gebhart/patrepeval huggingface dataset:
Identification of Novel N -(Morpholine-4-Carbonyloxy) Amidine Compounds as Potent Inhibitors against Hepatitis C Virus Replication (2011)

To identify novel compounds that possess antiviral activity against hepatitis C virus (HCV), we screened a library of small molecules with various amounts of structural diversity using an HCV replicon-expressing cell line and performed additional validations using the HCV-JFH1 infectious-virus cell culture. Of 4,004 chemical compounds, we identified 4 novel compounds that suppressed HCV replication with 50% effective concentrations of ranging from 0.36 to 4.81 μM. N'-(Morpholine-4-carbonyloxy)-2-(naphthalen-1-yl) acetimidamide (MCNA) was the most potent and also produced a small synergistic effect when used in combination with alpha interferon. Structure-activity relationship (SAR) analyses revealed 4 derivative compounds with antiviral activity. Further SAR analyses revealed that the N-(morpholine-4-carbonyloxy) amidine moiety was a key structural element for antiviral activity. Treatment of cells with MCNA activated nuclear factor κB and downstream gene expression. In conclusion, N-(morpholine-4-carbonyloxy) amidine and other related morpholine compounds specifically suppressed HCV replication and may have potential as novel chemotherapeutic agents.
Peroxisome proliferator‐activated receptor‐γ agonists prevent experimental autoimmune encephalomyelitis (2002)

The development of clinical symptoms in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE) involves T-cell activation and migration into the central nervous system, production of glial-derived inflammatory molecules, and demyelination and axonal damage. Ligands of the peroxisome proliferator-activated receptor (PPAR) exert anti-inflammatory effects on glial cells, reduce proliferation and activation of T cells, and induce myelin gene expression. We demonstrate in two models of EAE that orally administered PPARgamma ligand pioglitazone reduced the incidence and severity of monophasic, chronic disease in C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein peptide and of relapsing disease in B10.Pl mice immunized with myelin basic protein. Pioglitazone also reduced clinical signs when it was provided after disease onset. Clinical symptoms were reduced by two other PPARgamma agonists, suggesting a role for PPARgamma activation in protective effects. The suppression of clinical signs was paralleled by decreased lymphocyte infiltration, lessened demyelination, reduced chemokine and cytokine expression, and increased inhibitor of kappa B (IkB) expression in the brain. Pioglitazone also reduced the antigen-dependent interferon-gamma production from EAE-derived T cells. These results suggest that orally administered PPARgamma agonists could provide therapeutic benefit in demyelinating disease.
Intrastriatal Transplantation of Bone Marrow Nonhematopoietic Cells Improves Functional Recovery After Stroke in Adult Mice (2000)

The authors transplanted adult bone marrow nonhematopoietic cells into the striatum after embolic middle cerebral artery occlusion (MCAO). Mice (n = 23; C57BL/6J) were divided into four groups: (1) mice (n = 5) were subjected to MCAO and transplanted with bone marrow nonhematopoietic cells (prelabeled by bromodeoxyuridine, BrdU) into the ischemic striatum, (2) MCAO alone (n = 8), (3) MCAO with injection of phosphate buffered saline (n = 5), and (4) bone marrow nonhematopoietic cells injected into the normal striatum (n = 5). Mice were killed at 28 days after stroke. BrdU reactive cells survived and migrated a distance of approximately 2.2 mm from the grafting areas toward the ischemic areas. BrdU reactive cells expressed the neuronal specific protein NeuN in 1% of BrdU stained cells and the astrocytic specific protein glial fibrillary acidic protein (GFAP) in 8% of the BrdU stained cells. Functional recovery from a rotarod test (P < 0.05) and modified neurologic severity score tests (including motor, sensory, and reflex; P < 0.05) were significantly improved in the mice receiving bone marrow nonhematopoietic cells compared with MCAO alone. The current findings suggest that the intrastriatal transplanted bone marrow nonhematopoietic cells survived in the ischemic brain and improved functional recovery of adult mice even though infarct volumes did not change significantly. Bone marrow nonhematopoietic cells may provide a new avenue to promote recovery of injured brain.
Can Dynamic Contrast-Enhanced MRI (DCE-MRI) and Diffusion-Weighted MRI (DW-MRI) Evaluate Inflammation Disease (2016)

The aim of the study was to investigate diagnosis efficacy of dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted MRI (DW-MRI) in Crohn's disease (CD). To find out the correlations between functional MRI parameters including K, Kep, Ve, Vp, and apparent diffusion coefficient (ADC) with a serologic biomarker. The relationships between pharmacokinetic parameters and ADC were also studied.Thirty-two patients with CD (22 men, 10 women; mean age: 30.5 years) and 18 healthy volunteers without any inflammatory disease (10 men, 8 women; mean age, 34.11 years) were enrolled into this approved prospective study. Pearson analysis was used to evaluate the correlation between K, Kep, Ve, Vp, and C-reactive protein (CRP), ADC, and CRP respectively. The diagnostic efficacy of the functional MRI parameters in terms of sensitivity and specificity were analyzed by receiver operating characteristic (ROC) curve analyses. Optimal cut-off values of each functional MRI parameters for differentiation of inflammatory from normal bowel were determined according to the Youden criterion.Mean value of K in the CD group was significantly higher than that of normal control group. Similar results were observed for Kep and Ve. On the contrary, the ADC value was lower in the CD group than that in the control group. K and Ve were shown to be correlated with CRP (r = 0.725, P < 0.001; r = 0.533, P = 0.002), meanwhile ADC showed negative correlation with CRP (r = -0.630, P < 0.001). There were negative correlations between the pharmacokinetic parameters and ADC, such as K to ADC (r = -0.856, P < 0.001), and Ve to ADC (r = -0.451, P = 0.01). The area under the curve (AUC) was 0.994 for K (P < 0.001), 0.905 for ADC (P < 0.001), 0.806 for Ve (P < 0.001), and 0.764 for Kep (P = 0.002). The cut-off point of the K was found to be 0.931 min. This value provided the best trade-off between sensitivity (93.8%) and specificity (100%). The best cut-off point of ADC was 1.11 × 10 mm/s. At this level, sensitivity was 100% and specificity was 68.8%.DCE-MRI and DW-MRI were helpful in the diagnosis of CD. Quantitative MRI parameters could be used to assess the severity of inflammation. The relationships between pharmacokinetic parameters (K and Ve) and ADC reflected microstructure and microcirculation of CD to some extent.
Interallelic complementation among DER/flb alleles: implications for the mechanism of signal transduction by receptor-tyrosine kinases. (1991)

The large number of available embryonic lethal alleles in the Drosophila EGF receptor homolog (DER)/faint little ball locus allowed us to test the possibility of positive or negative interactions among different DER alleles. These interactions were monitored by examining the embryonic cuticular phenotypes of different heteroallelic combinations. Several positive interactions were identified, while negative interactions were restricted to a single allele. This is the first example of positive interactions within the same cell type among alleles of a receptor tyrosine kinase gene. The basis for these interactions is likely to arise from the mechanism of signal transduction by receptor tyrosine kinases, which involves receptor aggregation. A combination of two different DER mutant proteins defective in temporally distinct stages of the signal transduction process, may thus form a functional heterodimer. The mutation sites in four alleles showing positive interactions were localized. They identify regions within the protein which are likely to be important for these temporally distinct signal transduction processes.
Expression of LacZ from thehtrA, nirBandgroEpromoters in aSalmonellavaccine strain: Influence of growth in mammalian cells (1995)

Attenuated Salmonella strains are currently being evaluated as live vectors for the delivery of heterologous antigens to the mammalian mucosal and systemic immune systems. An approach to improving the stability of heterologous antigen expression during vaccination is to drive expression of the foreign protein from promoters, e.g. nirB, that become activated when Salmonella enter the host. Salmonella strains were constructed that harboured similar multicopy plasmids encoding the lacZ gene. In each strain, lacZ expression was driven from either the nirB, htrA or groE promoters. Expression of LacZ increased in all vaccine strains as they were shifted from conditions of low to high temperature. In addition, expression of lacZ driven from the htrA and nirB promoters significantly increased when the Salmonella entered eukaryotic cells, including macrophages. Expression of lacZ from the groE promoter was significantly elevated in macrophages but not in cells derived from epithelia. These promoters may be useful for optimising heterologous antigen expression within immune cells of the host.
Reduction of Nitro Compounds with Borohydride Exchange Resin - Nickel Acetate (1993)

Borohydride Exchange Resin (BER) - nickel acetate system readily reduces both aliphatic and aromatic nitro compounds to the corresponding amino compounds in excellent yields in methanol. This system tolerates hydroxymethyl, phenol, methoxy, acetal, acetyl, carboxylic acid, ester, cyano and halogen (Cl and Br) substituents on the benzene ring.
HIV-1 Tat protein mimicry of chemokines (1998)

The HIV-1 Tat protein is a potent chemoattractant for monocytes. We observed that Tat shows conserved amino acids corresponding to critical sequences of the chemokines, a family of molecules known for their potent ability to attract monocytes. Synthetic Tat and a peptide (CysL24-51) encompassing the "chemokine-like" region of Tat induced a rapid and transient Ca2+ influx in monocytes and macrophages, analogous to beta-chemokines. Both monocyte migration and Ca2+ mobilization were pertussis toxin sensitive and cholera toxin insensitive. Cross-desensitization studies indicated that Tat shares receptors with MCP-1, MCP-3, and eotaxin. Tat was able to displace binding of beta-chemokines from the beta-chemokine receptors CCR2 and CCR3, but not CCR1, CCR4, and CCR5. Direct receptor binding experiments with the CysL24-51 peptide confirmed binding to cells transfected with CCR2 and CCR3. HIV-1 Tat appears to mimic beta-chemokine features, which may serve to locally recruit chemokine receptor-expressing monocytes/macrophages toward HIV producing cells and facilitate activation and infection.
Bacteroides fragilis strains express multiple capsular polysaccharides (1993)

Previous studies by our group have demonstrated that the capsule of Bacteroides fragilis type strain NCTC 9343 consists of two chemically distinct polysaccharides, designated PS A and PS B. These polysaccharides can be isolated as an aggregate from the surface of the organism and give a complex multiprecipitin profile when they are reacted with homologous antiserum in an immunoelectrophoresis assay. Following structural analysis of PS A and PS B, we have determined that the complex precipitin profile is formed as a result of the differing electrophoretic and antigenic properties associated with each of these polymers. Presently, we have examined the capsular polysaccharides of 13 other strains of B. fragilis according to methods used for the prototype strain. The capsules of these strains were extracted, partially purified, and analyzed by immunoelectrophoresis at pH 7.3. Following reaction with homologous polyclonal antisera, each of the capsular preparations tested yielded a complex precipitin profile similar to that of the prototype strain. When reacted by immunoelectrophoresis with polyclonal antiserum to 9343 or with monoclonal antibodies to PS A and PS B, these capsular preparations appeared to be antigenically diverse; some preparations (50%) showed complete or partial cross-reaction. These results suggest that the dual polysaccharide motif seen with the prototype strain is a common feature of B. fragilis strains. In addition, the antigenic heterogeneity of B. fragilis capsular polysaccharides could be used for the development of a serological typing scheme.
A discrete element 3' of human immunodeficiency virus 1 (HIV-1) and HIV-2 mRNA initiation sites mediates transcriptional activation by an HIV trans activator. (1988)

An important point of regulation in the reproductive growth and latency of the human and simian immunodeficiency viruses (HIV and SIV, respectively) is provided by virally encoded trans-activators (tat), proteins capable of dramatically increasing viral gene expression. The mechanism of this autostimulatory pathway has remained unclear, however, with substantial effects having been reported at the level of either mRNA accumulation, translational efficiency, or both. Our previous findings indicated that trans-activation results primarily from induction of RNA levels but could not distinguish between the roles of transcriptional rate, RNA stabilization, and RNA transport in this event. In addition, the boundaries of tat-responding elements, which would be valuable in elucidating the mode of tat action, are not precisely known. In this study, HIV-1 and HIV-2 long terminal repeat-directed expression was characterized by using an in vitro nuclear transcription assay to clarify this mechanism, and a detailed mutational analysis was undertaken to localize precisely the sequences participating in this process. Two key findings were revealed: an increased transcription rate was the primary event in tat-mediated activation of HIV-1 and HIV-2, and trans-activation was impaired by mutations in two regions, the TATA box and sequences between +19 to +42, a region lacking enhancer activity. These results implicate a discrete 3' regulatory element in the transcriptional activation of the HIVs.
Selective induction of transforming growth factor beta in human monocytes by lipoarabinomannan of Mycobacterium tuberculosis (1996)

The induction of macrophage-deactivating (interleukin-10 [IL-10] and transforming growth factor beta [TGF-beta] and macrophage-activating (IL-1, IL-6, and tumor necrosis factor alpha [TNF-alpha] cytokines by lipoarabinomannan (LAM) from pathogenic Mycobacterium tuberculosis Erdman and H37Rv strains (ManLAM) and nonpathogenic mycobacteria (AraLAM) in human blood monocytes was examined. ManLAM was significantly less potent in induction of TNF-alpha, IL-1, IL-6, and IL-10 protein and mRNA, whereas its ability to induce TGF-beta was similar to that of AraLAM. Differences in induction of TNF-alpha mRNA by the two LAM preparations only became apparent at late time points of culture (24 h). The induction of TNF-alpha and IL-1 by purified protein derivative of M. tuberculosis was significantly stronger than that by ManLAM. Pretreatment of monocytes with ManLAM did not, however, interfere with cytokine induction by lipopolysaccharide or AraLAM. The extensive mannosyl capping of arabinose termini of ManLAM may underlie the lack of ability to induce some cytokines (IL-1, TNF-alpha, and IL-10) and the retained ability to induce TGF-beta. The latter may have a role in shifting the cytokine milieu in favor of survival of M. tuberculosis.
Tumor-Specific Novel Taxoid−Monoclonal Antibody Conjugates (2002)

Taxoids bearing methyldisulfanyl(alkanoyl) groups for taxoid-antibody immunoconjugates were designed, synthesized and their activities evaluated. A highly cytotoxic C-10 methyldisulfanylpropanoyl taxoid was conjugated to monoclonal antibodies recognizing the epidermal growth factor receptor (EGFR) expressed in human squamous cancers. These conjugates were shown to possess remarkable target-specific antitumor activity in vivo against EGFR-expressing A431 tumor xenografts in severe combined immune deficiency mice, resulting in complete inhibition of tumor growth in all the treated mice.
Plastic adherent stromal cells from the bone marrow of commonly used strains of inbred mice: Variations in yield, growth, and differentiation (1999)

Bone marrow stroma contains a unique cell population, referred to as marrow stromal cells (MSCs), capable of differentiating along multiple mesenchymal cell lineages. A standard liquid culture system has been developed to isolate MSCs from whole marrow by their adherence to plastic wherein the cells grow as clonal populations derived from a single precursor termed the colony-forming-unit fibroblast (CFU-F). Using this liquid culture system, we demonstrate that the relative abundance of MSCs in the bone marrow of five commonly used inbred strains of mice varies as much as 10-fold, and that the cells also exhibit markedly disparate levels of alkaline phosphatase expression, an early marker of osteoblast differentiation. For each strain examined, the method of isolating MSCs by plastic adherence yields a heterogeneous cell population. These plastic adherent cells also exhibit widely varying growth kinetics between the different strains. Importantly, of three inbred strains commonly used to prepare transgenic mice that we examined, only cells derived from FVB/N marrow readily expand in culture. Further analysis of cultures derived from FVB/N marrow showed that most plastic adherent cells express CD11b and CD45, epitopes of lymphohematopoietic cells. The later consists of both pre-B-cell progenitors, granulocytic and monocytic precursors, and macrophages. However, a subpopulation of the MSCs appear to represent bona fide mesenchymal progenitors, as cells can be induced to differentiate into osteoblasts and adipocytes after exposure to dexamethasone and into myoblasts after exposure to amphotericin B. Our results point to significant strain differences in the properties of MSCs and indicate that standard methods cannot be applied to murine bone marrow to isolate relatively pure populations of MSCs.
Repair and regrowth of Escherichia coli after low- and medium-pressure ultraviolet disinfection (2005)

Ultraviolet (UV) light disinfection has increasingly been used as an alternative method to replace conventional chlorine disinfection as it has been found to be a more efficient disinfection method. As UV disinfection only damages the nucleic acids of the microorganisms to prevent replication, there is a possibility of microorganisms repairing the damage sites. As few studies have investigated the reactivation of microorganisms after exposure to medium-pressure UV disinfection, it is essential for reactivation related to medium-pressure UV disinfection to be studied as medium-pressure lamps are gaining in popularity. Besides, disinfection by-products (DBPs) produced by UV disinfection have been discovered recently and may serve as a carbon source in the finished water, resulting in regrowth of the bacteria. It is therefore important to know the regrowth potential of bacteria with the existence of DBPs. In this study, the repair and regrowth of Escherichia coli after UV disinfection were investigated. Results showed that E. coli underwent photo repair (up to 5 log under fluorescent light conditions) more significantly than dark repair (up to 0.8 log in terms of bacterial count increase). The repair was generally found to be higher at low doses. At the same UV dose, it seems medium-pressure UV irradiation is able to control the repair to a lesser extent. In addition, the bacterial regrowth potential was studied with the addition of DBPs typically found in UV processes, such as acetic acid and formaldehyde. The maximum increase in bacterial count was found to be 0.3 log. Generally, the level of regrowth was insignificant compared with the increase of bacterial count due to bacterial repair.
The concept of a high-brightness, miniaturized gas field ion source (2004)

In this paper, we propose to miniaturize an argon (Ar) GFIS at micron or sub-micron scale. The source can be operated at room temperature and high pressure (100 mbar) and voltages below 140 Volts (i.e the minimum in the Paschen curve for Ar-gas) to avoid Ar gas discharges.
Preventing Pluripotent Cell Teratoma in Regenerative Medicine Applied to Hematology Disorders (2016)

Iatrogenic tumorigenesis is a major limitation for the use of human induced pluripotent stem cells (hiPSCs) in hematology. The teratoma risk comes from the persistence of hiPSCs in differentiated cell populations. Our goal was to evaluate the best system to purge residual hiPSCs before graft without compromising hematopoietic repopulation capability. Teratoma risk after systemic injection of hiPSCs expressing the reporter gene luciferase was assessed for the first time. Teratoma formation in immune-deficient mice was tracked by in vivo bioimaging. We observed that systemic injection of hiPSCs produced multisite teratoma as soon as 5 weeks after injection. To eliminate hiPSCs before grafting, we tested the embryonic-specific expression of suicide genes under the control of the pmiR-302/367 promoter. This promoter was highly active in hiPSCs but not in differentiated cells. The gene/prodrug inducible Caspase-9 (iCaspase-9)/AP20187 was more efficient and rapid than thymidine kinase/ganciclovir, fully specific, and without bystander effect. We observed that iCaspase-9-expressing hiPSCs died in a dose-dependent manner with AP20187, without reaching full eradication in vitro. Unexpectedly, nonspecific toxicity of AP20187 on iCaspase-9-negative hiPSCs and on CD34<sup>+</sup> cells was evidenced in vitro. This toxic effect strongly impaired CD34<sup>+</sup> -derived human hematopoiesis in adoptive transfers. Survivin inhibition is an alternative to the suicide gene approach because hiPSCs fully rely on survivin for survival. Survivin inhibitor YM155 was more efficient than AP20187/iCaspase-9 for killing hiPSCs, without toxicity on CD34<sup>+</sup> cells, in vitro and in adoptive transfers. hiPSC purge by survivin inhibitor fully eradicated teratoma formation in immune-deficient mice. This will be useful to improve the safety management for hiPSC-based medicine. Stem Cells Translational Medicine 2017;6:382-393.