gebhart/patrepeval huggingface dataset:
A Novel pH- and Time-Dependent System for Colonic Drug Delivery (2003)

A novel pH- and time-dependent delivery system was developed for delivering drugs to the colon. In vitro studies showed that this novel system could release the drug at a predetermined time, which was mainly controlled by the coating layers of the system. The delayed time of the press-coating layer was controlled by its erosion rate, which followed Hixson-Crowell equation. A proper selection of such factors as the viscosity grade of HPMC and tablet hardness, etc., can help reproduce the drug release profile as expected. The transit profiles in two healthy volunteers by gamma scintigraphy demonstrated that the tablets were able to pass through the stomach and small intestine intact and could safely reach the distal end of the small intestine, where the system began to release the drug contained in the core tablet. For both of the volunteers, disintegration of the tablets occurred in the ascending colon, which had highlighted the potential of this system for colonic drug delivery.
Light‐Activated Nanoimpeller‐Controlled Drug Release in Cancer Cells (2008)

Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2296/2008/smll200700903_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Orally Efficacious Broad-Spectrum Ribonucleoside Analog Inhibitor of Influenza and Respiratory Syncytial Viruses (2018)

Morbidity and mortality resulting from influenza-like disease are a threat, especially for older adults. To improve case management, next-generation broad-spectrum antiviral therapeutics that are efficacious against major drivers of influenza-like disease, including influenza viruses and respiratory syncytial virus (RSV), are urgently needed. Using a dual-pathogen high-throughput screening protocol for influenza A virus (IAV) and RSV inhibitors, we have identified <i>N</i><sup>4</sup>-hydroxycytidine (NHC) as a potent inhibitor of RSV, influenza B viruses, and IAVs of human, avian, and swine origins. Biochemical <i>in vitro</i> polymerase assays and viral RNA sequencing revealed that the ribonucleotide analog is incorporated into nascent viral RNAs in place of cytidine, increasing the frequency of viral mutagenesis. Viral passaging in cell culture in the presence of an inhibitor did not induce robust resistance. Pharmacokinetic profiling demonstrated dose-dependent oral bioavailability of 36 to 56%, sustained levels of the active 5'-triphosphate anabolite in primary human airway cells and mouse lung tissue, and good tolerability after extended dosing at 800 mg/kg of body weight/day. The compound was orally efficacious against RSV and both seasonal and highly pathogenic avian IAVs in mouse models, reducing lung virus loads and alleviating disease biomarkers. Oral dosing reduced IAV burdens in a guinea pig transmission model and suppressed virus spread to uninfected contact animals through direct transmission. Based on its broad-spectrum efficacy and pharmacokinetic properties, NHC is a promising candidate for future clinical development as a treatment option for influenza-like diseases.
Myosin-induced acute myocarditis is a T cell-mediated disease (1991)

The heart is a target organ in several autoimmune diseases, and therefore it is important to understand more about the effector cells involved in immune-mediated mechanisms of myocardial cell death. Because immune T lymphocytes are central to many immune responses, we wanted to study the role of T cells in causing cardiac specific inflammation. We used purified mouse cardiac myosin to cause acute myocarditis in mice. The adoptive transfer of purified T cells from C.B-17 mice with active myocarditis to SCID recipients successfully transferred the disease into SCID hosts. In contrast, transfer of serum with high-titer antimyosin antibodies to SCID hosts did not cause myocarditis. Using mAb to deplete A/J mice of CD4+ T cells, we showed that these mice were protected against the induction of myocarditis. Depletion of CD8+ T cells reduced the severity of inflammation but did not prevent induction of myocarditis. We were also able to prevent the induction of myocarditis using major histocompatibility class II protein-binding, nonimmunogenic, competitor peptides. These blocking studies also indicated that in H-2k mice, myocarditis is an I-Ak-restricted disease, and provided further evidence that CD4+ T cells are critical to the induction of disease. Together, these studies provide direct evidence that myosin-induced myocarditis is a T cell-mediated disease.
Peroxisome proliferator-activated receptor γ1 expression is diminished in human osteoarthritic cartilage and is downregulated by interleukin-1β in articular chondrocytes (2007)

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor involved in the regulation of many cellular processes. We and others have previously shown that PPARgamma activators display anti-inflammatory and chondroprotective properties in vitro and improve the clinical course and histopathological features in an experimental animal model of osteoarthritis (OA). However, the expression and regulation of PPARgamma expression in cartilage are poorly defined. This study was undertaken to investigate the quantitative expression and distribution of PPARgamma in normal and OA cartilage and to evaluate the effect of IL-1beta, a prominent cytokine in OA, on PPARgamma expression in cultured chondrocytes. Immunohistochemical analysis revealed that the levels of PPARgamma protein expression were significantly lower in OA cartilage than in normal cartilage. Using real-time RT-PCR, we demonstrated that PPARgamma1 mRNA levels were about 10-fold higher than PPARgamma2 mRNA levels, and that only PPARgamma1 was differentially expressed: its levels in OA cartilage was 2.4-fold lower than in normal cartilage (p < 0.001). IL-1 treatment of OA chondrocytes downregulated PPARgamma1 expression in a dose- and time-dependent manner. This effect probably occurred at the transcriptional level, because IL-1 decreases both PPARgamma1 mRNA expression and PPARgamma1 promoter activity. TNF-alpha, IL-17, and prostaglandin E2 (PGE2), which are involved in the pathogenesis of OA, also downregulated PPARgamma1 expression. Specific inhibitors of the mitogen-activated protein kinases (MAPKs) p38 (SB203580) and c-Jun N-terminal kinase (SP600125), but not of extracellular signal-regulated kinase (PD98059), prevented IL-1-induced downregulation of PPARgamma1 expression. Similarly, inhibitors of NF-kappaB signaling (pyrrolidine dithiocarbamate, MG-132, and SN-50) abolished the suppressive effect of IL-1. Thus, our study demonstrated that PPARgamma1 is downregulated in OA cartilage. The pro-inflammatory cytokine IL-1 may be responsible for this downregulation via a mechanism involving activation of the MAPKs (p38 and JNK) and NF-kappaB signaling pathways. The IL-1-induced downregulation of PPARgamma expression might be a new and additional important process by which IL-1 promotes articular inflammation and cartilage degradation.
Direct intrauterine sampling: The IUMC endometrial sampler (1997)

Endometrial cytology has been studied for more than 25 years, and a variety of cytologic devices have been developed for direct sampling of the endometrium. The quality of endometrial samples procured by various devices is markedly different and greatly affects the diagnostic accuracy. A new endometrial sampling device, the IUMC Endometrial Sampler, was developed at the Indiana University Medical Center and approved by the Food and Drug Administration for general medical use. This device is intended for the early detection of endometrial carcinoma and its precursors. It can be used to monitor the endometrial condition of patients receiving estrogen replacement therapy or tamoxifen. It is also useful for the procurement of uncontaminated endometrial samples for microbiologic studies from patients with suspected endometritis. It has the potential to be used for endometrial dating for patients with infertility disorders. In our clinical trials and sampling tests using hysterectomy specimens, adequate and representative endometrial samples without contamination from endocervix and vagina were consistently obtained by this device. The procedure of endometrial sampling using this device and the preparation techniques for endometrial brushing specimens are discussed and illustrated. Diagn. Cytopathol. 17:153–159, 1997. © 1997 Wiley-Liss, Inc.
Hsp90 and co‐chaperones twist the functions of diverse client proteins (2009)

Hsp90 molecular chaperones are required for the stability and activity of a diverse range of client proteins that have critical roles in signal transduction, cellular trafficking, chromatin remodeling, cell growth, differentiation, and reproduction. Mammalian cells contain three types of Hsp90s: cytosolic Hsp90, mitochondrial Trap-1, and Grp94 of the endoplasmic reticulum. Each of the Hsp90s, as well as the bacterial homolog, HtpG, hydrolyze ATP and undergo similar conformational changes. Unlike the other forms of Hsp90, cytosolic Hsp90 function is dependent on a battery of co-chaperone proteins that regulate the ATPase activity of Hsp90 or direct Hsp90 to interact with specific client proteins. This review will summarize what is known about Hsp90's ability to mediate the folding and activation of diverse client proteins that contribute to human diseases, such as cancer and fungal and viral infections.
Complete sequence analyses show that two defective interfering influenza viral RNAs contain a single internal deletion of a polymerase gene. (1982)

Defective interfering (DI) influenza viral RNAs arise by internal deletion of progenitor RNAs. By using recombinant DNA cloning and DNA sequence analysis techniques, we have deduced the complete sequence of two such RNAs (L2b and L3), both arising from the same polymerase (P1) gene of WSN influenza virus. We have also partially determined the sequence of the P1 polymerase gene, including the sequence at the point of deletion and the flanking regions. Our sequence study shows the following. (i) Both L2b and L3 arise by a simple deletion in the P1 gene. (ii) L2b and L3 are 683 and 441 nucleotides long, respectively. (iii) The first 413 and 244 nucleotides of the 5' ends of L2b and L3, respectively, are identical to those of the 5' end of the P1 gene. (iv) The last 270 nucleotides of L2b and 197 nucleotides of L3 are the same as those of the 3' end of the P1 gene. (v) The entire sequence of L3 is present in the sequence of L2b. (vi) Both the 5' and the 3' termini, including the transcription stop and poly(A) addition signals of the progenitor P1 gene, are present in both L2b and L3. (vii) The sequences at the deletion point and the flanking region of the P1 gene do not resemble the consensus splicing sequence of spliced mRNA suggesting that a replicational event rather than splicing is involved in the formation of influenza defective interfering RNAs.
A mutant pyruvate dehydrogenase E1 subunit allows survival of Escherichia coli strains defective in 1‐deoxy‐d‐xylulose 5‐phosphate synthase (2006)

The 2-C-methyl-D-erythritol 4-phosphate pathway has been proposed as a promising target to develop new antimicrobial agents. However, spontaneous mutations in Escherichia coli were observed to rescue the otherwise lethal loss of the first two enzymes of the pathway, 1-deoxy-D-xylulose 5-phosphate (DXP) synthase (DXS) and DXP reductoisomerase (DXR), with a relatively high frequency. A mutation in the gene encoding the E1 subunit of the pyruvate dehydrogenase complex was shown to be sufficient to rescue the lack of DXS but not DXR in vivo, suggesting that the mutant enzyme likely allows the synthesis of DXP or an alternative substrate for DXR.
Two-site immunochemiluminometric assay for human alpha 1-fetoprotein. (1983)

In this two-site immunochemiluminometric assay for human alpha 1-fetoprotein, acridinium ester-labeled monoclonal antibodies are used that have an average incorporation ratio of 0.3 mol of acridinium ester per mole of antibody. The solid-phase antibody consists of sheep anti-alpha 1-fetoprotein IgG covalently coupled to a diazonium derivative of reprecipitated aminoaryl cellulose. The assay involves a 1-h incubation after the simultaneous incubation of labeled and solid-phase antibodies. The subsequent quantification time is 10 s per tube. The assay has a working range of 20 to 246 kilo-int. units/L for CVs less than or equal to 10% and a sensitivity of detection of 1.3 kilo-int. units/L. Experiments with monoclonal antibodies labeled to an average incorporation ratio of 2.8 mol of acridinium ester per mole of antibody suggest that assay sensitivity increases with increased specific activity. alpha 1-Fetoprotein concentrations in the sera of pregnant women at 14-20 weeks of gestation, as measured by the present assay, agreed with the results of a conventional radioimmunoassay.
Microwave Interferometry for High Sensitivity VNA-FMR Measurements (2016)

Two-port vector network analyzer ferromagnetic resonance (VNA-FMR) measurements using coplanar waveguides (CPWs) are a fast and powerful tool for the analysis of ferromagnetic film parameters, including damping and effective field contributions like anisotropies, exchange coupling, and demagnetization fields. Thereby, VNA-FMR appears to be a good choice for the analysis of patterned magnetic nanostructures showing a rich spectrum of different anisotropy terms. However, due to their small volume, the absorption of nanostructures in FMR is low and the measurement signal is superimposed by the excitation signal. To eliminate the background signal, we propose an interferometric approach with the following two key features: 1) the reference path has the same geometry as the measurement path, including an identical but empty CPW parallel to the measurement CPW to remove spurious field dependent contributions to the signal and 2) additionally, we extend the reference path by 0.5 m of an RF coaxial cable. This path length difference leads to a frequency-dependent phase difference of the two paths, assuming a value of 180 ° in ≈ 500 MHz intervals. Here, the excitation RF signals from both paths add to zero. In broadband measurements, this simple approach allows to obtain a sufficient number of grid points for dispersion analysis without the need for a phase shifter. Our experiments reveal an improvement of the sensitivity by up to two orders in magnitude under optimum conditions. The amplitude and the shape of the resonance peaks will be discussed.
Specific HLA-DRB and -DQB Alleles and Haplotypes Confer Disease Susceptibility or Resistance in Bahraini Type 1 Diabetes Patients (2004)

Insofar as genetic susceptibility to type 1 diabetes is associated with HLA class II genes, with certain allelic combinations conferring disease susceptibility or resistance, this study assessed the distributions of HLA-DR and -DQ among 107 unrelated patients with type 1 diabetes and 88 healthy controls from Bahrain, all of Arab origin. The HLA-DRB and -DQB genotypes were determined by PCR-sequence-specific priming. The following alleles showed the strongest association with type 1 diabetes among patients versus controls according to their frequencies: DRB1*030101 (0.430 versus 0.097; P < 0.001), DRB1*040101 (0.243 versus 0.034; P < 0.001), DQB1*0201 (0.467 versus 0.193; P < 0.001), and DQB1*0302 (0.229 versus 0.091; P < 0.001). When the frequencies of alleles in controls were compared to those in patients, negative associations were seen for DRB1*100101 (0.085 versus 0.014; P < 0.001), DRB1*110101 (0.210 versus 0.060; P < 0.001), DQB1*030101 (0.170 versus 0.075; P = 0.006), and DQB1*050101 (0.335 versus 0.121; P < 0.001). In addition, the DRB1*030101-DQB1*0201 (70.1 versus 22.7%; P < 0.001) and DRB1*030101-DQB1*0302 (21.5 versus 0.0%; P < 0.001) genotypes were more prevalent among patients, thereby conferring disease susceptibility, whereas the DRB1*100101-DQB1*050101 (20.5 versus 2.8%; P < 0.001), DRB1*110101-DQB1*030101 (28.4 versus 8.4%; P < 0.001), and DRB1*110101-DQB1*050101 (30.7 versus 0.9%; P < 0.001) genotypes were more prevalent among controls, thus assigning a protective role. These results confirm the association of specific HLA-DR and -DQ alleles and haplotypes with type 1 diabetes and may underline several characteristics that distinguish Bahraini patients from other Caucasians patients.
The Effect of Reactive Oxygen Species on Equine Sperm Motility, Viability, Acrosomal Integrity, Mitochondrial Membrane Potential, and Membrane Lipid Peroxidation (2000)

ABSTRACT: The objective of this study was to examine the influence of reactive oxygen species (ROS), generated through the use of the xanthine (X)‐xanthine oxidase (XO) system, on equine sperm motility, viability, acrosomal integrity, mitochondrial membrane potential, and membrane lipid peroxidation. Equine spermatozoa were separated from seminal plasma on a discontinuous Percoll gradient, and spermatozoa were incubated with 0.6 mM X and 0.05 U/mL XO for 30 minutes. Catalase (150 U/mL), superoxide dismutase (SOD, 150 U/mL), or glutathione (GSH, 1.5 mM) were evaluated for their ability to preserve sperm function in the presence of the induced oxidative stress. At the end of the 30‐minute incubation, sperm motility was determined by computer‐assisted semen analysis. Viability and acrosomal integrity were determined by Hoechst‐ Pisum sativum staining, and mitochondrial membrane potential was determined by staining with JC‐1. Incubation with the X‐XO system led to a significant ( P &lt; .01) increase in hydrogen peroxide production and an associated decrease ( P &lt; .01) in motility parameters. Total motility was significantly ( P &lt; .01) lower in the presence of X‐XO compared with the case of the control (29% ± 9% vs 73% ± 1%, respectively). Catalase, but not SOD, prevented a decline in motility secondary to oxidative stress (71% ± 4% vs 30% ± 3%, respectively). The addition of glutathione had an intermediate effect in preserving sperm motility at the end of the 30‐minute incubation (53% ± 3%). No influence of X‐XO could be determined on viability, acrosomal integrity, or mitochondrial membrane potential. In order to promote lipid peroxidation, samples were incubated with ferrous sulfate (0.64 mM) and sodium ascorbate (20 mM) for 2 hours after the X‐XO incubation. No increase in membrane lipid peroxidation was detected. This study indicates that hydrogen peroxide is the major ROS responsible for damage to equine spermatozoa. The decrease in sperm motility associated with ROS occurs in the absence of any detectable decrease in viability, acrosomal integrity, or mitochondrial membrane potential or of any detectable increase in lipid peroxidation.
PEPTIDES AS WEAPONS AGAINST MICROORGANISMS IN THE CHEMICAL DEFENSE SYSTEM OF VERTEBRATES (1995)

The innate immunity of vertebrates to microbial invasion is arbitrated by a network of host-defense mechanisms involving both the long-lasting highly specific responses of the cell-mediated immune system and a nonspecific chemical defense system based on a series of broad-spectrum antimicrobial peptides that are analogous to those found in insects. Vertebrate antibiotic peptides secreted by nonlymphoid cells of the mucosal surfaces of the respiratory and gastrointestinal tracts as well as by the granular glands of the skin reportedly cause the lysis of numerous pathogenic microorganisms, including viruses, gram-positive and gram-negative bacteria, protozoa, yeasts, and fungi, as well as of cancer cells. Antimicrobial peptides isolated from vertebrates have three characteristic properties: They are relatively small (20-46 amino acid residues), basic (lysine- or arginine-rich), and amphipathic. Although these peptides differ widely in length and amino acid sequences, they may be grouped in four broad families based on characteristic structural features. Although the precise mechanism of action of these peptides remains to be defined, their microbicidal effect very likely results from their capacity to form channels or pores within the microbial membrane in order to permeate the cell and impair its ability to carry out anabolic processes. This secondary, chemical immune system provides vertebrates with a repertoire of small peptides that are promptly synthesized upon induction, easily stored in large amounts, and readily available for antimicrobial warfare.
Overview on Therapeutic Applications of Microparticulate Drug Delivery Systems (2016)

Research in novel drug delivery systems is being explored competitively in order to attain maximum therapeutic effect while minimizing the adverse effects. Despite several advancements in pharmaceutical formulations, one of the major challenges still persisting is sustained drug release. Microencapsulation enacts as an intelligent approach with a strong therapeutic impact and is in demand globally in medical technology due to its specific and attractive properties, including biocompatibility, stability, target specificity, uniform encapsulation, better compliance, and controlled and sustained release patterns that are responsible for diminishing the toxicity and dosage frequency. Microparticles are successful delivery systems that encapsulate both water-insoluble and sparingly water-soluble agents to elicit their efficacy with a great potential attributed to their unique properties: particle size, shape, structure, drug loading, entrapment efficiency, porosity, and release profile. Several marketed microparticle-based formulations are available, including risperidone, buserelin, and octreotide acetate, and some of them are in clinical trials. The present review highlights the detailed therapeutic applications of microparticles with advances from the last decade to treat various disease conditions, including cancer, diabetes, cardiovascular diseases, and neurological disorders, as well as for vaccine delivery, ocular and pulmonary delivery, gene transfer, etc., and exemplifies the future perspectives in these aspects. One day in the future, microparticle-based formulations may become broadly researched in drug delivery systems.
Theoretical analysis of triple-coupler ring-based optical guided-wave resonator (1995)

A comprehensive theoretical analysis of the triple-coupler ring-based optical guided-wave resonator (TCRR) is presented. Channel-passing and channel-dropping transmittance characteristics of the TCRR are derived by using a combination of transfer matrix and chain matrix formulations. The dependence of the transmittance characteristics on the amplitude coupling ratios of the three directional couplers are investigated, and optimum design relationships are determined. It is shown that the TCRR is ideally a nonterminating filter at antiresonance. An extensive comparison between the TCRR and a double-coupler ring resonator (DCRR) with same radius of curvature, waveguide propagation loss, coupling loss and finesse, is carried out. It is shown that the TCRR, by suitably sizing its waveguide lengths, has a free spectral range double that of the DCRR and features also higher transmission at resonance and better extinction ratio. These characteristics make the TCRR particularly advantageous for frequency selective filtering applications in optical frequency division multiplexing transmission systems.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>