gebhart/patrepeval huggingface dataset:
Regional innervation of rabbit ciliary ganglion cells by the terminals of preganglionic axons. (1984)

In the rabbit, ciliary ganglion neurons with dendrites maintain inputs from several different axons during the period of synaptic rearrangement that occurs in early postnatal life. Neurons without dendrites, on the other hand, lose the majority of their initial inputs and are innervated in maturity by the terminals of only one or two axons (Purves, D., and R.I. Hume (1981) J. Neurosci. 1: 441-452; Hume, R.I., and D. Purves (1981) Nature 293: 469-471). We have explored the basis of this phenomenon by individually marking preganglionic axons and the neurons they innervate with horseradish peroxidase. In general, the innervation of geometrically complex (multiply innervated) neurons by individual preganglionic axons is regional. That is, the synaptic contacts made by an axon on these neurons are limited to a portion of the postsynaptic surface that includes some, but not all, of the dendrites. This regional innervation of target neurons is consistent with the view that dendrites allow multiple innervation to persist by providing relatively separate postsynaptic domains for individual preganglionic axons. Such regional innervation may mitigate competitive interactions between the several axons which initially innervate the same neuron.
Tumor necrosis factor-alpha priming of phospholipase A2 activation in human neutrophils. An alternative mechanism of priming (1991)

The cytokine, TNF-alpha, interacts with human neutrophils (PMN) via specific membrane receptors and primes leukotriene B4 (LTB4) production in PMN for subsequent stimulation by calcium ionophores. We have further examined the effects of TNF-alpha on arachidonic acid (AA) release, LTB4 production, and platelet-activating factor (PAF) formation in PMN by prelabeling cells with either [3H]AA or [3H]lyso-PAF, priming with human rTNF-alpha, and then stimulating with the chemotactic peptide, FMLP. TNF-alpha, alone, had little effect; minimal AA release, LTB4 or PAF production occurred after PMN were incubated with 0 to 1000 U/ml TNF-alpha. However, when PMN were first preincubated with 100 U/ml TNF-alpha for 30 min and subsequently challenged with 1 microM FMLP, both [3H] AA release and LTB4 production were elevated two- to threefold over control values. Measurement of AA mass by gas chromatography and LTB4 production by RIA confirmed the radiolabeled results. TNF-alpha priming also increased PAF formation after FMLP stimulation. These results demonstrate that TNF-alpha priming before stimulation with a physiologic agonist can enhance activation of phospholipase A2 (PLA2) resulting in increased AA release and can facilitate the activities of 5-lipoxygenase (LTB4 production) and acetyltransferase (PAF formation). Reports in the literature have hypothesized that the priming mechanism involves either production of PLA2 metabolites, increased diglyceride (DG) levels, or enhanced cytosolic calcium levels induced by the priming agent. We investigated these possibilities in TNF-alpha priming of PMN and report that TNF-alpha had no direct effect on PLA2 activation or metabolite formation. Treatment of PMN with TNF-alpha did not induce DG formation and, in the absence of cytochalasin B, no increased DG production (measured by both radiolabel techniques and mass determinations) occurred after TNF-alpha priming followed by FMLP stimulation. TNF-alpha also had no effect on basal cytosolic calcium and did not enhance intracellular calcium levels after FMLP stimulation. These results suggest that an alternative, as yet undefined, mechanism is active in TNF-alpha priming of human PMN.
Proliferating Human Granulosa-Lutein Cells in Long Term Monolayer Culture: Expression of Aromatase, Cholesterol Side-Chain Cleavage, and 3β-Hydroxysteroid Dehydrogenase* (1990)

The development of long term culture conditions with which to study the regulation of expression of aromatase, cholesterol side-chain cleavage enzyme, and 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) in human granulosa-lutein cells is described in this report. Conditions have been established for the dispersal, growth, freezing, and storage of functional human granulosa cells isolated from preovulatory follicles of women undergoing laparoscopy for gamete intrafallopian tube transfer and in vitro fertilization procedures. Optimal growth conditions for human granulosa-lutein cells were determined by plating cells at a low density and testing the capacity of a variety of culture conditions to support growth. A combination of fetal bovine serum (FBS), horse serum, and the serum substitute UltroSer G was found to increase cell number to maximal levels, 8- to 10-fold higher than with sera alone. Human granulosa-lutein cells grown under these conditions had a doubling rate of 36-40 h and were morphologically distinct from human theca interna cells grown under similar conditions. Human granulosa-lutein cells treated with forskolin retracted and rounded up, whereas cultures of human ovarian theca interna cells or human fibroblasts treated similarly did not retract. Human granulosa-lutein cells were grown for successive passages and transferred to serum-free medium containing forskolin, LH, hCG, or cholera toxin. Addition of these agents resulted in a time- and dose-dependent increase in aromatase activity and progesterone secretion. In these studies FSH treatment was found not to increase aromatase activity. In a study of the time course of 3 beta HSD activity in the absence of forskolin under serum-free conditions, it was found that 3 beta HSD activity increased 3-fold during the 72-h treatment period. Forskolin-stimulated 3 beta HSD activity also increased in a time-dependent manner, with levels in treated cells 3-fold higher than those in control cells. Northern analysis performed on total RNA obtained from forskolin- or hCG-stimulated granulosa-lutein cells confirmed that the increase in aromatase activity was associated with a corresponding increase in levels of mRNA specific for aromatase cytochrome P-450. Levels of mRNA encoding cholesterol side-chain cleavage cytochrome P-450 were similarly increased in cells treated with forskolin compared with unstimulated values at each of the time points investigated. Under serum-free conditions in the absence of stimulation, the 3.4-kilobase band of aromatase cytochrome P-450 mRNA was detectable.(ABSTRACT TRUNCATED AT 400 WORDS)
High Mobility Group Box Chromosomal Protein 1 in Patients with Renal Diseases (2008)

HMGB1 was expressed in the sera of patients with renal diseases who underwent renal biopsies, especially among those who had vasculitis including ANCA-GN, Henoch-Schonlein purpura nephritis, and IgAN with glomerular crescents.
SPLICE SITE SELECTION IN PLANT PRE-mRNA SPLICING (1998)

▪ Abstract The purpose of this review is to highlight the unique and common features of splice site selection in plants compared with the better understood yeast and vertebrate systems. A key question in plant splicing is the role of AU sequences and how and at what stage they are involved in spliceosome assembly. Clearly, intronic U- or AU-rich and exonic GC- and AG-rich elements can influence splice site selection and splicing efficiency and are likely to bind proteins. It is becoming clear that splicing of a particular intron depends on a fine balance in the “strength” of the multiple intron signals involved in splice site selection. Individual introns contain varying strengths of signals and what is critical to splicing of one intron may be of less importance to the splicing of another. Thus, small changes to signals may severely disrupt splicing or have little or no effect depending on the overall sequence context of a specific intron/exon organization.
An evaluation of an eye tracker as a device for computer input2 (1986)

Since humans direct their visual attention by means of eye movements, a device which monitors eye movements should be a natural “pick” device for selecting objects visually present on a monitor. The results from an experimental investigation of an eye tracker as a computer input device are presented. Three different methods were used to select the object looked at; these were a button press, prolonged fixation or “dwell” and an on screen select button. The results show that an eye tracker can be used as a fast selection device providing that the target size is not too small. If the targets are small speed declines and errors increase rapidly.
Calcium β-Hydroxy-β-Methylbutyrate (1996)

The binding capacity of calcium beta-hydroxy-beta-methylbutyrate (calcium HMB), compared to other binders, was investigated in an in vitro study. Fifty milliequivalents of either calcium HMB, calcium acetate, calcium carbonate, aluminum hydroxide gel or non-gel aluminum hydroxide was added to a phosphate solution, titrated (HCl or NaOH), shaken and centrifuged to four different pH levels at 37 degrees C (simulating the gastrointestinal milieu). The difference in phosphate concentration between that of the initial and that of the supernatant represented from the bound phosphate in the precipitate. After 4 h at a pH of 6 (representing the intestinal condition after a meal), the binding percentage was: calcium acetate = 95.6%, calcium HMB = 92.6%, calcium carbonate = 46.4%, aluminum hydroxide gel = 33.4% and non-gel aluminum hydroxide = 17.8%. There was no significant difference (p > 0.05) between calcium HMB and calcium acetate. These results suggest that calcium HMB is an efficient phosphate binder in vitro, which may predict its effective role in vivo.
The role of segment polarity genes during early oogenesis in Drosophila (1996)

In the Drosophila ovary, hedgehog (hh) signaling from cells near the apical tip of the germarium stimulates the proliferation and specification of somatic cells in region 2 of the germarium, 2-5 cells away from the hh-expressing cells (A. J. Forbes, H. Lin, P. Ingham and A. Spradling (1996) Development 122, 1125-1135). This report examines the role during early oogenesis of several genes that are known to function in hh-mediated signaling during embryonic and larval development (P. Ingham (1995) Current Opin. Genetics Dev. 5, 528-534). As in imaginal discs, engrailed (en) is co-expressed with hh in the germarium, while patched (ptc) and cubitus interruptus (ci) are expressed in somatic cells throughout the germarium and in developing egg chambers, with ptc expression being elevated within 10 cell diameters of the source of the hh signal. Moreover, the somatic cell overproliferation caused by ectopic hh expression is accompanied by elevated levels of ptc and is phenocopied in ptc- somatic clones. These analyses suggest that ptc and ci are components of the hh signaling pathway in the germarium. However, unlike embryos and imaginal discs, neither wingless (wg) nor decapentaplegic (dpp) appear to mediate the ovarian hh signal. wg is expressed in 'cap cells,' a subset of hh-expressing cells located adjacent to germ-line stem cells, but is unaffected by ectopic hh expression. Nor does the ectopic expression of wg or dpp mimic the effect of ectopic hh expression. We propose that Hh diffuses from apical cells, including cap cells, and regulates the proliferation of nearby ovarian somatic cells by antagonizing the negative effects of ptc on ci activity in these cells, thereby allowing the transcription of ci-dependent genes, including ptc itself.
Synthesis and Solution Structure of the Antimicrobial Peptide Protegrin‐1 (1996)

Protegrins are members of a family of five Cys-rich, cationic antimicrobial peptides recently isolated from porcine cells. We have synthesised an 18-amino-acid peptide that corresponds to protegrin-1. After Cys oxidation, the peptide has bactericidal activity against gram-positive and gram-negative bacteria, similar to that described for the natural peptide. The solution structure of protegrin-1 was investigated by means of 1H-NMR spectroscopy in water and in (CD3)2SO, with distance-geometry and simulated-annealing calculations. The C6-C15 and C8-C13 disulfide pattern was determined on the basis of NMR-derived constraints. These two parallel disulfide bridges stabilised a beta-sheet structure which comprised two antiparallel strands (residues 5-9 and 12-16) linked by a distorted beta-turn (residues 9-12). The N-terminus and C-terminus were essentially disordered. The distribution of hydrophobic and hydrophilic residues at the peptide surface was found to be a structural feature shared with tachyplesin-1, a related peptide which displays cytolytic activity, and, to a lesser extent, with mammalian defensins. These findings led us to assume that the distribution pattern could be required for the cytolytic activity of these peptides.
ChemInform Abstract: A NEW TYPE OF CLAISEN REARRANGEMENT INVOLVING 1,3‐DIPOLAR INTERMEDIATES (1979)

Abstract Dichlorketen (I) reagiert mit den Allylethern, ‐sulfiden und ‐seleniden (II) unter [2 + 2]‐ Cycloaddition zu den Derivaten (III) und in einer [3,3]‐sigmatropen Umlagerung über 1,3‐dipolare Zwischenstufen zu den Derivaten (IV).
Virtual Reality Based Multi-Modal Teleoperation Using Mixed Autonomy (2008)

A multi modal teleoperation interface is introduced featuring an integrated virtual reality based simulation augmented by sensors and image processing capabilities on-board the remotely operated vehicle. The proposed virtual reality interface fuses an existing VR model with live video feed and prediction states, thereby creating a multi modal control interface. Virtual reality addresses the typical limitations of video-based teleoperation caused by signal lag and limited field of view thereby allowing the operator to navigate in a continuous fashion. The vehicle incorporates an on-board computer and a stereo vision system to facilitate obstacle detection. A vehicle adaptation system with a priori risk maps and real state tracking system enables temporary autonomous operation of the vehicle for local navigation around obstacles and automatic re-establishment of the vehicle’s teleoperated state. As both the vehicle and the operator share absolute autonomy in stages, the operation is referred to as mixed autonomous. Finally, the system provides real time update of the virtual environment based on anomalies encountered by the vehicle. The system effectively balances the autonomy between human and on board vehicle intelligence. The stereo vision based obstacle avoidance system is initially implemented on video based teleoperation architecture and experimental results are presented. The VR based multi modal teleoperation interface is expected to be more adaptable and intuitive when compared to other interfaces.
Beneficial effects of combining nilotinib and imatinib in preclinical models of BCR-ABL+ leukemias (2006)

Drug resistance resulting from emergence of imatinib-resistant BCR-ABL point mutations is a significant problem in advanced-stage chronic myelogenous leukemia (CML). The BCR-ABL inhibitor, nilotinib (AMN107), is significantly more potent against BCR-ABL than imatinib, and is active against many imatinib-resistant BCR-ABL mutants. Phase 1/2 clinical trials show that nilotinib can induce remissions in patients who have previously failed imatinib, indicating that sequential therapy with these 2 agents has clinical value. However, simultaneous, rather than sequential, administration of 2 BCR-ABL kinase inhibitors is attractive for many reasons, including the theoretical possibility that this could reduce emergence of drug-resistant clones. Here, we show that exposure of a variety of BCR-ABL+ cell lines to imatinib and nilotinib results in additive or synergistic cytotoxicity, including testing of a large panel of cells expressing BCR-ABL point mutations causing resistance to imatinib in patients. Further, using a highly quantifiable bioluminescent in vivo model, drug combinations were at least additive in antileukemic activity, compared with each drug alone. These results suggest that despite binding to the same site in the same target kinase, the combination of imatinib and nilotinib is highly efficacious in these models, indicating that clinical testing of combinations of BCR-ABL kinase inhibitors is warranted.
Formaldehyde as a probe of DNA structure. I. Reaction with exocyclic amino groups of DNA bases (1975)

A comprehensive description is given of both the equilibrium and the kinetic aspects of the reaction of formaldehyde with the exocyclic amino groups of derivatives of adenine, cytosine, and guanine; the results extend previous data in the literature to the point where formaldehyde can now be used as a quantitative probe of DNA structure and dynamic behavior. The main results are: (i) the reaction product is proven (by isolation followed by nuclear magnetic resonance (NMR) spectroscopy) to be a hydroxymethyl group; (ii) a dihydroxymethyl adduct is shown to exist at high formaldehyde concentrations; (iii) equilibrium constants at 25 degrees for forming the monoadduct with adenine and cytosine compounds are about 12 (M-1), while those for forming the dihydroxymethyl adduct are about 0.4 (M-1); (iv) the standard enthalpies for forming the monoadducts with adenine and cytosine compounds are about minus 4 to minus 6 kcal/mol; (v) indirect evidence is presented suggesting that a monohydroxymethyl group on adenine or cytosine derivatives exists preferentially as that rotational isomer which blocks Watson-Crick hydrogen bonding; (vi) in derivatives of guanine, it is shown that the N-1 endocyclic imino group can react with formaldehyde, as well as the amino group, the overall equilibrium constant being about 6 (M-1); (vii) all rate constants are reported, as well as their response to temperature, pH, and various solvent additives known to perturb DNA structure; (viii) using a series of substituted anilines, a linear free energy relation is obtained between the logarithm of both the forward and the reverse rate constant for the formaldehyde reaction and the amine pK, over a range of 10-8 change in amie basicity; (ix) using this relation, the pK's for protonating the nucleoside amino groups are estimated to lie in the range of minus 2 to minus 4; (x) a reaction mechanism is proposed; and (xi) some implications of these results forpolynucleotide studies are discussed.
Variations in Oligosaccharide−Protein Interactions in Immunoglobulin G Determine the Site-Specific Glycosylation Profiles and Modulate the Dynamic Motion of the Fc Oligosaccharides (1997)

Glycoproteins, such as immunoglobulin G (IgG), consist of an ensemble of glycosylated variants, or glycoforms, which have different oligosaccharides attached to a common peptide. Alterations in the normal glycoform populations of IgG are associated with certain disease states, notably rheumatoid arthritis and its remission during pregnancy. In this paper, we show that two sets of IgG Fc glycoforms have quite different physical properties. The first set has 1,6 arm terminal galactose residues which interact with the protein, resulting in glycan binding to the protein surface, in agreement with the crystal structure. In contrast, the second set of glycoforms which lack galactose does not bind to the protein surface. Recently developed HPLC techniques combined with enzymatic digestion and mass spectrometry have been used to assign the glycan structures on IgG, Fab, and Fc. Comparison of Fab with Fc shows that glycosylation is site-specific. Two major glycan structures are present on Fab (fucosylated digalacto-bianntenary with and without bisect) and three on Fc (fucosylated agalacto-, 1,6 arm monogalacto-, and digalacto-bianntenary). In comparison to Fab, Fc glycans contain (i) lower levels of bisecting GlcNAc, (ii) lower levels of galactose, (iii) higher than expected levels of 1,6 arm galactose relative to 1,3 arm, and (iv) no 1,6 arm sialylation. We interpret these differences to indicate a role for both the protein quaternary structure and specific protein-glycan interactions in determining the glycoform populations. NMR relaxation measurements have been used to probe the mobility of the glycans in the Fc. By comparing two samples with different glycoform populations, we conclude that this mobility is dependent on the primary sequence of the glycan. Glycans carrying a galactose residue on the 1,6 arm have relaxation properties very similar to those of the peptide backbone and thus do not have independent motion. Glycans lacking galactose have relaxation rates 30 times slower than that of the peptide and thus a higher degree of mobility. These agalactosyl glycans do not interact with the protein, resulting in exposure of previously covered regions of the peptide surface and making the glycan more accessible. This implies that at the early stages of glycan processing the Fc glycans are mobile and only partially protected by the protein quaternary structure. Immobilization of the glycans occurs as a consequence of addition of galactose to the 1,6 arm and results in increased protection.
Structural characterization of the lipid A component of Bacteroides fragilis strain NCTC 9343 lipopolysaccharide (1989)

The chemical structure of Bacteroides fragilis NCTC 9343 lipid A was characterized by using conventional chemical procedures, methylation analysis, and laser desorption mass spectrometry. It was found that B. fragilis lipid A consists of a beta-D-glucosaminyl-(1-6)-D-glucosaminyl-1-O-phosphate backbone whose hydroxyl groups in positions 4, 4' and 6' are free, the latter serving as the attachment site for the polysaccharide component in lipopolysaccharide. This backbone molecule carries up to of five molecules of ester- and amide-bound long chain non-hydroxylated and (R)-3-hydroxy fatty acids. With regard to the distribution on the fatty acids on the lipid A backbone, a considerable heterogeneity was revealed by laser desorption mass spectrometry. Despite this heterogeneity, a major species of B. fragilis lipid A could be defined in which the hydroxyl group at position 3' of the distal GlcN carries (R)-3-hydroxyhexadecanoic acid and the hydroxyl group at position 3 of the reducing GlcN is acylated by (R)-3-hydroxypentadecanoic acid. The amino group of the distal GlcN residue carries (R)-3-(13-methyltetradecanoyloxy)-15-methylhexadecanoic acid and that of the reducing GlcN group (R)-3-hydroxyhexadecanoic acid. The absence of ester-bound phosphate and ester-linked 3-acyloxyacyl groups, the presence of not more than five acyl residues and the predominance of fatty acids possessing 15-17 carbon atoms are unique features of B. fragilis lipid A which differentiate it from enterobacterial and other lipids A and which are likely to be related to its low endotoxic activity.
A Useful Methodology for the Synthesis of 2-Methyl-4-nitrobenzimidazoles (1992)

Cyclocondensation of 3-nitro-1,2-benzenediamines 2 with 2,4-pentanedione provides a convenient route for the preparation of 2-methyl-4-nitrobenzimidazoles 3. A discrepancy in the literature regarding the 5-chloro-, 5-methoxy- and 5-methyl derivatives of the title compounds is discussed.