gebhart/patrepeval huggingface dataset:
BpaB25 insulins. Photoactivatable analogues that quantitatively cross-link, radiolabel, and activate the insulin receptor. (1993)

Benzoylphenylalanine (Bpa), a photoactivatable amino acid was incorporated into the 25 position of the insulin B-chain by a combination of chemical synthesis and enzymatic semisynthesis. BpaB25 insulin binds specifically to the insulin receptor with an affinity approximately 40% that of native insulin. Addition of biotin or epsilon-amino-hexanoic acid-iminobiotin at the epsilon-LysB29 position to form BpaB25,B29 epsilon-biotinyl (BBpa) or BpaB25,B29 epsilon-(Aha-iminobiotin) analogues had little adverse effect on receptor binding affinity and provided a convenient handle for affinity purification, gel shift assays, and blotting of cross-linked complexes with avidin. The analogues were readily 125I-iodinated with the majority of 125I being incorporated at the TyrA14 position; the monoiodo-A14 derivative was easily separated from other forms by high performance liquid chromatography. Photolysis of a complex of the insulin receptor and either BpaB25 insulin or [125I]iodo-TyrA14,BpaB25 insulin yields a covalent insulin-receptor complex. The efficiency of cross-linking with these reagents was unusually high, ranging from 60 to 100%. Furthermore, cross-linking to the insulin receptor results in kinase activation in vitro, and in intact cells insulin receptor phosphorylation and internalization were both activated. Notably, even at saturating concentrations one molecule of BpaB25 insulin covalently cross-linked each alpha 2 beta 2 receptor, demonstrating that holoreceptor activation occurs with one high affinity insulin binding site occupied and, if a second insulin binds with lower affinity it must be in a different orientation. Bpa insulin analogues form a new class of photoaffinity reagents which facilitate studies relating insulin-insulin receptor structure and function.
The Clifford Paterson Lecture, 1999. Sentient computing (2000)

Sentient computing is the proposition that applications can be made more responsive and useful by observing and reacting to the physical world. It is particularly attractive in a world of mobile users and computers.The paper presents a classification and quantification of sensor information together with a description of a method for altering the behaviour of arbitrary terminal devices. It also presents a framework for ‘programming with space’ which can associate space–related events with actions. Consideration is given to the applications made possible by such systems.
NAPHTHYL‐ AND QUINOLYLLUCIFERIN: GREEN AND RED LIGHT EMITTING FIREFLY LUCIFERIN ANALOGUES (1989)

In the course of investigations on the possible involvement of the CIEEL (chemically initiated electron-exchange luminescence) mechanism in firefly bioluminescence, we have synthesized two novel firefly luciferin substrate analogues. D-Naphthylluciferin and D-quinolylluciferin were prepared by condensing D-cysteine with 2-cyano-6-hydroxynaphthalene and 2-cyano-6-hydroxyquinoline, respectively. These analogues are the first examples of bioluminescent substrates for firefly luciferase that do not contain a benzothiazole moiety. Firefly luciferase-catalyzed bioluminescence emission spectra revealed that compared to the normal yellow-green light of luciferin (lambda max = 559 nm), the emission from naphthylluciferin is significantly blue-shifted (lambda max = 524 nm); whereas quinolylluciferin emits orange-red light (lambda max = 608 nm). The fluorescence emission spectra, reaction pH optima, relative light yields, light emission kinetics and KM values of the analogues also were measured and compared to those of luciferin. Neither of the analogues produced the characteristic flash kinetics observed for the natural substrate. Instead, slower rise times to peak emission intensity were recorded. It appears that the formation of an intermediate from the analogue adenylates prior to the addition of oxygen is responsible for the slow rise times. The synthetic substrate analogues described here should be useful for future mechanistic studies.
Modulation of Kv3 Subfamily Potassium Currents by the Sea Anemone Toxin BDS: Significance for CNS and Biophysical Studies (2005)

Kv3 potassium channels, with their ultra-rapid gating and high activation threshold, are essential for high-frequency firing in many CNS neurons. Significantly, the Kv3.4 subunit has been implicated in the major CNS disorders Parkinson's and Alzheimer's diseases, and it is claimed that selectively targeting this subunit will have therapeutic utility. Previous work suggested that BDS toxins ("blood depressing substance," from the sea anemone Anemonia sulcata) were specific blockers for rapidly inactivating Kv3.4 channels, and consequently these toxins are increasingly used as diagnostic agents for Kv3.4 subunits in central neurons. However, precisely how selective are these toxins for this important CNS protein? We show that BDS is not selective for Kv3.4 but markedly inhibits current through Kv3.1 and Kv3.2 channels. Inhibition comes about not by "pore block" but by striking modification of Kv3 gating kinetics and voltage dependence. Activation and inactivation kinetics are slowed by BDS-I and BDS-II, and V(1/2) for activation is shifted to more positive voltages. Alanine substitution mutagenesis around the S3b and S4 segments of Kv3.2 reveals that BDS acts via voltage-sensing domains, and, consistent with this, ON gating currents from nonconducting Kv3.2 are markedly inhibited. The altered kinetics and gating properties, combined with lack of subunit selectivity with Kv3 subunits, seriously affects the usefulness of BDS toxins in CNS studies. Furthermore, our results do not easily fit with the voltage sensor "paddle" structure proposed recently for Kv channels. Our data will be informative for experiments designed to dissect out the roles of Kv3 subunits in CNS function and dysfunction.
Tumour-immune cell interactions modulated by chemokines (2008)

Experimental evidence from manipulation of the chemokine network in murine models and in vitro data are critically discussed, and the current status and potential future interventions therapeutically targeting chemokines for efficient and long-lasting tumour control in cancer patients are described.
Novel splice‐site mutations and a large intragenic deletion in PLA2G6 associated with a severe and rapidly progressive form of infantile neuroaxonal dystrophy (2010)

Infantile neuroaxonal dystrophy, INAD, is a severe progressive psychomotor disorder with infantile onset and characterized by the presence of axonal spheroids throughout the central and peripheral nervous systems. A subset of INAD patients shows also brain iron accumulation which represents instead the distinctive feature of the idiopathic neurodegeneration with brain iron accumulation, NBIA. These diseases share the same causative gene, PLA2G6, encoding iPLA2-VIA, a calcium-independent phospholipase. Mutations that lead to a complete absence of protein are associated with a severe INAD profile, while compound heterozygous mutations with possibly a residual protein activity are instead associated with the less severe NBIA phenotype. Here we describe two INAD patients both with an unusually rapid disease progression and a peculiar neuroradiological presentation in one of them. Compound heterozygosity for a large intragenic deletion and a nonsense mutation was found in one of them while the other is carrying two novel splice-site mutations. Breakpoint-sequence analysis suggests a non-allelic-homologous-recombination (NAHR) event, probably underlying the rearrangement. These findings, while supporting the genotype-phenotype correlation already observed in INAD patients, provide the first sequence characterization of a genomic rearrangement in PLA2G6 gene, thus orienting the search for missing mutant alleles in PLA2G6 related diseases.
Results on 'controlled polarity' modulation and coding (1989)

The authors present results on a controlled-polarity modulation/coding scheme. They review this scheme and describe how to choose certain code parameters for the purpose of comparing the controlled polarity scheme to conventional (d,k) coding with NRZI modulation. A computer simulation is then utilized to compare the different schemes in terms of effective signal-to-noise ratio (SNR) and peak shift. It is shown that the controlled polarity schemes have less peak shift than the conventional schemes, whereas the conventional schemes have a higher effective SNR. It appears that in systems with a high enough SNR, the loss in effective SNR could be outweighed by the decrease in average peak shift. This could be of particular interest in future systems using magnetoresistive heads which have the potential to yield substantially higher SNRs.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Quasi-elastic light scattering and analytical ultracentrifugation are indispensable tools for the purification and characterization of recombinant proteins (1998)

Conference Article| November 01 1998 Quasi-elastic light scattering and analytical ultracentrifugation are indispensable tools for the purification and characterization of recombinant proteins H.-J. Schönfeld; H.-J. Schönfeld 1 1To whom correspondence should be addressed. Search for other works by this author on: This Site PubMed Google Scholar B. Pöschl; B. Pöschl 1Pharmaceutical Preclinical Research — Infectious Diseases, F. Hoffmann-La Roche Ltd, CH-4070 Basel, Switzerland Search for other works by this author on: This Site PubMed Google Scholar F. Müller F. Müller 1Pharmaceutical Preclinical Research — Infectious Diseases, F. Hoffmann-La Roche Ltd, CH-4070 Basel, Switzerland Search for other works by this author on: This Site PubMed Google Scholar Author and article information Publisher: Portland Press Ltd Received: June 03 1998 Online ISSN: 1470-8752 Print ISSN: 0300-5127 © 1998 Biochemical Society1998 Biochem Soc Trans (1998) 26 (4): 753–758. https://doi.org/10.1042/bst0260753 Article history Received: June 03 1998 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation H.-J. Schönfeld, B. Pöschl, F. Müller; Quasi-elastic light scattering and analytical ultracentrifugation are indispensable tools for the purification and characterization of recombinant proteins. Biochem Soc Trans 1 November 1998; 26 (4): 753–758. doi: https://doi.org/10.1042/bst0260753 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: QLS, quasi-elastic light scattering This content is only available as a PDF. © 1998 Biochemical Society1998 Article PDF first page preview Close Modal You do not currently have access to this content.
Tamoxifen and Chemotherapy for Lymph Node-Negative, Estrogen Receptor-Positive Breast Cancer (1997)

Findings from this and other NSABP studies indicate that patients with breast cancer who meet NSABP protocol criteria, regardless of age, lymph node status, tumor size, or estrogen receptor status, are candidates for chemotherapy.
Epochal Evolution of GGII.4 Norovirus Capsid Proteins from 1995 to 2006 (2007)

Noroviruses are the causative agents of the majority of viral gastroenteritis outbreaks in humans. During the past 15 years, noroviruses of genotype GGII.4 have caused four epidemic seasons of viral gastroenteritis, during which four novel variants (termed epidemic variants) emerged and displaced the resident viruses. In order to understand the mechanisms and biological advantages of these epidemic variants, we studied the genetic changes in the capsid proteins of GGII.4 strains over this period. A representative sample was drawn from 574 GGII.4 outbreak strains collected over 15 years of systematic surveillance in The Netherlands, and capsid genes were sequenced for a total of 26 strains. The three-dimensional structure was predicted by homology modeling, using the Norwalk virus (Hu/NoV/GGI.1/Norwalk/1968/US) capsid as a reference. The highly significant preferential accumulation and fixation of mutations (nucleotide and amino acid) in the protruding part of the capsid protein provided strong evidence for the occurrence of genetic drift and selection. Although subsequent new epidemic variants differed by up to 25 amino acid mutations, consistent changes were observed in only five positions. Phylogenetic analyses showed that each variant descended from its chronologic predecessor, with the exception of the 2006b variant, which is more closely related to the 2002 variant than to the 2004 variant. The consistent association between the observed genetic findings and changes in epidemiology leads to the conclusion that population immunity plays a role in the epochal evolution of GGII.4 norovirus strains.
Impact of a Superhydrophobic Sphere onto Water (2007)

When a water drop hits a superhydrophobic solid surface, it bounces off the substrate like an elastic ball. Here we show that when a tiny superhydrophobic solid sphere impacts with water, it can bounce off the free surface just as it impacts with an elastic membrane. The motion of a sinking sphere is analytically calculated by solving a potential flow whose free boundary is determined by the Young-Laplace equation. To find conditions under which the solid sphere should sink, bounce off, or oscillate upon impact with water, we construct simple scaling laws which are shown to agree well with experimentally found boundaries between the distinct impact behaviors in a regime map based on dimensionless parameters.
Grid coding: A novel technique for image processing (1972)

The encoding of information as the modulation of a grid is explored as the means for allowing the extraction of relevant details or features from images. A major aspect of this approach is the replacement of the heuristics in certain image processing tasks by simple Fourier filtering. Specific examples and particular implementations of coding schemes are described in order to show the wide applicability of the concept. The examples chosen fall in the domains of scene analysis, difference extraction from successive images, automatic extraction of range, extraction of features such as planes, recording of three-dimentional imagery, and the processing of a single coded view to give a set of stereo related pairs.
Biosynthesis of Unusual Aminocyclitol-Containing Natural Products (2007)

The aminocyclitol family of natural products is a class of sugar-derived microbial secondary metabolites that demonstrate significant biological activities. Within this class of natural products are the C7N-aminocyclitol-containing compounds, which were originally associated with potent sugar-hydrolase inhibition. However, recent discoveries indicate a broader array of chemical structures and biological activities of this class of compounds. Using both conventional feeding experiments and contemporary molecular genetic approaches, some progress has been made in understanding the biosynthesis of this class of natural products. Results of in silico investigation also suggest a wide distribution of this class of natural products or closely related compounds across different classes of microorganisms, including cyanobacteria and fungi. This review describes our recent progress in the biosynthetic studies of a number of C7N-aminocyclitol-containing compounds and the potential use of bioinformatic approaches to search for novel aminocyclitol-containing natural products.
Preemptive Analgesia: Its Role and Efficacy in Anterior Cruciate Ligament Reconstruction (1998)

As more outpatient orthopaedic surgical procedures are performed, postoperative pain control has gained importance. The benefits of preemptive analgesia, the use of analgesics or anesthetics or both before painful stimuli to prevent or reduce pain, have been widely published in the anesthesia and general surgery literature, but not in orthopaedic literature. We prospectively compared the effects, on postoperative pain and narcotic use, of intraarticular preoperative injections of 1) placebo with epinephrine, 2) bupivacaine with epinephrine, and 3) bupivacaine and morphine with epinephrine. Thirty patients (10 in each group) underwent arthroscopic anterior cruciate ligament reconstruction using patellar tendon autograft under general anesthesia. Pain was assessed with a 10-point visual analog scale pre- and postoperatively, and postoperative narcotic pain medication use was recorded. Postoperative pain was significantly greater in group 1 (placebo) than in the preemptive-treatment groups (groups 2 and 3), and in group 2 than in group 3. The differences became less apparent with time, and after 1 hour, no significant differences in pain scores existed between the groups. However, intravenous narcotic pain medication was administered in the recovery room to patients with pain scores greater than 5, equalizing pain scores. Group 3 used significantly less postoperative narcotic medication than group 1. Preemptive analgesia using intraarticular bupivacaine and morphine with epinephrine resulted in lower pain scores during the 1st hour after an arthroscopic anterior cruciate ligament reconstruction than did preemptive treatment with bupivacaine and epinephrine or placebo and epinephrine.
Omega Navigation System Course Book. Volume 1. (1994)

This self-contained book on the Omega Navigation System is intended to provide theoretical and operational information needed by NAVCEN personnel to manage and maintain the Omega System. The book is composed of 13 chapters and seven appendices and can be used as a self-paced learning aid or in a classroom course environment. The course material addresses all major components of the Omega System, with emphasis placed on signal structure and utilization. Topics covered in the book include: Omega background, signal generation, navigation and propagation principles, operations, system performance evaluation, system utilization, and the future role of Omega in conjunction with other radionavigation systems. Several appendices are included to provide further detail on the material contained in the chapters. Omega History, Transmitting stations, Signal propagation, Navigation principles, System performance, Observed signal behavior
A Border Gateway Protocol 4 (BGP-4) (1994)

This memo, together with its companion document, Application of the
Border Gateway Protocol in the Internet, define an inter-autonomous
system routing protocol for the Internet. [STANDARDS-TRACK]
The Mx1 Gene Protects Mice against the Pandemic 1918 and Highly Lethal Human H5N1 Influenza Viruses (2007)

Mice carrying a wild-type Mx1 gene (Mx1+/+) differ from standard laboratory mice (Mx1-/-) in being highly resistant to infection with common laboratory strains of influenza A virus. We report that Mx1 also protects mice against the pandemic human 1918 influenza virus and a highly lethal human H5N1 strain from Vietnam. Resistance to H5N1 of Mx1+/+ but not Mx1-/- mice was enhanced if the animals were treated with a single dose of exogenous alpha interferon before infection. Thus, the interferon-induced resistance factor Mx1 represents a key component of the murine innate immune system that mediates protection against epidemic and pandemic influenza viruses.
The non‐peptidyl fungal metabolite L‐783,281 activates TRK neurotrophin receptors (2001)

Neurotrophin binding to the extracellular surface of the Trk family of tyrosine kinase receptors leads to the activation of multiple signalling cascades, culminating in neuroregenerative effects, including neuronal survival and neurite outgrowth. Since neurotrophins themselves are not ideal drug candidates due to their poor pharmacokinetic behaviour and bioavailability, small molecule neurotrophin mimetics may be beneficial in treating a number of neurodegenerative disorders. The present study demonstrates that L-783,281, a non-peptidyl fungal metabolite, is capable of stimulating TrkA, B and C phosphorylation to various extents in CHO cells stably expressing human Trk receptors. L-783,281 also stimulated Trk phosphorylation in a number of rat and human primary neuronal cultures, whereas the highly similar compound, L-767,827, was without effect. Mechanistic studies utilizing transiently transfected PDGF/TrkA and TrkA/PDGF chimeras, demonstrated that L-783,281 is likely to interact with the intracellular domain of the TrkA receptor. Further investigations suggested that L-783,281 was nevertheless able to instigate receptor dimerization by binding in a non-covalent manner. Although the cytotoxicity of the compound was shown to preclude its effects in neuronal survival and neurite outgrowth assays, it is a prototype for a small molecule neurotrophin mimetic that activates Trk by interacting at a site different from the neurotrophin-binding site.
Long Terminal Repeat CRISPR-CAR-Coupled “Universal” T Cells Mediate Potent Anti-leukemic Effects (2018)

Gene editing can be used to overcome allo-recognition, which otherwise limits allogeneic T cell therapies. Initial proof-of-concept applications have included generation of such "universal" T cells expressing chimeric antigen receptors (CARs) against CD19 target antigens combined with transient expression of DNA-targeting nucleases to disrupt the T cell receptor alpha constant chain (TRAC). Although relatively efficient, transgene expression and editing effects were unlinked, yields variable, and resulting T cell populations heterogeneous, complicating dosing strategies. We describe a self-inactivating lentiviral "terminal" vector platform coupling CAR expression with CRISPR/Cas9 effects through incorporation of an sgRNA element into the ΔU3 3' long terminal repeat (LTR). Following reverse transcription and duplication of the hybrid ΔU3-sgRNA, delivery of Cas9 mRNA resulted in targeted TRAC locus cleavage and allowed the enrichment of highly homogeneous (>96%) CAR<sup>+</sup> (>99%) TCR<sup>-</sup> populations by automated magnetic separation. Molecular analyses, including NGS, WGS, and Digenome-seq, verified on-target specificity with no evidence of predicted off-target events. Robust anti-leukemic effects were demonstrated in humanized immunodeficient mice and were sustained longer than by conventional CAR<sup>+</sup>TCR<sup>+</sup> T cells. Terminal-TRAC (TT) CAR T cells offer the possibility of a pre-manufactured, non-HLA-matched CAR cell therapy and will be evaluated in phase 1 trials against B cell malignancies shortly.
Review article: evolving concepts in treatment and disease modification in ulcerative colitis (2008)

Disease modification is increasingly becoming a treatment goal in the management of ulcerative colitis. However, long-term studies are needed to examine further the disease modifying role of 5-aminosalicylates.