gebhart/patrepeval huggingface dataset:
Inhibition of superoxide production in B lymphocytes by rac antisense oligonucleotides. (1992)

Rac1 and Rac2 gene products are small GTP-binding proteins showing 92% homology to each other. According to recent studies performed in cell-free systems, Rac1 and Rac2 proteins may be involved in the activation of NADPH-oxidase, the superoxide-generating enzymatic complex active in phagocytes. Epstein-Barr virus (EBV) transformed B lymphocytes, which express rac1 and rac2 genes, also efficiently release superoxide anions when triggered by various cell surface stimuli. To investigate the regulatory role of Rac proteins in living cells, we analyzed superoxide production in response to cross-linking of surface immunoglobulins or phorbol ester treatment in human EBV-transformed B lymphocytes pretreated with Rac sense and antisense oligonucleotides. We report here that (i) the rac protein content estimated by immunoblotting can be decreased by 60% in Rac antisense pretreated cells and (ii) a strong (50-60%), dose-dependent inhibition of superoxide production is observed in antisense pretreated cells whereas cells pretreated with sense oligonucleotide are unaffected. The data presented show, for the first time in whole cells, that superoxide production is modulated by the Rac protein content, thus demonstrating the physiological role of Rac proteins in the regulation of NADPH-oxidase.
Oral colon delivery: rationale and time-based drug design strategy. (2006)

Increasing efforts have recently been spent onto the accomplishment of oral colon targeting. Indeed, this has been related to a number of local as well as systemic highly interesting applications, such as a more effective and tolerable therapy of inflammatory bowel disease (IBD), the pharmacological prevention of colorectal adenocarcinoma, and a possible improvement in the oral bioavailability of peptide and protein drugs. For the purpose of colon targeting, a variety of delivery technologies have been described, which rely on typical variation patterns shown by selected physiological parameters throughout the gastrointestinal tract. In particular, this article is focused on time-based formulation approaches that exploit the relative consistency in the small intestinal transit time (SITT) of dosage forms.
Fluorescence Detection of Specific RNA Sequences Using 2′-Pyrene-Modified Oligoribonucleotides (2001)

Labeling the 2′-hydroxy function of RNA with a pyrenylmethyl group (Pyr) provides a useful probe of RNA because of its high fluorescent quantum efficiency on binding. The fluorescence exhibits sequence specificity and binds with a high affinity (see schematic representation).
Pulmonary Inflammation Induced by Incomplete or Inactivated Adenoviral Particles (1995)

One of the major obstacles to pulmonary-directed gene therapy using adenoviral vectors is the induction of inflammation. We investigated whether the adenoviral particles that constitute the initial inoculum can serve as an inflammatory stimulus, independent of their ability to express genes that they contain. Viral particles were prepared that are defective in gene expression by (i) isolating particles that have incomplete genomes by selecting those that have buoyant densities on CsCl density gradients lighter than complete viruses; and (ii) cross-linking viral DNA by exposure to ultraviolet light in the presence of 8-methoxypsoralen. The defective particles retained their icosahedral appearance when viewed by electron microscopy but lost their plaque-forming ability on 293 cells. High doses of intact, incomplete, or inactivated viral particles were instilled intratracheally into CBA/J mice, and after 6 days the amount of inflammation was quantified by counting inflammatory cells contained within lung tissue. We found that the inflammatory responses induced by the incomplete or inactivated viral vectors were quantitatively similar to those caused by intact, competent viral vectors. We conclude that high doses of adenoviral vectors that are used for gene therapy can induce pulmonary inflammation, independent of expressing the genes they contain.
Synthesis and Photochemical Properties of a New Water-Soluble Coumarin, Designed as a Chromophore for Highly Water-Soluble and Photolabile Protecting Group (2006)

Abstract The absorption spectra and fluorescence spectra of a coumarin derivative (1), designed to be a water-soluble photolabile protecting group for caged compounds, were successfully observed in aqueous buffer solutions at pH 2.0–12.5 for the first time. Coumarin 1 is highly soluble (&amp;gt;5 mM) in aqueous buffer at pH 7.2 and is stable in the dark at room temperature for up to a week. The pKa value for the protonation of anilino nitrogen in coumarin 1 was determined to be 4.5. Coumarin 1 has a fluorescence lifetime of 2.0 ns and undergoes intersystem crossing to the triplet state. Therefore, compound 1 can be used for the light absorbing part of the new water-soluble caged compounds, such as caged amino acids or caged nucleotides, which can release free amino acids or nucleotides, respectively, by excitation in the visible region.
Human Immunoglobulin G2 (IgG2) and IgG4, but Not IgG1 or IgG3, Protect Mice againstCryptococcus neoformansInfection (2007)

The encapsulated yeast Cryptococcus neoformans is a significant cause of meningitis and death in patients with AIDS. Some murine monoclonal antibodies (MAbs) against the glucuronoxylomannan (GXM) component of the C. neoformans capsular polysaccharide can prolong the lives of infected mice, while others have no effect or can even shorten survival. To date, no one has systematically compared the efficacies of antibodies with the same variable regions and different human constant regions with their unique combination of effector functions in providing protection against murine C. neoformans infection. In the present study, we examined the efficacies of anti-GXM MAbs of the four human immunoglobulin G (IgG) subclasses, which have identical variable regions but differ in their capacities to bind the three types of Fc receptors for IgG (FcgammaR), their abilities to activate complement, and their half-lives. IgG2 and IgG4 anti-GXM prolonged the lives of infected BALB/c mice, IgG3 anti-GXM did not affect animal survival, while mice treated with IgG1 anti-GXM died earlier than mice treated with phosphate-buffered saline or irrelevant isotype-matched MAbs. All MAbs decreased serum GXM in infected animals. Effector pathways traditionally believed to be important in defense against microbes, such as opsonophagocytosis and complement binding, negatively correlated with antibody efficacy. It is generally accepted that human IgG1 has the most favorable combination of effector functions for therapeutic use against infections. Therefore, our findings have significant implications for humanization of the mouse IgG1 currently in clinical trials for cryptococcal meningitis and for the design of antibody therapeutics to treat other infectious diseases as well.
The Quest for Transgenic Poultry: Birds are not Mice with Feathers (2005)

Although the production of transgenic mice for research is now routine, and the application of this technology to many livestock species has met with considerable success, the production of transgenic poultry has been severely hindered by biological obstacles that have prevented the direct application of mammalian technology to birds. Many of these obstacles have been overcome in recent years, resulting in success in the production of either chimeric or transgenic individuals by microinjection of naked DNA into the newly fertilized ovum, transfer of blastodermal cells or primordial germ cells from donor to recipient embryos, and development of replication-defective retroviral vectors for DNA insertion. Stable integration of foreign DNA into the poultry genome remains problematical, but recent research demonstrating the use of the Drosophila element mariner to integrate foreign DNA into the chicken chromosome with a high frequency of germline transmission seems promising. Much basic research remains in order to achieve the routine production of transgenic poultry and to regulate expression of transgenes in tissues and amounts that are appropriate for their intended use. The short generation time and large number of progeny possible with poultry species should ensure that interest in the production of transgenic poultry for research and commercial purposes will increase.
Rejection of pig liver xenografts in patients with liver failure: Implications for xenotransplantation (2001)

The pathophysiological state of rejection in liver xenotransplantation is poorly understood. Data from clinical pig liver perfusion suggest that pig livers might be rejected less vigorously than pig hearts or kidneys. Pig livers used in clinical xenoperfusions were exposed to blood from patients with liver failure. We have shown in an animal model that transplant recipients with liver failure are less capable of initiating hyperacute rejection of a xenografted liver than a healthy transplant recipient. The goal of this report is to examine the pathological characteristics of pig livers used in 2 clinical pig liver perfusions and combine this information with in vitro studies of pig-to-human liver xenotransplantation to determine whether the findings in the perfused pig livers could be explained in part by the diminished capacity of the patient with liver failure to respond to xenogeneic tissue. Pathological analysis of the perfused pig livers showed immunoglobulin M deposition in the sinusoids with little evidence of complement activation. Our in vitro studies showed that serum from patients with liver failure caused less injury to pig liver endothelium than serum from healthy subjects. Serum from patients with liver failure had similar levels of xenoreactive antibodies as serum from healthy humans. Incubation of serum from patients with liver failure with pig hepatic endothelial cells generated less iC3b, Bb fragment, and C5b-9 than serum from healthy subjects. We conclude that the altered injury in the perfused pig livers can be attributed to the relative complement deficiency that accompanies liver failure.
High prevalence of polyunsaturated-fatty-acid producing bacteria in arctic invertebrates (1997)

Bacteria producing the two long-chained polyunsaturated fatty acids eicosapentaenoic (20:5 n–3) and docosahexaenoic (22:6 n–3) acid, which principally have been associated with deep-sea environments, were found in the culturable flora of all species of a selection of 10 arctic and sub-arctic invertebrates and in one of four fish species. In total, 103 out of 330 strains which were tested carried this trait. Highest prevalences, i.e., more than 50% of total isolates were detected in two species of bivalves (Chlamys islandica and Astarte sp.) and in the amphipod Gammarus wilkitzkii. Standard taxonomic tests, supplemented with fatty-acid profile analysis, affiliated all polyunsaturated-fatty-acid producing strains either to the pseudomonad or vibrio main groups of marine bacteria.
Gene therapy. (1981)

Guidance is provided for the practicing physician confronted with patients inquiring about the applicability and potential benefits of gene therapy. The state of the art and the limitations of present techniques are reviewed, and general criteria for potential use of the procedures in humans are supplied. While gene therapy holds future promise for treatment of single gene defects, the technology has not evolved to the point where it should now be used in patient care.
Validation of Candidate Serum Ovarian Cancer Biomarkers for Early Detection (2007)

These results suggest that the biomarker panel consisting of apoA-I, TTR and TF may significantly improve early detection of OC.
Cellular Dysfunction of LQT5-MinK Mutants: Abnormalities of IKs, IKr and Trafficking in Long QT Syndrome (1999)

Mutations in the minK gene KCNE1 have been linked to the LQT5 variant of human long QT syndrome. MinK assembles with KvLQT1 to produce the slow delayed rectifier K+ current IKs and may assemble with HERG to modulate the rapid delayed rectifier IKr. We used electrophysiological and immunocytochemical methods to compare the cellular phenotypes of wild-type minK and four LQT5 mutants co-expressed with KvLQT1 in Xenopus oocytes and HERG in HEK293 cells. We found that three mutants, V47F, W87R and D76N, were expressed at the cell surface, while one mutant, L51H, was not. Co-expression of V47F and W87R with KvLQT1 produced IKs currents having altered gating and reduced amplitudes compared with WT-minK, co-expression with L51H produced KvLQT1 current rather than IKs and co-expression with D76N suppressed KvLQT1 current. V47F increased HERG current but to a lesser extent than WT-minK, while L51H and W87R had no effect and D76N suppressed HERG current markedly. Thus, V47F interacts with both KvLQT1 and HERG, W87R interacts functionally with KvLQT1 but not with HERG, D76N suppresses both KvLQT1 and HERG, and L51H is processed improperly and interacts with neither channel. We conclude that minK is a co-factor in the expression of both IKs and IKr and propose that clinical manifestations of LQT5 may be complicated by differing effects of minK mutations on KvLQT1 and HERG.
Divergent Immunoglobulin G Subclass Activity Through Selective Fc Receptor Binding (2005)

Subclasses of immunoglobulin G (IgG) display substantial differences in their ability to mediate effector responses, contributing to variable activity of antibodies against microbes and tumors. We demonstrate that the mechanism underlying this long-standing observation of subclass dominance in function is provided by the differential affinities of IgG subclasses for specific activating IgG Fc receptors compared with their affinities for the inhibitory IgG Fc receptor. The significant differences in the ratios of activating-to-inhibitory receptor binding predicted the in vivo activity. We suggest that these highly predictable functions assigned by Fc binding will be an important consideration in the design of therapeutic antibodies and vaccines.
CXCR4 inhibition in tumor microenvironment facilitates anti‐programmed death receptor‐1 immunotherapy in sorafenib‐treated hepatocellular carcinoma in mice (2014)

Anti-PD-1 treatment can boost antitumor immune responses in HCC models; when used in combination with sorafenib, anti-PD-1 immunotherapy shows efficacy only with concomitant targeting of the hypoxic and immunosuppressive microenvironment with agents such as CXCR4 inhibitors.
On the behavior of the Sierpinski multiband fractal antenna (1998)

The multiband behavior of the fractal Sierpinski (1915) antenna is described. Due to its mainly triangular shape, the antenna is compared to the well-known single-band bow-tie antenna. Both experimental and numerical results show that the self-similarity properties of the fractal shape are translated into its electromagnetic behavior. A deeper physical insight on such a behavior is achieved by means of the computed current densities over the antenna surface, which also display some similarity properties through the bands.
Labile Serum Factor and Its Effect on Arbovirus Neutralization (1971)

Enhancement of neutralization of Sindbis, Venezuelan equine encephalitis, Eastern equine encephalitis, Western equine encephalitis, and St. Louis encephalitis viruses by labile serum factor (LSF) in human serum and plasma was demonstrated. Human serum and plasma could be diluted 1:8 and 1:16 and still retain some LSF activity. Satisfactory storage temperatures for retention of LSF activity were -20 or -56 C. Repeated freeze-thaw cycles of serum did not alter LSF activity, but the activity was completely eliminated by heating at 56 C for 5 min. LSF of human serum equally enhanced neutralization by Sindbis immune mouse and rabbit sera; these results suggest a lack of species specificity. Rehydrated lyophilized gunea pig complement did not restore LSF activity to heated human plasma. Serum components responsible for LSF activity were not dialyzable. Discovery of fresh serum without LSF activity established the need to pretest all sera used as LSF sources.
Initial Results on High Enthalpy Plasma Generation in a Magnetized Coaxial Source (1994)

Initial investigation on high enthalpy plasma stream generation in the North Carolina State University Coaxial Plasma Source[1] (CPS) facility is presented. Tenuous, yet high enthalpy, flows are produced from this Magnetized Coaxial plasma Gun (MCG) which allow laboratory study of plasma streams with a wide variety of applications. The applicability includes, but is not limited to, advanced thrusters for electric space propulsion, astrophysical jets and critical ionization phenomena, magnetic fusion compact toroid devices and tokamak fueling, large scale plasma etching and deposition, etc.
CD26 is a potential therapeutic target by humanized monoclonal antibody for the treatment of multiple myeloma (2018)

CD26, a 110-kDa transmembrane glycoprotein that is expressed on several tumor cells including malignant lymphoma, has been implicated in tumorigenesis: however, little is known regarding its role in multiple myeloma (MM). Recently, we identified CD26 expression on human osteoclasts (OCs) and demonstrated that humanized IgG<sub>1</sub> monoclonal antibody targeting CD26, huCD26mAb, inhibits human OC differentiation. Herein, we show that CD26 expression was present on plasma cells in the bone marrow tissues of MM patients. In vitro immunostaining studies revealed that although CD26 expression was low or absent on MM cell lines cultured alone, it was intensely and uniformly expressed on MM cell lines co-cultured with OCs. The augmented CD26 expression in MM cells was exploited to enhance anti-MM efficacy of huCD26mAb via a substantial increase in antibody-dependent cytotoxicity (ADCC) but not complement-dependent cytotoxicity (CDC). Moreover, huCD26mAb in combination with novel agents synergistically enhanced huCD26mAb induced ADCC activity against CD26+ MM cells compared with each agent alone. huCD26mAb additionally reduced the ratio of the side population (SP) fraction in CD26+ MM cells by ADCC. Finally, huCD26mAb significantly reduced the MM tumor burden and OC formation in vivo. These results suggest that CD26 is a potential target molecule in MM and that huCD26mAb could act as a therapeutic agent.
Palladium‐Catalyzed CC Bond Formation (2004)

This chapter contains sections titled: Introduction Chemical Properties of Organopalladium Compounds Mechanisms of Pd-catalyzed CC Bond Formation Cross-coupling The Heck Reaction Homocoupling and Reduction of the Organyl Halide Homocoupling and Oxidation of the Carbon Nucleophile Transfer of Aryl Groups from the Phosphine Ligand ipso- vs cine-Substitution at Vinylboron and Vinyltin Derivatives Allylic Arylation and Hydrogenation as Side Reactions of the Heck Reaction Protodemetalation of the Carbon Nucleophile Sterically Hindered Substrates Cyclometalation Chelate Formation
Effect of Combination Therapy of Troglitazone and Sulphonylureas in Patients with Type 2 Diabetes Who Were Poorly Controlled by Sulphonylurea Therapy Alone (1996)

The clinical efficacy of troglitazone, a new oral hypoglycaemic agent was investigated in Type 2 diabetes in combination with sulphonylureas. Two hundred and ninety-one patients with Type 2 diabetes (age 21-81 years) whose previous glycaemic control by sulphonylureas was judged stable but unsatisfactory (fasting plasma glucose (FPG) > 8.3 mmol I-1) were randomly allocated into the troglitazone treatment group (troglitazone group, n = 145) or the placebo treatment group (placebo group, n = 146). They were treated by test drugs for 12 weeks in combination with the same dose of sulphonylureas before the trial. One hundred and twenty-two patients who received troglitazone and 126 patients who received placebo were evaluated for efficacy. The baseline characteristics did not differ significantly between the two groups. In the troglitazone group, FPG and HbA(1c) decreased significantly after the treatment (before vs after, FPG: 10.8 +/- 2.0 mmol I(-1) vs 9.2 +/- 2.5 mmol I(-1), p< 0.001; HbA(1c): 9.2 +/- 1.4% vs 8.5 +/- 1.5%, p< 0.001). FPG and HbA(1c) did not change after the treatment in the placebo group (before vs after, FPG: 10.5 +/- 1.7 mmol I(-1) vs 10.7 +/- 2.2 mmol I(-1); HbA(1c): 9.0 +/- 1.5% vs 9.2 +/- 1.6 %). Serum total cholesterol and HDL-cholesterol did not change in either group, however, serum triglyceride significantly decreased in the troglitazone group. No serious adverse events occurred in either group. In conclusion, troglitazone 400 mg day(-1) had a significant hypoglycaemic effect in combination with sulphonylureas without any serious adverse events. Troglitazone, developed as an insulin action enhancer, can be a useful hypoglycaemic agent in the treatment of patients with Type 2 diabetes who are not well controlled by sulphonylureas alone.
Effective Irinotecan (CPT‐11)‐containing Liposomes: Intraliposomal Conversion to the Active Metabolite SN‐38 (1999)

Irinotecan hydrochloride (CPT-11) is a prodrug of SN-38, which is an active metabolite with antitumor activity and side toxicity. The activities of CPT-11 and SN-38 depend on the closed lactone ring form of SN-38. We have examined the tissue distributions of the closed and open forms of CPT-11 and SN-38 in Lewis lung carcinoma-bearing mice after the administration of liposomal CPT-11 (S-Lip) and polyethyleneglycol (PEG)-modified S-Lip (S-PEG). The plasma concentrations of closed CPT-11 and SN-38 were increased by liposomalization, and their blood circulation was prolonged by the PEG modification. The concentrations of closed CPT-11 and SN-38 in tumors were elevated by both the liposomalization and PEG modification. The closed/total ratio of SN-38 in the tumors of the S-PEG group was greater than that of the CPT-11 solution (Sol) group. Thus, SN-38 was thought to be generated in intact liposomes containing CPT-11. The bile concentration of closed SN-38, which is responsible for CPT-11-induced intestinal disorder, was decreased by liposomalization. In an in vitro experiment, the SN-38/CPT-11 ratio in the tumor cells of the S-Lip group was found to be higher than that of the Sol group, and the ratio of the closed form of SN-38 was increased by the liposomalization. Laser scanning confocal microscopy showed the generation of SN-38 in the liposomal membrane after the incubation of S-Lip with carboxylesterase. It is therefore considered that a part of CPT-11 is converted to SN-38 in the intact liposomes.
On the Smoothing of Probability Density Functions (1958)

Summary We consider the estimation of a probability density function by linear smoothing of the observed density. A basis for estimation is obtained by assuming that the ordinates of the true density function have a prior distribution such that adjacent ordinates are highly correlated. An equation determining the optimum weighting function under these circumstances is derived, and solved in special cases. The properties of the estimate are discussed and the asymptotic behaviour of its mean squared deviation D 2 given. It is shown that as the sample size N increases, D 2 cannot decrease faster than N –1.