gebhart/patrepeval huggingface dataset:
Soluble CD22 as a tumor marker for hairy cell leukemia (2008)

CD22 is an important immunotherapeutic target on B-cell malignancies, particularly hairy cell leukemia (HCL), but its soluble extracellular domain, sCD22, has not yet been reported in the blood. By immunoaffinity and enzyme-linked immunosorbent assay techniques using anti-CD22 monoclonal antibodies, we identified the 100-kDa extracellular domain of CD22 and an 80-kDa processed form in serum of patients with HCL. The median sCD22 level measured by enzyme-linked immunosorbent assay was 18 ng/mL for 93 patients with HCL. sCD22 levels varied from 2.1 to 163 ng/mL and were higher (P < .001) than 23 normal donors (median, 0.6 ng/mL). More than 95% of normal donors had sCD22 levels less than 1.9 ng/mL. sCD22 levels were proportional to concentrations of circulating HCL cells (P = .002), and HCL spleen size (P < .001). sCD22 levels normalized with complete but not partial response to treatment. sCD22 levels up to 300 ng/mL had less than a 2-fold effect on the cytotoxicity of the anti-CD22 recombinant immunotoxin BL22. sCD22 levels may be useful to follow in patients with HCL and may be more specific than sCD25 in patients with CD22(+)/CD25(-) disease. Trials are listed on www.cancer.gov as NCT00002765, NCT00021983, NCT00074048, NCT00085085, NCT00337311, and NCT00462189.
Interdomain Communication in Hepatitis C Virus Polymerase Abolished by Small Molecule Inhibitors Bound to a Novel Allosteric Site (2005)

The hepatitis C virus (HCV) polymerase is required for replication of the viral genome and is a key target for therapeutic intervention against HCV. We have determined the crystal structures of the HCV polymerase complexed with two indole-based allosteric inhibitors at 2.3- and 2.4-Angstroms resolution. The structures show that these inhibitors bind to a site on the surface of the thumb domain. A cyclohexyl and phenyl ring substituents, bridged by an indole moiety, fill two closely spaced pockets, whereas a carboxylate substituent forms a salt bridge with an exposed arginine side chain. Interestingly, in the apoenzyme, the inhibitor binding site is occupied by a small alpha-helix at the tip of the N-terminal loop that connects the fingers and thumb domains. Thus, these molecules inhibit the enzyme by preventing formation of intramolecular contacts between these two domains and consequently precluding their coordinated movements during RNA synthesis. Our structures identify a novel mechanism by which a new class of allosteric inhibitors inhibits the HCV polymerase and open the way to the development of novel antiviral agents against this clinically relevant human pathogen.
CD45 isoform switching precedes the activation-driven death of human thymocytes by apoptosis (1991)

A recently described chimaeric organ culture system is employed to investigate the effects of antibodies to the CD3 and CD2 cell surface structures on the fate of developing human thymocyte populations. Engagement of CD3 as well as CD2 with reagents that stimulate peripheral human T cell results in the activation-induced death of human thymocytes in organ culture. Death is preceded by a characteristic phenotypic change; thymocytes that bear CD45RA (determinants associated with high-molecular-mass isoforms of the leukocyte common antigen family, CD45) are first induced to co-express CD45RO (the low-molecular-mass isoform of CD45), and subsequently lose CD45RA expression. This antigenic change is followed by cellular DNA fragmentation, characteristic of apoptosis. We conclude that engagement of CD3 as well as CD2 can recruit human CD45RA+ thymocytes into the CD45RO+ population, where cell death occurs. Our results suggest that this phenotype conversion is a marker for thymocytes destined for programmed cell death.
AGE RELATED CHANGES AND INTERRELATIONSHIPS BETWEEN PLASMA TESTOSTERONE, OESTRADIOL AND TESTOSTERONE-BINDING GLOBULIN IN NORMAL ADULT MALES (1973)

ABSTRACT Testosterone (T), oestradiol-17β (Oe 2 ) and binding capacity of the testosterone-binding globulin (TeBG) were measured in plasma of 84 adult males (22–90 years). The medians for age group I (22– 61 years, n = 50) were: T 545 ng/100 ml, Oe 2 1.66 ng/100 ml, TeBG capacity 1.44 μg T/100 ml; the medians for age group II (67–90 years, n = 34) were: T 459 ng/100 ml, Oe 2 2.56 ng/100 ml, TeBG capacity 2.05 μg T/100 ml. The decrease of T and the increase of Oe 2 and TeBG capacity with age were significant. The significant correlation ( P &lt; 0.01) for either age group between T and Oe 2 may be ascribed to a simultaneous secretion and/or a peripheral conversion of T to Oe 2 . The significant correlation ( P &lt; 0.05) between T and TeBG for the old age group probably reflects the comparatively high percentage of total plasma T bound to TeBG. The biological meaning of the correlation between Oe2 and TeBG is discussed.
DNA sequence of the gene encoding the Zc1 protein fromZea maysW64 A (1990)

The Zein-2 component named Zc 1 corresponds to a storage protein of an apparent M.W. of 16 kDa present in maize endosperm (1). A comparison of amino acid sequences between this protein and Zc2 (glutelin-2) shows that Zcl corresponds to a truncated Zc2 protein (2). In our laboratory we have isolated and sequenced a genomic clone (pZ3) of 3864 nucleotides coding for Zcl protein. This genomic fragment shows a length of 1241 bp for the 5' region, 551 bp for the coding region that appears underlined and 1062 bp for the 3' region. The putative TATA- box also appears underlined. The comparison with the sequence of the corresponding cDNA clone, shows the lack of introns in this gene. Furthermore, this is the first case for maize storage EMBL accession no. X53515 protein genes that sequences for a genomic clone and a cDNA clone fully coincide. The 5' region has been used for homology studies by comparison with the 5' sequence of Zc2 gene (these results are summarized in the next record). The availability of a large flanking sequence let us perform studies on gene expression.
Assembly of the α-Globin mRNA Stability Complex Reflects Binary Interaction between the Pyrimidine-Rich 3′ Untranslated Region Determinant and Poly(C) Binding Protein αCP (1999)

Globin mRNAs accumulate to 95% of total cellular mRNA during terminal erythroid differentiation, reflecting their extraordinary stability. The stability of human alpha-globin mRNA is paralleled by formation of a sequence-specific RNA-protein (RNP) complex at a pyrimidine-rich site within its 3' untranslated region (3'UTR), the alpha-complex. The proteins of the alpha-complex are widely expressed. The alpha-complex or a closely related complex also assembles at pyrimidine-rich 3'UTR segments of other stable mRNAs. These data suggest that the alpha-complex may constitute a general determinant of mRNA stability. One or more alphaCPs, members of a family of hnRNP K-homology domain poly(C) binding proteins, are essential constituents of the alpha-complex. The ability of alphaCPs to homodimerize and their reported association with additional RNA binding proteins such as AU-rich binding factor 1 (AUF1) and hnRNP K have suggested that the alpha-complex is a multisubunit structure. In the present study, we have addressed the composition of the alpha-complex. An RNA titration recruitment assay revealed that alphaCPs were quantitatively incorporated into the alpha-complex in the absence of associated AUF1 and hnRNP K. A high-affinity direct interaction between each of the three major alphaCP isoforms and the alpha-globin 3'UTR was detected, suggesting that each of these proteins might be sufficient for alpha-complex assembly. This sufficiency was further supported by the sequence-specific binding of recombinant alphaCPs to a spectrum of RNA targets. Finally, density sedimentation analysis demonstrated that the alpha-complex could accommodate only a single alphaCP. These data established that a single alphaCP molecule binds directly to the alpha-globin 3'UTR, resulting in a simple binary structure for the alpha-complex.
A Survey of Role Mining (2016)

Role-Based Access Control (RBAC) is the most widely used model for advanced access control deployed in diverse enterprises of all sizes. RBAC critically depends on defining roles, which are a functional intermediate between users and permissions. Thus, for RBAC to be effective, an appropriate set of roles needs to be identified. Since many organizations already have user-permission assignments defined in some form, it makes sense to identify roles from this existing information. This process, known as role mining, is one of the critical steps for successful RBAC adoption in any enterprise. In recent years, numerous role mining techniques have been developed, which take into account the characteristics of the core RBAC model, as well as its various extended features. In this article, we comprehensively study and classify the basic problem of role mining along with its several variants and the corresponding solution strategies. Categorization is done on the basis of the nature of the target RBAC system, the objective of role mining, and the type of solution. We then discuss the limitations of existing work and identify new areas of research that can lead to further enrichment of this field.
Study of the glucoamylase promoter in Aspergillus niger using green fluorescent protein (1999)

An Aspergillus niger strain expressing a red-shifted green fluorescent protein (GFP) in the cytoplasm under the control of the glucoamylase promoter (PglaA) was characterized with respect to its physiology and morphology. Although xylose acted as a repressor carbon source during batch cultivations, PglaA-driven GFP expression by the glucoamylase promoter could be demonstrated in xylose-limited continuous cultures. In these cultivations, the xylose concentration was therefore too low to cause repression. Transient experiments initiated with a maltose pulse did not further induce red-shifted GFP production in xylose-limited continuous cultures. Maltose induction under conditions of xylose repression was microscopically observed and quantified in a flow-through chamber. Red-shifted GFP was first produced after 5 h induction. Finally the strain was characterized in glucose-limited continuous cultures, and here the area of the mycelium stained with cytoplasmic GFP increased with increasing specific growth rate, indicating that GFP can be used as a marker of cellular activity in this type of cultivation.
Establishing the resting state default mode network derived from functional magnetic resonance imaging tasks as an endophenotype: A twins study (2014)

The resting state default mode network (DMN) has been shown to characterize a number of neurological and psychiatric disorders. Evidence suggests an underlying genetic basis for this network and hence could serve as potential endophenotype for these disorders. Heritability is a defining criterion for endophenotypes. The DMN is measured either using a resting-state functional magnetic resonance imaging (fMRI) scan or by extracting resting state activity from task-based fMRI. The current study is the first to evaluate heritability of this task-derived resting activity. 250 healthy adult twins (79 monozygotic and 46 dizygotic same sex twin pairs) completed five cognitive and emotion processing fMRI tasks. Resting state DMN functional connectivity was derived from these five fMRI tasks. We validated this approach by comparing connectivity estimates from task-derived resting activity for all five fMRI tasks, with those obtained using a dedicated task-free resting state scan in an independent cohort of 27 healthy individuals. Structural equation modeling using the classic twin design was used to estimate the genetic and environmental contributions to variance for the resting-state DMN functional connectivity. About 9-41% of the variance in functional connectivity between the DMN nodes was attributed to genetic contribution with the greatest heritability found for functional connectivity between the posterior cingulate and right inferior parietal nodes (P<0.001). Our data provide new evidence that functional connectivity measures from the intrinsic DMN derived from task-based fMRI datasets are under genetic control and have the potential to serve as endophenotypes for genetically predisposed psychiatric and neurological disorders.
Waveguide Integrated Ge p-i-n Photodetectors on a Silicon-on-Insulator Platform (2006)

We present selectively grown Ge p-i-n photodetectors coupled to high index contrast Si(core)/SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> (cladding) waveguides on a silicon-on-insulator (SOI) platform. Two coupling schemes, namely butt-coupling and vertical coupling, were demonstrated in this study. With the butt-coupling scheme we have achieved a high responsivity of 1.0 A/W at 1520 nm and a 3 dB bandwidth greater than 4.5 GHz at 1550 nm. With the vertical coupling scheme, where the light couples from a Si waveguide evanescently to the Ge detector on top of it, a responsivity of 0.22 A/W and a 3 dB bandwidth of ~1.5 GHz have been demonstrated at 1550 nm. The devices were fabricated on a standard 180 nm industrial complementary metal oxide semiconductor production (CMOS) line, and can be integrated with CMOS circuitry for electronic and photonic integrated circuits
A clinical trial of combined anti-androgen and anti-heavy metal therapy in autistic disorders. (2006)

This study provides the first clinical evidence for the benefit that combined anti-androgen and anti-heavy metal therapy may have on some children with ASDs. Additional studies should examine androgen and heavy metal mechanisms of action in ASDs, and future ASD treatment protocols should consider androgens and heavy metals.
Systemic vaccination with anti‐oligomeric monoclonal antibodies improves cognitive function by reducing Aβ deposition and tau pathology in 3xTg‐AD mice (2013)

Alzheimer's disease (AD) is a devastating disorder that is clinically characterized by a comprehensive cognitive decline. Accumulation of the amyloid-beta (Aβ) peptide plays a pivotal role in the pathogenesis of AD. In AD, the conversion of Aβ from a physiological soluble monomeric form into insoluble fibrillar conformation is an important event. The most toxic form of Aβ is oligomers, which is the intermediate step during the conversion of monomeric form to fibrillar form. There are at least two types of oligomers: oligomers that are immunologically related to fibrils and those that are not. In transgenic AD animal models, both active and passive anti-Aβ immunotherapies improve cognitive function and clear the parenchymal accumulation of amyloid plaques in the brain. In this report we studied effect of immunotherapy of two sequence-independent non-fibrillar oligomer specific monoclonal antibodies on the cognitive function, amyloid load and tau pathology in 3xTg-AD mice. Anti-oligomeric monoclonal antibodies significantly reduce the amyloid load and improve the cognition. The clearance of amyloid load was significantly correlated with reduced tau hyperphosphorylation and improvement in cognition. These results demonstrate that systemic immunotherapy using oligomer-specific monoclonal antibodies effectively attenuates behavioral and pathological impairments in 3xTg-AD mice. These findings demonstrate the potential of using oligomer specific monoclonal antibodies as a therapeutic approach to prevent and treat Alzheimer's disease.
Functional Interaction of Monoubiquitinated FANCD2 and BRCA2/FANCD1 in Chromatin (2004)

Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome with at least 11 complementation groups (A, B, C, D1, D2, E, F, G, I, J, and L), and eight FA genes have been cloned. The FANCD1 gene is identical to the breast cancer susceptibility gene, BRCA2. The FA proteins cooperate in a common pathway, but the function of BRCA2/FANCD1 in this pathway remains unknown. Here we show that monoubiquitination of FANCD2, which is activated by DNA damage, is required for targeting of FANCD2 to chromatin, where it interacts with BRCA2. FANCD2-Ub then promotes BRCA2 loading into a chromatin complex. FANCD2(-/-) cells are deficient in the assembly of DNA damage-inducible BRCA2 foci and in chromatin loading of BRCA2. Functional complementation with the FANCD2 cDNA restores BRCA2 foci and its chromatin loading following DNA damage. BRCA2(-/-) cells expressing a carboxy-terminal truncated BRCA2 protein form IR-inducible BRCA2 and FANCD2 foci, but these foci fail to colocalize. Functional complementation of these cells with wild-type BRCA2 restores the interaction of BRCA2 and FANCD2. The C terminus of BRCA2 is therefore required for the functional interaction of BRCA2 and FANCD2 in chromatin. Taken together, our results demonstrate that monoubiquitination of FANCD2, which is regulated by the FA pathway, promotes BRCA2 loading into chromatin complexes. These complexes appear to be required for normal homology-directed DNA repair.
Propagation of Infectious Canine Hepatitis Virus in Tissue Culture (1954)

The serial propagation of ICH virus by the roller tube method in dog kidney tissue culture through 15 consecutive passages is reported. The growth of the virus under these conditions causes a specific cytopatho-genic degeneration of the tissue growth, similar to that reported for poliomyelitis virus in the presence of human or monkey tissues. Identification of the tissue culture virus was made by both the complement-fixation and serum neutralization methods using a known infectious canine hepatitis fox immune serum.
Fabrication of Graphene–Quantum Dots Composites for Sensitive Electrogenerated Chemiluminescence Immunosensing (2011)

Abstract A novel strategy is reported for the fabrication of poly(diallyldimethylammonium chloride) (PDDA)‐protected graphene–CdSe (P‐GR‐CdSe) composites. An advanced electrogenerated chemiluminescence (ECL) immunosensor is proposed for the sensitive detection of human IgG (HIgG) by using the as‐prepared P‐GR‐CdSe composites. The P‐GR‐CdSe composite film shows high ECL intensity, good electronic conductivity, fast response, and satisfactory stability, all of which holds great promise for the fabrication of ECL biosensors with improved sensitivity. After two successive steps of amplification via the conjugation of PDDA and gold nanoparticles (GNPs) in the film, high ECL intensity is observed. The ECL immunosensor has an extremely sensitive response to HIgG in a linear range of 0.02–2000 pg mL −1 with a detection limit of 0.005 pg mL −1 . The proposed sensor exhibits high specificity, good reproducibility, and long‐term stability, and may become a promising technique for protein detection.
Chemotherapy for Glioblastoma Multiforme (1991)

Treatment for the patient with a glioblastoma multiforme often includes chemotherapy with many specific nursing implications directly associated with this form of treatment. While the four agents described share some common adverse effects such as nausea and vomiting, even with this relatively common adverse effect, the onset, duration and severity varies. Multiple other adverse effects like nephrotoxicity, ototoxicity, thrombocytopenia and leukocytopenia vary greatly from agent to agent in occurrence and severity. Knowing the mode of action for each agent, which adverse effects to expect, when to expect them and appropriate treatment measures will help the nurse, patient and family to better manage these effects and improve quality of life.
Sparsomycin analogs. IV. Synthesis and antitumor activity of pyrimidine-5-carboxamides and(E)-.BETA.-(pyrimidin-5-yl)-acrylamides. (1988)

Various pyrimidine-5-carboxamides (14, 16, 18, 20, and 21) and (E)-β-(pyrimidin-5-yl)acrylamides (15, 17, 19, and 22)were synthesized as sparsomycin analogs, and their antitumor activity was examined by cell growth inhibition assay against mouse leukemia L5178Y cells in vitro.Synthesis was carried out by condensation of appropriate acids (4, 6, 10, and 12) and amino acid methyl esters (13) by the mixed anhydride method using isobutyl chlorocarbonate. The condensation product was converted to the corresponding acid and alcohol derivatives by hydrolysis and LiBH4 reduction. The compounds having an ethylene linkage at the C-5 position and an ester moiety at the terminal amino acid functionality (15b, and 17b-g) exhibited remarkable antitumor activity.
Exploiting new technologies in animal breeding : genetic developments (1986)

Recent advances in the technology and techniques of genetic manipulation have caused an unprecedented expansion of possibilities for improvement in the breeding and development of livestock. This volume provides an up-to-date summary of work being done in this field, indicating how new discoveries can be integrated with established methods of breeding to create commercially competitive lines. It also considers future possibilities in research and development, and encourages researchers and graduate students in animal breeding, livestock improvement, molecular genetics, and reproductive physiology to consider new research methods.
PiggyBac Transposon-Mediated, Reversible Gene Transfer in Human Embryonic Stem Cells (2009)

Permanent and reversible genetic modifications are important approaches to study gene function in different cell types. They are also important for stem cell researchers to explore and test the therapeutic potential of stem cells. The piggyBac transposon from insects is a rising nonviral system that efficiently mutagenizes and mediates gene transfer into the mammalian genome. It is also characterized by its precise excision, leaving no trace sequence behind so that the genomic integrity of the mutated cell can be restored. Here, we use an optimized piggyBac transposon system to mediate gene transfer and expression of a bifunctional fluorescent reporter in human embryonic stem (ES) cells. We provide molecular evidence for transposase-mediated piggyBac integration events and functional evidence for successful expression of a transferred fluorescent protein genes in human ES cells and their in vitro differentiated derivatives. We also demonstrate that the integrated piggyBac transposon can be removed and an undisrupted insertion site can be restored, which implies potential applications for its use in gene therapy and genetics studies.
Activation of Angiogenic Signaling Pathways by Two Human tRNA Synthetases (2002)

Aminoacyl-tRNA synthetases establish the rules of the genetic code by joining amino acids to tRNAs that bear the anticodon triplets corresponding to the attached amino acids. The enzymes are thought to be among the earliest proteins to appear, in the transition from a putative RNA world to the theater of proteins. Over their long evolution, the enzymes have acquired additional functions that typically require specialized insertions or domain fusions. Recently, fragments of the closely related human tyrosyl- and tryptophanyl-tRNA synthetases were discovered to be active in angiogenesis signaling pathways. One synthetase fragment has proangiogenic activity, while the other is antiangiogenic. Activity was demonstrated in cell-based assays in vitro and in vivo in the chick embryo, and in the neonatal and adult mouse. The full-length, native enzymes are inactive in these same assays. Activation of angiogenesis activity requires fragment production from the native enzymes by protease cleavage or by translation of alternatively spliced pre-mRNA. Thus, these tRNA synthetases link translation to a major cell-signaling pathway in mammalian cells. The results with animals suggest that therapeutic applications are possible with these tRNA synthetases.
Calcium(II)-Catalyzed Aza-Piancatelli Reaction (2014)

The first examples of calcium-catalyzed aza-Piancatelli reactions between substituted 2-furylcarbinols and aniline derivatives are described. A variety of 4-aminocyclopentenones have been synthesized stereoselectively in high yields. The experimental procedure utilizes simple salts and does not require specific precautions.