gebhart/patrepeval huggingface dataset:
Towards More Effective Intervention in Natural Helping Networks (1984)

Fiscal constraints which are promoting a retreat from social welfare programming place increasing responsibility for care on natural helping networks of family and friends. Research has identified several characteristics of informal networks which are associated with support such as density, reciprocity, homogeneity, and multiplexity. Professional interventions have also responded to the potential supports available in networks. Professional practice concentrates primarily on self-help groups and the use of key persons in networks. There is, however, little correspondence between research findings and professional approaches to intervention. Little has been done to determine the possible impact of formal service provision on the dynamics of informal networks. More effective intervention in informal networks must consider the limitations of current practice, the development of assessment instruments, and the changes in network structures and processes over time.
Router Renumbering Guide (1997)

IP addresses currently used by organizations are likely to undergo changes in the near to moderate term. Change can become necessary for a variety of reasons, including enterprise reorganization, physical moves of equipment, new strategic relationships, changes in Internet Service Providers (ISP), new applications, and the needs of global Internet connectivity. Good IP address management may in general simplify continuing system administration; a good renumbering plan is also a good numbering plan. Most actions taken to ease future renumbering will ease routine network administration.
The contribution of oxidative stress to platelet senescence during storage (2019)

Platelets during storage became senescent and dysfunctional over time, and we found that oxidative stress might account for this decline. The addition of antioxidants effectively postponed senescence and ameliorated platelet storage lesion, which might provide a valuable reference to future platelet storage methodologies.
Evidence for the double-strand break repair model of bacteriophage lambda recombination. (1990)

We have obtained evidence for the repair of double-strand gaps promoted by the Red function of bacteriophage lambda. A double-strand gap was made in one of the two regions of homology in an inverted orientation on a plasmid DNA molecule. The gapped plasmid was introduced into Escherichia coli cells expressing the red alpha (exo) and red beta (bet) genes of lambda. The gap was repaired by DNA synthesis copying an intact duplex. This gap repair was sometimes accompanied by reciprocal recombination (crossing over). The gap stimulated recombination about 100-fold. Our results are compatible with previous proposals that lambda homologous recombination involves the following early steps: (i) generation of double-stranded ends by the packaging machinery or by the replication machinery; (ii) production of a single-stranded tail with a 3'-hydroxyl end by 5'----3' degradation by lambda exonuclease (red alpha gene product); (iii) pairing of the single-stranded tail with a complementary strand from a homologous duplex with the help of beta protein (red beta gene product); (iv) priming of DNA synthesis at this 3'-hydroxyl end to copy the second DNA molecule.
Kinetic Mechanism of the Enantioselective Conversion of Styrene Oxide by Epoxide Hydrolase from Agrobacterium radiobacter AD1 (1998)

Epoxide hydrolase from Agrobacterium radiobacter AD1 catalyzes the enantioselective hydrolysis of styrene oxide with an E value of 16. The (R)-enantiomer of styrene oxide is first converted with a k(cat) of 3.8 s(-1), and the conversion of the (S)-enantiomer is inhibited. The latter is subsequently hydrolyzed with a k(cat) of 10.5 s(-1). The pre-steady-state kinetic parameters were determined for both enantiomers with stopped-flow fluorescence and rapid-quench techniques. For (R)-styrene oxide a four-step mechanism was needed to describe the data. It involved the formation of a Michaelis complex that is in rapid equilibrium with free enzyme and substrate, followed by rapid and reversible alkylation of the enzyme. A unimolecular isomerization of the alkylated enzyme precedes the hydrolysis of the covalent intermediate, which could be observed due to an enhancement of the intrinsic protein fluorescence during this step. The conversion of (S)-styrene oxide could be described by a three-step mechanism, which also involved reversible and rapid formation of an ester intermediate from a Michaelis complex and its subsequent slow hydrolysis as the rate-limiting step. The unimolecular isomerization step has not been observed for rat microsomal epoxide hydrolase, for which a kinetic mechanism was recently established [Tzeng, H.-F., Laughlin, L. T., Lin, S., and Armstrong, R. N. (1996) J. Am. Chem. Soc. 118, 9436-9437]. For both enantiomers of styrene oxide, the Km value was much lower than the substrate binding constant K(S) due to extensive accumulation of the covalent intermediate. The enantioselectivity was more pronounced in the alkylation rates than in the rate-limiting hydrolysis steps. The combined reaction schemes for (R)- and (S)-styrene oxide gave an accurate description of the epoxide hydrolase catalyzed kinetic resolution of racemic styrene oxide.
Interqubit coupling mediated by a high-excitation-energy quantum object (2008)

We consider a system composed of two qubits and a high excitation energy quantum object used to mediate coupling between the qubits. We treat the entire system quantum mechanically and analyze the properties of the eigenvalues and eigenstates of the total Hamiltonian. After reproducing well-known results concerning the leading term in the mediated coupling, we obtain an expression for the residual coupling between the qubits in the off state. We also analyze the entanglement between the three objects, i.e., the two qubits and the coupler, in the eigenstates of the total Hamiltonian. Although we focus on the application of our results to the recently realized parametric-coupling scheme with two qubits, we also discuss extensions of our results to harmonic-oscillator couplers, couplers that are near resonance with the qubits and multiqubit systems. In particular, we find that certain errors that are absent for a two-qubit system arise when dealing with multiqubit systems.
Synergistic Cytotoxicity of Irinotecan and Cisplatin in Dual-Drug Targeted Polymeric Nanoparticles (2012)

The strategy of coencapsulating both I&C in a single NP targeted to a specific cell type could potentially be used to treat different types of cancer.
Selective Intracellular Delivery of Dexamethasone into Activated Endothelial Cells Using an E-Selectin-Directed Immunoconjugate (2002)

In chronic inflammatory diseases, the endothelium is an attractive target for pharmacological intervention because it plays an important role in leukocyte recruitment. Hence, inhibition of endothelial cell activation and consequent leukocyte infiltration may improve therapeutic outcome in these diseases. We report on a drug targeting strategy for the selective delivery of the anti-inflammatory drug dexamethasone to activated endothelial cells, using an E-selectin-directed drug-Ab conjugate. Dexamethasone was covalently attached to an anti-E-selectin Ab, resulting in the so-called dexamethasone-anti-E-selectin conjugate. Binding of the conjugate to E-selectin was studied using surface plasmon resonance and immunohistochemistry. Furthermore, internalization of the conjugate was studied using confocal laser scanning microscopy and immuno-transmission electron microscopy. It was demonstrated that the dexamethasone-anti-E-selectin conjugate, like the unmodified anti-E-selectin Ab, selectively bound to TNF-alpha-stimulated endothelial cells and not to resting endothelial cells. After binding, the conjugate was internalized and routed to multivesicular bodies, which is a lysosome-related cellular compartment. After intracellular degradation, pharmacologically active dexamethasone was released, as shown in endothelial cells that were transfected with a glucocorticoid-responsive reporter gene. Furthermore, intracellularly delivered dexamethasone was able to down-regulate the proinflammatory gene IL-8. In conclusion, this study demonstrates the possibility to selectively deliver the anti-inflammatory drug dexamethasone into activated endothelial cells, using an anti-E-selectin Ab as a carrier molecule.
Control of MEF2 Transcriptional Activity by Coordinated Phosphorylation and Sumoylation (2005)

A eukaryotic protein is often subject to regulation by multiple modifications like phosphorylation, acetylation, ubiquitination, and sumoylation. How these modifications are coordinated in vivo is an important issue that is poorly understood but is relevant to many biological processes. We recently showed that human MEF2D (myocyte enhancer factor 2D) is sumoylated on Lys-439. Adjacent to the sumoylation motif is Ser-444, which like Lys-439 is highly conserved among MEF2 proteins from diverse species. Here we present [corrected] several lines of evidence to demonstrate that Ser-444 of MEF2D is required for sumoylation of Lys-439. Histone deacetylase 4 (HDAC4) stimulated this modification by acting through Ser-444. In addition, phosphorylation of Ser-444 by Cdk5, a cyclin-dependent kinase known to inhibit MEF2 transcriptional activity, stimulated sumoylation. Opposing the actions of HDAC4 and Cdk5, calcineurin (also known as protein phosphatase 2B) dephosphorylated Ser-444 and inhibited sumoylation of Lys-439. This phosphatase, however, exerted minimal effects on the phosphorylation catalyzed by ERK5, an extracellular signal-regulated kinase known to activate MEF2D. These results identify [corrected] an essential role for Ser-444 in MEF2D sumoylation and reveal [corrected] a novel mechanism by which calcineurin selectively "edits" phosphorylation at different sites, thereby reiterating that interplay between different modifications represents a general mechanism for coordinated regulation of eukaryotic protein functions in vivo.
Hyaluronic acid hydrogel for controlled self-renewal and differentiation of human embryonic stem cells (2007)

Control of self-renewal and differentiation of human ES cells (hESCs) remains a challenge. This is largely due to the use of culture systems that involve poorly defined animal products and do not mimic the normal developmental milieu. Routine protocols involve the propagation of hESCs on mouse fibroblast or human feeder layers, enzymatic cell removal, and spontaneous differentiation in cultures of embryoid bodies, and each of these steps involves significant variability of culture conditions. We report that a completely synthetic hydrogel matrix can support (i) long-term self-renewal of hESCs in the presence of conditioned medium from mouse embryonic fibroblast feeder layers, and (ii) direct cell differentiation. Hyaluronic acid (HA) hydrogels were selected because of the role of HA in early development and feeder layer cultures of hESCs and the controllability of hydrogel architecture, mechanics, and degradation. When encapsulated in 3D HA hydrogels (but not within other hydrogels or in monolayer cultures on HA), hESCs maintained their undifferentiated state, preserved their normal karyotype, and maintained their full differentiation capacity as indicated by embryoid body formation. Differentiation could be induced within the same hydrogel by simply altering soluble factors. We therefore propose that HA hydrogels, with their developmentally relevant composition and tunable physical properties, provide a unique microenvironment for the self-renewal and differentiation of hESCs.
Continuous queries over append-only databases (1992)

In a database to which data is continually added, users may wish to issue a permanent query and be notified whenever data matches the query. If such continuous queries examine only single records, this can be implemented by examining each record as it arrives. This is very efficient because only the incoming record needs to be scanned. This simple approach does not work for queries involving joins or time. The Tapestry system allows users to issue such queries over a database of mail and bulletin board messages. The user issues a static query, such as “show me all messages that have been replied to by Jones,” as though the database were fixed and unchanging. Tapestry converts the query into an incremental query that efficiently finds new matches to the original query as new messages are added to the database. This paper describes the techniques used in Tapestry, which do not depend on triggers and thus be implemented on any commercial database that supports SQL. Although Tapestry is designed for filtering mail and news messages, its techniques are applicable to any append-only database.
Disulphide-bond pattern and molecular modelling of the dimeric disintegrin EMF-10, a potent and selective integrin α5β1 antagonist from Eristocophis macmahoni venom (2000)

The disulphide-bond pattern of the heterodimeric disintegrin EMF-10, a potent and selective integrin α5β1 antagonist from Eristocophis macmahoni venom, was established by combination of amino-acid analysis, N-terminal sequencing and collision-induced dissociation by nanoelectrospray ionization quadrupole ion-trap MS of fragments isolated by reversed-phase HPLC after degradation of EMF-10 with oxalic acid. Each EMF-10 subunit contains four intrachain disulphide bonds. Two interchain cystine residues join the EMF-10 polypeptides. The intrachain linkages are conserved in monomeric disintegrins. A molecular model of EMF-10 was built using averaged NMR co-ordinates of flavoridin as a template. The active hairpin loops of the EMF-10 subunits occupy opposite locations at the ends of an elongated disulphide-bond ladder. In the EMF-10 model the N-terminal polypeptide of EMF-10B is close to the RGD-loop of the EMF-10A subunit, suggesting that the N-terminal region of the B-subunit could potentially influence the biological activity of the A-subunit.
Optical metrology : coherent and incoherent optics for metrology, sensing and control in science, industry, and biomedicine (1987)

Foundations.- Optical Metrology - Some Personal Reflections.- Beam Deflection and Image Forming System.- Measurement of Surface Form by Laser Profilometry.- Three-Dimensional Inspection of Large Objects.- Laser Dimensional Metrology.- Distance Sensing Via Spectrographs Coding.- Interferometry, Velocimetry and Photon Correlation.- Some Recent Developments in Laser Interferometry.- Laser Heterodyne Probes.- Scanning Differential Phase Contrast Optical Microscope Application to Surface Studies and Micro Metrology.- Laser Velocimetry.- Velocity Measurements in a Rotating Tank Using and LDV System.- Sizing of Microscopic Particles by Photon Correlation.- Image Processing Techniques.- Optical Fourier Transform Construction.- Optical Metrology of Fish Scales.- Hybrid Coherent Optical and Electronic Filtering.- Hybrid Coherent Optical and Electronical Object Recognition.- Dynamical Digital Memory for Holography, Moire and E.S.P.I.- Automation in Manufacturing Intelligent Sensing.- Moire Methods.- Moire Interferometry and Its Developments in Strain Analysis.- Measurements of Fracture Toughness and Integrity by Moire Interferometry.- Phase-Measuring Moire Topography.- Holographic Metrology.- The Holo-Diagram, Sandwich-Holography and Light-in-Flight Recording.- Quantitative Interpretation of Time-Average Holograms in Vibration Analysis.- Matrix Methods in Hologram Interferometry and Speckle Metrology.- Optical Metrology and Computer Tomography for Measurement of Temperature and Density.- Unification of FEM with Laser Experimentation.- Moiee Evaluation with Fringe Patterns of Interferograms, Holograms, Moiregrams and Specklegrams.- Electronic Processing for Holographic Interferometry.- Holography in Medicine and Biology - State of the Art and The Problem of Increasing Militarization.- Holographic Cinematography with the Help of a Pulse Yag Laser.- Phase Conjugation Metrology.- Holographic Metrology and Nondestructive Testing - Past and Future.- Speckle Methods.- Speckle Metrology.- Recent Developments on Speckle Pattern Correlation by Photographical Means.- Heterodyne Speckle Photogrammetry.- Measuring Microvibrations by Heterodyne Speckle Interferometry.- Electronic Speckle Pattern Interferometry.- Convective Mass Transfer Coefficient Measurement by Holographic and Electronic Speckle Pattern Interferometry.- Improvements on Electronic Speckle Pattern Interferometry.- Speckle Reduction in Four-Wave Mixing Imaging with a Bi12 Si 020 Crystal.- Optical Fibre Metrology.- Single-Mode Fiber Optical Sensors.- Design of a Fiber Optic Hydrophone.- Fiber Optic Sensors as Dosimeters for Ionizing Radiation.- Picosecond Pulse Metrology.- Picosecond Metrology.- Optical SOLITONS: a short presentation.- Photoelasticity.- Photoelasticity.- Non-Destructive 3D Photoelasticity.- Further Topics.- Optical Metrology at Loughborough University.- Closing Remarks.- Conclusions and Future Events.- Remark: Holography and Relativity.
Critical current of a one-dimensional superconductor (1994)

We solve the Bogoliubov--de Gennes equations for a clean, one-dimensional superconductor in the presence of superfluid flow. The maximum electrical current occurs when the superfluid velocity ${\mathit{v}}_{\mathit{s}}$ equals the Landau depairing velocity \ensuremath{\Delta}/${\mathit{p}}_{\mathit{F}}$, where \ensuremath{\Delta} is the pairing potential of the superconductor and ${\mathit{p}}_{\mathit{F}}$ is the Fermi momentum. The resulting critical current is approximately 2/\ensuremath{\pi} times smaller than the value e\ensuremath{\Delta}/\ensuremath{\Elzxh} recently predicted for a superconducting point contact. The ``discretized'' critical current of (2/\ensuremath{\pi})(e\ensuremath{\Delta}/\ensuremath{\Elzxh}) arises when all the conducting electrons are forced to drift at the Landau depairing velocity.
Serotonin induces Rho/ROCK‐dependent activation of Smads 1/5/8 in pulmonary artery smooth muscle cells (2009)

Serotonin (5-HT) stimulates pulmonary artery smooth muscle cell proliferation and has been associated with pulmonary arterial hypertension (PAH). Bone morphogenetic protein receptor 2 (BMPR2) mutations similarly have been linked to PAH. However, possible crosstalk between 5-HT and BMPR signaling remains poorly characterized. We report here that 5-HT activates Smads 1/5/8 in bovine and human pulmonary artery smooth muscle cells (SMCs) and causes translocation of these Smads from cytoplasm to the nucleus. DN BMPR1A blocked 5-HT activation of Smads 1/5/8 by 5-HT and BMPR1A overexpression enhanced it. Activation of Smads by 5-HT occurred through the 5-HT 1B/1D receptor as it was blocked with the inhibitor GR 55562 but unaffected by inhibitors of the 5-HT transporter and a variety of 5-HT receptors. Activation of the Smads by 5-HT depended on Rho/Rho kinase signaling as it was blocked by Y27632, but unaffected by inhibitors of PI3K or MAPK. Transfection of cells with BMPR1A and ligation of the BMP receptor with BMP-2 also activated GTP-Rho A of these SMCs, while DN BMPR1A blocked the activation. 5-HT stimulated an increase in serine/threonine phosphorylation of BMPR1A, supporting the activation of BMPR1A by 5-HT in SMCs. Infusion of 5-HT into mice with miniosmotic infusion pumps caused activation of Smads 1/5/8 in lung tissue, demonstrating the effect in vivo. The studies support a unique concept that 5-HT transactivates the serine kinase receptor, BMPR 1A, to activate Smads 1/5/8 via Rho and Rho kinase in pulmonary artery SMCs. Rho and Rho kinase also participate in the activation of Smads by BMP.
Abstract 1800: The PARP inhibitor, rucaparib enhances the antitumor activity of 177Lu-DOTA-octreotate radionuclide therapy in preclinical models of neuroendocrine tumor (2015)

Abstract Purpose: Neuroendocrine tumors (NET) are a relatively rare, but heterogeneous group of tumors that arise predominantly in the gastrointestinal tract and bronchopulmonary system. While peptide receptor radionuclide therapy (PRRT) targeting somatostatin receptor 2 (SSTR2) has proved valuable in the treatment of NET, more effective clinical regimens are needed. In this study we investigated the efficacy of the combination of 177Lu-DOTA-octreotate (LuTate) PRRT and a poly (ADP-ribose) polymerase (PARP) inhibitor in well characterised preclinical NET models. Methods: A panel of seven cell lines with neuroendocrine features was characterised for SSTR2 expression, in vivo tumor growth properties, 68Ga-DOTA-octreotate (GaTate) uptake by positron emission tomography (PET) and sensitivity to LuTate. Representative tumor models were then selected to investigate the radiosensitizing potential of the PARP inhibitor, rucaparib when given in combination with LuTate. Results: Wide variation in SSTR2 mRNA and protein expression was observed between the various cell lines. Furthermore, immunohistochemical analysis revealed diffuse cytoplasmic expression of SSTR2 in vitro in contrast to strong cell membrane expression in vivo. Consistent with the in vivo cellular localisation, three tumor models demonstrated high tumor uptake of GaTate, an SSTR2 binding PET tracer used for the diagnosis and staging of NET. All three models responded to treatment with 20 MBq LuTate although the extent of the response was not predicted by SSTR2 expression or GaTate uptake. Treatment of A427-SSTR2 tumour bearing mice with two fortnightly cycles of 25 MBq Lutate in combination with rucaparib (15 mg/kg QD, IP) on days 1-5 of each cycle was well tolerated as assessed by the absence of any body weight loss. LuTate therapy alone induced tumour regression (56%) to day 32 after which the tumours began to regrow. Tumour regression in the combination treated group reached a maximum of 86% on day 35 (P&amp;lt; 0.05 vs LuTate alone), after which the tumors began to regrow. The median conditional survival time of 93 days in the LuTate alone group was significantly increased to greater than 161 days in the combination treated group (P&amp;lt; 0.01, Mantel Cox log rank test). Conclusions: Therapeutic regimens combining LuTate PRRT and PARP inhibitors as radiosensitizers may be an effective strategy for improving cellular responses in NET and warrants further clinical evaluation. Citation Format: Carleen Cullinane, Kelly Waldeck, Peter Eu, Rodney J. Hicks. The PARP inhibitor, rucaparib enhances the antitumor activity of 177Lu-DOTA-octreotate radionuclide therapy in preclinical models of neuroendocrine tumor. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1800. doi:10.1158/1538-7445.AM2015-1800