gebhart/patrepeval huggingface dataset:
Additive effect of oxitropium bromide in combination with inhaled corticosteroids in the treatment of elderly patients with chronic asthma (1999)

The efficacy of the addition of inhaled oxitropium bromide in combination with inhaled corticosteroids in the treatment of elderly asthmatic patients whose asthma is not well controlled was evaluated. A randomized, open-label cross-over trial comparing 4-week treatment periods with and without regular inhalation of 200 μg of oxitropium bromide four times per day was performed. Twenty-four patients (mean age ± SD: 62 ± 7 years) completed the study. The dose of beclomethasone dipropionate in this patient group was 1300 ± 800 μg/day. Forced expiratory volume in 1 second (FEV1) was significantly improved after treatment with regular inhalation of oxitropium bromide when compared with FEV1 after treatment without oxitropium (1.73 ± 0.60 vs 1.63 ± 0.68). Both morning and evening peak expiratory flow rates were significantly greater during the treatment period with regular inhalation of oxitropium bromide. The score for dyspnea/chest tightness was also significantly improved during the oxitropium bromide period. There was no statistically significant improvement in forced vital capacity, scores for other symptoms or the frequency of rescue inhalation of fenoterol. The results of this study demonstrated that the addition of regular inhalation of oxitropium bromide is beneficial in elderly asthmatics whose asthma is not well controlled, even when treated with high-dose inhaled steroids.
The nuclear pore complex protein Nup88 is overexpressed in tumor cells. (1999)

It has been previously shown (J. Schneider et al., Br. J. Cancer, 77: 1015-1020, 1998) that an antibody directed against Candida albicans proteins (C6) recognizes specifically a protein in human ovarian tumors. We have now performed an immunoscreening of a human cDNA library using this antibody and identified the antigen as Nup88, a protein localized preferentially at the nuclear membrane and probably implicated in nucleocytoplasmic transport. Our results show that Nup88 is strongly expressed in a series of human tumor cell lines compared with nontransformed cell lines at the RNA and the protein levels. Furthermore, we observed that in 76% of 21 ovarian tumors analyzed, the protein is also overexpressed in malignant tissue when compared with healthy adjacent tissue. Nup88 may, therefore, be considered as a putative marker for tumor growth and is probably related to increased cell cycling.
Design, Synthesis, and Biological Activity of Hybrid Compounds between Uramustine and DNA Minor Groove Binder Distamycin A (2002)

The design, synthesis, characterization, DNA binding properties, and cytotoxic activity of a novel series of hybrids, namely, a molecular combination of the natural antibiotic distamycin A and the antineoplastic agent uramustine, are reported, and the structure-activity relationships are discussed. This homologous series 29-34 consisted of the minor groove binder distamycin A joined to uramustine (uracil mustard) by suitable aliphatic carboxylic acid moieties containing a flexible polymethylene chain that is variable in length [(CH(2))(n)(), where n = 1-6). All the hybrid compounds in this series exhibit enhanced activity compared to both distamycin A and uramustine derivatives 22-27 used for conjugation, giving IC(50) values in the range 7.26-0.07 microM following a 1 h exposure of human leukemic K562 cells, with maximal activity shown when n = 6. The distance between the uramustine and distamycin frame is crucial for the cytotoxicity, with compounds having linker lengths of four to six being at least 20-fold more cytotoxic than linker lengths one to three. Taq polymerase stop experiments demonstrated selective covalent binding of uramustine-distamycin hybrids to A/T rich DNA sequences, which was again more efficient with compounds 32-34 with a longer linker length. Two consequences can be derived from our study: (a) the distamycin moiety directs binding to the minor groove of A/T rich DNA sequences and, consequently, is responsible for the alkylation regioselectivity found in footprinting studies; (b) the higher flexibility due to a longer linker between the distamycin and uracil moieties allows the formation of complexes with the mustard moiety situated more deeply in the minor groove and, hence, with better alkylating properties.
Tutorial Signal and noise separation: Art and science (1999)

The separation of signal and noise is a central issue in seismic data processing. The noise is both random and coherent in nature, the coherent part often masquerading as signal. In this tutorial, we present some approaches to signal isolation, in which stacking is a central concept. Our methodology is to transform the data to a domain where noise and signal are separable, a goal that we attain by means of inversion. We illustrate our ideas with some of our favorite transformations: wavelets, eigenvectors, and Radon transforms. We end with the notion of risk, baseball, and the Stein estimator.
High speed and nonvolatile Si nanocrystal memory for scaled flash technology using highly field-sensitive tunnel barrier (2004)

For the first time, a nitride/oxide/nitride stacked tunnel structure is adopted as highly field-sensitive tunnel barrier to improve both program/erase speed and data retention of nanocrystal memory. Product-adaptive nonvolatility (>10 years at 85/spl deg/C) and cycling endurance (>10/sup 6/) were obtained with the program time of 10 /spl mu/s at V/sub G/=8 V and the erase time of 100 /spl mu/s at V/sub G/=-8 V with 0.84 V threshold window. The program speed was 100 times faster and the voltage was about 10 V smaller than those of a conventional NAND type flash memory cell. These results strongly suggest that nanocrystal floating gate memory becomes a promising solution to overcome the scaling limitation of the conventional floating gate memory cell.
A New Acoustic Model for Valveless Pulsejets and Its Application to Optimization Thrust (2008)

Due to its simplicity, the valveless pulsejet may be an ideal low cost propulsion system. In this paper, a new acoustic model is described, which can accurately predict the operating frequency of a valveless pulsejet. Experimental and computational methods were used to investigate how the inlet and exhaust area and the freestream velocity affect the overall performance of a 50cm pulsejet. Pressure and temperature were measured at several axial locations for different fuel flow rates and different geometries. Computer simulations were performed for exactly the same geometries and fuel flow rates using a commercial CFD package (CFX) to develop further understanding of the factors that affect the performance of a valveless pulsejet. An acoustic model was developed to predict the frequency of these valveless pulsejets. The new model treats the valveless pulsejet engine as a combination of a Helmholtz resonator and a wave tube. This new model was shown to accurately predict geometries for maximum thrust. The model was further extended to account for the effect of freestream velocity. Evidence is provided that valveless pulsejet generates the highest thrust when the inherent inlet frequency matches the inherent exhaust frequency.
An anatomy of normal and malignant gene expression (2002)

A gene's expression pattern provides clues to its role in normal physiology and disease. To provide quantitative expression levels on a genome-wide scale, the Cancer Genome Anatomy Project (CGAP) uses serial analysis of gene expression (SAGE). Over 5 million transcript tags from more than 100 human cell types have been assembled. To enhance the utility of this data, the CGAP SAGE project created SAGE Genie, a web site for the analysis and presentation of SAGE data (http://cgap.nci.nih.gov/SAGE). SAGE Genie provides an automatic link between gene names and SAGE transcript levels, accounting for alternative transcription and many potential errors. These informatics advances provide a rapid and intuitive view of transcript expression in the human body or brain, displayed on the SAGE Anatomic Viewer. We report here an easily accessible view of nearly any gene's expression in a wide variety of malignant and normal tissues.
Hierarchical genetic algorithms operating on populations of computer programs (1989)

Existing approaches to artificial intelligence problems such as sequence induction, automatic programming, machine learning, planning, and pattern recognition typically require specification in advance of the size and shape of the solution to the problem (often in a unnatural and difficult way). This paper reports on a new approach in which the size and shape of the solution to such problems is dynamically created using Darwinian principles of reproduction and survival of the fittest. Moreover, the resulting solution is inherently hierarchical. The paper describes computer experiments, using the author's 4341 line LISP program, in five areas of artifical intelligence, namely (1) sequence induction (e.g. inducing a computational procedure for the recursive Fibonacci sequence and inducing a computational procedure for a cubic polynomial sequence), (2) automatic programming (e.g. discovering a computational procedure for solving pairs of linear equations, solving quadratic equations for complex roots, and discovering trigonometric identities), (3) machine learning of functions (e.g. learning a Boolean multiplexer function previously studied in neural net and classifier system work and learning the exclusive-or and parity function), (4) planning (e.g. developing a robotic action sequence that can stack an arbitrary initial configuration of blocks into a specified order), and (5) pattern recognition (e.g. translation-invariant recognition of a simple one dimensional shape in a linear retina).
Displacement current and multiple pulse effects in plasma source ion implantation (1993)

In plasma source ion implantation (PSII), a target to be implanted is immersed in a weakly ionized plasma and pulsed to a high negative voltage. Plasma ions are accelerated toward the target and implanted in its surface. In this article, two factors in the analysis of these discharges are examined for the first time: (1) displacement current across the expanding sheath results in increased implant current and decreased implanted ion energy, with respect to existing models; and (2) ion depletion around the target due to high pulse repetition rates results in decreased implant current and dose. These effects are studied with analytic models and particle-in-cell simulations. Simulation results are compared to previously published PSII models.
Doxorubicin selectively inhibits muscle gene expression in cardiac muscle cells in vivo and in vitro. (1990)

The anthracycline antibiotic doxorubicin produces a characteristic myopathy in cardiac muscle that limits its use in cancer therapy. We have shown in cultured neonatal rat cardiac muscle cells that doxorubicin treatment resulted in a rapid, selective decrease in the expression of muscle-specific genes, which preceded other changes characteristic of doxorubicin cardiomyopathy. Doxorubicin selectively and dramatically decreased the levels of mRNA for the sarcomeric genes, alpha-actin, troponin I, and myosin light chain 2, as well as the muscle-specific, but nonsarcomeric M isoform of creatine kinase. However, doxorubicin did not affect nonmuscle gene transcripts (pyruvate kinase, ferritin heavy chain, and beta-actin). Actinomycin D, an inhibitor of DNA-dependent RNA polymerase, did not show a similar selective decrease of muscle-specific mRNAs but, rather, produced a nonspecific, dose-dependent decrease of muscle and nonmuscle transcripts. The doxorubicin effect on muscle gene expression was limited to cardiac muscle; cultured skeletal myocytes were resistant to the effects of doxorubicin at 100-fold greater doses than those causing changes in mRNA levels in cardiac muscle cells. These effects of doxorubicin were reproduced in vivo; rats injected with doxorubicin showed a dose-dependent decrease in the levels of mRNAs for alpha-actin, troponin I, myosin light chain 2, and M isoform of creatine kinase in cardiac but not skeletal muscle. These selective changes in gene expression in cardiocyte cultures and cardiac muscle precede classical ultrastructural changes and may explain the myofibrillar loss that characterizes doxorubicin cardiac injury.
Incidence and distribution of experimental metastases in mutant mice with defective organ microenvironments (genotypes Sl/Sld and W/Wv). (1992)

Mice carrying mutations at the Sl (steel) and W (dominant white spotting) loci develop abnormalities on 3 migratory embryonic stem cell populations: hematopoietic stem cells, neural crest-derived melanocytes, and primordial germ cells. Transplantation experiments have indicated that the Sl locus affects the microenvironment where stem cells migrate, proliferate, and differentiate, while the W locus affects the migratory cells themselves. The Sl locus encodes for a multipotent growth factor known as stem cell factor. The W locus encodes the c-kit protein tyrosine kinase receptor whose ligand is the stem cell factor. We have investigated the incidence and organ distribution of experimental metastases after systemic intra-arterial injection of B16-G3.26 melanoma cells into mutant Sl/Sld and W/Wv mice. Both mutant mouse strains had a markedly lower incidence of ovarian metastases when compared with their congenic +/+ mice. In contrast to the rare colonization of the ovaries, Sl/Sld and W/Wv mice developed metastases in the myocardium, kidney, and stomach--anatomic sites that were infrequently or never affected in their congenic nonmutant mice. The only organs in which the average number of metastatic colonies differed between Sl/Sld and W/Wv mice were the bone marrow and kidneys. The average number of colonized bones per mouse in the Sl/Sld group was 5.0 +/- 3.1 (SD), compared with 12.7 +/- 5.3 in the W/Wv group. The average number of metastatic nodules in the kidneys of Sl/Sld mice was 24.6 +/- 9, while W/Wv mice had 15.5 +/- 2.5. Mutant mice with multiple metastatic nodules in the kidneys, heart, and stomach were also found to have forestomach papillomas, an enlarged duodenum, kidney abnormalities, and small body size. The results of this study provide useful information on potential mechanisms of interaction of metastatic cells with their target organs, and suggest that there are additional organ defects associated with the mutations in the Sl and W loci. They also document the importance of mutant mice in metastasis research.
Microsphere capture and perfusion in microchannels using flexural plate wave structures (2003)

A standing acoustic field excited by an ultrasonic flexural plate wave (FPW) device is shown to trap microspheres and cells suspended in a pressure-driven flowing liquid. Capture is achieved by counteracting the viscous drag forces on a particle with acoustic radiation pressure. The suitability of this technique for biochemical analysis is demonstrated with two experiments: (1) acoustically trapped streptavidin-coated 1 /spl mu/m microspheres conjugated to fluorescent 200 nm biotinylated microspheres; and (2) perfusion of the membrane permeant fluorescein diacetate across acoustically trapped cells. Biochemical interaction was monitored with a fluorescence microscope. Efforts to integrate acoustic traps with on-chip FPW microfluidic pumps are also described.
Characterization of MicroRNA Expression Levels and Their Biological Correlates in Human Cancer Cell Lines (2007)

MicroRNAs are small noncoding RNAs that function by regulating target gene expression posttranscriptionally. They play a critical role in developmental and physiologic processes and are implicated in the pathogenesis of several human diseases including cancer. We examined the expression profiles of 241 human microRNAs in normal tissues and the NCI-60 panel of human tumor-derived cell lines. To quantify microRNA expression, we employed a highly sensitive technique that uses stem-loop primers for reverse transcription followed by real-time PCR. Most microRNAs were expressed at lower levels in tumor-derived cell lines compared with the corresponding normal tissue. Agglomerative hierarchical clustering analysis of microRNA expression revealed four groups among the NCI-60 cell lines consisting of hematologic, colon, central nervous system, and melanoma tumor-derived cell lines clustered in a manner that reflected their tissue of origin. We identified specific subsets of microRNAs that provide candidate molecular signatures characteristic of the tumor-derived cell lines belonging to these four clusters. We also identified specific microRNA expression patterns that correlated with the proliferation indices of the NCI-60 cell lines, and we developed evidence for the identification of specific microRNAs as candidate oncogenes and tumor suppressor genes in different tumor types. Our results provide evidence that microRNA expression patterns may mark specific biological characteristics of tumors and/or mediate biological activities important for the pathobiology of malignant tumors. These findings call attention to the potential of microRNAs to provide etiologic insights as well as to serve as both diagnostic markers and therapeutic targets for many different tumor types.
POLYMORPHISMS OF ANDROGEN RECEPTOR GENE IN CHILDHOOD AND ADOLESCENT MALES WITH FIRST-ONSET MAJOR DEPRESSIVE DISORDER AND ASSOCIATION WITH RELATED SYMPTOMATOLOGY (2007)

This study was designed to explore the association between CAG repeats in AR gene and major depressive disorder (MDD) in male children and adolescents. The results showed that there were differences between adolescent depressive patients and adolescent controls in CAG repeats' length and alleles' distributions, and the severity of depression and anxiety was negatively correlated with the length of CAG repeats in adolescent patients. This suggested that AR gene might be involved in the depressive upset in adolescents, and the age- and sex-related prevalent differences might also be associated to CAG repeats.
Suicidality and Risk of Suicide—Definition, Drug Safety Concerns, and a Necessary Target for Drug Development (2010)

The term suicidality is not as clinically useful as more specific terminology (ideation, behavior, attempts, and suicide). Most participants applauded the FDA's encouragement of standard definitions and definable expectations for investigators and industry sponsors. Further research of available assessment instruments is needed to verify their utility, reliability, and validity in identifying suicide-associated treatment-emergent adverse effects and/or a signal of efficacy in suicide prevention trials. The FDA needs to systematically monitor postmarketing events by encouraging the development of a validated instrument for postmarketing surveillance of suicidal ideation, behavior, and risk. Over time, the FDA, industry, and clinical researchers should evaluate the impact of the requirement that all central nervous system clinical drug trials must include a Columbia Classification Algorithm of Suicide Assessment (C-CASA)-compatible screening instrument for assessing and documenting the occurrence of treatment-emergent suicidal ideation and behavior. Finally, patients at high risk for suicide can safely be included in clinical trials, if proper precautions are followed.
High-Throughput Kinetic Screening of Hybridomas to Identify High-Affinity Antibodies Using Bio-Layer Interferometry (2014)

Kinetic analysis of antibodies is crucial in both clone selection and characterization. Historically, antibodies in supernatants from hybridomas are selected based on a solid-phase enzyme-linked immunosorbent assay (ELISA) in which the antigen is immobilized on the assay plate. ELISA selects clones based on a combination of antibody concentration in the supernatant and affinity. The antibody concentration in the supernatant can vary significantly and is typically unknown. Using the ELISA method, clones that express high levels of a low-affinity antibody can give an equivalent signal as clones that express low levels of a high-affinity antibody. As a consequence, using the ELISA method, superior clones can be overshadowed by inferior clones. In this study, we have applied Bio-Layer Interferometry to screen hybridoma clones based on disassociation rates using the OctetRED 384 platform. Using the OctetRED platform, we were able to screen 2000 clones within 24 hours and select clones containing high-affinity antibodies for further expansion and subsequent characterization. Using this method, we were able to identify several clones producing high-affinity antibodies that were missed by ELISA.
Identification of a Sequence within the Integrin β6 Subunit Cytoplasmic Domain That Is Required to Support the Specific Effect of αvβ6 on Proliferation in Three-dimensional Culture (1996)

The integrin alphavbeta6 augments the proliferation of epithelial cells in collagen gels and in vivo. This effect depends on the presence of a unique carboxyl-terminal region of the beta6 subunit cytoplasmic domain. In the present study, we have utilized deletional and alanine substitution mutagenesis within this region to map the amino acids responsible for alphavbeta6-mediated proliferation in more detail. Replacement or deletion of any of 6 amino acids (glutamic acid 778, lysine 779, lysine 781, valine 782, aspartic acid 783, and leucine 784) largely abolished the proliferative effects of alphavbeta6, but none of the mutants examined interfered with alphavbeta6-mediated cell adhesion or with localization of alphavbeta6 to focal adhesions. These findings suggest that residues contained within the sequence EKXKVDL are critical for the effects of alphavbeta6 on proliferation in collagen gels and that pathways initiated by interaction with this sequence are distinct from those required for integrin-mediated cell attachment or focal adhesion formation.
Forced linear oscillations of microbubbles in blood capillaries (2004)

A theoretical investigation of the forced linear oscillations of a gas microbubble in a blood capillary, whose radius is comparable in size to the bubble radius is presented. The natural frequency of oscillation, the thermal and viscous damping coefficients, the amplitude resonance, the energy resonance, as well as the average energy absorbed by the system, bubble plus vessel, have been computed for different kinds of gas microbubbles, containing air, octafluropropane, and perflurobutane as a function of the bubble radius and applied frequency. It has been found that the bubble behavior is isothermal at low frequencies and for small bubbles and between isothermal and adiabatic for larger bubbles and higher frequencies, with the viscous damping dominating over the thermal damping. Furthermore, the width of the energy resonance is strongly dependent on the bubble size and the natural frequency of oscillation is affected by the presence of the vessel wall and position of the bubble in the vessel. Therefore, the presence of the blood vessel affects the way in which the bubble absorbs energy from the ultrasonic field. The motivation of this study lies in the possibility of using gas microbubbles as an aid to therapeutic focused ultrasound treatments.
Effects of Continuous Enhanced Vagal Tone on Dual Atrioventricular Node and Accessory Pathways (2003)

Enhanced vagal tone produces disparate effects on the refractoriness of the slow and fast AV nodal conduction pathways, with the anterograde fast pathway being the most sensitive. These changes are conducive to induction of AVNRT with a premature atrial complex and may explain in part the relatively common occurrence of AVNRT during sleep or other periods of presumed increased parasympathetic tone.