gebhart/patrepeval huggingface dataset:
Fate of tetanus toxin bound to the surface of primary neurons in culture: evidence for rapid internalization. (1985)

We examined the nature of the tetanus toxin receptor in primary cultures of mouse spinal cord by ligand blotting techniques. Membrane components were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transferred to nitrocellulose sheets, which were overlaid with 125I-labeled tetanus toxin. The toxin bound only to material at or near the dye front, which was lost when the cells were delipidated before electrophoresis. Gangliosides purified from the lipid extract were separated by thin-layer chromatography and the chromatogram was overlaid with 125I-toxin. The toxin bound to gangliosides corresponding to GD1b and GT1b. Similar results were obtained with brain membranes; thus, gangliosides rather than glycoproteins appear to be the toxin receptors both in vivo and in neuronal cell cultures. To follow the fate of tetanus toxin bound to cultured neurons, we developed an assay to measure cell-surface and internalized toxin. Cells were incubated with tetanus toxin at 0 degree C, washed, and sequentially exposed to antitoxin and 125I-labeled protein A. Using this assay, we found that much of the toxin initially bound to cell surface disappeared rapidly when the temperature was raised to 37 degrees C but not when the cells were kept at 0 degree C. Some of the toxin was internalized and could only be detected by our treating the cells with Triton X-100 before adding anti-toxin. Experiments with 125I-tetanus toxin showed that a substantial amount of the toxin bound at 0 degree C dissociated into the medium upon warming of the cells. Using immunofluorescence, we confirmed that some of the bound toxin was internalized within 15 min and accumulated in discrete structures. These structures did not appear to be lysosomes, as the cell-associated toxin had a long half-life and 90% of the radioactivity released into the medium was precipitated by trichloroacetic acid. The rapid internalization of tetanus toxin into a subcellular compartment where it escapes degradation may be important for its mechanism of action.
Schema evolution in OODBs using class versioning (1993)

This paper describes work carried out on a model for the versioning of class definitions in an object-oriented database. By defining update and backdate functions on attributes of the previous and current version of a class definition, instances of any version of the class can be converted to instances of any other version. This allows programs written to access an old version of the schema to still use data created in the format of the changed schema.
Determining the Role of Hydration Forces in Protein Folding (1999)

This article describes a combined experimental, theoretical, and computational effort to show how the complexity of aqueous hydration can influence the structure, folding and aggregation, and stability of model protein systems. The unification of the theoretical and experimental work is the development or discovery of effective amino acid interactions that implicitly include the effects of aqueous solvent. We show that consideration of the full range of complexity of aqueous hydration forces such as many-body effects, long-ranged character of aqueous solvation, and the assumptions made about the degree of protein hydrophobicity can directly impact the observed structure, folding, and stability of model protein systems.
Reversible excitation light‐induced enhancement of fluorescence of live mammalian mitochondria (2000)

During continuous irradiation with near-ultraviolet light (l = 36510 nm; 16 mW/mm(2)) for 2-3 min, live mammalian cells increased reversibly the intensity of one or more peaks of their autofluorescence spectrum from an initial ('ground') level to a two- to threefold higher ('active') level. The effect is characterized by the existence of two states of quantum efficiency and a mechanism of transition that expresses a threshold and a refractory period. It appears that mitochondria are the principal sources of the rising autofluorescence intensity; however, not all mitochondria are capable of expressing it. Studying cells from various organisms that belong to various branches of the phylogenetic tree, we found the rapid increase of autofluorescence only in placental mammalian cells. We speculate that the effect may point to the ability of placental mammalian mitochondria to generate pulsating light signals.
Meige's syndrome associated with neuroleptic treatment (1988)

Meige's syndrome is characterized by blepharospasm and oromandibular dystonia. Three cases are presented; two were associated with long-term neuroleptic administration. This drug-induced syndrome may be a variant of tardive dystonia, and prompt discontinuation of neuroleptic treatment may be therapeutic.
Production of Recombinant Proteins: Challenges and Solutions (2004)

Efficient strategies for the production of recombinant proteins are gaining increasing importance, as more applications that require high amounts of high-quality proteins reach the market. Higher production efficiencies and, consequently, lower costs of the final product are needed for obtaining a commercially viable process. In this chapter, common problems in recombinant protein production are reviewed and strategies for their solution are discussed. Such strategies include molecular biology techniques, as well as manipulation of the culture environment. Finally, specific problems relevant to different hosts are discussed.
Suppression of mutant phenotypes of the Agrobacterium tumefaciens VirB11 ATPase by overproduction of VirB proteins (1997)

The Agrobacterium tumefaciens VirB11 ATPase is postulated to assemble with VirB proteins and the VirD4 protein into a transport system which is dedicated to the export of oncogenic nucleoprotein particles to plant cells. To gain genetic evidence for interactions between VirB11 and other subunits of this transport system, we screened a PCR-mutagenized virB11 library for alleles that diminish the virulence of the wild-type strain A348. Two classes of alleles displaying negative dominance were identified. One class failed to complement a delta virB11 mutation, indicating that the corresponding mutant proteins are nonfunctional. The second class complemented the delta virB11 mutation, indicating that the mutant proteins are fully functional in strains devoid of native VirB11. Mutations of both classes of alleles were in codons for residues clustered in two regions of VirB11, both located outside the Walker A nucleotide binding motif. All dominant alleles were suppressed at least to some extent by multicopy expression of the virB9, virB10, and/or virB11 genes. Taken together, results of these investigations indicate that (i) a functional T-complex transporter is composed of more than one VirB11 subunit and (ii) VirB11 undergoes complex formation with VirB9 and VirB10 during transporter biogenesis.
Sodium Ion-Driven Serine/Threonine Transport in Porphyromonas gingivalis (2001)

Porphyromonas gingivalis is an asaccharolytic, gram-negative bacterium that relies on the fermentation of amino acids for metabolic energy. When grown in continuous culture in complex medium containing 4 mM (each) free serine, threonine, and arginine, P. gingivalis assimilated mainly glutamate/glutamine, serine, threonine, aspartate/asparagine, and leucine in free and/or peptide form. Serine and threonine were assimilated in approximately equal amounts in free and peptide form. We characterized serine transport in this bacterium by measuring uptake of the radiolabeled amino acid in washed cells of P. gingivalis energized with a tetrapeptide not containing serine. Serine was transported by a single system with an affinity constant for transport (K(t)) of 24 microM that was competitively inhibited by threonine. Serine transport was dependent on sodium ion concentration in the suspending buffer, and the addition of the ionophore gramicidin caused the inhibition of serine uptake. Together these data indicate that serine transport was sodium ion-motive force driven. A P. gingivalis gene potentially encoding a serine transporter was identified by sequence similarity to an Escherichia coli serine transporter (SstT). This P. gingivalis gene, designated sstT, was inactivated by insertion of a Bacteroides tetQ gene, producing the mutant W50ST. The mutant was unable to transport serine, confirming the presence of a single serine transporter in this bacterium under these growth conditions. The transport of serine by P. gingivalis was dependent on the presence of free cysteine in the suspension buffer. Other reducing agents were unable to stimulate serine uptake. These data show that P. gingivalis assimilates free serine and threonine from culture media via a cysteine-activated, sodium ion-motive force-driven serine/threonine transporter.
TARGETING AND ASSEMBLY OF PERIPLASMIC AND OUTER-MEMBRANE PROTEINS IN ESCHERICHIA COLI (1998)

Escherichia coli must actively transport many of its proteins to extracytoplasmic compartments such as the periplasm and outer membrane. To perform this duty, E. coli employs a collection of Sec (secretion) proteins that catalyze the translocation of various polypeptides through the inner membrane. After translocation across the inner membrane, periplasmic and outer-membrane proteins are folded and targeted to their appropriate destinations. Here we review our knowledge of protein translocation across the inner membrane. We also discuss the various signal transduction systems that monitor extracytoplasmic protein folding and targeting, and we consider how these signal transduction systems may ultimately control these processes.
Quantitative Structural Characterization of Local N-Glycan Microheterogeneity in Therapeutic Antibodies by Energy-Resolved Oxonium Ion Monitoring (2012)

Site-specific characterization of glycoform heterogeneity currently requires glycan structure assignment and glycopeptide quantification in two independent experiments. We present here a new method combining multiple reaction monitoring mass spectrometry with energy-resolved structural analysis, which we termed "energy-resolved oxonium ion monitoring". We demonstrated that monitoring the yields of oligosaccharide-derived fragment ions (oxonium ions) over a wide range of collision induced dissociation (CID) energy applied to a glycopeptide precursor exhibits a glycan structure-unique fragmentation pattern. In the analysis of purified immunoglobulin glycopeptides, the energy-resolved oxonium ion profile was shown to clearly distinguish between isomeric glycopeptides. Moreover, limit of detection (LOD) of glycopeptide detection was 30 attomole injection, and quantitative dynamic range spanned 4 orders magnitude. Therefore, both quantification of glycopeptides and assignment of their glycan structures were achieved by a simple analysis procedure. We assessed the utility of this method for characterizing site-specific N-glycan microheterogeneity on therapeutic antibodies, including validation of lot-to-lot glycoform variability. A significant change in the degree of terminal galactosylation was observed in different production lots of trastuzumab and bevacizumab. Cetuximab Fab glycosylation, previously known to cause anaphylaxis, was also analyzed, and several causative antigens including Lewis X motifs were quantitatively detected. The data suggests that energy-resolved oxonium ion monitoring could fulfill the regulatory requirement on the routine quality control analysis of forthcoming biosimilar therapeutics.
Biospecimens and Biorepositories: From Afterthought to Science (2012)

Biospecimens are recognized as critical components of biomedical research, from basic studies to clinical trials and epidemiologic investigations. Biorepositories have existed in various forms for more than 150 years, from early small collections in pathology laboratories to modern automated facilities managing millions of samples. As collaborative science has developed, it has been recognized that biospecimens must be of consistent quality. Recent years have seen a proliferation of best practices and the recognition of the field of "biospecimen science." The future of this field will depend on the development of more evidence-based practices in both the research and clinical settings. As the field matures, educating a new generation of biospecimen/biobanking scientists will be an important need.
Potent and Selective Non-Benzodioxole-Containing Endothelin-A Receptor Antagonists (1997)

The benzodioxole ((methylenedioxy)benzene) group is present in a number of endothelin (ET) receptor antagonists thus far reported. As part of our own endothelin antagonist program we have developed (2R*,3R*,4S*)-1-(N,N-dibutylacetamido)-4-(1,3-benzodioxol-5- yl)-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid (A-127722). This is a potent antagonist, binding to the ETA and ETB receptor subtypes with affinities (IC50) of 0.4 and 520 nM, respectively, and also contains the aforementioned benzodioxole. While this compound was seemingly optimized at its N-terminus, no effort had been directed toward understanding the contributions to binding affinity or receptor subtype selectivity conferred by the benzodioxole. Substitution by 1- or 2-naphthyl yielded weak antagonists. Oxygenated benzenes, such as p-anisyl, were potent compounds with IC50s in the low-nanomolar range. Simple deletion of either of the two oxygen atoms (dihydrobenzofurans) yielded extremely potent agents, possessing subnanomolar affinity for the ETA receptor. Additionally, the compounds showed enhanced selectivity, binding to the ETB receptor subtype in the micromolar range. This paper describes the development of this novel class of compounds.
Structural and Spectroscopic Analysis of the Kinase Inhibitor Bosutinib and an Isomer of Bosutinib Binding to the Abl Tyrosine Kinase Domain (2012)

Chronic myeloid leukemia (CML) is caused by the kinase activity of the BCR-Abl fusion protein. The Abl inhibitors imatinib, nilotinib and dasatinib are currently used to treat CML, but resistance to these inhibitors is a significant clinical problem. The kinase inhibitor bosutinib has shown efficacy in clinical trials for imatinib-resistant CML, but its binding mode is unknown. We present the 2.4 Å structure of bosutinib bound to the kinase domain of Abl, which explains the inhibitor's activity against several imatinib-resistant mutants, and reveals that similar inhibitors that lack a nitrile moiety could be effective against the common T315I mutant. We also report that two distinct chemical compounds are currently being sold under the name "bosutinib", and report spectroscopic and structural characterizations of both. We show that the fluorescence properties of these compounds allow inhibitor binding to be measured quantitatively, and that the infrared absorption of the nitrile group reveals a different electrostatic environment in the conserved ATP-binding sites of Abl and Src kinases. Exploiting such differences could lead to inhibitors with improved selectivity.
Practical quantum cryptography for secure free-space communications (1999)

Quantum cryptography is an emerging technology in which two parties may simultaneously generate shared, secret cryptographic key material using the transmission of quantum states of light. The security of these transmissions is based on the inviolability of the laws of quantum mechanics and information-theoretically secure post-processing methods. An adversary can neither successfully tap the quantum transmissions, nor evade detection, owing to Heisenberg's uncertainty principle. In this paper we describe the theory of quantum cryptography, and the most recent results from our experimental free-space system with which we have demonstrated for the first time the feasibility of quantum key generation over a point-to-point outdoor atmospheric path in daylight. We achieved a transmission distance of 0.5 km, which was limited only by the length of the test range. Our results provide strong evidence that cryptographic key material could be generated on demand between a ground station and a satellite (or between two satellites), allowing a satellite to be securely re-keyed on orbit. We present a feasibility analysis of surface-to-satellite quantum key generation.
Mobile networking through Mobile IP (1998)

Mobile IP is a proposed standard protocol that builds on the Internet Protocol by making mobility transparent to applications and higher level protocols like TCP. Mobile IP (RFC 2002) is a standard proposed by a working group within the Internet Engineering Task Force; it allows the mobile node to use two IP addresses: a fixed home address and a care-of address that changes at each new point of attachment. The article presents the Mobile IP standard in moderate technical detail and points the reader toward a wealth of further information. Is also describes how Mobile IP will change with IP version 6, the product of a major effort within the IETF to engineer an eventual replacement for the current version of IP. Although IPv6 will support mobility to a greater degree than IPv4, it will still need Mobile IP to make mobility transparent to applications and higher level protocols such as TCP. There is a great deal of interest in mobile computing and apparently in Mobile IP as a way to provide for it. A quick Web search for items related to Mobile IP returned over 60,000 hits-impressive even given the notorious lack of selectivity for such procedures. Mobile IP forms the basis either directly or indirectly of many current research efforts and products. The Cellular Digital Packet Data (CDPD), for example, has created a widely deployed communications infrastructure based on a previous draft specification of the protocol. In addition, most major router vendors have developed implementations for Mobile IP.
Eyeball model-based iris center localization for visible image-based eye-gaze tracking systems (2013)

In general, the visible image-based eye-gaze tracking system is heavily dependent on the accuracy of the iris center (IC) localization. In this paper, we propose a novel IC localization method based on the fact that the elliptical shape (ES) of the iris varies according to the rotation of the eyeball. We use the spherical model of the human eyeball and estimate the radius of the iris from the frontal and upright-view image of the eye. By projecting the eyeball rotated in pitch and yaw onto the 2-D plane, a certain number of the ESs of the iris and their corresponding IC locations are generated and registered as a database (DB). Finally, the location of IC is detected by matching the ES of the iris of the input eye image with the ES candidates in the DB. Moreover, combined with facial landmark points-based image rectification, the proposed IC localization method can successfully operate under natural head movement. Experimental results in terms of the IC localization and gaze tracking show that the proposed method achieves superior performance compared with conventional ones.
Principles of Optimal Page Replacement (1971)

ABSTP~CT. A formal model is presented for paging algorithms under /-order nonstationary assumptions about program behavior. When processing a program under paging in a given memory, a given paging policy generates a certain (expected) number of page calls, i.e., its "cost." Under usual assumptions about memory system organization, minimum cost is always achieved by a demand paging algorithm. The minimum cost for /-order program behavior assumptions is expressed as a dynamic programming problem whose solution yields an optimal replacement algorithm. Solutions are exhibited in several 0-order cases of interest. Paging algorithms that implement and approximate the minimum cost are discussed.
Characterization of salicylic acid‐responsive, Arabidopsis Dof domain proteins: overexpression of OBP3 leads to growth defects (2000)

Summary Dof proteins are unique to plants and contain a single zinc finger DNA‐binding domain called the Dof domain. OBP1, an Arabidopsis Dof protein, was previously isolated through an interaction with OBF4, an ocs element‐binding protein. Two additional Dof proteins, called OBP2 and OBP3, were isolated through homologous screening. All three OBP proteins contain transcriptional activation domains in their C‐terminal region. While no significant differences were found between the OBP proteins in terms of their DNA and protein‐binding properties, tissue‐specific RNA expression patterns were found. The RNA expression levels of all three OBP proteins increased following treatment with auxin, salicylic acid (SA) or cycloheximide, although the level of induction varied among the different proteins and in the tissues tested. These results suggest that even though they have similar DNA binding and protein–protein interaction properties, the different OBP proteins are likely to have distinct functions in specific parts of the plant. There is a good correlation between the expression of the OBP proteins and the ocs element, a stress‐response element which is also induced by auxin, SA and cycloheximide. To begin to analyze the function of the OBP proteins, transgenic lines overexpressing OBP3 were generated. These plants showed a severe growth defect with altered root development and yellowish leaves. The severity of the growth defects correlated with OBP3 expression levels and in some cases led to death, suggesting that some Dof proteins play important roles in plant growth and development.
Cyclization of Polyubiquitin by the E2-25K Ubiquitin Conjugating Enzyme (2000)

For most substrates of ubiquitin (Ub)-dependent degradation, recognition by the proteasome is mediated by a covalently attached signal assembled from multiple ubiquitins linked to each other via the C terminus of one Ub and the epsilon-amine of Lys(48) of another Ub. Among Ub-conjugating enzymes, E2-25K is unique in its ability to synthesize in vitro unanchored Lys(48)-linked poly-Ub chains from mono- or poly-Ub, E1, and ATP; thus, E2-25K has distinct binding sites for donor and acceptor (poly)Ub. During studies of chain assembly by E2-25K, we observed that Lys(48)-linked tri-Ub was efficiently converted to a new species that upon SDS-polyacrylamide gel electrophoresis migrated between linear di-Ub and tri-Ub. Analysis of this product by mass spectrometry and tryptic digestion showed that it was a cyclic form of tri-Ub. Cyclization of tri-Ub requires E1, E2-25K, ATP, and that the linear substrate has a free Gly(76) C terminus on the proximal end Ub and a Lys(48) side chain available on the distal end Ub. E2-25K similarly can catalyze the cyclization of longer poly-Ub chains, including tetra- and penta-Ub. Although cyclic tri-Ub resists hydrolysis by the PA700 or isopeptidase T deubiquitinating enzymes, it can be disassembled to Ub monomers by isopeptidase(s) in a red blood cell extract. Thus, if cyclic poly-Ub forms in vivo, it will not accumulate as a dead-end product.
Invariant image recognition by Zernike moments (1990)

The problem of rotation-, scale-, and translation-invariant recognition of images is discussed. A set of rotation-invariant features are introduced. They are the magnitudes of a set of orthogonal complex moments of the image known as Zernike moments. Scale and translation invariance are obtained by first normalizing the image with respect to these parameters using its regular geometrical moments. A systematic reconstruction-based method for deciding the highest-order Zernike moments required in a classification problem is developed. The quality of the reconstructed image is examined through its comparison to the original one. The orthogonality property of the Zernike moments, which simplifies the process of image reconstruction, make the suggest feature selection approach practical. Features of each order can also be weighted according to their contribution to the reconstruction process. The superiority of Zernike moment features over regular moments and moment invariants was experimentally verified.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>