gebhart/patrepeval huggingface dataset:
Triple-helix formation in the antiparallel binding motif of oligodeoxynucleotides containing N9- and N7-2-aminopurine deoxynucleosides (2001)

Triplex-forming oligodeoxynucleotide 15mers, designed to bind in the antiparallel triple-helical binding motif, containing single substitutions (Z) of the four isomeric alphaN(7)-, betaN(7)-, alphaN(9)- and betaN(9)-2-aminopurine (ap)-deoxyribonucleosides were prepared. Their association with double-stranded DNA targets containing all four natural base pairs (X-Y) opposite the aminopurine residues was determined by quantitative DNase I footprint titration in the absence of monovalent metal cations. The corresponding association constants were found to be in a rather narrow range between 1.0 x 10(6) and 1.3 x 10(8) M(-1). The following relative order in Z x X-Y base-triple stabilities was found: Z = alphaN(7)ap: T-A > A-T> C-G approximately G-C; Z = betaN(7)ap: A-T > C-G > G-C > T-A; Z = alphaN(9)ap: A-T = G-C > T-A > C-G; and Z = betaN(9)ap: G-C > A-T > C-G > T-A.
CFTR-Regulated Chloride Transport at the Ocular Surface in Living Mice Measured by Potential Differences (2005)

CFTR provides a major pathway for mouse ocular surface Cl(-) secretion, suggesting the application of CFTR activators as therapy for dry eye. Amiloride-sensitive Na(+) transporters facilitate Na(+) absorption. PD measurements provide a robust and reproducible means of assessing ocular surface ion transporting mechanisms.
Peroxyoxalate Chemiluminescence of N,N‘-Bistosyl-1H,4H-quinoxaline-2,3-dione and Related Compounds. Dependence on Electronic Nature of Fluorophores (2002)

The title compound N,N'-bistosyl-1H,4H-quinoxaline-2,3-dione (TsQD) provides peroxyoxalate chemiluminescence (PO-CL) when reacted with hydrogen peroxide in the presence of fluorophores. The chemiluminescence (CL) efficiency of TsQD was superior to that of other related compounds such as bis(2,4,6-trichlorophenyl) oxalate (TCPO), a typical oxalate for the peroxyoxalate PO-CL, under an aqueous condition. Factors affecting the PO-CL efficiency are discussed from the viewpoint of the structures of the substrates and the electronic nature of the fluorophores. A linear correlation of the logarithmic values evaluated from the CL quantum yields with the oxidation potentials of the aromatic fluorophores supports the involvement of the chemically initiated electron exchange luminescence (CIEEL) mechanism in both TsQD- and TCPO-CL systems. Also, an excellent Hammett relationship was derived from the correlation between the sigma(+) values and the relative singlet excitation yields in TsQD-CL enhanced by a series of fluorescent para,para'-disubstituted distyrylbenzenes.
Dabigatran versus Warfarin in Patients with Atrial Fibrillation (2009)

In patients with atrial fibrillation, dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin, as well as lower rates of major hemorrhage. Dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage. (ClinicalTrials.gov number, NCT00262600.)
Recent Applications of Polyacrylamide as Biomaterials (2008)

The synthetic polymer, polyacrylamide derived from acrylamide monomer, was originally introduced for use as a support matrix for electrophoresis in 1959. Later, because of its applicability and economy, polyacrylamide has found widespread applications ranging from microanalysis to macro-fractionation for proteins, nucleic acid, and other biomolecules. On the other hand, recent years also witnessed increasing research interests in the potential of polyacrylamide acting as biomaterials. This review article will comprehensively present and discuss recent interesting patents classified according to the following highlights: (1) Enzyme immobilization within polyacrylamide gels; (2) Carriers for delivery of drugs and bioactive compounds; (3) Smart materials able to respond with stimulus; (4) Polyacrylamide-based matrices in extracorporeal toxin removal modalities; (5) Non-absorbable soft tissue fillers used for body contouring in reconstructive surgery or for cosmetic purposes. In summary, current researches and achievements of polyacrylamide have therefore well demonstrated its versatility and usefulness as biomaterials. Further developments of polyacrylamide-associated technologies will undoubtedly enhance the value and broaden the possibilities of applications of polyacrylamide in the field of biomaterials. Keywords: Polyacrylamide, biomaterial, enzyme immobilization, drug delivery, extracorporeal toxin removal, smart materials, soft tissue fillers
Sequence Polymorphism in the Glycosylation Island and Flagellins of Pseudomonas aeruginosa (2004)

A genomic island consisting of 14 open reading frames, orfA to orfN was previously identified in Pseudomonas aeruginosa strain PAK and shown to be essential for glycosylation of flagellin. DNA microarray hybridization analysis of a number of P. aeruginosa strains from diverse origins showed that this island is polymorphic. PCR and sequence analysis confirmed that many P. aeruginosa strains carry an abbreviated version of the island (short island) in which orfD, -E and -H are polymorphic and orfI, -J, -K, -L, and -M are absent. To ascertain whether there was a relationship between the inheritance of the short island and specific flagellin sequence variants, complete or partial nucleotide sequences of flagellin genes from 24 a-type P. aeruginosa strains were determined. Two distinct flagellin subtypes, designated A1 and A2, were apparent. Strains with the complete 14-gene island (long island) were almost exclusively of the A1 type, whereas strains carrying the short island were associated with both A1- and A2-type flagellins. These findings indicate that P. aeruginosa possesses a relatively low number of distinct flagellin types and probably has the capacity to further diversify this antigenic surface protein by glycosylation.
Fish and Long-Chain ω-3 Fatty Acid Intake and Risk of Coronary Heart Disease and Total Mortality in Diabetic Women (2003)

A higher consumption of fish and long-chain omega-3 fatty acids was associated with a lower CHD incidence and total mortality among diabetic women.
Histidine 332 of the D1 Polypeptide Modulates the Magnetic and Redox Properties of the Manganese Cluster and Tyrosine YZ in Photosystem II (1999)

An electron spin-echo envelope modulation study [Tang, X.-S., Diner, B. A., Larsen, B. S., Gilchrist, M. L., Jr., Lorigan, G. A., and Britt, R. D. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 704-708] and a recent Fourier transform infrared study [Noguchi, T., Inoue, Y., and Tang, X.-S. (1999) Biochemistry 38, 10187-10195], both conducted with [(15)N]histidine-labeled photosystem II particles, show that at least one histidine residue coordinates the O(2)-evolving Mn cluster in photosystem II. Evidence obtained from site-directed mutagenesis studies suggests that one of these residues may be His332 of the D1 polypeptide. The mutation D1-H332E is of particular interest because cells of the cyanobacterium Synechocystis sp. PCC 6803 that contain this mutation evolve no O(2) but appear to assemble Mn clusters in nearly all photosystem II reaction centers [Chu, H.-A., Nguyen, A. P. , and Debus, R. J. (1995) Biochemistry 34, 5859-5882]. Photosystem II particles isolated from the Synechocystis D1-H332E mutant are characterized in this study. Intact D1-H332E photosystem II particles exhibit an altered S(2) state multiline EPR signal that has more hyperfine lines and narrower splittings than the S(2) state multiline EPR signal observed in wild-type PSII particles. However, the quantum yield for oxidizing the S(1) state Mn cluster is very low, corresponding to an 8000-fold slowing of the rate of Mn oxidation by Y(Z)(*), and the temperature threshold for forming the S(2) state is approximately 100 K higher than in wild-type PSII preparations. Furthermore, the D1-H332E PSII particles are unable to advance beyond the Y(Z)(*)S(2) state, as shown by the accumulation of a narrow "split" EPR signal under multiple turnover conditions. In Mn-depleted photosystem II particles, charge recombination between Q(A)(*)(-) and Y(Z)(*) in D1-H332E is accelerated in comparison to wild-type, showing that the mutation alters the redox properties of Y(Z) in addition to those of the Mn cluster. These results are consistent with D1-His332 being located near the Mn-Y(Z) complex and perhaps ligating Mn.
DNA Display II. Genetic Manipulation of Combinatorial Chemistry Libraries for Small-Molecule Evolution (2004)

Biological in vitro selection techniques, such as RNA aptamer methods and mRNA display, have proven to be powerful approaches for engineering molecules with novel functions. These techniques are based on iterative amplification of biopolymer libraries, interposed by selection for a desired functional property. Rare, promising compounds are enriched over multiple generations of a constantly replicating molecular population, and subsequently identified. The restriction of such methods to DNA, RNA, and polypeptides precludes their use for small-molecule discovery. To overcome this limitation, we have directed the synthesis of combinatorial chemistry libraries with DNA "genes," making possible iterative amplification of a nonbiological molecular species. By differential hybridization during the course of a traditional split-and-pool combinatorial synthesis, the DNA sequence of each gene is read out and translated into a unique small-molecule structure. This "chemical translation" provides practical access to synthetic compound populations 1 million-fold more complex than state-of-the-art combinatorial libraries. We carried out an in vitro selection experiment (iterated chemical translation, selection, and amplification) on a library of 10(6) nonnatural peptides. The library converged over three generations to a high-affinity protein ligand. The ability to genetically encode diverse classes of synthetic transformations enables the in vitro selection and potential evolution of an essentially limitless collection of compound families, opening new avenues to drug discovery, catalyst design, and the development of a materials science "biology."
Multistep Small-Molecule Synthesis Programmed by DNA Templates (2002)

The translation of DNA sequences into synthetic products is a key requirement of our approach to evolving synthetic molecules through iterated cycles of translation, selection, and amplification. Here we report general linker and purification strategies for sequence-specific DNA-templated synthesis that collectively enable the product of a DNA-templated reaction to be isolated and to undergo subsequent DNA-templated reactions. Using these strategies, we have achieved the first multistep nucleic acid-templated small-molecule syntheses to generate two different molecules. In addition to representing a method for translating DNA templates sequence-specifically into corresponding multistep synthetic products, our findings also provide experimental support for previously proposed models invoking multistep nucleic acid-templated synthesis as mediating the prebiotic translation of replicable information into the earliest functional molecules.
Human Papillomavirus Infection of the Cervix (1992)

During the years 1982-1989, 2627 women were recruited into eight studies analyzing the relationship between human papillomavirus (HPV) infection and cervical neoplasia. Subsequently, each individual was assigned as either a case or control, and each cervical sample was rescreened for HPV DNA by low-stringency Southern blot hybridization. Positive samples were retested at high stringency with specific probes for HPVs 6/11, 16, 18, 31, 33, 35, 42, 43, 44, 45, 51, 52, 56, and (in most instances) 58. Most cases (153 cancers, 261 high-grade and 377 low-grade squamous intraepithelial lesions) had target or cone biopsies; all 270 borderline atypia subjects and more than 85% of the 1566 normal controls had cytology plus colposcopy/cytology. Scientists performing HPV testing were masked to the clinical diagnoses. Human papillomavirus DNA was detected in 79.3% of specimens from women with definite cervical disease (627 of 791), in 23.7% of borderline atypia subjects (64 of 270), and in 6.4% of normal subjects (101 of 1566). Graphic analysis of odds ratios at each point in the diagnostic spectrum defined four categories: 1) "low risk" (HPVs 6/11, 42, 43, and 44), present in 20.2% (76 of 377) of low-grade lesions but absent in all 153 cancers; 2) "intermediate risk" (HPVs 31, 33, 35, 51, 52, and 58), detected in 23.8% (62 of 261) of high-grade squamous intraepithelial lesions but only 10.5% (16 of 153) of cancers; 3) "high risk/HPV 16," associated with 47.1% of both high-grade intraepithelial lesions (123 of 261) and cancers (72 of 153); and 4) "high risk/HPV 18" (HPVs 18, 45, and 56), found in 26.8% (41 of 153) of invasive carcinomas but only 6.5% (17 of 261) of high-grade intraepithelial lesions. The presence of an oncogenic HPV type conferred relative risks ranging at 65.1-235.7 for the occurrence of a high-grade lesion and 31.1-296.1 for an invasive cancer.
Expression of Podocalyxin Inhibits Cell–Cell Adhesion and Modifies Junctional Properties in Madin-Darby Canine Kidney Cells (2000)

Podocalyxin is a major membrane protein of the glomerular epithelium and is thought to be involved in maintenance of the architecture of the foot processes and filtration slits characteristic of this unique epithelium by virtue of its high negative charge. However, until now there has been no direct evidence for podocalyxin's function. Podocalyxin is a type 1 transmembrane sialoprotein with an N-terminal mucin-like domain. To assess its function, we cloned rat podocalyxin and examined the effects of its expression on the cell adhesion properties of stably transfected Chinese hamster ovary (CHO)-K1 and Madin-Darby canine kidney (MDCK) cells and inducible ecdysone receptor-expressing (EcR)-CHO cells. In a cell aggregation assay, CHO-K1 cells expressing high levels of podocalyxin showed complete inhibition of cell aggregation, and MDCK transfectants showed greatly reduced aggregation ( approximately 60-80%) compared with parental cells. In EcR-CHO cells, the expression level of podocalyxin induced by increasing levels of ecdysone analogue correlated closely with the antiadhesion effect. The inhibitory effect of podocalyxin was reversed by treatment of the cells with Arthrobacter ureafaciens sialidase, indicating that sialic acid is required for inhibition of cell adhesion. Overexpression of podocalyxin also affected transepithelial resistance and the distribution of junctional proteins in MDCK cells by an unknown mechanism that may involve interaction with the actin cytoskeleton. These results provide direct evidence that podocalyxin functions as an antiadhesin that maintains an open filtration pathway between neighboring foot processes in the glomerular epithelium by charge repulsion.
Synthesis and Biological Evaluation of [18F]Bicalutamide, 4-[76Br]Bromobicalutamide, and 4-[76Br]Bromo-thiobicalutamide as Non-Steroidal Androgens for Prostate Cancer Imaging (2007)

Androgen receptors (AR) are overexpressed in most primary and metastatic prostate cancers. To develop a nonsteroidal AR-mediated imaging agent, we synthesized and radiolabeled several analogs of the potent antiandrogen bicalutamide: [18F]bicalutamide, 4-[76Br]bromobicalutamide, and [76Br]bromo-thiobicalutamide. Two of these analogs, 4-[76Br]bromobicalutamide and [76Br]bromo-thiobicalutamide, were found to have a substantially increased affinity for the androgen receptor (AR) compared to that of bicalutamide. The synthesis of [18F]bicalutamide utilized a pseudocarrier approach to effect addition of a carbanion generated from tracer-level amounts of a radiolabeled precursor to an unlabeled carbonyl precursor. 4-[76Br]Bromobicalutamide and [76Br]bromo-thiobicalutamide were labeled through electrophilic bromination of a tributylstannane precursor. The former could be prepared in high specific activity, and its tissue distribution was tested in vivo. Androgen target tissue uptake was evident in castrated adult male rats; however, in DES-treated, AR-positive, tumor-bearing male mice, tumor uptake was low.
CCR6 expression distinguishes mouse myeloid and lymphoid dendritic cell subsets: demonstration using a CCR6 EGFP knock-in mouse (2002)

The homing properties of subsets of lymphocytes and dendritic cells (DC) are regulated in part by the profile of chemokine receptors expressed. To determine how CCR6 influences cell trafficking, a mutant allele of the mouse CCR6 gene was produced that includes an enhanced green fluorescent protein (EGFP) reporter under the control of the CCR6 promoter. In mice heterozygous for the EGFP/CCR6 knock-in, CCR6 expression was detected on all mature B cells, subpopulations of splenic CD4(+) and CD8(+) T cells, and on some CD11c(+) DC. Most CD11b(+) myeloid DC expressed CCR6, but CD8alpha(+) lymphoid DC were negative for CCR6. Among myeloid DC, the CD4(+) subset was uniformly positive for CCR6 expression and the CD4(-) subset was mostly CCR6 positive. Epidermal Langerhans cells (LC) also expressed CCR6, but at lower levels than splenic myeloid DC. Culture of bone marrow precursors from the knock-in mice with GM-CSF for 4 to 6 days led to the appearance of a subset of CD11c(+) DC expressing CCR6. The differences in CCR6 expression among the major DC subsets indicate that CCR6 and its chemokine ligand MIP-3alpha participate in determining the positioning of DC subsets in epithelial and lymphoid tissues.
Regulatory T cells (Treg) and Their Roles in Immune System with Respect to Immunopathological Disorders (2010)

Regulatory T cells (Tregs) are a specialized subpopulation of T cells that act to suppress immune response, thereby maintaining homeostasis and self-tolerance. It has been shown that Tregs are able to inhibit T cell proliferation and cytokine production and play a critical role in preventing autoimmunity. Different subsets with various functions of Treg cells exist. Tregs can be usually identified by flow cytometry. The most specific marker for these cells is FoxP3, which is localized intracellulary. Selected surface markers such as CD25high (high molecular density) and CD127low (low molecular density) could serve as surrogate markers to detect Tregs in a routine clinical practice. Dysregulation in Treg cell frequency or functions may lead to the development of autoimmune disease. Therapeutical Treg modulation is considered to be a promising therapeutical approach to treat some selected disorders, such as allergies, and to prevent allograft rejection.
Using a new photoimageable dielectric for PWB sequential build-up technology (2002)

Shipley has been developing products to meet the demands of sequential build-up (SBU) technology for about five years. Shipley has worked closely with customers in evaluating these technologies, and are also involved in a US government initiative for low cost PWBs produced using a sequential manufacturing process. Our initial photodielectric, Multiposit(R) 9500, exhibited excellent plated metal adhesion, good imaging, aqueous developability, and outstanding material properties. As part of the ongoing effort, a new material, Multiposit(R) XP-96700, is under development. This new material exhibits the same material properties, including plated metal adhesion and good electrical properties, as Multiposit(R) 9500, but also exhibits improved processing, via shape, and photospeed. This new material is the centrepiece of a total process solution under development which uses the concept of a "factory within a factory" to allow the coating and imaging of this material in a clean environment within the normal PWB manufacturing shop floor. This paper presents preliminary information on a new photodielectric material, including data on via resolution and plating, plated metal adhesion, and physical and electrical properties of the cured material. We discuss and analyse some of the challenges facing SBU technology with regard to cost, reliability, planarization, PTH processing, and yield. Our goal is to explore the use and characterization of this new dielectric material using an integrated approach of imaging and metallization through to final board finish and testing.
New Interfacial Microtubule Inhibitors of Marine Origin, PM050489/PM060184, with Potent Antitumor Activity and a Distinct Mechanism (2013)

We have investigated the target and mechanism of action of a new family of cytotoxic small molecules of marine origin. PM050489 and its dechlorinated analogue PM060184 inhibit the growth of relevant cancer cell lines at subnanomolar concentrations. We found that they are highly potent microtubule inhibitors that impair mitosis with a distinct molecular mechanism. They bind with nanomolar affinity to unassembled αβ-tubulin dimers, and PM050489 binding is inhibited by known Vinca domain ligands. NMR TR-NOESY data indicated that a hydroxyl-containing analogue, PM060327, binds in an extended conformation, and STD results define its binding epitopes. Distinctly from vinblastine, these ligands only weakly induce tubulin self-association, in a manner more reminiscent of isohomohalichondrin B than of eribulin. PM050489, possibly acting like a hinge at the association interface between tubulin heterodimers, reshapes Mg(2+)-induced 42 S tubulin double rings into smaller 19 S single rings made of 7 ± 1 αβ-tubulin dimers. PM060184-resistant mutants of Aspergillus nidulans map to β-tubulin Asn100, suggesting a new binding site different from that of vinblastine at the associating β-tubulin end. Inhibition of assembly dynamics by a few ligand molecules at the microtubule plus end would explain the antitumor activity of these compounds, of which PM060184 is undergoing clinical trials.
Heart Attacks in Middle-Aged Women (2004)

What is the leading cause of death in American women? Surprisingly, the answer is not breast cancer; heart disease is the number one killer of women. Many women believe that cancer is more of a threat than heart attacks, but they are wrong. Heart disease is not just man’s disease. According to the American Heart Association (2003), nearly twice as many women in the United States die of heart disease and strokes than all other forms of cancer, including breast cancer. Thirteen percent of women, age 45 and over, have had a heart attack. By middle age, women have spent the majority of their time caring for their children and families, but now, it is important for them to take care of themselves. Further exploration of heart attacks in middle-aged women is an important topic of discussion. Therefore it is crucial for middle-aged women to pay more attention on the hazard for ignoring the heart disease.
Cranberry Juice and Urinary Tract Infection (2004)

Cranberries have long been the focus of interest for their beneficial effects in preventing urinary tract infections (UTIs). Cranberries contain 2 compounds with antiadherence properties that prevent fimbriated Escherichia coli from adhering to uroepithelial cells in the urinary tract. Approximately 1 dozen clinical trials have been performed testing the effects of cranberries on the urinary tract. However, these trials suffer from a number of limitations. Most importantly, the trials have used a wide variety of cranberry products, such as cranberry juice concentrate, cranberry juice cocktail, and cranberry capsules, and they have used different dosing regimens. Further research is required to clarify unanswered questions regarding the role of cranberries in protecting against UTI in general and in women with anatomical abnormalities in particular.