gebhart/patrepeval huggingface dataset:
Time-Resolved Fluorescence of Lanthanide Probes and Applications in Biotechnology (1987)

The relaxation of excited molecular states is often followed by the emission of light. Molecular excited states are related to the orbital, vibrational, and rotational levels of the orbital electrons. In addition, the electron spin determines the singlet and triplet states. In the singlet state the spin of an electron is paired, whereas in the triplet state the spin is not paired. When a molecule is excited to an upper singlet energy level, such as S2 (Figure 1), it can rapidly (10−10 sec) go to the lowest excited state S1 without emission of light. From S1 the molecule may go to any of the rotational and vibrational levels of the ground electronic state S0. This happens either by fluorescence emission or by nonradiative internal processes, referred to as intersystem crossing. From T1, the molecule can return to S0 by nonradiative processes or by a radiative process called phosphorescence. Under suitable conditions S1 and T1 can also transfer their excitation energy to other molecules.
Hetero-oligomerization of CCR2, CCR5, and CXCR4 and the Protean Effects of “Selective” Antagonists (2009)

Chemokine receptors constitute an attractive family of drug targets in the frame of inflammatory diseases. However, targeting specific chemokine receptors may be complicated by their ability to form dimers or higher order oligomers. Using a combination of luminescence complementation and bioluminescence resonance energy transfer assays, we demonstrate for the first time the existence of hetero-oligomeric complexes composed of at least three chemokine receptors (CCR2, CCR5, and CXCR4). We show in T cells and monocytes that negative binding cooperativity takes place between the binding pockets of these receptors, demonstrating their functional interaction in leukocytes. We also show that specific antagonists of one receptor (TAK-779 or AMD3100) lead to functional cross-inhibition of the others. Finally, using the air pouch model in mice, we show that the CCR2 and CCR5 antagonist TAK-779 inhibits cell recruitment promoted by the CXCR4 agonist SDF-1 alpha, demonstrating that cross-inhibition by antagonists also occurs in vivo. Thus, antagonists of the therapeutically important chemokine receptors regulate the functional properties of other receptors to which they do not bind directly with important implications for the use of these agents in vivo.
Development of a Streptavidin-Conjugated Single-Chain Antibody That Binds Bacillus cereus Spores (1998)

Control of microorganisms such as Bacillus cereus spores is critical to ensure the safety and a long shelf life of foods. A bifunctional single chain antibody has been developed for detection and binding of B. cereus T spores. The genes that encode B. cereus T spore single-chain antibody and streptavidin were connected for use in immunoassays and immobilization of the recombinant antibodies. A truncated streptavidin, which is smaller than but has biotin binding ability similar to that of streptavidin, was used as the affinity domain because of its high and specific affinity with biotin. The fusion protein gene was expressed in Escherichia coli BL21 (DE3) with the T7 RNA polymerase-T7 promoter expression system. Immunoblotting revealed an antigen specificity similar to that of its parent native monoclonal antibody. The single-chain antibody-streptavidin fusion protein can be used in an immunoassay of B. cereus spores by applying a biotinylated enzyme detection system. The recombinant antibodies were immobilized on biotinylated magnetic beads by taking advantage of the strong biotin-streptavidin affinity. Various liquids were artificially contaminated with 5 x 10(4) B. cereus spores per ml. Greater than 90% of the B. cereus spores in phosphate buffer or 37% of the spores in whole milk were tightly bound and removed from the liquid phase by the immunomagnetic beads.
Transferrin-binding protein B isolated from Neisseria meningitidis discriminates between apo and diferric human transferrin (1998)

Neisseria meningitidis utilization of human serum transferrin (hTF)-bound iron is an important pathogenicity determinant. The efficiency of this system would clearly be increased through preferential binding of diferric hTF over the iron-free form. To characterize this process, functionally active meningococcal transferrin-binding protein A (TbpA) and TbpB have been purified from N. meningitidis using a novel purification procedure. The association of isolated Tbps and Tbps in the presence of hTF was investigated by gel filtration. Co-purified TbpA+B formed a complex of molecular mass 300 kDa which bound 1-2 molecules of hTF. Purified TbpA formed a complex of 200 kDa, indicating association as a dimer, whereas TbpB aggregated to form multimers of variable sizes. On recombining TbpA and TbpB, a stable complex of equivalent size to co-purified TbpA+B was formed. This complex may be composed of a single TbpA dimer and 1 molecule of TbpB. The technique of surface plasmon resonance (SPR) was used to demonstrate clearly that TbpB of either high (85 kDa) or low (68 kDa) molecular-mass preferentially bound diferric hTF in comparison with iron-free hTF. This selectivity was not observed with TbpA, but was found at low levels with co-purified TbpA+B. Individual TbpA and TbpB, recombined in a 1:1 molecular ratio, showed iron-mediated discriminatory binding at an intermediate level. SPR was also used to show that TbpA and TbpB bound to distinct regions of hTF, and that prior saturation with TbpB reduced subsequent TbpA binding. The results demonstrated that hTF bound more TbpA than TbpB, with an approximate ratio of 2:1. We have demonstrated that in vitro, TbpA+B exists as a receptor complex composed of a TbpA dimer and one molecule of TbpB, and that TbpB selectively binds diferric hTF. We propose that, in vivo, TbpA and TbpB also exist as a receptor complex, with TbpB selectively binding diferric hTF, bringing it close to TbpA, the transmembrane component, where the ferric iron can be transported to the periplasm.
Chemical and Physical Aspects of the Formation of Carbon Fibres from PAN-based Precursors (1990)

An analysis of current knowledge of the chemical reactions and the simultaneously occurring morphological changes in the conversion of PAN-based precursor fibres to carbon fibres is presented. This is discussed in the context of the evolution of the mechanical properties of carbon fibres. Needs that remain unfulfilled and the potential mechanisms for accomplishing them are also discussed briefly.
Monoclonal anti-human factor VII antibodies. Detection in plasma of a second protein antigenically and genetically related to factor VII. (1985)

Several murine monoclonal anti-human Factor VII antibodies were produced using hybridoma technology. Two noncompetitive monoclonal antibodies were used to examine by Western blotting the Factor VII cross-reactive material (CRM) in normal human plasma and three commercially available congenitally Factor VIIdeficient plasmas, and to construct a facile "sandwich" immu- noassay for plasma Factor VII. A second, previously undescribed, form of Factor VII CRM was detected in human plasma, which on Western blotting stained with an apparent intensity 5-8% that of Factor VII. This glycoprotein, tentatively called VII*, has a molecular weight 4,500 D less than Factor VII, lacks de- tectable Factor VII functional activity, does not bind to barium citrate, and is not recognized by a monoclonal antibody that rec- ognizes Factor VII but not a-chymotrypsin-treated Factor VII. VII* was not proteolytically produced from Factor VII during in vitro coagulation or after infusion of human Factor VII into rabbits. As determined by Western blotting, the human hepatoma cell line, HepG2, cultured in the presence of vitamin K, secreted relatively greater levels of VII* in proportion to VII (75%) than that found in human plasma. Warfarin treatment of HepG2 cells decreased the quantity of VII secreted by 77%, whereas it only inhibited the secretion of VII* by 14%. Immunologic studies of the plasmas from a patient on chronic warfarin therapy and an individual given a short course of high dose warfarin therapy corroborated the in vitro synthetic studies obtained with HepG2 cells. The data are consistent with the production of VII* by posttranslational, proteolytic, modification of VII, that, at least in the HepG2 cells studied, occurs intracellularly. However, other mechanisms for the production of VII*, in particular, alternative RNA splicing of the transcript from a single gene, cannot be excluded.
MAP4K3/GLK in autoimmune disease, cancer and aging (2019)

MAP4K3 (also named GLK) is a serine/threonine kinase, which belongs to the mammalian Ste20-like kinase family. At 22 years of age, GLK was initially cloned and identified as an upstream activator of the MAPK JNK under an environmental stress and proinflammatory cytokines. The data derived from GLK-overexpressing or shRNA-knockdown cell lines suggest that GLK may be involved in cell proliferation through mTOR signaling. GLK phosphorylates the transcription factor TFEB and retains TFEB in the cytoplasm, leading to inhibition of cell autophagy. After generating and characterizing GLK-deficient mice, the important in vivo roles of GLK in T-cell activation were revealed. In T cells, GLK directly interacts with and activates PKCθ through phosphorylating PKCθ at Ser-538 residue, leading to activation of IKK/NF-κB. Thus, GLK-deficient mice display impaired T-cell-mediated immune responses and decreased inflammatory phenotypes in autoimmune disease models. Consistently, the percentage of GLK-overexpressing T cells is increased in the peripheral blood from autoimmune disease patients; the GLK-overexpressing T cell population is correlated with disease severity of patients. The pathogenic mechanism of autoimmune disease by GLK overexpression was unraveled by characterizing T-cell-specific GLK transgenic mice and using biochemical analyses. GLK overexpression selectively promotes IL-17A transcription by inducing the AhR-RORγt complex in T cells. In addition, GLK overexpression in cancer tissues is correlated with cancer recurrence of human lung cancer and liver cancer; the predictive power of GLK overexpression for cancer recurrence is higher than that of pathologic stage. GLK directly phosphorylates and activates IQGAP1, resulting in induction of Cdc42-mediated cell migration and cancer metastasis. Furthermore, treatment of GLK inhibitor reduces disease severity of mouse autoimmune disease models and decreases IL-17A production of human autoimmune T cells. Due to the inhibitory function of HPK1/MAP4K1 in T-cell activation and the promoting effects of GLK on tumorigenesis, HPK1 and GLK dual inhibitors could be useful therapeutic drugs for cancer immunotherapy. In addition, GLK deficiency results in extension of lifespan in Caenorhabditis elegans and mice. Taken together, targeting MAP4K3 (GLK) may be useful for treating/preventing autoimmune disease, cancer metastasis/recurrence, and aging.
Distributed optimization in sensor networks (2004)

Wireless sensor networks are capable of collecting an enormous amount of data over space and time. Often, the ultimate objective is to derive an estimate of a parameter or function from these data. This paper investigates a general class of distributed algorithms for "in-network" data processing, eliminating the need to transmit raw data to a central point. This can provide significant reductions in the amount of communication and energy required to obtain an accurate estimate. The estimation problems we consider are expressed as the optimization of a cost function involving data from all sensor nodes. The distributed algorithms are based on an incremental optimization process. A parameter estimate is circulated through the network, and along the way each node makes a small adjustment to the estimate based on its local data. Applying results from the theory of incremental subgradient optimization, we show that for a broad class of estimation problems the distributed algorithms converge to within an e-ball around the globally optimal value. Furthermore, bounds on the number incremental steps required for a particular level of accuracy provide insight into the trade-off between estimation performance and communication overhead. In many realistic scenarios, the distributed algorithms are much more efficient, in terms of energy and communications, than centralized estimation schemes. The theory is verified through simulated applications in robust estimation, source localization, cluster analysis and density estimation.
How do endothelial cells orientate? (2005)

In sprouting angiogenesis, endothelial cells must orientate in the tissue environment in order to effectively invade tissues and form vascular patterns according to the local needs. Here, we review recent data indicating that sprouting angiogenesis is a guided process resembling axonal guidance and insect trachea formation. Angiogenesis requires functional specialization of endothelial cells within the sprout. Cells situated at the tip of the sprouts sense and navigate the environment using long filopodia, whereas cells in the sprout stalks proliferate and form a vascular lumen. Migration of the tip cells depends on a graded distribution of VEGF-A and activation of VEGFR2 located on the tip-cell filopodia. Proliferation in the stalk is concomitantly regulated by the local VEGF-A levels. Thus, the shape of the VEGF-A gradient controls the balance between tip cell migration and stalk cell proliferation, which in turn determines the initial vascular pattern. An imbalance between the two processes may explain why abnormal vascular patterns develop in pathological angiogenesis.
Site Isolation Organic Synthesis in Polystyrene Networks (1986)

Reagents supported in solvent-swollen, cross-linked polystyrenes are less mobile than reagents in solution. As a result, the rate of reaction between two polymer-supported species can be retarded relative to the rate of reaction of a polymer-supported species with a soluble reagent or with itself. With 2-10% cross-linked polystyrenes in swelling solvents, reduced mobility provides 1-10 minute lifetimes of polymer-supported reactive intermediates such as an ester enolate, a benzyne, and a glycine active ester. Trapping of the reactive intermediate in less than the lifetime gives kinetically effective site isolation synthesis on a polymer support. Polymer chain mobility decreases with decreased swelling, increased cross-linking, and decreased temperature. Organometallic catalysts can be effectively site isolated by low coverage on the surface of a highly cross-linked macroporous polymer. Within a polymer gel, amine and phosphine ligands provide equilibria between supported organometallic complexes, catalytic activities, and selective reactions different from those in solution.
Composition of the Organic Phase Species in the Synergistic Extraction of Sr2+by Mixtures of Di(2‐Ethylhexyl) Alkylenediphosphonic Acids and Dicyclohexano‐18‐crown‐6 (2003)

Abstract The extraction of Sr2+, Ba2+ and Ra2+ from aqueous nitric acid solutions by P,P′‐di(2‐ethylhexyl) ethylene‐ (H2DEH[EDP]) and butylene‐ (H2DEH[BuDP]) diphosphonic acids in o‐xylene is synergized by the cis‐syn‐cis and cis‐anti‐cis stereoisomers of dicyclohexano‐18‐crown‐6 (DCH18C6). However, no information is available on the composition of the synergistic complexes. In this work a detailed investigation of the composition of the organic phase species formed in these systems has been performed using Sr2+ as a probe, with a variety of techniques such as infrared spectroscopy, vapor pressure osmometry, and distribution methods. The latter methods have been employed under conditions ranging from trace metal concentration to organic phase saturation. The results from these experiments indicate that for the H2DEH[BuDP] system, the synergistic complex contains one Sr2+ ion, one crown ether molecule, and two diphosphonic acid trimers. For the H2DEH[EDP] system, the predominant synergistic complex has the 1:1:1 metal ion:crown ether:diphosphonic acid hexamer stoichiometry. Some of the results, however, indicate that a complex containing two H2DEH[EDP] hexamers can also be formed.
Enhancement and inhibition of radiation in cylindrically symmetric, periodic structures (1993)

The effects of a two-dimensional, cylindrically symmetric periodic structure on the radiation from a source located inside the structure are considered. The coupling of the source radiation to the cylindrical cavity is analyzed classically by consideration of the interaction of a current line source with its own radiated field supported by the cavity. The analysis predicts variations in the radiative damping rate (inverse lifetime) and associated shifts in the oscillation frequency of the source. It is found that significant enhancement and inhibition of the radiation are possible even when the source is not at the center of the structure. Frequency shifts induced by the cavity are found to be negligible relative to the size of the band gap of the Bragg structure. The class of periodic structures analyzed has potential application to planar waveguide devices, such as concentric-circle gratings, surface-emitting lasers, and cylindrically symmetric lasers and amplifiers.
Changes to the Natural Killer Cell Repertoire after Therapeutic Hepatitis B DNA Vaccination (2010)

ClinicalTrials.gov NCT00988767.
Hyperphosphorylation and Cleavage at D421 Enhance Tau Secretion (2012)

It is well established that tau pathology propagates in a predictable manner in Alzheimer's disease (AD). Moreover, tau accumulates in the cerebrospinal fluid (CSF) of AD's patients. The mechanisms underlying the propagation of tau pathology and its accumulation in the CSF remain to be elucidated. Recent studies have reported that human tau was secreted by neurons and non-neuronal cells when it was overexpressed indicating that tau secretion could contribute to the spreading of tau pathology in the brain and could lead to its accumulation in the CSF. In the present study, we showed that the overexpression of human tau resulted in its secretion by Hela cells. The main form of tau secreted by these cells was cleaved at the C-terminal. Surprisingly, secreted tau was dephosphorylated at several sites in comparison to intracellular tau which presented a strong immunoreactivity to all phospho-dependent antibodies tested. Our data also revealed that phosphorylation and cleavage of tau favored its secretion by Hela cells. Indeed, the mimicking of phosphorylation at 12 sites known to be phosphorylated in AD enhanced tau secretion. A mutant form of tau truncated at D421, the preferential cleavage site of caspase-3, was also significantly more secreted than wild-type tau. Taken together, our results indicate that hyperphosphorylation and cleavage of tau by favoring its secretion could contribute to the propagation of tau pathology in the brain and its accumulation in the CSF.
Dissolution Behavior of Lipid Monolayer-Coated, Air-Filled Microbubbles:  Effect of Lipid Hydrophobic Chain Length (2002)

The gas transport properties and dissolution behavior of the lipid monolayer shell coating a micron-scale bubble (microbubble) are of particular interest for developing stable ultrasound contrast agents, drug delivery vehicles, and efficient oxygen carriers. In the current study, Epstein and Plesset's model for the dissolution of a bubble into a quiescent, degassed medium was modified to include a term for the gas permeation resistance of the lipid shell. The shell resistances for a homologous series of phospholipids were determined by comparing this model to experimental data of lipid-coated, air-filled microbubbles dissolving in a degassed aqueous medium. The gas permeation resistance is a significant factor in controlling the dissolution rate of lipid-coated microbubbles and was found to increase monotonically with lipid hydrophobic chain length. During the dissolution process, lipid was shed from the shell in a continuous manner for short-chain lipids to accommodate the shrinking volume of the gas core. A cyclic process of buckling and lipid shedding was observed for long-chain lipids and a mechanism involving adhesive zippering of apposing monolayers is proposed to describe this phenomenon.
Programmable cellular logic arrays (1970)

In recent years, technological advances have provided the designer of computing hardware with the ability to batch-fabricate large numbers of logic components on a single semiconductor slice. Numerous researchers have investigated the synthesis of various kinds of digital logic by using arrays of identical cells. The dissertation considers cellular arrays whose individual cell functions are determined by parameter flip-flops and logic gates in the cell, rather than by a physical customizing operation during manufacture. Potential advantages of this technique include functional variability after manufacture, more efficient testing, and enhanced failure tolerance. Arrays may be classified according to their generality, i.e., the number and range of the tasks which they are designed to perform. Two significantly different examples of low-generality arrays are presented and analyzed. A new cell schema is introduced which exhibits properties important in the synthesis of high-generality functions. Techniques are presented for improving the match between an array design and the target class of tasks. (Author)
Cellular contribution of bone graft to fusion (2000)

Although a number of studies have examined the fate of graft-derived cells during the process of fusion, there remains no consensus regarding their exact contribution to bone formation within the fusion mass. We developed two chimeric mouse isograft fusion models that allowed us to track the fate of graft cells within the host fusion bed. Cortical/cancellous bone graft (1:1 ratio of pelvic to vertebral body bone) from male mice was placed between (a) the tibia and fibula or (b) the coccygeal spine transverse processes of syngeneic female hosts. Both models were characterized histologically and histochemically. Graft-derived cells were then identified by fluorescent in situ hybridization for Y-chromosome sequences present in only the graft (male) cells. When the fusion mass was healing but not yet fused (at 1 and 2 weeks), numerous graft-derived cells were observed throughout the fusion site. The predominant graft-derived cell types included chondrocytes, osteoblasts, and fibroblasts. Chondrocytes arose from precursor cells in the graft de novo. as cartilage was not transplanted during the surgical procedure. By the time a mature fusion mass had formed (at 6 weeks), graft-derived cells persisted as osteocytes within the cortical rim surrounding the fusion mass. These osteocytes likely differentiated from graft-derived precursors that had directly formed bone, because transplanted osteocytes within cortical bone graft fragments were noted to rarely survive even at 1 and 2 weeks. Collectively, our results demonstrate for the first time that bone graft contributes cells that, in conjunction with host cells, directly form bone within the fusion mass during all phases of fusion rather than just the early phases.