gebhart/patrepeval huggingface dataset:
Practical selection of antiemetics. (2004)

An understanding of the pathophysiology of nausea and the mechanisms of antiemetics can help family physicians improve the cost-effectiveness and efficacy of therapy. Nausea and vomiting are mediated primarily by visceral stimulation through dopamine and serotonin, by vestibular and central nervous system causes through histamine and acetylcholine, and by chemoreceptor trigger zone stimulation through dopamine and serotonin. Treatment is directed at these pathways. Antihistamines and anticholinergic agents are most effective in patients with nausea resulting from vestibular and central nervous system causes. Dopamine antagonists block dopamine in the intestines and chemoreceptor trigger zone; indications for these agents are similar to those for serotonin antagonists. Serotonin antagonists block serotonin in the intestines and chemoreceptor trigger zone, and are most effective for treating gastrointestinal irritation and postoperative nausea and vomiting. Complementary and alternative therapies, such as ginger, acupressure, and vitamin B6, have variable effectiveness in the treatment of pregnancy-induced nausea.
Transgenic and gene-targeted mice as models for chronic obstructive pulmonary disease: Fig. 1— (2007)

Animal models play an important role in the understanding of the pathogenesis of chronic obstructive pulmonary disease (COPD). The applicability of findings to human COPD depends upon several factors, including the disease model, and similarities in mouse structure and function between species. There are many examples in the literature of transgenic mice that have contributed to the understanding of COPD. Several studies demonstrate the complexity of inflammatory networks and how unexpected findings in animal models have led to the search for new potential mediators in human disease. Gene-targeting studies into alpha(1)-antitrypsin (alpha(1)-AT) and emphysema in mice have demonstrated that the genetic locus for alpha(1)-AT in mice is very complex and that the loss of one gene is lethal in embryo lung development. This underlines the differences between mice and humans that limit the ability to translate between systems in some instances. Gene targeting has also highlighted complex roles for transforming growth factor-beta in COPD and has been used to determine important molecules and pathways in COPD. Both transgenic and gene-targeted models suffer limitations and their applicability to human chronic obstructive pulmonary disease may be dependant on several factors, some of which are still being learnt. The more that is known about similarities and differences, the better the knowledge will be that is gained to develop for chronic obstructive pulmonary disease.
Mode-selective bond fission: Comparison between the photodissociation of HOD (0,0,1) and HOD (1,0,0) (1991)

The 193 nm photodissociation of individual rotational levels of HOD molecules excited with one quantum of O–H or O–D stretching vibrational energy is described. Stimulated Raman excitation and coherent anti-Stokes Raman scattering are used to prepare and detect, respectively, the (0,0,1) (O–H stretch) or (1,0,0) (O–D stretch) vibrationally excited HOD. The OD and OH fragments are detected by laser-induced fluorescence. In the photodissociation of HOD (0,0,1), the yield of both fragments is enhanced [relative to HOD (0,0,0)], but the yield of OD is increased 2.5±0.5 times more than that of OH. In the photodissociation of HOD (1,0,0), no enhancement of the yield of the fragments is obtained. Our results show that even the very lowest possible level of vibrational excitation can be ‘‘leveraged’’ to effect selective bond breaking. Also, these results demonstrate that bond cleavage does not necessarily occur on the weakened bond and they agree with theoretical calculations indicating that the yield of OD and OH fragments depends on the Franck–Condon overlap of the vibrational wave function with the repulsive surface of the upper state.
Different Glycosylation in Acetylcholinesterases from Mammalian Brain and Erythrocytes (1992)

Acetylcholinesterases (EC 3.1.1.7, AChE) have varying amounts of carbohydrates attached to the core protein. Sequence analysis of the known primary structures gives evidence for several asparagine-linked carbohydrates. From the differences in molecular mass determined on sodium dodecyl sulfate-polyacrylamide gel before and after deglycosylation with N-glycosidase F (EC 3.2.2.18), it is seen that dimeric AChE from red cell membranes is more heavily glycosylated than the tetrameric brain enzyme. Furthermore, dimeric and tetrameric forms of bovine AChE are more heavily glycosylated than the corresponding human enzymes. Monoclonal antibodies 2E6, 1H11, and 2G8 raised against detergent-soluble AChE from electric organs of Torpedo nacline timilei as well as Elec-39 raised against AChE from Electrophorus electricus cross-reacted with AChE from bovine and human brain but not with AChE from erythrocytes. Treatment of the enzyme with N-glycosidase F abolished binding of monoclonal antibodies, suggesting that the epitope, or part of it, consists of N-linked carbohydrates. Analysis of N-acetylglucosamine sugars revealed the presence of N-acetylglucosamine in all forms of cholinesterases investigated, giving evidence for N-linked glycosylation. On the other hand, N-acetylgalactosamine was not found in AChE from human and bovine brain or in butyrylcholinesterase (EC 3.1.1.8) from human serum, indicating that these forms of cholinesterase did not contain O-linked carbohydrates. Despite the notion that within one species, the different forms of AChE arise from one gene by different splicing, our present results show that dimeric erythrocyte and tetrameric brain AChE must undergo different postsynthetic modifications leading to differences in their glycosylation patterns.
An experimental evaluation of continuous testing during development (2004)

Continuous testing uses excess cycles on a developer's workstation to continuously run regression tests in the background, providing rapid feedback about test failures as source code is edited. It is intended to reduce the time and energy required to keep code well-tested and prevent regression errors from persisting uncaught for long periods of time. This paper reports on a controlled human experiment to evaluate whether students using continuous testing are more successful in completing programming assignments. We also summarize users' subjective impressions and discuss why the results may generalize.The experiment indicates that the tool has a statistically significant effect on success in completing a programming task, but no such effect on time worked. Participants using continuous testing were three times more likely to complete the task before the deadline than those without. Participants using continuous compilation were twice as likely to complete the task, providing empirical support to a common feature in modern development environments. Most participants found continuous testing to be useful and believed that it helped them write better code faster, and 90% would recommend the tool to others. The participants did not find the tool distracting, and intuitively developed ways of incorporating the feedback into their workflow.
Serotonin transporter promoter polymorphism is associated with attenuated prolactin response to fenfluramine (2001)

Disturbances in central serotonin (5-HT) function may have a role in impulsive aggression in patients with a wide range of psychiatric diagnoses. The underlying mechanism, however, remains unknown. There are several naturally occurring mutations in the 5-HT signaling pathway that may underlie differences in 5-HT function and responsivity to drugs that affect 5-HT functioning. In the present study, we examined the relationship between polymorphisms in the promoter region of the gene coding for the neuronal 5-HT transporter, fenfluramine-induced prolactin release, and aggressive impulsivity (as measured by Barratt Impulsivity Scale, Buss-Durkee Hostility Inventory, and Brown-Goodwin Aggression Scale scores), in a group of abstinent alcoholic patients and healthy volunteers. We report here that possession of the short variant of the 5-HT transporter promoter polymorphism was associated with a blunting of overall central 5-HT function, as measured by fenfluramine-induced prolactin release. We found no relationship between aggressive, hostile, or impulsive traits and fenfluramine-induced prolactin release or between these traits and polymorphisms in the 5-HT transporter promoter. Thus, we have shown that a 5-HT transporter promoter genotype, which has previously been associated with anxiety-based behaviors, alters an in vivo measure of central 5-HT function (fenfluramine-induced prolactin release), providing an important mechanism for linkage between a gene, physiological function, and behavior. Published 2001 Wiley-Liss, Inc.
Geodesic exponential kernels: When curvature and linearity conflict (2015)

We consider kernel methods on general geodesic metric spaces and provide both negative and positive results. First we show that the common Gaussian kernel can only be generalized to a positive definite kernel on a geodesic metric space if the space is flat. As a result, for data on a Riemannian manifold, the geodesic Gaussian kernel is only positive definite if the Riemannian manifold is Euclidean. This implies that any attempt to design geodesic Gaussian kernels on curved Riemannian manifolds is futile. However, we show that for spaces with conditionally negative definite distances the geodesic Laplacian kernel can be generalized while retaining positive definiteness. This implies that geodesic Laplacian kernels can be generalized to some curved spaces, including spheres and hyperbolic spaces. Our theoretical results are verified empirically.
Swept-carrier time-domain optical memory (1992)

A new time-domain approach to frequency-selective optical data storage is described. In this approach, a spatial storage cell is exposed to two cotemporal, spatially angled, frequency-chirped excitation fields whose duration can greatly exceed the homogeneous dephasing time of the storage material employed. The two beams have a fixed frequency offset, and one is temporally encoded with data. The new method averts several of the drawbacks of existing approaches to time- and frequency-domain optical memories.
A microdevice for multiplexed detection of T-cell-secreted cytokines (2008)

Cytokines are produced by immune cells in response to viral or bacterial pathogens and therefore have significant diagnostic value. The goal of the present study was to develop a miniature device for detection of interleukin (IL)-2 and interferon (IFN)-gamma cytokines secreted by a small population of CD4 and CD8 T-cells. Microarrays of T-cell- and cytokine-specific Ab spots were printed onto poly(ethylene glycol) (PEG) hydrogel-coated glass slides and enclosed inside a microfluidic device, creating a miniature ( approximately 3 microL) immunoreaction chamber. Introduction of the red blood cell (RBC) depleted whole human blood into the microfluidic device followed by washing at a pre-defined shear stress resulted in isolation of pure CD4 and CD8 T-cells on their respective Ab spots. Importantly, the cells became localized next to anti-IL-2 and -IFN-gamma Ab spots. Mitogenic activation of the captured T-cells was followed by immunofluorescent staining (all steps carried out inside a microfluidic device), revealing concentration gradients of surface-bound cytokine molecules. A microarray scanner was then used to quantify the concentration of IFN-gamma and IL-2 near CD4 and CD8 T-cells. This study represents one of the first demonstrations of a microdevice for capturing desired T-cell subsets from a small blood volume and determining, on-chip, cytokine profiles of the isolated cells. Such a microdevice is envisioned as an immunology tool for multi-parametric analysis of T-cell function with direct applications in diagnosis/monitoring of HIV and other infectious diseases.
Characterisation of Lignin from CAD and OMT DeficientBm Mutants of Maize (1997)

Internodes of the maize cell line W401 and bm1 and bm3 mutants expressed in W401 were harvested 5 days after anthesis (A5) and at silage (S) stage. The normal maize had a higher total phenolic (TP) content (80·5–90·5 g kg-1 cell wall DM) than both bm1 and bm3 mutants (74·4–86·4 and 66·0– 84·2 g kg-1 cell wall DM, respectively). TP were inversely related to cellulase digestibility with values of 85·4–91·5, 89·3–92·1 and 91·3–94·1% for normal, bm1 and bm3. Marked differences in p-coumaric acid concentrations were found ranging from 20·9 to 26·3 g kg-1 cell wall DM for normal, 14·9 to 15·3 g kg-1 for bm1 to 10·1 to 14·4 g kg-1 for bm3. The ferulate pattern was entirely different with the bm1 genotype providing the lowest total (9·1–10·7 g kg-1) and etherified (1·9–2·3 g kg-1) values. Although the bm3 contained more total ferulate (11·5–13·1 vs 10·9–11·7 g kg-1), the normal variety had a significantly greater amount of etherified ferulate (2·8–3·4 vs 3·2–4.1 g kg-1) implying a greater extent of cross-linking between wall polymers. Recovery of guaiacyl and syringyl residues was greatest in the normal maize with the bm1 occupying the middle position between the two extremes. Calculated S: G ratios from 4 M NaOH digestion and NMR were in good agreement with the normal line giving the highest ratio, bm1 intermediate and bm3 the lowest. Colorimetric analysis revealed a large increase in the aldehyde content of the in situ bm1 lignin compared to normal and bm3 genotypes although NMR failed to reveal significant numbers of aldehydic resonances. © 1997 SCI.
Sequence-specific cleavage of RNA in the absence of divalent metal ions by a DNAzyme incorporating imidazolyl and amino functionalities (2004)

Two modified 2'-deoxynucleoside 5'-triphosphates have been used for the in vitro selection of a modified deoxyribozyme (DNAzyme) capable of the sequence-specific cleavage of a 12 nt RNA target in the absence of divalent metal ions. The modified nucleotides, a C5-imidazolyl-modified dUTP and 3-(aminopropynyl)-7-deaza-dATP were used in place of TTP and dATP during the selection and incorporate two extra protein-like functionalities, namely, imidazolyl (histidine analogue) and primary amino (lysine analogue) into the DNAzyme. The functional groups are analogous to the catalytic Lys and His residues employed during the metal-independent cleavage of RNA by the protein enzyme RNaseA. The DNAzyme requires no divalent metal ions or other cofactors for catalysis, remains active at physiological pH and ionic strength and can recognize and cleave a 12 nt RNA substrate with sequence specificity. This is the first example of a functionalized, metal-independent DNAzyme that recognizes and cleaves an all-RNA target in a sequence-specific manner. The selected DNAzyme is two orders of magnitude more efficient in its cleavage of RNA than an unmodified DNAzyme in the absence of metal ions and represents a rate enhancement of 10(5) compared with the uncatalysed hydrolysis of RNA.
Visual embedding of wavelet transform coefficients (2002)

In wavelet image compression using embedded quantization, visual quality can be improved by limiting the number of bits used to refine each significant coefficient to some maximum which is different for each sub-band. At a fixed bit rate, the bits saved are used to augment the number of coefficients coded. In this work, a refinement strategy for just noticeable degradation is obtained experimentally for a 5-scale wavelet decomposition, giving a specification for visually lossless quantization. For a range of higher compression ratios, psychovisual experimentation to determine viewer preferences produces a scheme for the allocation of refinement bits at low bit rates. The results are consistent between subjects and across a range of standard test images. The work is a step towards wavelet image coding in which the data stream is fully embedded for optimum visual quality.
Modulation of human natural killer cell function by l-leucine methyl ester: monocyte-dependent depletion from human peripheral blood mononuclear cells. (1985)

L-leucine methyl ester (Leu-OMe) causes lysosomal disruption and death of human monocytes (M phi). In addition, Leu-OMe removed natural killer cell (NK) activity from human peripheral mononuclear cells (PBM). Thus, a brief preincubation of PBM with Leu-OMe (greater than 1 mM) caused irreversible loss of NK function as assessed by the lysis of K562 targets. By contrast, a variety of other amino acid methyl esters, including L-glutamic dimethyl ester, L-valine methyl ester, and L-isoleucine methyl ester caused reversible inhibition of NK activity in a manner that was similar to other lysosomotropic agents such as chloroquine and ammonium chloride, but did not cause irreversible loss of all NK function. Leu-OMe appeared to cause actual removal of NK effector cells from PBM, because K562 target binding cells, Leu-11b+ lymphocytes, and OKM1+ lymphocytes were depleted. If M phi were removed from PBM before the incubation, Leu-OMe caused only reversible inhibition of NK function in a manner similar to that observed with other amino acid methyl esters. Upon the addition of freshly isolated M phi, polymorphonuclear leukocytes, or sonicates of these cells to M phi-depleted lymphocyte populations, irreversible ablation of NK function was again observed as a result of Leu-OMe exposure. After in vitro culture, M phi lost their susceptibility to Leu-OMe toxicity and the ability to mediate the irreversible deletion of NK cells resulting from Leu-OMe incubation. These results indicate that in the absence of M phi, Leu-OMe and a variety of other amino acid methyl esters are reversible inhibitors of NK function. However, Leu-OMe is unique in that it can interact with M phi or granulocytes to effect an irreversible loss of NK activity from human peripheral blood lymphocytes.
CELL TO CELL INTERACTION IN THE IMMUNE RESPONSE (1968)

In this series of papers it has been shown that the immune response of mice to sheep erythrocytes requires the participation of two classes of lymphoid cells. Thymus-derived cells initially react with antigen and then interact with another class of cells, the antibody-forming cell precursors, to cause their differentiation to antibody-forming cells. Antilymphocyte globulin depressed the ability of mice to respond to sheep erythrocytes. This effect was more marked when the antigen was injected intraperitoneally than intravenously, and occurred only when the antilymphocyte globulin was given before or simultaneously with antigen. Injection of thymus cells restored to near normal the ability to respond to an intravenous injection of sheep erythrocytes. Spleen cells from antilymphocyte globulin-treated mice gave a weak adoptive immune response in irradiated recipients. The addition of thymus cells however enabled a response similar to that given by normal spleen cells. When thymectomized irradiated recipients were used, normal spleen cells continued to give a higher response to a challenge of sheep erythrocytes at 2 and 4 wk postirradiation than did spleen cells from ALG-treated donors. This result is more consistent with the notion that thymus-derived target cells are eliminated, rather than temporarily inactivated, by antilymphocyte globulin. These findings suggest that, in vivo, antilymphocyte globulin acts selectively on the thymus-derived antigen-reactive cells.
Microfabricated porous glass channels for electrokinetic separation devices (2005)

Electrically insulated porous SiO2 channels for electrokinetic separation devices were fabricated based on a mask-less etching process for creation of high aspect ratio needles in silicon. The silicon needles are converted to SiO2 by oxidation and integrated within the interior of a fluidic channel network. The channels are about 5 microm high with a pore size of 0.5+/-0.2 microm. An electrophoretic separation of a mixture of fluorescein and 5-carboxyfluorescein using epi-fluorescence detection was performed to verify proper electrokinetic transport in the porous channels. The plate height was about 170,000 m-1 for a field strength of 170 V cm-1. In the near future, it is intended to extend the fabrication scheme to include an array of porous pillars for capillary electrochromatography experiments.
The promoter of the barley aleurone‐specific gene encoding a putative 7 kDa lipid transfer protein confers aleurone cell‐specific expression in transgenic rice (1994)

This paper describes the aleurone-specific gene Ltp2 from barley, which encodes a putative 7 kDa non-specific lipid transfer protein. As shown by Northern and in situ hybridization analyses, the Ltp2 transcript is present in barley aleurone cells shortly after the initiation of aleurone cell differentiation. The expression of Ltp2 increases until grain mid-maturity, but the mRNA is absent from mature grains. The Ltp2 transcript is undetectable in the embryo and vegetative tissues, confirming the aleurone specificity of the Ltp2 gene. The ability of the isolated 801 bp Ltp2 promoter to direct aleurone-specific expression in immature barley grains is demonstrated by particle bombardment experiments. In these experiments, the activity of the Ltp2 promoter is 5% of the activity of the strong constitutive Actin1 promoter from rice, as quantified by GUS activity measurements. In stably transformed rice plants containing the Ltp2 promoter-Gus construct, the specificity of the Ltp2 promoter is confirmed in vivo by the presence of GUS activity exclusively in the aleurone layer. This study demonstrates the conserved nature of the regulatory signals involved in aleurone-specific gene transcription in cereal grains.
T cell receptor signalling (2001)

Upon engagement of the TCR by antigen presented on major histocompatibility complex (MHC) molecules, the Src family kinase Lck is activated and proceeds to phosphorylate immunoreceptor tyrosine-based activation motifs (ITAMs) on the e, δ, γ and ζ subunits of the TCR. Phosphorylated ITAMs promote the recruitment and subsequent activation of another tyrosine kinase ZAP-70. Two known substrates of ZAP70 are the adapter molecules LAT and SLP-76. Phosphorylation of tyrosine residues on LAT and SLP-76 results in recruitment of a number of other proteins involved in activation of the Ras pathway, calcium mobilization and cytoskeletal reorganization.
Synthesis and characterization of zeolite (MFI) membranes on porous ceramic supports (1992)

Continuous polycrystalline films of ZSM-5 (MFI-type) crystals have been grown on porous ceramic (clay) supports. The films are thermomechanically stable upon calcination at 400 °C in air to remove template ions (tetrapropylammonium), during which process the porous support seems to have a stabilizing effect. When the hydrothermal conditions induce substantial aluminium leaching from the support, large analcime crystals are grown on the support. Gas permeation experiments with both pure gases (permanent gases, alkanes and difluorodichloromethane) and mixtures thereof have been performed on the MFI composite to investigate the separation potential of this new type of membrane. Expected selectivities as a result of large differences in diffusivity are found to be strongly reduced by differences in sorption of the same order of magnitude, and the reduced mobility of weakly adsorbing (fast moving) molecules caused by the slower moving species. However, from the observed low permeation rates it is expected that, owing to the presence of a porous support with relatively low porosity, the molecular sieving effect is reduced as well.