gebhart/patrepeval huggingface dataset:
The Amadori Rearrangement Product as an Intermediate in the Browning Reaction (1960)

In relation to the elucidation of the mechanism of the browning reaction, isolation in crystalline form, structure and characterization of the intermediate compounds are studied. Glycine-isoglucos-amine (1-deoxy-l-glycino-D-fructose) was prepared in crystalline form by conversions of glycine-N-D-glucoside and -N-D-mannoside (both Na salt) and also from heated solLion of glycine and D-glucose. Similarly, crystalline glycine-isogalactosamine (I-deoxy-l-glycino-D-tagatose) (m.p. 165_??_168°C) was obtained by rearrangement of glycine-N-D-galactoside (Na salt) and from the browning mixture of glycine and D-galactose. Infrared studies indicated that the absorption near 3, 500 cm -1 is characteristic to isoglucosamines but not to isogalactsamine. On the infrared and periodate oxidation data, the structure of the amino acid-isoglycosamines is considered.
Interacting with Large Distributed Datasets Using Sketch (2016)

We present Sketch, a library and a distributed runtime for building interactive tools for exploring large datasets, distributed across multiple machines. We have built several applications using Sketch; here we describe a billionrow spreadsheet, and a distributed-systems performance analyzer. Sketch applications allow interactive and responsive exploration of complex distributed datasets, scaling effectively to use large computational resources.
Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated (2011)

The initial antibody response to HIV-1 is targeted to envelope (Env) gp41, and is nonneutralizing and ineffective in controlling viremia. To understand the origins and characteristics of gp41-binding antibodies produced shortly after HIV-1 transmission, we isolated and studied gp41-reactive plasma cells from subjects acutely infected with HIV-1. The frequencies of somatic mutations were relatively high in these gp41-reactive antibodies. Reverted unmutated ancestors of gp41-reactive antibodies derived from subjects acutely infected with HIV-1 frequently did not react with autologous HIV-1 Env; however, these antibodies were polyreactive and frequently bound to host or bacterial antigens. In one large clonal lineage of gp41-reactive antibodies, reactivity to HIV-1 Env was acquired only after somatic mutations. Polyreactive gp41-binding antibodies were also isolated from uninfected individuals. These data suggest that the majority of gp41-binding antibodies produced after acute HIV-1 infection are cross-reactive responses generated by stimulating memory B cells that have previously been activated by non-HIV-1 antigens.
Cancer Therapies Utilizing the Camptothecins: A Review of thein VivoLiterature (2010)

This review summarizes the in vivo assessment-preliminary, preclinical, and clinical-of chemotherapeutics derived from camptothecin or a derivative. Camptothecin is a naturally occurring, pentacyclic quinoline alkaloid that possesses high cytotoxic activity in a variety of cell lines. Major limitations of the drug, including poor solubility and hydrolysis under physiological conditions, prevent full clinical utilization. Camptothecin remains at equilibrium in an active lactone form and inactive hydrolyzed carboxylate form. The active lactone binds to DNA topoisomerase I cleavage complex, believed to be the single site of activity. Binding inhibits DNA religation, resulting in apoptosis. A series of small molecule camptothecin derivatives have been developed that increase solubility, lactone stability and bioavailability to varying levels of success. A number of macromolecular agents have also been described wherein camptothecin(s) are covalently appended or noncovalently associated with the goal of improving solubility and lactone stability, while taking advantage of the tumor physiology to deliver larger doses of drug to the tumor with lower systemic toxicity. With the increasing interest in drug delivery and polymer therapeutics, additional constructs are anticipated. The goal of this review is to summarize the relevant literature for others interested in the field of camptothecin-based therapeutics, specifically in the context of biodistribution, dosing regimens, and pharmacokinetics with the desire of providing a useful source of comparative data. To this end, only constructs where in vivo data is available are reported. The review includes published reports in English through mid-2009.
Transcellular Transport of Organic Anions Across a Double-transfected Madin-Darby Canine Kidney II Cell Monolayer Expressing Both Human Organic Anion-transporting Polypeptide (OATP2/SLC21A6) and Multidrug Resistance-associated Protein 2 (MRP2/ABCC2) (2002)

Human organic anion transporting polypeptide 2 (OATP2/SLC21A6) and multidrug resistance-associated protein 2 (MRP2/ABCC2) play important roles in the vectorial transport of organic anions across hepatocytes. In the present study, we have established a double-transfected Madin-Darby canine kidney (MDCK II) cell monolayer, which expresses both OATP2 and MRP2 on basal and apical membranes, respectively. The basal-to-apical transport of 17 beta estradiol 17 beta-d-glucuronide (E(2)17 beta G), pravastatin, and leukotriene C(4) (LTC(4)), which are substrates of OATP2 and MRP2, was significantly higher than that in the opposite direction in the double-transfected cells. Such vectorial transport was also observed for taurolithocholate sulfate, which is transported by rat oatp1 and Mrp2. The K(m) values of E(2)17 beta G and pravastatin for the basal-to-apical flux were 27.9 and 24.3 microm, respectively, which were comparable with those reported for OATP2. Moreover, the MRP2-mediated export of E(2)17 beta G across the apical membrane was not saturated. In contrast, basal-to-apical transport of estrone-3-sulfate and dehydroepiandrosterone sulfate, which are significantly transported by OATP2, but not by MRP2, was not stimulated by MRP2 expression. The double-transfected MDCK II monolayer expressing both OATP2 and MRP2 may be used to analyze the hepatic vectorial transport of organic anions and to screen the transport profiles of new drug candidates.
Applications of dioxetane chemiluminescent probes to molecular biology (1990)

DNA probes and synthetic oligonucleotides in general present one of the key tools in modern molecular biology research and increasingly also in commercial applications. Along with the many applications that have been developed for and with DNA probes, faster and more sensitive detection methods are being developed. One of the most promising recent developments presents a method based on enzymatically triggered chemiluminescence. Details of this chemistry along with applications in molecular biology and immunology will be discussed and compared to conventional methods.
Alteration of coenzyme specificity of malate dehydrogenase from Thermus flavus by site-directed mutagenesis. (1993)

On the basis of the crystal structure of the NAD-dependent cytoplasmic malate dehydrogenase (MDH) and its alignment with NADP-dependent counterparts, the loop region between beta-strand B and alpha-helix C in the dinucleotide-binding fold was predicted as a principal determinant for the coenzyme specificity. Two mutants, EX7 and EX3, of NAD-dependent MDH from Thermus flavus were constructed. In the EX7 mutant, the seven loop amino acids in positions 41-47, Glu-Ile-Pro-Gln-Ala-Met-Lys, were replaced by the corresponding loop residues in the NADP-dependent MDH from chloroplasts, Gly-Ser-Glu-Arg-Ser-Phe-Gln. In the EX3 mutant, Glu-41, Ile-42, and Ala-45 were substituted with the corresponding 3 amino acids in the NADP-dependent chloroplast MDH. In both mutations the coenzyme specificity was altered from NAD to NADP. Especially, the EX7 mutation resulted in a more than 1000-fold improvement in overall catalytic efficiency with NADPH and a 600-fold decrease in the efficiency with NADH as cofactors. Consequently, EX7 mutant was 132 times more efficient with NADPH than NADH without a large decrease in turnover number.
Epirubicin: a review of the pharmacology, clinical activity, and adverse effects of an adriamycin analogue. (1986)

Epirubicin (4'-epidoxorubicin) is an antineoplastic agent derived from doxorubicin. The compounds differ in the configuration of the hydroxyl group at the 4' position. Epirubicin, like doxorubicin, exerts its antitumor effects by interference with the synthesis and function of DNA and is most active during the S phase of the cell cycle. Epirubicin is administered by intravenous (IV) injection. It is metabolized by the liver and primarily eliminated in the bile. About 10% of the drug is eliminated in the urine. Dosage adjustments are recommended for patients with liver metastases or elevated liver function tests. The elimination half-life of epirubicin is 30 to 40 hours. Clinical studies indicate activity in breast cancer, non-Hodgkin's lymphomas, ovarian cancer, soft-tissue sarcomas, and pancreatic cancer. There is also evidence of activity against gastric cancer, small-cell lung cancer, and acute leukemia. Epirubicin has limited activity as a single agent against head and neck tumors or non-small-cell lung cancer, but may be beneficial in combination with other agents. The overall activity of epirubicin appears to be comparable with that of doxorubicin. However, more studies are needed to define its role in combination chemotherapeutic regimens. The acute dose-limiting toxicity of epirubicin is myelosuppression. Nausea, vomiting, and alopecia are also common. Epirubicin may cause transient cardiac arrhythmias and alterations of the electrocardiogram. Chronic therapy is limited, but available data indicate that epirubicin can be administered in higher cumulative doses than doxorubicin before cardiotoxicity limits further therapy.
Ironie as sleutel tot die verstaan van Psalm 14 (1995)

Irony as key to the interpretation of Psalm 14. The Gattung of a psalm is generally still regarded as the key to its interpretation. Since Psalm 14 shows relatedness to a number of different genres, inter alia to wisdom literature and prophecy, there is little or no consensus on how it should be interpreted. It is argued in this paper that the textual strategy of a poem such as Psalm 14 should be regarded as the key to its interpretation rather than a genre classification. Through a poetic analysis of Psalm 14 it is shown that irony plays such a key role in the psalm. Cognizance of this feature of the psalm focusses attention on its coherence and unity and opens up a new avenue of understanding.
Vaccination against autoimmune mouse diabetes with a T-cell epitope of the human 65-kDa heat shock protein. (1991)

Insulin-dependent diabetes mellitus is caused by autoimmune destruction of the insulin-producing beta cells resident in the pancreatic islets. We recently discovered that the pathogenesis of diabetes in NOD strain mice was associated with T-cell reactivity to an antigen cross-reactive with a mycobacterial 65-kDa heat shock protein. To identify peptide epitopes critical to the insulin-dependent diabetes mellitus of NOD mice, we studied the specificities of helper T-cell clones capable of causing hyperglycemia and diabetes. We now report the identification of a functionally important peptide within the sequence of the human variant of the 65-kDa heat shock protein molecule. T-cell clones recognizing this peptide mediate insulitis and hyperglycemia. Alternatively, the T cells can be attenuated and used as therapeutic T-cell vaccines to abort the diabetogenic process. Moreover, administration of the peptide itself to NOD mice can also down-regulate immunity to the 65-kDa heat shock protein and prevent the development of diabetes. Thus, T-cell vaccination and specific peptide therapy are feasible in spontaneous autoimmune diabetes.
Incidence and Natural History of Cytomegalovirus Disease in Patients with Advanced Human Immunodeficiency Virus Disease Treated with Zidovudine (1992)

Data were analyzed from a multicenter observational cohort study of 1002 persons with AIDS or AIDS-related complex (ARC) and total CD4 cell count < 0.25 x 10(9)/L treated with zidovudine between April 1987 and April 1988. Cytomegalovirus (CMV) disease developed in 109 patients (10.9%), with a 2-year actuarial risk of 15%. Manifestations included retinitis (93 patients), esophagitis (10), colitis (8), gastritis (1), hepatitis (1), and encephalitis (1). The probability of CMV disease at 2 years for patients with initial counts < 0.1 x 10(9)/L was 21.4%, compared with 10.3% for patients with initial counts > or = 0.1 x 10(9)/L (P < .001). By proportional hazards analysis, baseline CD4 cell count < 0.1 x 10(9)/L, enrollment diagnosis of AIDS, and homosexuality were significantly associated with subsequently developing CMV disease. Median survival after diagnosis of CMV disease was 173 days, and CMV was an independent predictor of death. CMV contributes to AIDS-related morbidity and mortality. As new anti-CMV drugs become available, prophylaxis should be targeted at individuals with CD4 cell counts < 0.1 x 10(9)/L.
Structure-Based Design of Transcription Factors (1995)

Computer modeling suggested that transcription factors with novel sequence specificities could be designed by combining known DNA binding domains. This structure-based strategy was tested by construction of a fusion protein, ZFHD1, that contained zinc fingers 1 and 2 from Zif268, a short polypeptide linker, and the homeodomain from Oct-1. The fusion protein bound optimally to a sequence containing adjacent homeodomain (TAATTA) and zinc finger (NGGGNG) subsites. When fused to an activation domain, ZFHD1 regulated promoter activity in vivo in a sequence-specific manner. Analysis of known protein-DNA complexes suggests that many other DNA binding proteins could be designed in a similar fashion.
Microencapsulated Hepatocytes: an in Vitro and in Vivo Study (1987)

Using a modified alginate-polylysine membrane, we have successfully encapsulated rat hepatocytes with little loss of viability. Urea and albumin release from encapsulated liver cells was comparable to that from non-encapsulated cells during the first 4 days in culture. Histological studies also showed that more than 50% of the encapsulated hepatocytes remained viable 35 days after implantation in the peritoneal cavity of both normal rats and rats with galactosamine induced fulminant hepatic failure. Transplantation of microencapsulated hepatocytes provides a potential clinical treatment for liver failure.
Regulatory T Cells Induced by 1α,25-Dihydroxyvitamin D3 and Mycophenolate Mofetil Treatment Mediate Transplantation Tolerance (2001)

1alpha,25-dihydroxyvitamin D3, the active form of vitamin D3, and mycophenolate mofetil, a selective inhibitor of T and B cell proliferation, modulate APC function and induce dendritic cells (DCs) with a tolerogenic phenotype. Here we show that a short treatment with these agents induces tolerance to fully mismatched mouse islet allografts that is stable to challenge with donor-type spleen cells and allows acceptance of donor-type vascularized heart grafts. Peritransplant macrophages and DCs from tolerant mice express down-regulated CD40, CD80, and CD86 costimulatory molecules. In addition, DCs from the graft area of tolerant mice secrete, upon stimulation with CD4+ cells, 10-fold lower levels of IL-12 compared with DCs from acutely rejecting mice, and induce a CD4+ T cell response characterized by selective abrogation of IFN-gamma production. CD4+ but not CD8+ or class II+ cells from tolerant mice, transferred into naive syngeneic recipients, prevent rejection of donor-type islet grafts. Graft acceptance is associated with impaired development of IFN-gamma-producing type 1 CD4+ and CD8+ cells and an increased percentage of CD4+CD25+ regulatory cells expressing CD152 in the spleen and in the transplant-draining lymph node. Transfer of CD4+CD25+ cells from tolerant but not naive mice protects 100% of the syngeneic recipients from islet allograft rejection. These results demonstrate that a short treatment with immunosuppressive agents, such as 1alpha,25-dihydroxyvitamin D3/mycophenolate mofetil, induces tolerance to islet allografts associated with an increased frequency of CD4+CD25+ regulatory cells that can adoptively transfer transplantation tolerance.
Cytokine signal transduction and the JAK family of protein tyrosine kinases (1994)

Cytokine receptors fall into two basic classes: those with their own intrinsic protein tyrosine kinase (PTK) domain, and those lacking a PTK domain. Nonetheless, PTK activity plays a fundamental role in the signal transduction processes lying downstream of both classes of receptor. It now seems likely that many of those cytokine receptors that lack their own PTK domain use members of the JAK family of PTKs to propagate their intracellular signals. Moreover, the involvement of the JAK kinases in a newly defined pathway which links membrane receptors directly to the activation of nuclear genes, via latent cytoplasmic transcription factors known as STATs (for Signal Transducers and Activators of Transcription), appears to be a theme common to cytokine receptors of both classes.
Rectification of Ionic Current in a Nanofluidic Diode (2007)

We demonstrate rectification of ionic transport in a nanofluidic diode fabricated by introducing a surface charge discontinuity in a nanofluidic channel. Device current-voltage (I-V) characteristics agree qualitatively with a one-dimensional model at moderate to high ionic concentrations. This study illustrates ionic flow control using surface charge patterning in nanofluidic channels under high bias voltages.
20 In Vitro Selection of Functional RNA Sequences (1993)

A critical but seldom articulated assumption common to models of the evolution of an RNA world is that prebiotically synthesized polynucleotides of random sequence were the source of the first self-replicating molecules. However, the probability of finding functional molecules of any sort in a mixture of random sequences is unknown. A high probability would favor the origin of life, whereas a very low probability would make the origin of life more difficult. To address this problem, we developed an iterative method for the isolation of nucleic acid sequences with specific ligand-binding or catalytic properties from very large pools of random sequences. The key to this method is the use of cycles of in vitro selection to enrich the pool for RNA species with the desired properties, followed by amplification of the selected molecules. This cycle of in vitro selection and amplification can be repeated as many times as necessary to isolate a population of molecules composed entirely of binding species, which can then be cloned and characterized individually. We used cycles of affinity chromatography followed by polymerase chain reaction (PCR) amplification to isolate ligand-binding RNAs and DNAs. We found that roughly 10 −10 of the original sequences in our random pools were able to bind to organic dyes and other small ligands, including amino acids. If these results can be extrapolated to the binding of the transition states of chemical transformations, it is likely that a wide range of RNA catalysts might be found in pools of random sequence RNA molecules...
Subcutaneous interleukin-2, interferon alfa-2a, and continuous infusion of fluorouracil in metastatic renal cell carcinoma: a multicenter phase II trial. Groupe Français d'Immunothérapie. (1998)

This regimen of IL-2, IFNalpha, and 5-FU in patients with metastatic renal cell carcinoma was ineffective. The results raise the question of the dose and schedule of subcutaneous cytokines that must be used in metastatic renal carcinoma.
Fast Approximation Algorithms for the Knapsack and Sum of Subset Problems (1975)

Given a positive integer M and n pairs of positive integers (p~, cD, , (p. , c.), maximize the sum~ ~p~ subject to the constramts~ ~c, < M and ~, = 0 or 1 This is the well-known 0/1 knapsack problem An algorithm is presented which finds for any 0 < e < 1 an approximate solution P satisfying (P* -P)/P* < ~, where P* is the desired optimal sum Moreover, for any fixed e, the algorithm has time complexity 0(n log n) and space complexity O(n) Modification of the algorithm for the unbounded knapsack problem where the ~,'s can be any nonnegative integer results in a O(n) computing time A hnear-time algorithm is also obtained for a special class of 0/1 knapsack problems having the property that p,/c, is the same for all 1 < z < n KEY WORDS AND PHRASES.
Pseudoknots: RNA Structures with Diverse Functions (2005)

Just as proteins form distinct structural motifs, certain structures are commonly adopted by RNA molecules. Amongst the most prevalent is the RNA pseudoknot.
Ginseng Saponins: Influence on Neurotransmitter Uptake in Rat Brain Synaptosomes (1985)

The total ginsenoside (n-butanol extract) fraction inhibited the uptake of radioactive γ-aminobutyrate (GABA), glutamate (Glu), dopamine (DA), noradrenaline (NA), serotonin (5-HT), but not the uptake of 2-deoxy-D-glucose (2-DG) and leucine (Leu) into rat brain Synaptosomes. Among the ginsenoside fractions investigated, Fraction III which contains mainly Rd was most effective in reducing the uptake of neurotransmitters. The inhibition was in the order of GABA = NA > DA > Glu > 5-HT, and this effect was concentration-dependent. This inhibitory effect appears to be specific as this fraction, at several concentrations, failed to influence the uptake of 2-DG and Leu significantly. Similar studies indicated that ginsenoside Rc could affect neurotransmitter uptake specifically as well. Since the GABA uptake was most sensitive to the inhibitory action of these ginsenosides, it is postulated that ginseng may exert its action(s) in the central nervous system by affecting the removal of neurotransmitter substances in synaptic regions and that the GABA-nergic neurons may be one of the major sites of action.
DNA Repair Gene Polymorphisms and Risk of Pancreatic Cancer (2009)

These observations suggest that genetic variations in DNA repair may act alone or in concert with other risk factors on modifying a patient's risk for pancreatic cancer.
An Exact Correction to the “Cheng-Prusoff” Correction (1988)

The use of graphical estimation techniques in pharmacology is well entrenched, yet can sometimes lead to confusion and errors. The widely used Cheng-Prusoff correction for obtaining the inhibition constant Ki from the graphical mid point or ED50 of a displacement or inhibition curve is not exact, contrary to popular belief. We show that under many commonly used experimental conditions, the Cheng-Prusoff rule can lead to a substantial 3- to 6-fold or larger error in the estimate of Ki. Surprisingly, an explicit, relatively simple exact correction rule is available. We derive this rule and show the conditions under which its use is required.
On the performance of Eigen based Beamforming in LTE-Advanced (2009)

For the channel reciprocity property, Eigen-based Beamforming (EBB) has been attracting more and more attentions in LTE-Advanced system. In this paper, single user beamforming with rank adaptation and multi-user beamforming using block diagonal algorithm are studied to make full use of the spatial multiplexing gain. In addition, power control and power allocation are discussed to improve the performance. At last, a novel smart power allocation and power control scheme had been proposed for multi-user beamforming usage. The simulation results showed that the proposed schemes have got significant gain over traditional methods. All the results are provided using dynamic system level simulator based on LTE-Advanced.