gebhart/patrepeval huggingface dataset:
Lentivirus Vectors Pseudotyped with Filoviral Envelope Glycoproteins Transduce Airway Epithelia from the Apical Surface Independently of Folate Receptor Alpha (2003)

The practical application of gene therapy as a treatment for cystic fibrosis is limited by poor gene transfer efficiency with vectors applied to the apical surface of airway epithelia. Recently, folate receptor alpha (FR alpha), a glycosylphosphatidylinositol-linked surface protein, was reported to be a cellular receptor for the filoviruses. We found that polarized human airway epithelia expressed abundant FR alpha on their apical surface. In an attempt to target these apical receptors, we pseudotyped feline immunodeficiency virus (FIV)-based vectors by using envelope glycoproteins (GPs) from the filoviruses Marburg virus and Ebola virus. Importantly, primary cultures of well-differentiated human airway epithelia were transduced when filovirus GP-pseudotyped FIV was applied to the apical surface. Furthermore, by deleting a heavily O-glycosylated extracellular domain of the Ebola GP, we improved the titer of concentrated vector severalfold. To investigate the folate receptor dependence of gene transfer with the filovirus pseudotypes, we compared gene transfer efficiency in immortalized airway epithelium cell lines and primary cultures. By utilizing phosphatidylinositol-specific phospholipase C (PI-PLC) treatment and FR alpha-blocking antibodies, we demonstrated FR alpha-dependent and -independent entry by filovirus glycoprotein-pseudotyped FIV-based vectors in airway epithelia. Of particular interest, entry independent of FR alpha was observed in primary cultures of human airway epithelia. Understanding viral vector binding and entry pathways is fundamental for developing cystic fibrosis gene therapy applications.
First-Line Single Agent Treatment With Gefitinib in Patients With Advanced Non–Small-Cell Lung Cancer: A Phase II Study (2005)

Single agent treatment with gefitinib is active in chemotherapy-naïve patients with advanced NSCLC, but produces unacceptably frequent ILD in the Japanese population.
Expression of E-cadherin in meningioma and its relationship with meningioma pathology grading (2015)

Objective To observe the expression of E‐cadherin in meningioma ,and discuss its the relationship with and meningioma pathology grading ,further explore the effect of E cadherin in invasive behavior and recurrence ,and analyze the clinical significance of E‐cadherin in the diagnosis and treatment of meningioma.Methods 48 cases of patients with meningioma from January 2005 to January 2014 in our hospital were selected as research objects. Immunohistochemical method was used to test the expression of E‐cadherin for patients with meningioma. Expressions under the conditions of invasive behavior and re‐currence in different pathological grading ,and edema were studied. The relationship between E‐cadherin and meningioma path‐ological grading were explored. Results Based on the expression result of E‐cadherin under different pathological grading ,the negative expression rate of grade Ⅰ was 10.3% ,grade Ⅱ was 60.0% ,and grade Ⅲ was 100%. The difference was significant (P<0.05);Based on the expression result of E‐cadherin under different edema grading ,the negative expression rate of grade 1 was 15.8% ,grade 2 was 62.5% ,and grade 3 was 100.0%. The difference was significant(P<0.05);the specimens were di‐vided in invasiveness group and no invasion group based on the invasion condition. The negative expression rate of the invasive‐ness group was 53.8% ,and no invasion group was 14.3%. The difference was statistically significant(P<0.05). The speci‐mens were divided into recurrence group and no recurrence group based on recurrence condition. The negative expression rate of the recurrence group was 66.7% ,and rate of no recurrence group was 15.4%. The difference was significant(P<0.05). Con‐clusion E‐cadherin expression is closely related with meningioma pathological grading ,edema ,recurrence rate ,and invasion. Testing the expression of E‐cadherin in the meningioma helps to explore the biological behavior of meningioma ,which is signifi‐cant for disease progression and prognosis.
Software profiling for hot path prediction (2000)

Recently, there has been a growing interest in exploiting profile information in adaptive systems such as just-in-time compilers, dynamic optimizers and, binary translators. In this paper, we show that sophisticated software profiling schemes that provide highly accurate information in an offline setting are ill-suited for these dynamic code generation systems. We experimentally demonstrate that hot path predictions must be made early in order to control the rising cost of missed opportunity that result from the prediction delay. We also show that existing sophisticated path profiling schemes, if used in an online setting, offer no prediction advantages over simpler schemes that exhibit much lower runtime overheads.Based on these observation we developed a new low-overhead software profiling scheme for hot path prediction. Using an abstract metric we compare our scheme to path profile based prediction and show that our scheme achieves comparable prediction quality. In our second set of experiments we include runtime overhead and evaluate the performance of our scheme in a realistic application: Dynamo, a dynamic optimization system. The results show that our prediction scheme clearly outperforms path profile based prediction and thus confirm that less profiling as exhibited in our scheme will actually lead to more effective hot path prediction.
Nightguard vital bleaching: how safe is it? (1991)

The conservative technique for bleaching vital teeth using a nightguard and a 10% carbamide peroxide solution has captured the esthetic interests of the dental profession. The purpose of this article is to assess the safety of the products used in this bleaching technique based on results from past related research and current research. Ten percent carbamide peroxide solutions used in numerous studies have demonstrated tissue-healing properties as well as a propensity for the reduction of plaque and gingivitis. None of these clinical studies revealed any untoward or detrimental side effects, and all demonstrated beneficial effects. Although some concern exists regarding the potentiating effects of peroxide solutions in the presence of known carcinogens, concerns of toxicity or damage to hard and soft tissues appear unfounded. The majority of current and past research and literature indicates that the current use of a 10% carbamide peroxide solution in the method advocated for bleaching vital teeth is apparently safe when administered properly under the supervision of a dentist.
On Combining Recursive Partitioning and Simulated Annealing To Detect Groups of Biologically Active Compounds (2002)

Statistical data mining methods have proven to be powerful tools for investigating correlations between molecular structure and biological activity. Recursive partitioning (RP), in particular, offers several advantages in mining large, diverse data sets resulting from high throughput screening. When used with binary molecular descriptors, the standard implementation of RP splits on single descriptors. We use simulated annealing (SA) to find combinations of molecular descriptors whose simultaneous presence best separates off the most active, chemically similar group of compounds. The search is incorporated into a recursive partitioning design to produce a regression tree for biological activity on the space of structural fingerprints. Each node is characterized by a specific combination of structural features, and the terminal nodes with high average activities correspond, roughly, to different classes of compounds. Using LeadScope structural features as descriptors to mine a database from the National Cancer Institute, the merging of RP and SA consistently identifies structurally homogeneous classes of highly potent anticancer agents.
Genomic changes defining the genesis, progression, and malignancy potential in solid human tumors: A phenotype/genotype correlation (1999)

The transition of normal epithelium to invasive carcinoma occurs sequentially. In colorectal and cervical carcinogenesis, this transition is reflected by histomorphologically defined grades of increasing dysplasia that untreated may progress to invasive disease. In an attempt to understand the role of chromosomal aberrations during tumorigenesis we have applied comparative genomic hybridization using DNA extracted from defined stages of colorectal and cervical tumors, from low- and high-grade astrocytic tumors and from diploid and aneuploid breast carcinomas. Genetic instability, as measured by the number of chromosomal copy alterations per case, increases significantly at the transition from precursor lesions to invasive carcinomas and continues to increase with tumor stage. Aggressive tumors have a higher number of copy alterations per case. High-level copy number changes (amplifications) become more prevalent in advanced-stage disease. Subtractive karyograms of chromosomal gains and losses were used to map tumor stage-specific chromosomal aberrations and clearly showed that nonrandom chromosomal aberrations occur during disease progression. In colorectal and cervical tumors, chromosomal copy number changes were correlated with nuclear DNA content, proliferative activity, expression levels of the tumor suppressor gene TP53, and the cyclin-dependent kinase inhibitor p21/WAF1, as well as the presence of viral genomes. Here we summarize and review the results of this comprehensive phenotype/genotype correlation and discuss the relevance of stage-specific chromosomal aberrations with respect to diagnostic applications.
Total Synthesis of (+)-Zaragozic Acid C (2000)

A total synthesis of (+)-zaragozic acid C is described. Key features of the synthesis are the use of a double Sharpless asymmetric dihydroxylation reaction of diene 6 to control stereochemistry at four contiguous stereocenters from C3 to C6; the introduction of the C1-side chain by reaction between the anion derived from the dithiane monosulfoxide 27 and the core aldehyde 12; a high yielding, acid-mediated simultaneous acetonide deprotection−dithiane removal−ketalization procedure leading exclusively to the 2,8-dioxabicyclo[3.2.1]octane core 34; and a novel triple oxidation procedure allowing installation of the tricarboxylic acid.
Multiple Roles of a Conserved GAF Domain Tyrosine Residue in Cyanobacterial and Plant Phytochromes (2005)

The phytochrome family of red/far-red photoreceptors has been optimized to support photochemical isomerization of a bound bilin chromophore, a process that triggers a conformational change and modulates biochemical output from the surrounding protein scaffold. Recent studies have established that the efficiency of this photochemical process is profoundly altered by mutation of a conserved tyrosine residue (Tyr176) within the bilin-binding GAF domain of the cyanobacterial phytochrome Cph1 [Fischer, A. J., and Lagarias, J. C. (2004) Harnessing phytochrome's glowing potential, Proc. Natl. Acad. Sci. U.S.A. 101, 17334-17339]. Here, we show that the equivalent mutation in plant phytochromes behaves similarly, indicating that the function of this tyrosine in the primary photochemical mechanism is conserved. Saturation mutagenesis of Tyr176 in Cph1 establishes that no other residue can support comparably efficient photoisomerization. The spectroscopic consequences of Tyr176 mutations also reveal that Tyr176 regulates the conversion of the porphyrin-like conformation of the bilin precursor to a more extended conformation. The porphyrin-binding ability of the Tyr176Arg mutant protein indicates that Tyr176 also regulates the ligand-binding specificity of apophytochrome. On the basis of the hydrogen-bonding ability of Tyr176 substitutions that support the nonphotochemical C15-Z,syn to C15-Z,anti interconversion, we propose that Tyr176 orients the carboxyl side chain of a conserved acidic residue to stabilize protonation of the bilin chromophore. A homology model of the GAF domain of Cph1 predicts a C5-Z,syn, C10-Z,syn, C15-Z,anti configuration for the chromophore and implicates Glu189 as the proposed acidic residue stabilizing the extended conformation, an interpretation consistent with site-directed mutagenesis of this conserved acidic residue.
Carbazole–pyrrolo[2,1-c][1,4]benzodiazepine conjugates: design, synthesis, and biological evaluation (2011)

A series of carbazole–pyrrolobenzodiazepine conjugates (4a–g and 5a–f) have been designed, and synthesized as anticancer agents. These compounds are prepared by linking the C8-position of DC-81 with a carbazole moiety through simple alkane spacers as well as piperazine side-armed alkane spacers in good yields. The DNA binding ability of these conjugates has been determined by thermal denaturation studies and also supported by molecular docking studies. These conjugates showed potent anticancer activity with GI50 ranging from 5.27–0.01 μM. The FACS analysis and BrdU assay of selected conjugates (4c, 4f, 5a and 5f) on MCF-7 cell lines disclosed the increased G1 cell cycle arrest and one of the conjugates 5f has exhibited significant anticancer activity. The analysis of the intrinsic factors involved in causing the G1 arrest in MCF-7 cell lines by 5f conjugate has been demonstrated on the proteins which play a vital role in G1 arrest followed by apoptosis (Cyclin D1, CDK4, c-Jun, JunB, CREB, p53, JNK1/2, procaspase-7, cleaved PARP, pRb, and BAX). Thus, these PBD conjugates (in particular 5f) have promising potency for combating human carcinoma.
Solar Thermochemical Water-Splitting Ferrite-Cycle Heat Engines (2008)

Thermochemical cycles are a type of heat engine that utilize high-temperature heat to produce chemical work. Like their mechanical work producing counterparts, their efficiency depends on the operating temperature and on the irreversibility of their internal processes. With this in mind, we have invented innovative design concepts for two-step solar-driven thermochemical heat engines based on iron oxide and iron oxide mixed with other metal oxide (ferrites) working materials. The design concepts utilize two sets of moving beds of ferrite reactant materials in close proximity and moving in opposite directions to overcome a major impediment to achieving high efficiency—thermal recuperation between solids in efficient countercurrent arrangements. They also provide an inherent separation of the product hydrogen and oxygen and are an excellent match with a high-concentration solar flux. However, they also impose unique requirements on the ferrite reactants and materials of construction as well as an understanding of the chemical and cycle thermodynamics. In this paper, the counter-rotating-ring receiver∕reactor∕recuperator solar thermochemical heat engine concept is introduced, and its basic operating principles are described. Preliminary thermal efficiency estimates are presented and discussed. Our results and development approach are also outlined.
Total Synthesis and Structure−Activity Investigation of the Marine Natural Product Neopeltolide (2009)

The total synthesis and biological evaluation of neopeltolide and analogs are reported. The key bond-forming step utilizes a Lewis acid-catalyzed intramolecular macrocyclization that installs the tetrahydropyran ring and macrocycle simultaneously. Independent of each other, neither the macrolide nor the oxazole side chain substituents of neopeltolide can inhibit the growth of cancer cell lines. The biological data of the analogs indicate that alterations to either the ester side chain or the stereochemistry of the macrolide result in a loss of biological activity.
The expression pattern of a novel gene encoding brain-fatty acid binding protein correlates with neuronal and glial cell development (1994)

Fatty acid binding proteins (FABPs) are a multigene family of small intracellular proteins that bind hydrophobic ligands. In this report we describe the cloning and expression pattern of a novel member of this gene family that is specifically expressed in the developing and adult nervous system and thus was designated brain (B)-FABP. B-FABP is closely related to heart (H)-FABP with 67% amino acid identity. B-FABP expression was first detected at mouse embryonic day 10 in neuroepithelial cells and its pattern correlates with early neuronal differentiation. Upon further development, B-FABP was confined to radial glial cells and immature astrocytes. B-FABP mRNA and protein were found in glial cells of the peripheral nervous system such as satellite cells of spinal and cranial ganglia and ensheathing cells of the olfactory nerve layer from as early as embryonic day 11 until adulthood. In the adult mouse brain, B-FABP was found in the glia limitans, in radial glial cells of the hippocampal dentate gyrus and Bergman glial cells. These findings suggest a function of B-FABP during neurogenesis or neuronal migration in the developing nervous system. The partially overlapping expression pattern with that of cellular retinoid binding proteins suggests that B-FABP is involved in the metabolism of a so far unknown hydrophobic ligand with potential morphogenic activity during CNS development.
Comparison of conventional susceptibility tests with direct detection of penicillin-binding protein 2a in borderline oxacillin-resistant strains of Staphylococcus aureus (1991)

Six selected strains of Staphylococcus aureus classified as borderline oxacillin-resistant, according to standard disk diffusion and microdilution susceptibility test methods, and seven methicillin-resistant and seven methicillin-susceptible control strains were examined for the presence of penicillin-binding protein 2a (PBP 2a) by fluorography and immunoblotting and for DNA hybridization with a mec-specific probe in a dot blot assay. Oxacillin agar screen tests with and without NaCl supplementation were also performed with all strains. PBP 2a was detected both by fluorography and by immunoblotting in all seven methicillin-resistant control strains and in none of the susceptible controls. PBP 2a was detected in two borderline strains. Results of agar screen tests performed without NaCl supplementation were completely concordant with susceptibility determined by PBP 2a and mec detection methods. Agar screening with NaCl supplementation was less accurate. These findings were confirmed with 20 additional borderline strains. Direct detection methods for the presence of PBP 2a or mec, the gene encoding it, allow accurate and definitive classification of borderline strains. Further efforts to develop a rapid, clinically useful, antibody detection system for PBP 2a are warranted.
Population Suppression of Subterranean Termites by Slow-Acting Toxicants (1991)

Historic background and the concept of slow-acting toxicants for population suppression of subterranean termites are reviewed. Information needed for development of bait-toxicants and studies needed to generate such information are summarized.
Targeting Bacteriophage to Mammalian Cell Surface Receptors for Gene Delivery (1998)

Filamentous bacteriophages represent one of nature's most elegant ways of packaging and delivering DNA. In an effort to develop novel methods for ligand discovery via phage gene delivery, we conferred mammalian cell tropism to filamentous bacteriophages by attaching basic fibroblast growth factor (FGF2), transferrin, or epidermal growth factor (EGF) to their coat proteins and measuring CMV promoter-driven reporter gene expression in target cells. In this system, FGF2 was a more effective targeting agent than transferrin or EGF. The detection of green fluorescent protein (GFP) or beta-galactosidase (beta-Gal) activity in cells required FGF2 targeting and was phage concentration dependent. Specificity of the targeting for high-affinity FGF receptors was demonstrated by competing the targeted phage with FGF2, by the failure of FGF2-targeted bacteriophage to transduce high-affinity FGF receptor-negative cells, and by their ability to transduce these same cells when stably transfected with FGFR1, a high-affinity FGF receptor. Long-term transgene expression was established by selecting colonies for G418 resistance, suggesting that with the appropriate targeted tropism, filamentous bacteriophage can serve as a vehicle for targeted gene delivery to mammalian cells.
The Expanding Horizons of Asparagine-Linked Glycosylation (2011)

Asparagine-linked glycosylation involves the sequential assembly of an oligosaccharide onto a polyisoprenyl donor, followed by the en bloc transfer of the glycan to particular asparagine residues within acceptor proteins. These N-linked glycans play a critical role in a wide variety of biological processes, such as protein folding, cellular targeting and motility, and the immune response. In the past decade, research in the field of N-linked glycosylation has achieved major advances, including the discovery of new carbohydrate modifications, the biochemical characterization of the enzymes involved in glycan assembly, and the determination of the biological impact of these glycans on target proteins. It is now firmly established that this enzyme-catalyzed modification occurs in all three domains of life. However, despite similarities in the overall logic of N-linked glycoprotein biosynthesis among the three kingdoms, the structures of the appended glycans are markedly different and thus influence the functions of elaborated proteins in various ways. Though nearly all eukaryotes produce the same nascent tetradecasaccharide (Glc(3)Man(9)GlcNAc(2)), heterogeneity is introduced into this glycan structure after it is transferred to the protein through a complex series of glycosyl trimming and addition steps. In contrast, bacteria and archaea display diversity within their N-linked glycan structures through the use of unique monosaccharide building blocks during the assembly process. In this review, recent progress toward gaining a deeper biochemical understanding of this modification across all three kingdoms will be summarized. In addition, a brief overview of the role of N-linked glycosylation in viruses will also be presented.
Characterization of receptors for platelet‐activating factor on platelets, polymorphonuclear leukocytes and macrophages (1988)

1. We have compared the potency of the putative platelet-activating factor (Paf) receptor antagonists (WEB 2086, L-652,731 and BN 52021) against Paf-induced aggregation of rabbit and guinea-pig platelets, aggregation of rabbit polymorphonuclear leukocytes (PMNLs) and prostacyclin generation by guinea-pig resident peritoneal macrophages. 2. On rabbit washed platelets and PMNLs WEB 2086, L-652,731 and BN 52021 each antagonized competitively Paf-induced aggregation. The rank order of potency was WEB 2086 congruent to L-652,731 greater than BN 52021 and was the same for the two cell types. 3. The pA2 values for each of the three antagonists were similar on rabbit washed platelets and PMNLs. Moreover, the pA2 for WEB 2086 on rabbit platelets (7.58) did not differ significantly from that on guinea-pig platelets (7.69). 4. On guinea-pig resident peritoneal macrophages WEB 2086 was 10 fold less potent for receptors mediating increased generation of 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha) than for those mediating platelet aggregation. 5. The potencies of L-652,731 and BN 52021 were also markedly less (2 log units) for the macrophage receptors than for platelet or PMNL receptors and BN 52021 was more potent than L-652,731 in the macrophages. 6. WEB 2086 and L-652,731 significantly reduced basal 6-oxo-PGF1 alpha produced by macrophages, but none of the antagonists affected 6-oxo-PGF1 alpha production during stimulation by A23187. 7. These data raise the possibility that there may be a Paf receptor-subtype mediating prostacyclin generation in macrophages that is different from that on the platelet and PMNL. Hence, the potency of Paf antagonists against platelet aggregation would not be a good predictor of antagonist potency in disorders involving macrophages.