gebhart/patrepeval huggingface dataset:
Identification and characterization of a bipotent (erythroid and megakaryocytic) cell precursor from the spleen of phenylhydrazine-treated mice (2000)

We have identified a cell population expressing erythroid (TER-119) and megakaryocyte (4A5) markers in the bone marrow of normal mice. This population is present at high frequency in the marrows and in the spleens involved in the erythroid expansion that occurs in mice recovering from phenylhydrazine (PHZ)-induced hemolytic anemia. TER-119(+)/4A5(+) cells were isolated from the spleen of PHZ-treated animals and were found to be blast-like benzidine-negative cells that generate erythroid and megakaryocytic cells within 24-48 hours of culture in the presence of erythropoietin (EPO) or thrombopoietin (TPO). TER-119(+)/4A5(+) cells represent a late bipotent erythroid and megakaryocytic cell precursors that may exert an important role in the recovery from PHZ-induced anemia. (Blood. 2000;95:2559-2568)
Moderate and Severe Traumatic Brain Injury: Epidemiologic, Imaging and Neuropathologic Perspectives (2004)

This article examines 3 contexts in which moderate or severe traumatic brain injury can be approached. The epidemiologic background of moderate and severe traumatic brain injury is presented, with particular attention paid to new findings from the study of a national hospital inpatient database. We review aspects of neuroimaging and how new imaging modalities can reveal fine detail about traumatic brain injury. Finally we examine the current state of neuropathologic evaluation of, and recent developments in, understanding of the neural disruptions that occur following traumatic brain injury, together with cellular reactions to these disruptions.
Synthesis and characterization of dextran-methacrylate hydrogels and structural study by SEM (2000)

The objectives of this study were to develop a simple and reproducible method for the preparation of the hydrogel precursor dextran-methacrylate and to conduct a visual observation of the interior structure of the swollen dextran-methacrylate hydrogel with minimum artifacts. A dextran-methacrylate hydrogel precursor was synthesized by reacting dextran with methacrylic anhydride in the presence of triethylamine as a catalyst. The effects of reaction time, temperature, concentration, and catalyst amount were studied to obtain a wide range of degree of substitution (DS) in dextran by methacrylate. The dextran-methacrylate synthesized showed an enhanced solubility in water and common organic solvents. UV irradiation of dextran-methacrylate by a long-wave UV lamp (365 nm) generated a photocrosslinked hydrogel. This dextran-methacrylate hydrogel showed a range of swelling ratio from 67 to 227% and exhibited an increase in swelling ratio with a decrease in methacrylate substitution. The pH of the swelling media did not affect the swelling behavior of the dextran-methacrylate hydrogels at all the degrees of substitution used. Special cryofixation and cryofracturing techniques were used to prepare aqueous swollen dextran-methacrylate hydrogel samples for SEM observation of their surface and interior structures. A unique three-dimensional porous structure was observed in the swollen hydrogel but was absent in the unswollen hydrogel. Different pore sizes and morphologies between the surface and the interior of swollen hydrogels also were observed.
Glycosylation Variations with Expression Systems and Their Impact on Biological Activity of Therapeutic Immunoglobulins (2003)

soluble serum glycoproteins involved in the defense mechanism of the immune system. IgGs are the major components of the five different classes of immunoglobulins (namely IgA, IgD, IgE, IgG, and IgM; Figure 1 provides a schematic representation) (1). The serum concentration of IgG is up to 13.5 mg/mL (Figure 1). The four isotypes of IgGs are classified as IgG1, IgG2, IgG3 and IgG4 (Figure 2). These IgG isotypes have different numbers and arrangements of interchain disulfide bonds (2). In IgG1 the disulfide bond linking the light and heavy chains goes to the hinge region (Figure 2), whereas in the IgG2, IgG3, and IgG4 subclasses the disulfide bond linking the light and heavy chains goes to the junction between the variable and constant regions. Among the four isotypes, IgG1 molecules exhibit predominant effector functions (Table 1) (3). The IgG2, IgG3, and IgG4 isotypes contain very minimal effector functions. The N-linked oligosaccharides present in the constant CH2 domain of the Fc have greater influence on the effector functions of IgG1 molecules (Figure 3 shows domain structure). These N-linked oligosaccharides of IgGs are highly heterogeneous (also referred to as microheterogeneity) and vary considerably with the expression system (4). Variations in conditions of production systems greatly influence the heterogeneity of IgG oligosaccharides (5). Thus, glycosylation of rIgGs varies from lot to lot and among different cellculture conditions. These variations often affect the biological activities of therapeutic antibodies. This might lead to potency changes in drug substances and drug products. Because of this, regulatory agencies around the world are very vigilant about glycosylation variations of therapeutic antibodies. This article examines the issues related to glycosylation variations with particular emphasis on expression systems and their impact on the effector functions of therapeutic antibodies.
A Unique Structure for Epidermal Growth Factor Receptor Bound to GW572016 (Lapatinib) (2004)

GW572016 (Lapatinib) is a tyrosine kinase inhibitor in clinical development for cancer that is a potent dual inhibitor of epidermal growth factor receptor (EGFR, ErbB-1) and ErbB-2. We determined the crystal structure of EGFR bound to GW572016. The compound is bound to an inactive-like conformation of EGFR that is very different from the active-like structure bound by the selective EGFR inhibitor OSI-774 (Tarceva) described previously. Surprisingly, we found that GW572016 has a very slow off-rate from the purified intracellular domains of EGFR and ErbB-2 compared with OSI-774 and another EGFR selective inhibitor, ZD-1839 (Iressa). Treatment of tumor cells with these inhibitors results in down-regulation of receptor tyrosine phosphorylation. We evaluated the duration of the drug effect after washing away free compound and found that the rate of recovery of receptor phosphorylation in the tumor cells reflected the inhibitor off-rate from the purified intracellular domain. The slow off-rate of GW572016 correlates with a prolonged down-regulation of receptor tyrosine phosphorylation in tumor cells. The differences in the off-rates of these drugs and the ability of GW572016 to inhibit ErbB-2 can be explained by the enzyme-inhibitor structures.
Hepsin activates pro‐hepatocyte growth factor and is inhibited by hepatocyte growth factor activator inhibitor‐1B (HAI‐1B) and HAI‐2 (2005)

Hepsin, a type II transmembrane serine protease, is highly upregulated in prostate cancer and promotes tumor progression and metastasis. We generated a soluble form of hepsin comprising the entire extracellular domain to show that it efficiently converts single-chain hepatocyte growth factor (pro-HGF) into biologically active two-chain HGF. Hepsin activity was potently inhibited by soluble forms of the bi-Kunitz domain inhibitors HAI-1B (IC(50) 21.1+/-2.7 nM) and HAI-2 (IC(50) 1.3+/-0.3 nM). Enzymatic assays with HAI-1B Kunitz domain mutants (R260A and K401A) further demonstrated that inhibition was due to Kunitz domain-1. The results suggest a functional link between hepsin and the HGF/Met pathway, which may contribute to tumor progression.
Human coagulation factor X deficiency caused by a mutant signal peptide that blocks cleavage by signal peptidase but not targeting and translocation to the endoplasmic reticulum. (1993)

Human factor Xsantois a form of coagulation factor X in which a mutation within the signal peptide region of the precursor protein has been correlated genetically with a severe deficiency of factor X in the affected individual.A point mutation results in substitution of Arg for Gly at the critical -3 position of the factor X signal peptide.To determine the biochemical effect of this mutation on the biosynthesis of factor X, the wild-type and mutant factor X cDNAs were subcloned into a vector for transcription and translation in vitro.Translation products of mRNAs encoding portions of both mutant and wild-type proteins were used in a systematic biochemical approach to evaluate directly the effect of the mutation on targeting, transport, and proteolytic processing in vitro.The results show that targeting and transport of factor XsantoDomingo to the endoplasmic reticulum are functionally dissociated from the removal of the signal peptide by signal peptidase.Factor Xsanto D~~~~~~ is translocated into the endoplasmic reticulum but not processed by signal peptidase.Transient expression of the wild-type and mutant factor X in human embryonic kidney 293 cells revealed apparently normal secretion of the glycosylated two-chain form of factor X but no secretion of factor Xsanto D ~~~~~~.Thus, the inability of signal peptidase to cleave factor Xsanto &,,,ingo is directly responsible for the absence of circulating factor X and leads to the bleeding diathesis in the affected individual.Secreted proteins are generally synthesized as precursors having NH2-terminal signal sequences which target nascent secretory proteins to the endoplasmic reticulum (ER)' and are then removed by signal peptidase (1).Although signal GM32861 (to M. 0. L.) and HL48322 and HL06350 (to K. A. H.).
Hierarchical classification for automatic image annotation (2007)

In this paper, a hierarchical classification framework has been proposed for bridging the semantic gap effectively and achieving multi-level image annotation automatically. First, the semantic gap between the low-level computable visual features and users' real information needs is partitioned into four smaller gaps, and multiple approachesallare proposed to bridge these smaller gaps more effectively. To learn more reliable contextual relationships between the atomic image concepts and the co-appearances of salient objects, a multi-modal boosting algorithm is proposed. To enable hierarchical image classification and avoid inter-level error transmission, a hierarchical boosting algorithm is proposed by incorporating concept ontology and multi-task learning to achieve hierarchical image classifier training with automatic error recovery. To bridge the gap between the computable image concepts and the users' real information needs, a novel hyperbolic visualization framework is seamlessly incorporated to enable intuitive query specification and evaluation by acquainting the users with a good global view of large-scale image collections. Our experiments on large-scale image databases have also obtained very positive results.
Reduction of Vinblastine Neurotoxicity in Mice Utilizing a Collagen Matrix Carrier (1990)

Vinblastine sulfate (VLB) suspended within a collagen matrix (CM) as a diffusion limiting drug delivery vehicle was examined in vitro, as well as in mouse subcutaneous and brain tumor models. Against RIF-1 and KHT subcutaneous tumors, there was enhancement of antitumor activity with intratumoral (i.t.) delivery of VLB when it was combined with CM and/or epinephrine (epi) provided as a vasoactive agent to limit diffusion of VLB away from the injection site. Furthermore, in pharmacokinetic studies an 3-fold enhancement of tumor exposure to drug (AUC) with the CM-formulation was observed relative to the administration of free VLB i.t. Craniotactic injection of VLB into mouse brain in doses from 0.2 to 2 mg/kg revealed that the CM association markedly reduced the acute toxicity of VLB in normal mouse brain. Furthermore, mice with stereotactically implanted KHT brain tumors treated with 0.2 mg/kg VLB in CM had less tumor present in the brain histologically compared to the free VLB and untreated control groups.
Tunable Solvents for Homogeneous Catalyst Recycle (2004)

A novel class of tunable solvents facilitates recycle of homogeneous catalysts for both economic and environmental advantages. In a mixed organic−aqueous tunable solvent (OATS), reactions between water-soluble catalysts and moderately hydrophobic substrates can be run homogeneously, with subsequent phase separation for product purification and catalyst reuse. One example demonstrated is the dimethyl ether (DME)−water system, which has been employed as a benign alternative to organic solvents for alcohol dehydrogenase (ADH)-catalyzed reduction of hydrophobic ketones coupled with regeneration of the cofactor NADH. We also show the feasibility of a biphasic DME−water separation scheme to couple with the biocatalytic reaction. The subsequent downstream processing offers the advantages of easily isolating water-insoluble products from the aqueous phase and recycling enzyme−cofactor. Other OATS systems are discussed where the preferential dissolution of modest pressures of CO2 causes phase separations, which result in very large distribution coefficients of target molecules in the biphasic organic−aqueous system, with substantial promise as tunable solvents for biocatalysis.
Prognostic Values of microRNAs in Colorectal Cancer. (2006)

The functions of non-coding microRNAs (miRNAs) in tumorigenesis are just beginning to emerge. Previous studies from our laboratory have identified a number of miRNAs that were deregulated in colon cancer cell lines due to the deletion of the p53 tumor suppressor gene. In this study, the in vivo significance of some of these miRNAs was further evaluated using colorectal clinical samples. Ten miRNAs (hsa-let-7b, hsa-let-7g, hsa-miR-15b, hsa-miR-181b, hsa-miR-191, hsa-miR-200c, hsa-miR-26a, hsa-miR-27a, hsa-miR-30a-5p and hsa-miR-30c) were evaluated for their potential prognostic value in colorectal cancer patients. Forty eight snap frozen clinical colorectal samples (24 colorectal cancer and 24 paired normal patient samples) with detailed clinical follow-up information were selected. The expression levels of 10 miRNAs were quantified via qRT-PCR analysis. The statistical significance of these markers for disease prognosis was evaluated using a two tailed paired Wilcoxon test. A Kaplan-Meier survival curve was generated followed by performing a Logrank test. Among the ten miRNAs, hsa-miR-15b (p = 0.0278), hsa-miR-181b (p = 0.0002), hsa-miR-191 (p = 0.0264) and hsa-miR-200c (p = 0.0017) were significantly over-expressed in tumors compared to normal colorectal samples. Kaplan-Meier survival analysis indicated that hsa-miR-200c was significantly associated with patient survival (p = 0.0122). The patients (n = 15) with higher hsa-miR-200c expression had a shorter survival time (median survival = 26 months) compared to patients (n = 9) with lower expression (median survival = 38 months). Sequencing analysis revealed that hsa-miR-181b (p = 0.0098) and hsa-miR-200c (p = 0.0322) expression were strongly associated with the mutation status of the p53 tumor suppressor gene. Some of these miRNAs may function as oncogenes due to their over-expression in tumors. hsa-miR-200c may be a potential novel prognostic factor in colorectal cancer.
Abstract data types and the development of data structures (1977)

Abstract data types can play a significant role in the development of software that is reliable, efficient, and flexible. This paper presents and discusses the application of an algebraic technique for the specification of abstract data types. Among the examples presented is a top-down development of a symbol table for a block structured language; a discussion of the proof of its correctness is given. The paper also contains a brief discussion of the problems involved in constructing algebraic specifications that are both consistent and complete.
Adenovirus type 5 early region 1b gene product is required for efficient shutoff of host protein synthesis (1984)

To determine the role adenovirus 5 early region 1b-encoded 21- and 55-kilodalton proteins play in adenovirus productive infection, mutants have been isolated which were engineered to contain small deletions or insertions at 5.8, 7.9, or 9.6 map units. By using an overlap recombination procedure involving H5dl314 (delta 3.7 to 4.6 map units) DNA cleaved at 2.6 map units with ClaI and the adenovirus 5 XhoI-C (0 to 15.5 map units) fragment containing the desired mutation, viral mutants were isolated by their ability to produce plaques on KB cell line 18, which constitutively expresses only viral early region 1b functions (Babiss et al., J. Virol. 46:454-465, 1983). DNA sequence analysis of the viral mutants isolated (H5dl118, H5dl110, H5in127, and H5dl163) indicates that all of the viruses contain mutations which affect the 55-kilodalton protein, whereas dl118 should also produce a truncated form of the 21-kilodalton protein. When analyzed for their replication characteristics in HeLa cells, all of the mutant viruses exhibited extended eclipse periods and effected yields that were reduced to 10% or less of that produced by H5sub309 (parent virus of the mutants which is phenotypically identical to wild-type adenovirus 5). When compared with characteristics of sub309, the early and late transcription and DNA replication of the mutants were similar, but synthesis of late polypeptides and late cytoplasmic mRNAs was greatly reduced. Quantitation of mutant virus-specific late mRNAs associated with polysomes revealed a threefold reduction when compared with that of sub309. Analysis of infected cell extracts further revealed that these mutants were incapable of efficiently shutting off host cell protein synthesis, suggesting that the 55-kilodalton protein plays a role in this process. These data suggest that early region 1b products may function by interacting with additional viral or host cell macromolecules to modulate host cell shutoff or that some late viral mRNA or polypeptide may potentiate this reaction.
CD30 distribution. Immunohistochemical study on formaldehyde-fixed, paraffin-embedded Hodgkin's and non-Hodgkin's lymphomas. (1992)

Two hundred Hodgkin's and non-Hodgkin's lymphomas were immunohistochemically studied for the presence of the CD30 (Ki-1) activation antigen using a monoclonal antibody BerH2 on paraffin-embedded, formaldehyde-fixed tissue. Immunohistochemistry was performed by using the avidin-biotin complex technique and was preceded by enzymatic digestion with pepsin (0.05% for 20 minutes). Ninety percent (56/64) of cases of Hodgkin's disease, other than lymphocyte predominance type, showed positive tumor cells, although the positivity was often focal. In contrast, lymphocyte predominance type showed CD30 in only two of nine cases. CD30 was commonly seen in non-Hodgkin's lymphomas. Five of 37 large-cell lymphomas showed extensive CD30 positivity and morphologically represented large-cell anaplastic lymphomas ("Ki-1 lymphomas"). Apart from this, occasional CD30-positive cells were seen in nine of 32 large-cell non-Hodgkin's lymphomas. About half of the nodular small cleaved-cell lymphomas contained CD30-positive cells, two of them showing large numbers of positive cells both within and outside the nodules. Lymphocytic lymphoma sometimes (6/17) showed a few CD30-positive cells. Peripheral T-cell lymphomas showed positive cells in three of eight cases. The positive cases were one lymphoma with small groups of epithelioid cells (Lennert's lymphoma) and two immunoblastic lymphadenopathylike peripheral T-cell lymphomas. The results show that CD30 is more widespread than originally thought in non-Hodgkin's lymphomas and that especially nodular small cleaved-cell lymphomas often contain positive cells. These findings have to be considered in the immunohistochemical differential diagnosis of lymphomas. Obviously, CD30 alone cannot be used to differentiate between Hodgkin's and non-Hodgkin's lymphomas. The CD30-positive cells in non-Hodgkin's lymphoma may represent a link between Hodgkin's and non-Hodgkin's lymphomas.
Deletion of the Carboxyl Terminus of Tie2 Enhances Kinase Activity, Signaling, and Function (2002)

Tie2 is an endothelial receptor tyrosine kinase that is required for both embryonic vascular development and tumor angiogenesis. There is considerable interest in understanding the mechanisms of Tie2 activation for therapeutic purposes. The recent solution of the Tie2 crystal structure suggests that Tie2 activity is autoinhibited by its carboxyl terminus. Here we investigated the role of the C tail in Tie2 activation, signaling, and function both in vitro and in vivo by deleting the C terminus of Tie2 (Delta CT). Compared to wild type Tie2, in vitro autophosphorylation and kinase activity were significantly enhanced by the Delta CT mutation. In NIH 3T3 cells expressing chimeric Tie2 receptors, both basal and ligand-induced tyrosine phosphorylation were markedly enhanced compared to wild type in several independent clones of Tie2-Delta CT. Moreover, the Delta CT mutation enhanced basal and ligand-dependent activation of Akt and extracellular signal-regulated kinase. Enhanced Akt activation correlated with significant inhibition of staurosporine-induced apoptosis. These findings demonstrate that the Tie2 C tail performs a novel negative regulatory role in Tie2 signaling and function, and they provide important insights into the mechanisms by which the Tie2 kinase is activated.
Human Serum Amyloid P Component is a Single Uncomplexed Pentamer in Whole Serum (2000)

Human SAP exists within serum as single uncomplexed pentamers in the presence or absence of calcium. This oligomeric assembly, thus, does not require a calcium-dependent small molecule interaction. The usual >2000-fold molar excess of albumin over SAP in plasma is apparently sufficient to keep SAP in its physiological conformation.
Frequencies of HLA-A, B and DRB1 alleles in a large normal population living in the city of Mashhad, Northeastern Iran. (2017)

This study is the first on the HLA class I and II allele frequencies in Northeastern Iranian population living in Mashhad. Distribution of HLA-A and B loci showed some similarities with those of other Iranians. Some difference in HLA-DRB1 polymorphisms however was observed. Considering the highly mixed population of Mashhad, the finding was not unexpected.
T-box genes in human disorders (2003)

The T-box gene family encodes a large family of transcription factors with more than 20 members identified in humans so far, and homologues in many other organisms. A number of human disorders have been linked to mutations in T-box genes, confirming their medical importance. They include Holt- Oram syndrome/TBX5, Ulnar-Mammary syndrome/TBX3, and more recently DiGeorge syndrome/TBX1, ACTH deficiency/TBX19 and cleft palate with ankyloglossia/TBX22. This review describes the key features of these disorders and the involvement of T-box genes in their phenotype.