gebhart/patrepeval huggingface dataset:
Utilization of Lipophilic Ionic Additives in Liquid Polymer Film Optodes for Selective Anion Activity Measurements (1997)

Lipophilic anionic and cationic additives are investigated as components for use in liquid polymer film-based optodes. These ionic additives are known to strongly influence the selectivity behavior of anion-selective electrodes. They also make it possible to construct ion coextraction optodes that can measure anion activities. Theoretical, thermodynamic anion-optode equilibria formalisms were derived to help understand the influence these additives have on the overall optode response and on the selectivity behavior. Neutral and charged anion carrier film configurations are described and tested for two anion ionophores with known modes of action, ruthenium(II) octaethylporphyrin and a vitamin B12 derivative (cyanoaquacobyrinic acid heptakis(2-phenylethyl ester)). These film configurations were further tested using a less well-understood ionophore, indium(III) octaethylporphyrin. Notable is the indium(III) octaethylporphyrin optode, which has a dynamic range appropriate for physiological measurements of chloride at neutral pH values. Also of interest is the optode with the vitamin B12 derivative ionophore, which has a dynamic range appropriate for some physiological measurements of nitrite at neutral pH values.
The relationship between graft tensioning and the anterior—posterior laxity in the anterior cruciate ligament reconstructed goat knee (2001)

The tension applied to the anterior cruciate ligament (ACL) graft at time of fixation is thought to influence graft healing, knee kinematics, and joint contact forces; however, the optimal tensioning procedure remains unclear. An animal model provides a means by which the effect of graft tensioning on healing can be studied. Prior to using the model, the relationship between graft tensioning and knee kinematics at time of surgery should be established. Our objective was to explore the relationship between graft tensioning and anterior-posterior (A-P) laxity of the reconstructed goat knee. Eight cadaver knees were tested. The A-P laxity values of the intact knee were measured with the knee at 30 degrees, 60 degrees. and 90 degrees flexion. The ACL was then severed and the laxity measurements were repeated. The ACL was reconstructed using a bone-patellar tendon-bone autograft. The laxity measurements were repeated for nine different tensioning conditions; three tension magnitudes (30, 60, and 90 N), each applied with the knee at three angles (30 degrees, 60 degrees and 90 degrees). Both graft tension and the knee angle at which it was applied produced significant changes on A-P laxity values. An increase in tension reduced laxity values. A tension level of 60 N applied with the knee flexed to 30 degrees was the best combination for restoring normal A-P laxity values at all knee angles tested.
Tau – an inhibitor of deacetylase HDAC6 function (2009)

Analysis of brain microtubule protein from patients with Alzheimer's disease showed decreased alpha tubulin levels along with increased acetylation of the alpha tubulin subunit, mainly in those microtubules from neurons containing neurofibrillary tau pathology. To determine the relationship of tau protein and increased tubulin acetylation, we studied the effect of tau on the acetylation-deacetylation of tubulin. Our results indicate that tau binds to the tubulin-deacetylase, histone deacetylase 6 (HDAC6), decreasing its activity with a consequent increase in tubulin acetylation. As expected, increased acetylation was also found in tubulin from wild-type mice compared with tubulin from mice lacking tau because of the tau-mediated inhibition of the deacetylase. In addition, we found that an excess of tau protein, as a HDAC6 inhibitor, prevents induction of autophagy by inhibiting proteasome function.
Protective Immunity of Pneumococcal Glycoconjugates (2003)

Pneumococcal polysaccharides (PSs), designated as T-cell independent type 2 (TI-2) antigens, induce poor immune responses in young children. Splenic marginal zone B cells, associated with CD21, CD19 and C3d, play an important role in TI-2 antibody responses, and provide host defense against bacterial pathogens. Antibody response, avidity, and opsonophagocytic activity of antisera were examined in mice immunized with type 9V PS conjugated to inactivated pneulmolysin (Ply) or to autolysin (Aly). Compared to mice given 9V PS alone, serum IgG and IgM concentrations against the 9V PS were higher in mice immunized with conjugates. High concentrations of serum antibodies were maintained for over 12 weeks. The relative avidities of IgG and IgM antibodies and opsonophagocytic activity against 9V pneumococci were high in mice immunized with conjugates. Thus, conjugate vaccines can induce high as well as long duration of antibody response and effective functional activity. In another study, mice received intranasal immunization with type 9V conjugate or 9V PS. These animals produced 9V PS IgG and IgA antibodies in their serum, spleen, intestine, lung, Peyer's patch and fecal extract samples. Mice immunized with these glycoconjugates exhibited opsonophagocytic activity and rapid bacterial clearance from blood and provided homologous and cross-protection against challenge with virulent pneumococci. These results indicate that intranasal immunization with glycoconjugate vaccines may serve as an alternative and convenient approach for prevention of pneumococcal infection.
A Rapid Method for Simultaneous Detection of Phenotypic Resistance to Inhibitors of Protease and Reverse Transcriptase in Recombinant Human Immunodeficiency Virus Type 1 Isolates from Patients Treated with Antiretroviral Drugs (1998)

Combination therapy with protease (PR) and reverse transcriptase (RT) inhibitors can efficiently suppress human immunodeficiency virus (HIV) replication, but the emergence of drug-resistant variants correlates strongly with therapeutic failure. Here we describe a new method for high-throughput analysis of clinical samples that permits the simultaneous detection of HIV type 1 (HIV-1) phenotypic resistance to both RT and PR inhibitors by means of recombinant virus assay technology. HIV-1 RNA is extracted from plasma samples, and a 2.2-kb fragment containing the entire HIV-1 PR- and RT-coding sequence is amplified by nested reverse transcription-PCR. The pool of PR-RT-coding sequences is then cotransfected into CD4+ T lymphocytes (MT4) with the pGEMT3deltaPRT plasmid from which most of the PR (codons 10 to 99) and RT (codons 1 to 482) sequences are deleted. Homologous recombination leads to the generation of chimeric viruses containing PR- and RT-coding sequences derived from HIV-1 RNA in plasma. The susceptibilities of the chimeric viruses to all currently available RT and/or PR inhibitors is determined by an MT4 cell-3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-based cell viability assay in an automated system that allows high sample throughput. The profile of resistance to all RT and PR inhibitors is displayed graphically in a single PR-RT-Antivirogram. This assay system facilitates the rapid large-scale phenotypic resistance determinations for all RT and PR inhibitors in one standardized assay.
Improved Chips for Sequencing by Hybridization (1991)

The SHOM method (Sequencing by Hybridization with Oligonucleotide Matrix) developed in 1988 is a new approach to nucleic acid sequencing by hybridization to an oligonucleotide matrix composed of an array of immobilized oligonucleotides. The original matrix proposed for sequencing by SHOM had to contain at least 65,536 octanucleotides. The present work describes a new family of matrices, which allows one to reduce the number of synthesized oligonucleotides 5-15 times without essentially decreasing the resolving power of the method.
Sloppy Reasoning, Misused Data (1993)

Many Kappan readers probably shared my irritation with George Will's column of September 12, in which he used Scholastic Aptitude Test (SAT) scores to prove that there is no correlation between school funding and school quality. Eight days later, however, The Herald Times (Bloomington, Indiana) carried a response to George Will from Brian Powell, and associate professor of sociology at Indiana University. With the permission of The Herald-Times, we are reprinting a slightly shortened version of Powell's column in this space. Access to the information that Powell provides will help Kappan readers push the mass media to stick to the facts and to keep the record straight with regard to the performance of American education. FOR someone so concerned about the quality of American public schools, George Will should do his homework. In a recent column, Will attempts to discount the argument that public expenditures for schooling are linked to educational productivity. Using the SAT as a barometer of the success of American schools, he notes that the five states with the highest SAT scores -- Iowa, North Dakota, South Dakota, Utah, and Minnesota -- do not rank especially high in per-pupil expenditures. He also implies that pupil/teacher ratios are not associated with SAT scores, making reference to Utah, which has the fourth-highest SAT score, the lowest per-pupil expenditure, and the highest pupil/teacher ratio. (Interestingly, Will conveniently ignores the fact that three of the other four states he lauds have among the lowest pupil/teacher ratios in the United States.) In his zeal to prove his point, Will apparently is willing to ignore some facts. For example, when comparing per-pupil expenditures and teacher salaries, he forgets to mention that the cost of living varies considerably across states -- and that one reason teachers may earn more in New Jersey than in North Dakota is that it is more expensive to live in the former. Nor does he indicate that in North Dakota the average income of teachers is higher than the average household income, whereas New Jersey teachers fare worse financially than the average household. Will is troubled that public expenditures have soared in the past 20 years. He overlooks the fact that a large portion of the increase has been for programs for the handicapped. But perhaps the most glaring error in his reasoning has to do with SAT scores. While Will is correct that Iowa, North Dakota, South Dakota, Utah, and Minnesota have the highest SAT scores, he neglects to provide an equally important piece of information: very few students in those states take the SAT. According to the College Board, more than 40% of high school seniors in the U.S. take the SAT. By contrast, only 4% of graduating seniors in Utah take the SAT, making Utah the state with the lowest participation rate. …
Free‐solution interaction assay of carbonic anhydrase to its inhibitors using back‐scattering interferometry (2010)

Back-scattering interferometry (BSI) is a label-free, free-solution, small-volume technique used for characterizing binding interactions, which is also relevant to a growing number of biosensing applications including drug discovery. Here, we use BSI to characterize the interaction of carbonic anhydrase enzyme II with five well-known carbonic anhydrase enzyme II inhibitors (± sulpiride, sulfanilamide, benzene sulfonamide, dansylamide, and acetazolamide) in the presence of DMSO. Dissociation constants calculated for each interaction were consistent with literature values previously obtained using surface plasmon resonance and fluorescence-based competition assays. Results demonstrate the potential of BSI as a drug-screening tool which is fully compatible with DMSO and does not require immobilization or labeling, therefore allowing binding interactions to be characterized in the native state. BSI has the potential for reducing labor costs, sample consumption, and assay time while providing enhanced reliability over existing techniques.
Ligand binding to heme proteins. An evaluation of distal effects. (1983)

The O2, CO, and alkyl isocyanide-binding properties of a variety of vertebrate and invertebrate heme proteins have been compared in detail to those of protoheme mono-3-(1-imidazoyl)-propylamide monomethyl ester in aqueous suspensions of soap micelles. The proteins examined include: cytochrome P-450cam from Pseudomonas putida, beef heart cytochrome c oxidase, yeast cytochrome c peroxidase, alpha and beta subunits of human hemoglobin, sheep hemoglobin, carp hemoglobin, sperm whale myoglobin, horse heart myoglobin, a monomeric hemoglobin from Glycera dibranchiata, erythrocruorin from Chironomusthummii, soybean leghemoglobin, and several hemoglobins that lack distal histidines. The smallest bimolecular rates were observed for cytochrome P-450 containing bound camphor, cytochrome c oxidase, and cytochrome c peroxidase. In the case of P-450, the extremely low isonitrile binding rates (approximately 1 M-1 S-1 at 20 degrees C) are due to steric exclusion by bound camphor molecules. For the oxidase and peroxidase, inhibition of CO and isonitrile binding appears to be due to the polar nature of the active sites. In the cases of animal hemoglobins and myoglobins, the sixth coordination positions appear to be designed to accommodate diatomic molecules with no steric hindrance by distal protein residues. Protein resistance to the diffusion of CO and O2 does not limit the observed association rate constants. In contrast, ligands containing three or more atoms are sterically hindered both in their final bound positions and during diffusion to the active site. The magnitude of this hindrance (greater than or equal to 2 kcal/mol) exhibits a complex dependence on ligand size and shape. The most important protein residue appears to be His E7. In addition to restricting the size of the sixth coordination position, the distal histidine is also capable of forming a hydrogen bond with bound oxygen molecules. The strength of this hydrogen bond was estimated to be -2 and -1 kcal/mol for mammalian myoglobins and hemoglobins, respectively, and accounts for the smaller CO/O2 partition constants (M values) observed for these proteins in comparison to the constants observed for pentacoordinate model heme compounds.
Increased frequency of interleukin 2-responsive T cells specific for myelin basic protein and proteolipid protein in peripheral blood and cerebrospinal fluid of patients with multiple sclerosis. (1994)

Equal numbers of CD4+ T cells recognizing myelin basic protein (MBP) and proteolipid protein (PLP) are found in the circulation of normal individuals and multiple sclerosis (MS) patients. We hypothesized that if myelin-reactive T cells are critical for the pathogenesis of MS, they would exist in a different state of activation as compared with myelin-reactive T cells cloned from the blood of normal individuals. This was investigated in a total of 62 subjects with definitive MS. While there were no differences in the frequencies of MBP- and PLP-reactive T cells after primary antigen stimulation, the frequency of MBP or PLP but not tetanus toxoid-reactive T cells generated after primary recombinant interleukin (rIL-2) stimulation was significantly higher in MS patients as compared with control individuals. Primary rIL-2-stimulated MBP-reactive T cell lines were CD4+ and recognized MBP epitopes 84-102 and 143-168 similar to MBP-reactive T cell lines generated with primary MBP stimulation. In the cerebrospinal fluid (CSF) of MS patients, MBP-reactive T cells generated with primary rIL-2 stimulation accounted for 7% of the IL-2-responsive cells, greater than 10-fold higher than paired blood samples, and these T cells also selectively recognized MBP peptides 84-102 and 143-168. In striking contrast, MBP-reactive T cells were not detected in CSF obtained from patients with other neurologic diseases. These results provide definitive in vitro evidence of an absolute difference in the activation state of myelin-reactive T cells in the central nervous system of patients with MS and provide evidence of a pathogenic role of autoreactive T cells in the disease.
Cephalosporins having a heterocyclic catechol in the C3 side chain. II. Improvement of pharmacokinetic profile. (1993)

7-[(Z)-2-(2-Aminothiazol-4-yl)-2-methoxy-(or hydroxy)-iminoacetamido]-3- [propen-1-yl]-cephalosporins having a variety of heterocyclic catechol in 3-position of the propenyl group were synthesized. Among them, 6,7-dihydroxyisoquinoline derivatives, 2a and 2b, showed very high and prolonged blood levels after intramuscular administration to mice and higher in vivo antibacterial activity than expected from their in vitro activity. The former cephalosporin (2a) gave well-balanced in vitro and in vivo antibacterial spectra including anti-methicillin-resistant Staphylococcus aureus (MRSA) activity. The latter cephalosporin (2b) also showed good in vitro and in vivo activities against Gram-positive bacteria, especially against S. aureus A15036, a strain of MRSA, the in vivo activity being comparable to vancomycin but was lacking in anti-pseudomonal activity.
Gadolinium‐labeled liposomes containing various amphiphilic Gd‐DTPA derivatives: Targeted MRI contrast enhancement agents for the liver (1991)

Unique paramagnetic liposomal contrast agents were synthesized and utilized for selective augmentation of T1 MR imaging of the livers of normal Balb/c mice. A series of amphipathic gadolinium complexes, which mimic phospholipids, was incorporated into the lamella of small unilamellar liposomes such that they become an integral part of its surface. The amphipathic complexing agents consisted of DTPA reagents in which two stearyl chains are attached via amide, ester, and thioester linkages. The in vitro stability and the in vivo lifetimes of the new amphipathic agents were dependent on the method used to attach the long-chain alkyl groups.
Cellular mechanisms of heparinase III protection in rat traumatic shock (1998)

Pentobarbital-anesthetized rats subjected to traumatic shock developed a shock state characterized by marked hypotension to 65-70 mmHg, a survival time of 88 +/- 13 min, significant increases in ileal myeloperoxidase activity (P < 0.01), and severe endothelial dysfunction as evidenced by a significant (P < 0.01) decrease in vasorelaxation to endothelium-dependent dilators. Treatment with heparinase III (45 microg . kg-1 . min-1) 10 min posttrauma prolonged survival time to 223 +/- 19 min (P < 0.001), significantly attenuated ileal myeloperoxidase activity (P < 0.01), and significantly preserved endothelial function (P < 0.05). Intravital microscopy of the rat mesentery showed that infusion of heparinase III (45-67 microg . kg-1 . min-1) significantly (P < 0.01) attenuated both leukocyte rolling and adherence in the rat mesenteric microvasculature in response to NG-nitro-L-arginine methyl ester stimulation. Immunohistochemical localization of surface-expressed P-selectin on mesenteric venules showed that heparinase III infusion at 45-67 microg . kg-1 . min-1 significantly (P < 0.05) attenuated the increase in surface P-selectin expression. The beneficial effects of heparinase III are mediated at least in part by attenuating leukocyte-endothelial cell interactions via a P-selectin-dependent mechanism.
Synthesis of Degradable Miktoarm Star Copolymers via Atom Transfer Radical Polymerization (2005)

Both nondegradable and degradable miktoarm star copolymers were synthesized via ATRP using the “in−out” method. The synthesis consisted of three steps: synthesis of a linear macroinitiator (MI) using the first monomer, a core-forming reaction with a divinyl compound, and then further chain extension with the second monomer. Various characterization methods, including GPC, NMR, and GC, were used to analyze the initial star polymers and to identify the optimal experimental conditions for the synthesis of the multifunctional star initiators and the miktoarm star copolymers. During the synthesis of miktoarm star copolymers, both interstar and intrastar arm−arm couplings were observed. The initiating efficiency of the alkyl bromide sites in the core of the star polymers was determined by analysis of the linear block copolymers, obtained after cleavage of the degradable star and miktoarm star copolymers. The results confirmed that the initiation efficiency was reduced by the highly cross-linked star core. In the case of degradable miktoarm star copolymers, only 19% of the total Br functionality incorporated into the first star copolymer initiated the polymerization of the second monomer.
CCAAT/enhancer binding protein alpha is sufficient to initiate the 3T3-L1 adipocyte differentiation program. (1994)

Previous studies showed that CCAAT/enhancer binding protein alpha (C/EBP alpha) is required for differentiation of 3T3-L1 preadipocytes induced by exogenous hormonal agents. It was not possible to ascertain, however, whether C/EBP alpha alone is sufficient to induce differentiation because its antimitogenic activity precluded propagating 3T3-L1 cell lines that constitutively express C/EBP alpha at high levels. This problem was circumvented by using 3T3-L1 preadipocytes stably transfected with an isopropyl beta-D-thiogalactoside (IPTG)-inducible p42 C/EBP alpha expression vector system. IPTG-induced expression of the 42-kDa isoform of C/EBP alpha in preadipocytes caused expression of several endogenous adipocyte-specific genes (genes encoding the 422 adipose P2 protein, glucose transporter 4, and C/EBP alpha) and the accumulation of cytoplasmic triglyceride. Thus, C/EBP alpha is not only necessary but also is sufficient to trigger differentiation of growth-arrested 3T3-L1 preadipocytes without use of exogenous hormonal agents.
Gonadotropin-releasing hormone receptor in gynecologic tumors. Frequent expression in adenocarcinoma histologic types (1994)

Background. Gonadotropin-releasing hormone (GnRH) analogs have been used in the therapy of the endocrine-dependent cancers. The authors attempted to determine the frequency with which Gn-RH receptor (Gn-RHR) is present in gynecological cancers. Methods. Experiments were performed on gynecologic tumors that had been surgically removed and their cloned cell lines. Gn-RHR was characterized by [3H]Gn-RH binding to plasma membrane preparations. Gn-RHR messenger ribonucleic acid was determined by reverse transcription-polymerase chain reaction using oligonucleotide primers synthesized according to the published human Gn-RHR sequence. Results. High affinity binding sites with nanomolar range of Kd and Gn-RHR mRNA were detected in a high proportion (over 90%) of the specimens from endometrium (6 of 6) and endometrial carcinomas (16 of 17), myometrium (6 of 6) and myomas (4 of 5), epithelial carcinoma (21 of 23), and stromal tumors (3 of 3) of the ovary. There was no substantial Gn-RHR in cervical carcinomas or germ cell-derived tumors of the ovary. Cloned cell lines gave identical results to those obtained in their respective mother tumors. Conclusions. We detected Gn-RHR in a wide range of the carcinomas and tissues originating from the endometrium and ovary, but not in the uterine cervix or germ cell-derived tumors. The expression of Gn-RH receptor raises the possibility that Gn-RH may play a direct regulatory role in the growth of these carcinomas, and provides a possible point of attack for therapeutic approaches using Gn-RH analogs in these malignancies.