligo-CRM and PRP-T conjugate vaccines elicit higher avidity antibody than PRP-OMPC, and high-avidity antibody is more potent than low-avidity antibody in serum bactericidal assays. Consideration should be given to including measurement of antibody avidity in assessment of new vaccines since avidity may affect the ability of serum antibody to confer protection against disease. (<i>JAMA</i>. 1992;267:1489-1494)
Characterization of a DNA mismatch-binding activity in yeast extracts. (1993)

An activity present in nuclear extracts of the yeast Saccharomyces cerevisiae binds specifically to oligonucleotides containing DNA mismatches, as judged by a band shift assay. The specificity of this activity for mismatched DNA was confirmed by competition experiments; binding to radiolabeled heteroduplexes was abolished in the presence of excess unlabeled heteroduplex but not when excess unlabeled homoduplex was added. Both T/G and T/- (single base deletion) mispairs were recognized in each of two sequence contexts. Binding was also observed with G/G, G/A, A/C, and T/C mismatches, but recognition of a C/C mispair was very weak. Competition studies with the various mismatches were consistent with the idea that a single activity recognizes all mispairs tested. Extracts from strains mutant in either or both of two putative mismatch recognition functions, MSH2 and MSH3, were also tested. Mismatch-binding activity was present in extracts of msh3- strains but completely absent in msh2- strains. The molecular weight of the major binding protein was estimated by UV cross-linking experiments to be approximately 110 kDa, in good agreement with the size predicted for Msh2 protein (Reenan, R. A. and Kolodner, R. D. (1992) Genetics 132, 963-973).
Highly nonlinear optical fiber for all optical processing applications (1995)

We have designed and fabricated highly nonlinear dispersion-shifted germania-doped silica fibers for use in the EDFA gain window, and measured a 9-fold increase in the fiber nonlinearity, compared to conventional dispersion-shifted fiber. We have also measured the contribution of the germania index-raising dopant to the effective fiber nonlinearity. We believe that our new fiber design will afford a significant reduction in the required fiber length for nonlinear switching, leading to a broader wavelength switching window, and allowing compact device packaging.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Enhancement of membrane insertion and function in a type IIIb membrane protein following introduction of a cleavable signal peptide. (1992)

The human beta 2 adrenergic receptor is a type IIIb membrane protein. It has a putative seven-transmembrane topology but lacks an amino-terminal cleavable signal sequence. The mechanism by which the amino terminus of the beta 2 receptor is translocated across the endoplasmic reticulum membrane is unknown. Furthermore, it is not known if translocation as a type IIIb protein is essential for the proper folding. Our studies indicate that conversion of beta 2 receptor from a type IIIb to a type IIIa membrane protein by introducing an NH2-terminal cleavable signal sequence enhances translocation of the receptor into the endoplasmic reticulum membrane, thereby facilitating expression of functional receptor.
Granular hydroxyapatite and allogeneic demineralized bone matrix in rabbit skull defect augmentation. (1993)

To study the effect of hydroxyapatite (HA) granules on new bone formation induced by allogeneic demineralized bone matrix (DBM) and to ascertain the specific dose response of bone regeneration in rabbit calvarial defects, implantation with different doses of DBM, HA granules and a mixture of DBM with HA, respectively, was undertaken. The results showed that the largest quantity of cartilage in the fourth week and woven and remodeled bone covering almost the whole area of the defect in the tenth and twelfth week, was visible in the 20-30 mg but not in the 40 mg DBM groups. New bone formation in the defects implanted with DBM and HA was markedly less than in those implanted with DBM alone and a large amount of fibrous tissue was initiated by HA granules. A significant negative correlation between new bone formation and fibrous tissue ingrowth was noted. HA granules, as disturbing the bone regeneration induced by DBM, are thus not a desirable combination, and a dose-block phenomenon according to the amount of DBM must be anticipated in repairing skull defects.
Microtubule-interfering Agents Stimulate the Transcription of Cyclooxygenase-2 (2000)

We investigated whether microtubule-interfering agents (MIAs: taxol, colchicine, nocodazole, vinblastine, vincristine, 17-beta-estradiol, 2-methoxyestradiol) altered cyclooxygenase-2 (COX-2) expression in human mammary epithelial cells. MIAs enhanced prostaglandin E(2) synthesis and increased levels of COX-2 protein and mRNA. Nuclear run-off assays revealed increased rates of COX-2 transcription after treatment with MIAs. Calphostin C, an inhibitor of protein kinase C, blocked the induction of COX-2 by MIAs. The stimulation of COX-2 promoter activity by MIAs was inhibited by overexpressing dominant negative forms of Rho and Raf-1. MIAs stimulated ERK, JNK, and p38 mitogen-activated protein kinases (MAPK); pharmacological inhibitors of MAPK kinase and p38 MAPK blocked the induction of COX-2 by MIAs. Overexpressing dominant negative forms of ERK1 or p38 MAPK inhibited MIA-mediated activation of the COX-2 promoter. MIAs stimulated the binding of the activator protein-1 transcription factor complex to the cyclic AMP response element in the COX-2 promoter. A dominant negative form of c-Jun inhibited the activation of the COX-2 promoter by MIAs. Additionally, cytochalasin D, an agent that inhibits actin polymerization, stimulated COX-2 transcription by the same signaling pathway as MIAs. Thus, microtubule- or actin-interfering agents stimulated MAPK signaling and activator protein-1 activity. This led, in turn, to induction of COX-2 gene expression via the cyclic AMP response element site in the COX-2 promoter.
Molecular Ionization from Carbon Nanotube Paper (2014)

Ambient ionization is achieved by spraying from a carbon nanotube (CNT)-impregnated paper surface under the influence of small voltages (≥3 V). Organic molecules give simple high-quality mass spectra without fragmentation in the positive or negative ion modes. Conventional field ionization is ruled out, and it appears that field emission of microdroplets occurs. Microscopic examination of the CNT paper confirms that the nanoscale features at the paper surface are responsible for the high electric fields. Raman spectra imply substantial current flows in the nanotubes. The performance of this analytical method was demonstrated for a range of volatile and nonvolatile compounds and a variety of matrices.
Pertussis toxin stimulates hypersensitivity and enhances nerve-mediated antigen uptake in rat intestine (1994)

We previously reported that intestine from rats sensitized to ovalbumin (Ova), using Bordetella pertussis vaccine as adjuvant, demonstrated a rapid secretory response [increase in short-circuit current (Isc)] to Ova upon secondary challenge. Here, we examined the role of pertussis toxin, the active component of the vaccine, in the response. Sensitization of Sprague-Dawley rats by intraperitoneal injection of recombinant wild-type pertussis toxin (wPT) plus Ova enhanced intestinal responses (at day 14: approximately 20-fold for luminal antigen, approximately 2.5-fold for serosal antigen) compared with rats sensitized by injection of Ova alone. In contrast, sensitization with an enzymatically inactive mutant pertussis toxin (mPT, different in two amino acids) produced no significant effect. Ova-specific immunoglobulin (Ig) E and IgG2a antibodies and greater numbers of mucosal mast cells were documented in wPT-sensitized rats. In addition, the Isc response to electrical transmural stimulation of nerves in intestinal preparations was significantly augmented. Neurotoxin inhibited the secretory response to luminal but not serosal antigen. Immunophysiological stimulation by wPT was still evident 8 mo postsensitization. Our studies indicate that pertussis toxin causes long-lasting hypersensitivity to coadministered antigens, involving increased production of reaginic antibodies, hyperplasia of mucosal mast cells, and enhanced neurally mediated uptake of antigen across the intestinal epithelium. These findings suggest a potential role for bacterial products in the development of immunophysiological reactions to ingested antigens.
Adaptive main memory compression (2006)

Applications that use large data sets frequently exhibit poor performance because the size of their working set exceeds the real memory, causing excess page faults, and ultimately exhibit thrashing behavior.

This paper describes a memory compression solution to this problem that adapts the allocation of real memory between uncompressed and compressed pages and also manages fragmentation without user involvement. The system manages its resources dynamically on the basis of the varying demands of each application and also on the situational requirements that are data dependent. The technique used to localize page fragments in the compressed area allows the system to reclaim or add space easily if it is advisable to shrink or grow the size of the compressed area.

The design is implemented in Linux, runs on both 32- bit and 64-bit architectures, and has been demonstrated to work in practice under complex workload conditions and memory pressure. The benefits from our approach depend on the relationship between the size of the compressed area, the application's compression ratio, and the access pattern of the application. For a range of benchmarks and applications, the system shows an increase in performance by a factor of 1.3 to 55.
Enantioselective Synthesis of Substituted 3-Quinolyl Alkanols and Their Application to Asymmetric Autocatalysis (2004)

Enantioenriched 3-quinolyl alkanols act as asymmetric autocatalysts in the addition of diisopropylzinc to the corresponding substituted quinoline-3-carbaldehydes, to afford themselves with an amplified enantiomeric excess (ee) of up to 97%.
Anti-Mycobacterium avium SS Paratuberculosis (MAP) Therapy and Fistula Closure in Patients with Severe Crohnʼs Disease (2006)

Purpose: Crohn's disease is thought by some to be caused by Mycobacterium avium ss paratuberculosis (MAP). In clinical practice, treatment with antibiotics targeting MAP has occasionally resulted in fistula closure. In one patient, fistula closure occurred whilst on anti-MAP therapy, but only after the fistula was curetted. This unexpected healing prompted anti-MAP to be offered to Crohn's patients with fistulae, with the option to curette. The purpose of this abstract is to report fistula healing in patients with severe Crohn's disease when treated with anti-MAP and optional curetting. Methods: This was a retrospective review of 13 patients on anti-MAP therapy with fistulae arising from severe colonic Crohn's disease. Of these, only 6 (2M, 4F; 15–39y) were included, as they had a minimum of one year follow-up. Patients received rifabutin (up to 600mg/d), clofazimine (up to 100mg/d) and clarithromycin (up to 1g/d) for between 2 to 9 years. Patients started on a ramp-up dosing schedule and were reviewed to monitor progress. Results: Five patients had symptomatically active fistulae before starting anti-MAP and 1 patient developed a fistula 2 weeks after commencing treatment. Several patients had more than one type of fistula throughout treatment. Six peri-anal fistulae, 2 recto-vaginal fistulae and 1 ano-vaginal fistula were reported. Four of the 6 patients reviewed (66.6%) achieved complete fistula healing whilst on anti-MAP. Five out of 6 patients had been curetted. Curetting was performed between 2 months and 5 years (mean = 18.4 months) after fistulae had opened. Of the patients curetted, 3/5 (60.0%) achieved complete fistula healing, none of which have since recurred, 1/5 (20.0%) achieved partial healing, and 1/5 (20.0%) remained active. Time to resolution of fistulae for curetted patients was between 6 to 12 months (mean = 9 months). One non-responsive patient was thought to have a complex fistula and underwent a second curette at the time of this review. Another patient's fistula closed after 1 year of anti-MAP, without curetting. However, this closure was temporary, as fistula re-opened a year after reported closure. Conclusions: 1. The administration of anti-MAP therapy combined with curetting if required, may result in partial or prolonged complete healing of fistulae for patients with severe colonic Crohn's disease. 2. This new method offers another option for Crohn's patients to heal fistulae.