gebhart/patrepeval huggingface dataset:
Dynamic Calcium Metal–Organic Framework Acts as a Selective Organic Solvent Sponge (2010)

Herein, we present a Ca-based metal-organic framework named AEPF-1, which is an active and selective catalyst in olefin hydrogenation reactions. AEPF-1 exhibits a phase transition upon desorption of guest molecules. This structural transformation takes place by a crystal to crystal transformation accompanied by the loss of single-crystal integrity. Powder diffraction methods and computational studies were applied to determine the structure of the guest-free phase. This work also presents data on the exceptional adsorption behavior of this material, which is shown to be capable of separating polar from nonpolar organic solvents, and is a good candidate for selective solvent adsorption under mild conditions.
The Thiocarboxanilide Nonnucleoside UC781 Is a Tight-Binding Inhibitor of HIV-1 Reverse Transcriptase (1997)

The thiocarboxanilide nonnucleoside inhibitor (NNI) UC781 inhibited HIV-1 reverse transcriptase (RT) DNA polymerase activity at a 1:1 molar ratio of inhibitor to enzyme. Inhibition was linear uncompetitive with respect to template/primer (T/P) and mixed noncompetitive with respect to deoxynucleoside triphosphate (dNTP), typical of NNI. When the RT-T/P binary complex was incubated with UC781 and then separated from unbound inhibitor, recovery of enzyme activity was slow, with only about 60% activity recovered after 25 min. The inactivation of the RT-T/P complex was prevented by the presence of a large excess of UC84, another carboxanilide NNI that interacts with this RT mechanistic form. UC781 protected the RT-T/P-dNTP ternary complex from irreversible inactivation by a photoactivatable azido analog of nevirapine, implying that UC781 binds to the NNI pocket of this RT mechanistic form. UC781 did not photoprotect either the free enzyme or the RT-T/P binary complex; however, protein fluorescence quenching studies indicated that UC781 interacted with all RT mechanistic forms, with the order of affinity being RT-T/P-dNTP ternary complex > RT-T/P binary complex > free RT. Reaction progress curve analysis showed that the binding of UC781 to RT is rapid (k(on) approximately 1.7 x 10(6) M(-1) s(-1)), but that dissociation is slow (k(off) approximately 1.6 x 10(-3) s(-1)). UC781 is therefore a rapid tight-binding inhibitor of HIV-1 RT, the first NNI to demonstrate this property.
Progress in Prediction and Interpretation of Clinically Relevant Metabolic Drug-Drug Interactions: a Minireview Illustrating Recent Developments and Current Opportunities (2017)

During the past 10 years, a highly mechanistic understanding has been developed in the area of CYP-mediated metabolic DDIs enabling the prediction of clinical outcome based on preclinical studies. The combination of good quality in vitro data and physiologically based pharmacokinetic modeling may now be used to evaluate DDI risk prospectively and are increasingly accepted in lieu of dedicated clinical studies.
Synthesis, Molecular Modeling Studies, and Pharmacological Activity of Selective A1Receptor Antagonists (2002)

We present a combined computational study aimed at identifying the three-dimensional structural properties required for different classes of compounds to show antagonistic activity toward the A(1) adenosine receptor (AR). Particularly, an approach combining pharmacophore mapping, molecular alignment, and pseudoreceptor generation was applied to derive a hypothesis of the interaction pathway between a set of A(1) AR antagonists taken from the literature and a model of the putative A(1) receptor. The pharmacophore model consists of seven features and represents an improvement of the N(6)-C8 model, generally reported as the most probable pharmacophore model for A(1) AR agonists and antagonists. It was used to build up a pseudoreceptor model able to rationalize the relationships between structural properties and biological data of, and external to, the training set. In fact, to further assess its statistical significance and predictive power, the pseudoreceptor was employed to predict the free energy of binding associated with compounds constituting a test set. While part of these molecules was also taken from the literature, the remaining compounds were designed and synthesized by our research group. All of the new compounds were tested for their affinity toward A(1), A(2a), and A(3) AR, showing interesting antagonistic activity and A(1) selectivity.
Elevated expression of microRNAs 155, 203, 210 and 222 in pancreatic tumors is associated with poorer survival (2009)

Pancreatic cancer is the eighth most common cancer and has an overall 5-year survival rate lower than 10%. Because of their ability to regulate gene expression, microRNAs can act as oncogenes or tumor-suppressor genes and so have garnered interest as possible prognostic and therapeutic markers during the last decade. However, the prognostic value of microRNA expression in pancreatic cancer has not been thoroughly investigated. We measured the levels of miR-155, miR-203, miR-210, miR-216, miR-217 and miR-222 by quantitative RT-PCR in a cohort of 56 microdissected pancreatic ductal adenocarcinomas (PDAC). These microRNAs were chosen as they had previously been shown to be differentially expressed in pancreatic tumors compared to normal tissues. The possible association of microRNA expression and patients' survival was examined using multivariate Cox's regression hazard analyses. Interestingly, significant correlations between elevated microRNA expression and overall survival were observed for miR-155 (RR = 2.50; p = 0.005), miR-203 (RR = 2.21; p = 0.017), miR-210 (RR = 2.48; p = 0.005) and miR-222 (RR = 2.05; p = 0.035). Furthermore, tumors from patients demonstrating elevated expression levels of all 4 microRNAs possessed a 6.2-fold increased risk of tumor-related death compared to patients whose tumors showed a lower expression of these microRNAs. This study provides the first evidence for an oncogenic activity of miR-155, miR-203, miR-210 and miR-222 in the development of pancreatic cancer as has been reported for other tumor types. Furthermore, the putative target genes for these microRNAs suggest a complex signaling network that can affect PDAC tumorigenesis and tumor progression.
Angiotensin II Receptor Subtypes (1992)

The octapeptide, angiotensin II (Ang II), the biologically active component of the renin-angiotensin system, elicits its multiple actions through the stimulation of specific surface receptors on various target organs. Although the existence of Ang II receptor subtypes has been suspected for some time, definitive evidence for Ang II receptor heterogeneity has been obtained only with the recently introduced nonpeptide Ang II receptor antagonists, exemplified by the prototypic compounds DuP 753 and PD 123177. The sites having high affinity for DuP 753 are designated as site 1 (AT1 receptors) and those having a high affinity for PD 123177 as site 2 (AT2 receptors). Unlike Ang I, Ang II, Ang III, and peptide antagonists, such as saralasin, which all are relatively nonselective ligands for both Ang II receptors, the peptides CGP42112A and p-aminophenylalanine6-Ang II show a marked preference for the AT2 site. The occurrence of the AT1 and AT2 receptor subtypes/binding sites identified so far appears widespread. The presence and proportion of these receptors vary significantly among different tissues/organs of the same species and within the same tissue/organ of different species. Despite the abundance of the AT2 site, its functional correlates remain to be determined. The DuP 753-sensitive site (AT1 receptor) mediates all the major Ang II-induced biological effects, including adrenal aldosterone and catecholamine secretion, release of catecholamines from sympathetic ganglia, central nervous system responses, and vasoconstriction.
Bacteria mature preproinsulin to proinsulin. (1980)

By inserting the rat preproinsulin gene into the bacterial prepenicillinase gene, we formed a variety of hybrid bacterial-eukaryotic signal sequences attached to proinsulin. Among these were the four following constructions: rat proinsulin attached to the entire penicillinase signal sequence and rat preproinsulin fused to all of, to half of, or only to the first four amino acids of the bacterial signal sequence. In all four cases, more than 90% of the rat insulin antigen appeared in the periplasmic space. By immunoprecipitation and determination of the amino acid sequences of the radiolabeled products, we show that the bacteria correctly process both the bacterial and the eukaryotic signal sequences of these hybrid proteins. The cleavage of the eukaryotic signal by bacterial peptidase, in this case, generates proinsulin.
Assessment of White Spot Lesions and In-Vivo Evaluation of the Effect of CPP-ACP on White Spot Lesions in Permanent Molars of Children (2016)

CPP-ACP therapy minimum for 12 weeks is highly recommended as post-orthodontic treatment need in management of smooth surface white spot lesions on teeth undergoing fixed orthodontic therapy according to the present study.
Transurethral Balloon Laser Thermotherapy: Effects of a Directionally Shielded Balloon in Canine Prostates (1996)

TUBAL-T, which has been performed in clinical cases of benign prostatic hyperplasia, might be useful in selective irradiation of adenoma if a shielded balloon is used.
Sulfated Glycans Stimulate Endocytosis of the Cellular Isoform of the Prion Protein, PrPC, in Cultured Cells (1995)

There is currently no effective therapy for human prion diseases. However, several polyanionic glycans, including pentosan sulfate and dextran sulfate, prolong the incubation time of scrapie in rodents, and inhibit the production of the scrapie isoform of the prion protein (PrPSc), the major component of infectious prions, in cultured neuroblastoma cells. We report here that pentosan sulfate and related compounds rapidly and dramatically reduce the amount of PrPC, the non-infectious precursor of PrPSc, present on the cell surface. This effect results primarily from the ability of these agents to stimulate endocytosis of PrPC, thereby causing a redistribution of the protein from the plasma membrane to the cell interior. Pentosan sulfate also causes a change in the ultrastructural localization of PrPC, such that a portion of the protein molecules are shifted into late endosomes and/or lysosomes. In addition, we demonstrate, using PrP-containing bacterial fusion proteins, that cultured cells express saturable and specific surface binding sites for PrP, many of which are glycosaminoglycan molecules. Our results raise the possibility that sulfated glycans inhibit prion production by altering the cellular localization of PrPC precursor, and they indicate that endogenous proteoglycans are likely to play an important role in the cellular metabolism of both PrPC and PrPSc.
<title>Surveillance, detection, and 3D infrared tracking of bullets, rockets, mortars, and artillery</title> (2001)

We describe test results using the FIRST (Fast InfraRed Sniper Tracker) to detect, track, and range to bullets in flight for determining the location of the bullet launch point. The technology developed for the FIRST system can be used to provide detection and accurate 3D track data for other small threat objects including rockets, mortars, and artillery in addition to bullets. We discuss the radiometry and detection range for these objects, and discuss the trade-offs involved in design of the very fast optical system for acquisition, tracking, and ranging of these targets.
MAMMALIAN PAX GENES (1994)

Orthologs and paralogs are two fundamentally different types of homologous genes that evolved, respectively, by vertical descent from a single ancestral gene and by duplication. Orthology and paralogy are key concepts of evolutionary genomics. A ...Read More
Selective induction of the beta chemokine C10 by IL-4 in mouse macrophages. (1994)

The beta chemokines are a family of 8- to 12-kDa leukocyte chemoattractants that are typically produced by activated macrophages or lymphocytes. We examined the expression in primary macrophages of a recently described, and as yet functionally uncharacterized, murine beta chemokine, C10, and contrasted its regulation with that of several other beta chemokines. Although three other beta chemokines, macrophage inflammatory protein-1 alpha (MIP-1 alpha), JE, and RANTES, were all induced by LPS treatment of bone marrow-derived macrophages (BMM) and/or resident peritoneal macrophages (RPM), LPS stimulation of C10 was never observed. Conversely, IL-3 and granulocyte macrophage-CSF (GM-CSF) strongly induced C10 in both macrophage populations, whereas MIP-1 alpha and RANTES showed a weaker induction restricted to BMM. JE was strongly induced but only in BMM. Finally, IL-4 strongly induced C10 in a dose-dependent manner in both BMM and RPM but failed to stimulate any of the other three beta chemokines. The accumulation of C10 protein in culture supernatants paralleled the induction of mRNA, and the combination of IL-4 and GM-CSF led to enhanced protein levels. The expression of the C10 message in response to cytokines was completely blocked by cycloheximide, whereas the other three chemokines were all overexpressed in the presence of this inhibitor. These results demonstrate a sharp divergence between the regulation of C10 expression and that of other chemokines and suggest that this molecule may have distinct functions in host defense.
Recovery of human neutrophils from complement attack: removal of the membrane attack complex by endocytosis and exocytosis. (1987)

Nucleated cells can resist lysis by and recover from complement attack even after formation of the potentially cytolytic membrane attack complex on the cell surface. We have found that human neutrophils resist complement lysis by the physical removal of membrane attack complexes by both endocytic and exocytic process. The latter mechanism predominates, vesiculation being detectable within 60 sec of initiating the complement cascade. Sixty-five percent of the formed complexes are removed on plasma membrane vesicles, although only 2% of the cell surface is lost. Ultrastructural examination revealed that these vesicles were covered with ring-like "classical" complement lesions. Analysis of these vesicles by gel electrophoresis indicated that C9 was present exclusively in the form of a sodium dodecyl sulfate-resistant, high m.w. complex. In contrast, the 35% of C9 that remained associated with the cells was found to be inaccessible to a C9-specific monoclonal antibody, and was partly degraded, suggesting internalization of the membrane attack complex and proteolysis of some C9 molecules. The molar ratio of C9 to C8 was 12 to 1 on shed vesicles and on recovered cells.
A GaAsxP1−x/GaP strained-layer superlattice (1982)

Strained−layer superlattices form a broad new class of semiconductor materials with tailorable electronic properties. We have succeeded in growing a GaAsxP1−x/GaP(100) strained−layer superlattice (SLS). The structure was grown by alternate metalorganic chemical vapor deposition of thin (60 Å)layers (20 each) of GaAs0.4P0.6 and GaP. These layers were grown onto a GaAsxP1−x layer which was graded in composition from x = 0 (composition of underlying GaP substrate)to x = 0 (average composition of the SLS). Photoluminescense studies of the SLS were carried out to determine the optical band gap. At T = 78 K, the spectrum shows a dominant band−edge peak at 2.03 eV as well as weaker peaks at higher energies. Tight binding and effective mass calculations, also carried out, predict a direct band gap (due to zone folding) of 2.02 eV and higher lying transition energies which are in good agreement with these data.
Circulating cellular fibronectin may be a natural ligand for the hepatic asialoglycoprotein receptor: Possible pathway for fibronectin deposition and turnover in the rat liver (1998)

It has been postulated that the in vivo removal of many plasma glycoproteins after desialylation is mediated by their interaction with a specific endocytic receptor on hepatocytes called the asialoglycoprotein receptor (ASGP-R), which is known to have a high affinity for specific carbohydrate residues, such as galactose. However, this mechanism has never been proven in vivo, nor has a naturally occurring ligand for the ASGP-R been identified. We investigated the influence of the terminal galactose residues on plasma fibronectin (pFn) on its liver deposition and turnover in adult rats, using neuraminidase to remove sialic acid residues to expose galactose residues. We also tested the hypothesis that the normal presence of a large amount of terminal galactose residues in cellular Fn (cFn) may allow cFn to serve as a natural ligand readily able to interact with the ASGP-R. In contrast to the slow clearance of normal pFn from the blood, cFn and desialylated pFn (aFn) displayed a rapid plasma clearance (P < .001) with greater than 50% of both the 125I-cFn or 125I-aFn depositing in the liver within 15 minutes. The enhanced plasma removal and liver deposition of both 125I-cFn and 125I-aFn was competitively inhibited (P < .01) by prior intravenous infusion of excess asialofetuin, which can selectively bind to the ASGP-R. The enzymatic addition of terminal sialic acid residues onto cFn to "mask" or "cap" the normally exposed galactose residues delayed the rapid plasma removal of cFn. Accelerated degradation of 125I-aFn and 125I-cFn as compared with 125I-pFn was demonstrated in vitro by both primary cultures of normal rat hepatocytes or incubated (37 degrees C) tissue slices of livers harvested from normal rats after in vivo preloading with tracer 125I-Fn forms. Thus, the ASGP-R appears to directly participate in the rapid in vivo removal of cFn from the blood, while native pFn may be removed by an alternative pathway unless it can become desialylated in vivo. These findings suggest that cFn may be a naturally occurring ligand that does not require desialylation before removal by the ASGP-R on hepatocytes.
Replication of Wild-Type and Mutant Human Cytomegalovirus in Life-Extended Human Diploid Fibroblasts (2000)

A cDNA encoding the catalytic subunit of human telomerase was used to generate life-extended derivatives of primary human diploid fibroblasts. The life-extended cells supported efficient human cytomegalovirus (HCMV) replication. A subclone of the life-extended cells was generated containing the HCMV UL82 gene and used to isolate and propagate a virus that exhibited a profound growth defect after infection at a low input multiplicity.
D - band silicon impatt diode (2005)

This paper reports the progress in D-band CW silicon IMPATT diode. The small-signal. computer simulation of a diode has been performed. The preliminary experiments of the single-drift IMPATT diode show a aw output power of 73 mW at 116.7GHz and 34mW at 126GHz, respectively.
CRISPR/Cas9 nickase-mediated disruption of hepatitis B virus open reading frame S and X (2015)

Current antiviral therapies cannot cure hepatitis B virus (HBV) infection; successful HBV eradication would require inactivation of the viral genome, which primarily persists in host cells as episomal covalently closed circular DNA (cccDNA) and, to a lesser extent, as chromosomally integrated sequences. However, novel designer enzymes, such as the CRISPR/Cas9 RNA-guided nuclease system, provide technologies for developing advanced therapy strategies that could directly attack the HBV genome. For therapeutic application in humans, such designer nucleases should recognize various HBV genotypes and cause minimal off-target effects. Here, we identified cross-genotype conserved HBV sequences in the S and X region of the HBV genome that were targeted for specific and effective cleavage by a Cas9 nickase. This approach disrupted not only episomal cccDNA and chromosomally integrated HBV target sites in reporter cell lines, but also HBV replication in chronically and de novo infected hepatoma cell lines. Our data demonstrate the feasibility of using the CRISPR/Cas9 nickase system for novel therapy strategies aiming to cure HBV infection.
An Improved Method for the Purification of Human Insulin-Like Growth Factors I and II* (1986)

Insulin-like growth factors (IGFs) I and II have been purified from Cohn fraction IV-1 of human plasma. After acid-ethanol extraction, the consecutive use of conventional gel filtration and reverse phase liquid chromatography has permitted the rapid isolation of these polypeptides. Purification was monitored by the use of specific RIAs. In both chromatography systems, separation was optimized by performing it on the same stationary phase but successively with mobile phases of different pH or different solute selectivity. The two polypeptides were shown to be pure by their unique amino acid composition, particularly by the absence of specific amino acids (histidine, tryptophan, and methionine), and their unique amino-terminal sequences. In addition, the lack of cross-contamination of the two growth factors with each other was established by the unique isoelectric focusing patterns of IGF-I at pI 8.25 and IGF-II at pI 6.5. From 900 g Cohn fraction IV-1, which is equivalent to 66 liters human plasma, approximately 100 micrograms of each IGF can be obtained by our procedure, which can easily be carried out in a clinical research laboratory.
Immune Responses to Epidermal Growth Factor Receptor (EGFR) and Their Application for Cancer Treatment (2016)

Epidermal growth factor receptor (EGFR) is a prototypic cell-surface receptor belonging to the ErbB/HER onocogene family. Overexpression or somatic mutations of EGFR have been reported to play an important role in tumorigenesis in various types of epithelial cancers. Therefore, targeting of EGFR with specific blocking antibodies or inhibitors have been developing for treatment for EGFR-associated tumors. Immune responses to HER2, another molecule of the ErbB/HER onocogene family, have been well studied, but only limited information on the immune responses to EGFR in cancer has been currently available. In this review, we have summarized the available data and discussed potential clinical importance of the anti-EGFR immune responses and EGFR-mediated immune regulation in cancer. Several lines of evidence suggest that cellular and humoral immune responses to EGFR might be useful as a marker and/or target for cancer therapy against EGFR-associated tumors. In addition, recent studies suggest the critical roles of EGFR-mediated signaling in regulation of expression of an immune checkpoint molecule, programmed death-ligand 1 (PD-L1) in tumor cells. Further studies are warranted to clarify the impact of the anti-EGFR immune responses and EGFR-mediated immunomodulation for clinical application for cancer treatment.
Activity of rabbit leukocyte peptides against Candida albicans (1985)

Six related cysteine-rich, low-molecular-weight peptides were purified from rabbit peritoneal granulocytes and tested in vitro for fungicidal activity against Candida albicans. Two peptides (NP-1 and NP-2) were highly effective, one (NP-3a) was moderately active, and three (NP-3b greater than NP-4 much greater than NP-5) had substantially less potency. There was a general, but imperfect, correlation between the candidacidal potency of each peptide and its net cationic charge. Candidacidal activity by NP-1 was concentration and time dependent and occurred rapidly under optimal low-ionic-strength conditions. It was inhibited by increasing either the ionic strength or Ca2+ concentration of the incubation mixtures, but was relatively unaffected by Mg2+. Candidacidal activity was independent of H+ concentrations between pH 5 and 8, but decreased below pH 5. Candidacidal activity was temperature sensitive and was virtually abolished when NP-1 was incubated with C. albicans at 0 degrees C. Cysteine-rich antimicrobial peptides such as NP-1 and NP-2 may equip leukocytes to deal with infections caused by C. albicans and other fungi that are susceptible to their microbicidal effects.