gebhart/patrepeval huggingface dataset:
Biologic Activity of Polyethylene Glycol12000–Interferon-α2b Compared with Interferon-α2b: Gene Modulatory and Antigrowth Effects in Tumor Cells (2003)

The relative activities of interferon-alpha2b (IFN-alpha2b) and polyethylene glycol(12000)-IFN-alpha2b (PEG-IFN-alpha2b) were assessed in cell culture studies using WM9 melanoma or ACHN renal cell carcinoma cell lines. Interferon-alpha2b and PEG-IFN-alpha2b had identical antiproliferative activities when tested in cell proliferation studies conducted with equivalent antiviral units of each IFN preparation. Neither IFN formulation was effective in inducing apoptosis in WM9 melanoma cells, but both increased slightly the percentage of ACHN cells undergoing apoptosis as assessed by Annexin V staining. Interferon-alpha2b and PEG-IFN-alpha2b both activated signal transducer and activator of transcription complexes, and the duration of complex activation was similar for both IFN formulations. Induction of different IFN-stimulated genes was assessed by Northern blotting and the quantitative real-time reverse transcription-coupled polymerase chain reaction (RT-PCR) in WM9 melanoma, ACHN renal cell carcinoma, U937 lymphoma, and MOLT-4 and Mono Mac 6 leukemia cell lines. Interferon-alpha2b and PEG-IFN-alpha2b had equivalent gene-modulatory activities within each of these tumor cell lines, although cell line-specific induction patterns were observed. When compared with the antiviral 50% inhibitory concentration (IC(50)) values, the dose-dependent gene expression data correlated with cell sensitivity to IFN treatment. Together, the drug comparability and cell sensitivity data suggest a predictive relation between dose, time, antiviral activity, and gene transcription effects. Therefore, although the specific activity of IFN-alpha2b is approximately three times greater than PEG-IFN-alpha2b, the two preparations have identical in vitro biologic activities when applied to cells at equivalent antiviral units.
Epigenetic dysregulation of KCa3.1 channels induces poor prognosis in lung cancer (2015)

Epigenomic changes are an important feature of malignant tumors. How tumor aggressiveness is affected by DNA methylation of specific loci is largely unexplored. In genome-wide DNA methylation analyses, we identified the KCa 3.1 channel gene (KCNN4) promoter to be hypomethylated in an aggressive non-small-cell lung carcinoma (NSCLC) cell line and in patient samples. Accordingly, KCa 3.1 expression was increased in more aggressive NSCLC cells. Both findings were strong predictors for poor prognosis in lung adenocarcinoma. Increased KCa 3.1 expression was associated with aggressive features of NSCLC cells. Proliferation and migration of pro-metastatic NSCLC cells depended on KCa 3.1 activity. Mechanistically, elevated KCa 3.1 expression hyperpolarized the membrane potential, thereby augmenting the driving force for Ca(2+) influx. KCa 3.1 blockade strongly reduced the growth of xenografted NSCLC cells in mice as measured by positron emission tomography-computed tomography. Thus, loss of DNA methylation of the KCNN4 promoter and increased KCa 3.1 channel expression and function are mechanistically linked to poor survival of NSCLC patients.
Mutation-Directed Chemical Cross-Linking of Human Immunodeficiency Virus Type 1 gp41 Oligomers (1998)

The human immunodeficiency virus type 1 transmembrane protein gp41 oligomer anchors the attachment protein, gp120, to the viral envelope and mediates viral envelope-cell membrane fusion following gp120-CD4 receptor-chemokine coreceptor binding. We have used mutation-directed chemical cross-linking with bis(sulfosuccinimidyl)suberate (BS3) to investigate the architecture of the gp41 oligomer. Treatment of gp41 with BS3 generates a ladder of four bands on sodium dodecyl sulfate-polyacrylamide gels, corresponding to monomers, dimers, trimers, and tetramers. By systematically replacing gp41 lysines with arginine and determining the mutant gp41 cross-linking pattern, we observed that gp41 N termini are cross-linked. Lysine 678, which is close to the transmembrane sequence, was readily cross-linked to Lys-678 on other monomers within the oligomeric structure. This arrangement appears to be facilitated by the close packing of membrane-anchoring sequences, since the efficiency of assembly of heterooligomers between wild-type and mutant Env proteins is improved more than twofold if the mutant contains the membrane-anchoring sequence. We also detected close contacts between Lys-596 and Lys-612 in the disulfide-bonded loop/glycan cluster of one monomer and lysines in the N-terminal amphipathic alpha-helical oligomerization domain (Lys-569 and Lys-583) and C-terminal alpha-helical sequence (Lys-650 and Lys-660) of adjacent monomers. Precursor-processing efficiency, gp120-gp41 association, soluble recombinant CD4-induced shedding of gp120 from cell surface gp41, and acquisition of gp41 ectodomain conformational antibody epitopes were unaffected by the substitutions. However, the syncytium-forming function was most dependent on the conserved Lys-569 in the N-terminal alpha-helix. These results indicate that gp160-derived gp41 expressed in mammalian cells is a tetramer and provide information about the juxtaposition of gp41 structural elements within the oligomer.
An Improved Method for the Purification of Blood Cells of Turkeys (1991)

Methods were developed to purify monocytes, heterophils, or erythrocytes from the whole blood of turkeys. After the bulk of thrombocytes was removed by centrifugation, blood was fractionated over a Ficoll-Hypaque discontinuous gradient. Five fractions were harvested separately, and two were further purified by attachment to a plastic surface and/or by lysis of erythrocytes. The monocyte fraction contained 41% +/- 1% monocytes, and the heterophil fraction contained 96% +/- 1% heterophils. The erythrocyte fraction showed a purity of 99.4% +/- 0.3%. These methods would be useful for various in vitro studies that require purified populations of blood cells.
Advances in hydrotropic solutions: An updated review (2015)

Approximately a century ago, in 1916, the term 'hydrotropy' was coined by the scientist Carl A. Neuberg to address anionic organic salts which considerably augmented the aqueous solubility of poorly soluble solutes. Currently hydrotropic solutions possess high industrial demand due to their unique features such as easy availability, good recovery, absence of fire hazards, higher separation factors without any solutes emulsification problem and eco-friendly nature. The present review takes the readers through a concise overview, geometrical features of hydrotropic agents, hypothetical mechanisms and their different advances toward drug delivery. Moreover, this review would provide an insight of the future perspectives concerned with the drug delivery and hydrotropism.
A Rating Scale for Drug-Induced Akathisia (1989)

A rating scale for drug-induced akathisia has been derived that incorporates diagnostic criteria for pseudoakathisia, and mild, moderate, and severe akathisia. It comprises items for rating the observable, restless movements which characterise the condition, the subjective awareness of restlessness, and any distress associated with the akathisia. In addition, there is an item for rating global severity. A standard examination procedure is recommended. The inter-rater reliability for the scale items (Cohen's kappa) ranged from 0.738 to 0.955. Akathisia was found in eight of 42 schizophrenic in-patients, and nine had pseudoakathisia, where the typical sense of inner restlessness was not reported.
Crystal Structure of a Group I Ribozyme Domain: Principles of RNA Packing (1996)

Group I self-splicing introns catalyze their own excision from precursor RNAs by way of a two-step transesterification reaction. The catalytic core of these ribozymes is formed by two structural domains. The 2.8-angstrom crystal structure of one of these, the P4-P6 domain of the Tetrahymena thermophila intron, is described. In the 160-nucleotide domain, a sharp bend allows stacked helices of the conserved core to pack alongside helices of an adjacent region. Two specific long-range interactions clamp the two halves of the domain together: a two-Mg2+-coordinated adenosine-rich corkscrew plugs into the minor groove of a helix, and a GAAA hairpin loop binds to a conserved 11-nucleotide internal loop. Metal- and ribose-mediated backbone contacts further stabilize the close side-by-side helical packing. The structure indicates the extent of RNA packing required for the function of large ribozymes, the spliceosome, and the ribosome.
Altered expression of MUC2 and MUC5AC in progression of colorectal carcinoma (2010)

Alterations in MUC expression occur during colorectal tumorigenesis. The transformation process in MC and SRCC may be different from that in the traditional adenoma-carcinoma sequence.
Chemoimmunotherapy Reinduction With Epratuzumab in Children With Acute Lymphoblastic Leukemia in Marrow Relapse: A Children's Oncology Group Pilot Study (2008)

Treatment with epratuzumab plus standard reinduction chemotherapy is feasible and acceptably tolerated in children with relapsed CD22-positive ALL. CD22 targeting was efficient, and the majority of patients achieved favorable early responses.
HLA-G expression is associated with an unfavorable outcome and immunodeficiency in chronic lymphocytic leukemia (2004)

The human leukocyte antigen G (HLA-G) molecule exhibits limited tissue distribution and exerts multiple immunoregulatory functions. Recent studies indicate an ectopic up-regulation in tumor cells that may favor their escape from antitumor immune responses. The role of HLA-G in B-cell chronic lymphocytic leukemia (B-CLL) has not been defined. HLA-G expression was studied retrospectively in circulating B-CLL cells from 47 patients by flow cytometry using the anti-HLA-E specific monoclonal antibody MEM/G9. The proportion of leukemic cells expressing HLA-G varied from 1% to 54%. Patients with 23% or fewer HLA-G-positive cells (according to receiver operating characteristics [ROC] analysis; designated as HLA-G-negative group) had a significantly longer progression-free survival (PFS) time than patients with more than 23% positive cells (median PFS: 120 versus 23 months; P = .0001). In multivariate analysis, HLA-G expression (hazard ratio: 4.8; P = .002) was an even better independent prognostic factor than the zeta-associated protein 70 (ZAP-70) or CD38 status. Humoral and cellular immunosuppression were significantly more prominent in the HLA-G-positive compared with the HLA-G-negative patient group. In B-CLL, the level of HLA-G expression is correlated with the degree of immunosuppression and prognosis. HLA-G may contribute to the impairment of immune responses against tumor cells and infections. Thus, these findings need to be confirmed in a prospective study.
Some characteristics of a porcine retrovirus from a cell line derived from swine malignant lymphomas (1985)

The characteristics of the enzyme of porcine retrovirus from a cell line derived from swine malignant lymphomas fit with the template specificity and divalent cation requirement for reverse transcriptase. It is further found that the virus particle contains a high molecular mass 70 S RNA as viral genome.
Mass Spectrometric Quantitation of Peptides and Proteins Using Stable Isotope Standards and Capture by Anti-Peptide Antibodies (SISCAPA) (2004)

A method (denoted SISCAPA) for quantitation of peptides in complex digests is described. In the method, anti-peptide antibodies immobilized on 100 nanoliter nanoaffinity columns are used to enrich specific peptides along with spiked stable-isotope-labeled internal standards of the same sequence. Upon elution from the anti-peptide antibody supports, electrospray mass spectrometry is used to quantitate the peptides (natural and labeled). In a series of pilot experiments, tryptic test peptides were chosen for four proteins of human plasma (hemopexin, alpha1 antichymotrypsin, interleukin-6, and tumor necrosis factor-alpha) from a pool of 10,203 in silico tryptic peptide candidates representing 237 known plasma components. Rabbit polyclonal antibodies raised against the chosen peptide sequences were affinity purified and covalently immobilized on POROS supports. Binding and elution from these supports was shown to provide an average 120-fold enrichment of the antigen peptide relative to others, as measured by selected ion monitoring (SIM) or selected reaction monitoring (SRM) electrospray mass spectrometry. The columns could be recycled with little loss in binding capacity, and generated peptide ion current measurements with cycle-to-cycle coefficients of variation near 5%. Anti-peptide antibody enrichment will contribute to increased sensitivity of MS-based assays, particularly for lower abundance proteins in plasma, and may ultimately allow substitution of a rapid bind/elute process for the time-consuming reverse phase separation now used as a prelude to online MS peptide assays. The method appears suitable for rapid generation of assays for defined proteins, and should find application in the validation of diagnostic protein panels in large sample sets.
Fingerprinting G-protein-coupled receptors (1994)

Recently we reported the design of a discriminating fingerprint for rhodopsin-like G-protein-coupled receptors (GPCRs). The fingerprint encodes the seven putative membrane-spanning motifs and was potently diagnostic of all GPCRs (52 in all) in version 8.1 of the OWL composite sequence database, readily distinguishing them from all other integral membrane proteins. With a 3-fold increase in the size of OWL, the fingerprint has been updated and now finds 332 receptors that match all the motifs. The situation, however, has grown in complexity: 61 sequences make imperfect matches with the fingerprint, yielding a total of 393 ‘hits’. The bulk of the partial hits are olfactory receptors: these appear to fall into discrete subfamilies in which one or more of the transmembrane motifs are either poorly matched or are not matched at all. These results are supported by preliminary phylogenetic analyses, which show the olfactory and various other partial matches clustering away from the main body of true hits. The approach has provided a powerful diagnostic tool for identifying GPCRs, and results are consistent with previous observations that the pheromone, cAMP and secretin-like receptors belong to separate families-these bear their own unique sequence fingerprints by which they may be distinguished from the rhodopsin-like superfamily
Deanol Affects Choline Metabolism in Peripheral Tissues of Mice (1981)

Administration of 2-dimethylaminoethanol (deanol) to mice induced an increase in both the concentration and the rate of turnover of free choline in blood. Treatment with deanol also caused an increase in the concentration of choline in kidneys, and markedly inhibited the rates of oxidation and phosphorylation of intravenously administered [3H-methyl]choline. In the liver, deanol inhibited the rate of phosphorylation of [3H-methyl]choline, but did not inhibit its rate of oxidation or cause an increase in the level of free choline. These findings suggest that deanol increases the choline concentration in blood by inhibition of its metabolism in tissues. Deanol may ultimately produce its central cholinergic effects by inhibition of choline metabolism in peripheral tissues, causing free choline choline to accumulate in blood, enter the brain, and stimulate cholinergic receptors.
Dexmedetomidine for the Treatment of Hyperactive Delirium Refractory to Haloperidol in Nonintubated ICU Patients: A Nonrandomized Controlled Trial* (2016)

In the study conditions, dexmedetomidine shows to be useful as a rescue drug for treating agitation due to delirium in nonintubated patients in whom haloperidol has failed, and it seems to have a better effectiveness, safety, and cost-benefit profile than does haloperidol.
Self-Assembled Organic Monolayers: Model Systems for Studying Adsorption of Proteins at Aurfaces (1991)

Self-assembled monolayers (SAMs) of omega-functionalized long-chain alkanethiolates on gold films are excellent model systems with which to study the interactions of proteins with organic surfaces. Monolayers containing mixtures of hydrophobic (methyl-terminated) and hydrophilic [hydroxyl-, maltose-, and hexa(ethylene glycol)-terminated] alkanethiols can be tailored to select specific degrees of adsorption: the amount of protein adsorbed varies monotonically with the composition of the monolayer. The hexa(ethylene glycol)-terminated SAMs are the most effective in resisting protein adsorption. The ability to create interfaces with similar structures and well-defined compositions should make it possible to test hypotheses concerning protein adsorption.
Nephrogenic Adenomas as Renal Tubular Outposts (2002)

Nephrogenic adenomas, which are rare intraurothelial lesions that occur in the bladder, ureter, or urethra, most often present with hematuria or discomfort on voiding. Some patients have no symptoms at all, but occasionally, obstruction develops. These lesions are generally discovered long after an apparent urologic insult or the initiation of immunosuppression, and their origin is enigmatic. The growths consist of tubule-like microstructures, but whether these lesions originate from mesothelial rests, represent squamous metaplasia, or derive from exfoliated renal tubular cells is unclear. In this issue of the Journal, Mazal et al.1 present compelling evidence that these unusual adenomas originate from . . .
Loss of periplakin expression is associated with pathological stage and cancerspecific survival in patients with urothelial carcinoma of the urinary bladder (2014)

The objective of this study was to determine periplakin expression in normal urothelium and bladder cancer tissues and the relationship to clinicopathological findings. Immunohistochemical staining for periplakin was carried out in 92 archival radical cystectomy specimens, with immunoreactivity being stratified on a 0-6 scale. Immunohistochemical staining for periplakin was shown to be significantly lower in bladder cancer tissues compared to non-cancerous tissues including inflammation,hyperplasia and normal urothelium. Loss of periplakin expression was associated with pathological stage (P=0.04). In multivariate Cox regression analysis, loss of periplakin expression and positive lymph node status were independent prognostic factors for cancer-specific survival (P=0.03 and 0.015; odds ratio=2.29 and 2.66; 95% confidence interval=1.085-4.814 and 1.214-5.845, respectively). This new molecular marker may aid in identifying and selecting bladder cancer patients undergoing radical cystectomy who may potentially benefit from neoadjuvant or adjuvant therapy.
Diels–Alder reactions of oxindolylideneacetone (1966)

Oxindolylideneacetone has been shown to react with a variety of acetylenic dienophiles to yield derivatives of naphthostyril. The dimerisation of oxindolylideneacetone is also a Diels–Alder addition reaction and a probable structure is advanced for the dimer.
Defined Conditions for Development of Functional Hepatic Cells from Human Embryonic Stem Cells (2005)

Human embryonic stem (hES) cells provide an important means to evaluate specific soluble and cell-bound stimuli that regulate development of specific cell lineages. Here, we examined specific cytokines and extracellular matrix (ECM) proteins that support differentiation of hES cells to hepatocytes. Tests of several different conditions determined that addition of fibroblast growth factor (FGF)-4 and hepatocyte growth factor in completely serum-free cultures of hES cell-derived embryoid bodies subsequently allowed to attach to type I collagen-coated dishes led to maximal differentiation into cells, not only with the morphologic and phenotypic characteristics of hepatocytes but also the functional characteristics. Expression of common hepatic transcription factors including HNF-3beta, HNF-1, and GATA-4 were all significantly induced under these conditions. Hepatocyte function was demonstrated by multiple complementary criteria: production of urea and albumin, phenobarbital-induced cytochrome P450 expression, and uptake of indocyanine green. These hES cell-derived hepatocytes will serve as a resource to understand normal human hepatocyte development and for applications such as cell replacement therapies and screening of pharmacologic drugs.
Control of large chromosomal duplications in Escherichia coli by the mismatch repair system. (1991)

Excessive recombination between repeated, interspersed, and diverged DNA sequences is a potential source of genomic instability. We have investigated the possibility that a mechanism exists to suppress genetic exchange between these quasi-homologous (homeologous) sequences. We examined the role of the general mismatch repair system of Escherichia coli because previous work has shown that the mismatch repair pathway functions as a barrier to interspecies recombination between E. coli and Salmonella typhimurium. The formation of large duplications by homeologous recombination in E. coli was increased some tenfold by mutations in the mutL and mutS genes that encode the mismatch recognition proteins. These findings indicate that the mismatch recognition proteins act to prevent excessive intrachromosomal exchanges. We conclude that mismatch repair proteins serve as general controllers of the fidelity of genetic inheritance, acting to suppress chromosomal rearrangements as well as point mutations.
Use of Plasmid DNA for Direct Gene Transfer and Immunization (1995)

Direct gene transfer by intramuscular injection of plasmid DNA encoding an antigenic protein may be used for the purpose of immunization. Several factors influence the uptake and expression of plasmid DNA in skeletal muscle, which in turn influence the immune response to the expressed protein. Physical barriers and other factors may impede the diffusion of the DNA within the muscle tissue or its entry into the muscle fibers. Although the efficiency of gene transfer in normal mouse muscle is low (< 100 fibers per injection site), both humoral and cell-mediated immune responses to the hepatitis B surface antigen (HBsAg) are obtained after the expression of a transferred gene, and these are dose dependent. The efficacy of the immune response can be improved by injection of the DNA in or following pretreatment with a hypertonic solution or with the local anesthetic bupivacaine, and even more so by injecting the DNA into regenerating muscle.
A System for Rapid DNA Sequencing with Fluorescent Chain-Terminating Dideoxynucleotides (1987)

A DNA sequencing system based on the use of a novel set of four chain-terminating dideoxynucleotides, each carrying a different chemically tuned succinylfluorescein dye distinguished by its fluorescent emission is described. Avian myeloblastosis virus reverse transcriptase is used in a modified dideoxy DNA sequencing protocol to produce a complete set of fluorescence-tagged fragments in one reaction mixture. These DNA fragments are resolved by polyacrylamide gel electrophoresis in one sequencing lane and are identified by a fluorescence detection system specifically matched to the emission characteristics of this dye set. A scanning system allows multiple samples to be run simultaneously and computer-based automatic base sequence identifications to be made. The sequence analysis of M13 phage DNA made with this system is described.