gebhart/patrepeval huggingface dataset:
Optimized Fluorescent Trimethoprim Derivatives for in vivo Protein Labeling (2007)

The combined technologies of optical microscopy and selective probes allow for real-time analysis of protein function in living cells. Synthetic chemistry offers a means to develop specific, protein-targeted probes that exhibit greater optical and chemical functionality than the widely used fluorescent proteins. Here we describe pharmacokinetically optimized, fluorescent trimethoprim (TMP) analogues that can be used to specifically label recombinant proteins fused to E. coli dihydrofolate reductase (eDHFR) in living, wild-type mammalian cells. These improved fluorescent tags exhibited high specificity and fast labeling kinetics, and they could be detected at a high signal-to-noise ratio by using fluorescence microscopy and fluorescence-activated cell sorting (FACS). We also show that fluorescent TMP-eDHFR complexes are complements to green fluorescent protein (GFP) for two-color protein labeling experiments in cells.
The Gatekeeping Role in Civil Litigation and the Abdication of Legal Values in Favor of Scientific Values (2003)

Beginning almost two decades ago, I wrote a series of law review articles about the nature of legal proof in the context of probabilistic evidence or analysis. In these articles, I explored, in passing, some of the differences between the legal system’s concept of proof of facts, especially in the context of civil litigation, and the same subject as seen by scientists, especially those analyzing empirical data. I put that endeavor aside for what turned out to be an extended period while my career took a different turn, focusing on the intricacies of commercial law. In the last decade, much of my time has been devoted to the problems of international commercial transactions. In particular, a major portion of my work during this time has involved the negotiation of various principles to govern international transactions. In one case, I was the chair of a task force within the drafting committee preparing Revised Article 9 of the Uniform Commercial Code which developed Article 9’s rules governing international secured transactions from the perspective of domestic United States law. In another case, I spent several years as a member of the United States delegation to the working group of the United Nations Commission on International Trade Law (“UNCITRAL”) which developed an international convention (now
LSD1 engages a corepressor complex for the activation of the estrogen receptor α by estrogen and cAMP (2016)

The estrogen receptor α (ERα) is a transcription factor that can be directly activated by estrogen or indirectly by other signaling pathways. We previously reported that activation of the unliganded ERα by cAMP is mediated by phosphorylation of the transcriptional coactivator CARM1 by protein kinase A (PKA), allowing CARM1 to bind ERα directly. This being insufficient by itself to activate ERα, we looked for additional factors and identified the histone H3 demethylase LSD1 as a substrate of PKA and an important mediator of this signaling crosstalk as well as of the response to estrogen. Surprisingly, ERα engages not only LSD1, but its partners of the CoREST corepressor complex and the molecular chaperone Hsp90. The recruitment of Hsp90 to promote ERα transcriptional activity runs against the steroid receptor paradigm and suggests that it might be involved as an assembly factor or scaffold. In a breast cancer cell line, which is resistant to the anti-estrogen tamoxifen because of constitutively activated PKA, some interactions are constitutive and drug combinations partially rescue tamoxifen sensitivity. In ERα-positive breast cancer patients, high expression of the genes encoding some of these factors correlates with poor prognosis. Thus, these mechanisms might contribute to ERα-driven breast cancer.
Agent services for situation aware control of power systems with distributed generation (2009)

Electric Power system of Denmark exhibits some unique characteristics. An increasing part of the electricity is produced by distributed generators (DGs). Most of these DGs are connected to the network at the distribution level. At the same time the concept of vehicle to grid (V2G) is already in the process of realization. This situation has created an incentive in electric power industry to utilize modern information and communication technologies (ICT) for improving the distribution system automation. This paper describes our work on how significantly increased amount of distributed generation could be exploited for the robust control of electric power systems. In particular, we present our work on the implementation of a dynamic service oriented system, in which autonomous agents represent different components of low voltage grid. These agents could offer and utilize electric power control services. We present results from several experiments where agents offer and utilize services in order to achieve distributed and autonomous control for subgrid operation of a distribution system. Finally it is discussed how the service oriented architecture can be combined with knowledge based reasoning to implement situation awareness required in complex control situations.
Polymerase chain reaction in detection of CMV DNA in renal allograft recipients (1992)

This study investigates the use of polymerase chain reaction (PCR) in comparison with viral culture and serology for monitoring of cytomegalovirus (CMV) infection in 21 consecutive renal allograft recipients treated with a quadruple immunosuppression protocol. In addition, an attempt is made to explore the significance of quantitation of CMV signals obtained from peripheral blood leucocytes. CMV infection developed in 16 patients with seven of these patients having organ involvement. All of these 16 patients had a fourfold rise in antibody titres as well as positive identification of CMV DNA in peripheral blood leucocytes by PCR. Blood viral cultures were negative in two of these patients. All five patients who remained PCR negative also remained culture negative with no antibody change. PCR detected CMV infection on average 15 days and 20 days earlier than viral culture and serology respectively. All except one of the patients with CMV organ involvement had an initial peak of CMV DNA followed by prolonged carriage of detectable CMV. The majority of patients with fever only or asymptomatic CMV infection had a transient peak of CMV DNA. A high incidence of CMV disease with organ involvement occurred in seronegative recipients of kidneys from seropositive donors (3/5) and in seropositive recipients of kidneys from seronegative donors (3/7). OKT3 was associated with a higher incidence of CMV organ involvement compared to Antilymphocytic globulin (3/5 v 4/16) but there was a higher incidence of CMV mismatched patients in the OKT3 treated group.(ABSTRACT TRUNCATED AT 250 WORDS)
Peptide-directed co-assembly of nanoprobes on multimaterial patterned solid surfaces (2012)

Biocombinatorially selected solid-binding peptides, through their unique material affinity and selectivity, are a promising platform for building up complex hierarchical assemblies of nanoscale materials and molecular probes, targeted to specific practical solid surfaces. Here, we demonstrate the material-specific characteristics of engineered gold-binding and silica-binding peptides through co-assembly onto micro- and nano-patterned gold surfaces on silica substrates. To build hierarchical nanostructures on patterned solid surfaces, we utilize peptides as molecular tools and monitor their behavior by either conjugating biotin to them for specific affinity to streptavidin-coated QDot nanoparticles or labelling them with small fluorescent labels. This biomimetic peptide-based approach could be used as an alternative to conventional chemical coupling and surface functionalization techniques with substantial advantages, allowing simultaneous assembly of two or more inorganic nano-entities and/or molecular probes onto patterned inorganic solid substrates. The results have significant implications in a wide range of potential applications, including controlled assembly of hybrid nanostructures in bionanophotonic and biosensing devices.
Molecular organization of transverse tubule/sarcoplasmic reticulum junctions during development of excitation-contraction coupling in skeletal muscle. (1994)

The relationship between the molecular composition and organization of the triad junction and the development of excitation-contraction (E-C) coupling was investigated in cultured skeletal muscle. Action potential-induced calcium transients develop concomitantly with the first expression of the dihydropyridine receptor (DHPR) and the ryanodine receptor (RyR), which are colocalized in clusters from the time of their earliest appearance. These DHPR/RyR clusters correspond to junctional domains of the transverse tubules (T-tubules) and sarcoplasmic reticulum (SR), respectively. Thus, at first contact T-tubules and SR form molecularly and structurally specialized membrane domains that support E-C coupling. The earliest T-tubule/SR junctions show structural characteristics of mature triads but are diverse in conformation and typically are formed before the extensive development of myofibrils. Whereas the initial formation of T-tubule/SR junctions is independent of association with myofibrils, the reorganization into proper triads occurs as junctions become associated with the border between the A band and the I band of the sarcomere. This final step in triad formation manifests itself in an increased density and uniformity of junctions in the cytoplasm, which in turn results in increased calcium release and reuptake rates.
Synthesis and Evaluation of a Series of C3-Substituted CBI Analogues of CC-1065 and the Duocarmycins (2001)

The synthesis and evaluation of a series of C3-substituted 1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-one (CBI) analogues of the CC-1065 and duocarmycin alkylation subunits are detailed, including methyl and the full series of halogens. Introduction of the key substituent was accomplished through directed metalation of the seco-CBI core followed by reaction of the resultant aryllithium with an appropriate electrophile. C3-Bromo and iodo substituents were only effectively installed on the hindered aryllithium intermediate using a novel halogen source, 1-bromo- and 1-iodophenylacetylene, that should prove generally useful beyond the studies we describe. X-ray crystal structures of the series show substantial distortion in the vinylogous amide due to unfavorable steric interactions between the C3-substituent and the N(2)-carbamate. In the halogen series, the N2-C2a bond length and the torsional angle chi(1) smoothly increase with the increasing size of the C3 substituent indicative of decreasing vinylogous amide conjugation through the series (H > F > Cl > Br > I). Unlike N-Boc-CBI, this series of substituted CBI analogues proved remarkably reactive toward solvolysis even at pH 7, where the reaction is uncatalyzed and the reactivity order (I > Br > Cl > F > H) follows a trend consistent with the extent of vinylogous amide conjugation and stabilization. The implications of these observations on the source of catalysis for the DNA alkylation reaction of the natural products are discussed.
Single-longitudinal-mode 1.3-µm DFB-DC-PBH laser diodes (1984)

Single-longitudinal-mode (SLM) operation of rapidly modulated InGaAsP/InP semiconductor lasers is attractive for long-haul wideband fiber-optic communication systems. Among several schemes of SLM LDs, DFB1,2 or DBR3 lasers are most promising for their stable SLM operation potentially in a wide-temperature and high-power range. DFB lasers reported so far have not exhibited sufficient performance for practical use with respect to lasing characteristics and particularly for reproducibility. In this paper high lasing performance as well as preliminary results on SLM in-wafer uniformity is described for InGaAsP/InP DFB LDs with a double-channel planar buried heterostructure (DC-PBH).4
Galvanic Replacement-Free Deposition of Au on Ag for Core–Shell Nanocubes with Enhanced Chemical Stability and SERS Activity (2014)

We report a robust synthesis of Ag@Au core-shell nanocubes by directly depositing Au atoms on the surfaces of Ag nanocubes as conformal, ultrathin shells. Our success relies on the introduction of a strong reducing agent to compete with and thereby block the galvanic replacement between Ag and HAuCl4. An ultrathin Au shell of 0.6 nm thick was able to protect the Ag in the core in an oxidative environment. Significantly, the core-shell nanocubes exhibited surface plasmonic properties essentially identical to those of the original Ag nanocubes, while the SERS activity showed a 5.4-fold further enhancement owing to an improvement in chemical enhancement. The combination of excellent SERS activity and chemical stability may enable a variety of new applications.
CRE-Transcription Factor Decoy Oligonucleotide Inhibition of MCF-7 Breast Cancer Cells:  Cross-Talk with p53 Signaling Pathway (2000)

The CRE, 5'-TGACGTCA-3', has been described as the consensus sequence for the cis-element that directs cAMP-regulated gene expression. Many transcription factors bind to this element and regulate the expression of a wide variety of cellular and viral genes. We have shown that CRE-transcription factor decoy oligonucleotide restrains the growth of cancer cells in vitro and in vivo [Park, Y. G., Nesterova, M., Agrawal, S., and Cho-Chung, Y. S. (1999) J. Biol. Chem. 274, 1573-1580]. The growth inhibition was accompanied by changes in cell morphology and apoptosis. To elucidate the molecular mechanism(s) of the growth inhibition by the CRE-decoy oligonucleotide, we investigated the p53 signaling pathway. Herein, we report that CRE-decoy oligonucleotide treatment results in an increase in the p53 protein level in MCF-7 human breast cancer cells that express wild-type p53. The p21WAF1/Cip1 protein levels were also increased in the CRE-decoy oligonucleotide treated cells accompanying a reduction in Cdk2- and cyclin E-dependent kinase activity and pRb phosphorylation. Pulse-chase experiments reveal that the p53 upregulation was due to increased stability of the protein. The decoy oligonucleotide treatment also enhanced the p53 promotor-directed transcription in vivo along with the increase in p53-CBP (CREB-binding protein) complex formation. Thus, the stabilization and activation of p53 may have contributed to the growth inhibition induced by CRE-transcription factor decoy oligonucleotide in MCF-7 breast cancer cells. This decoy oligonucleotide approach offers great promise as a tool for defining cellular regulatory processes and treating cancer and other diseases.
The Use of Denaturing High-Performance Liquid Chromatography (DHPLC) for the Analysis of Genetic Variations: Impact for Diagnostics and Pharmacogenetics (2003)

Over the past five years, denaturing high-performance liquid chromatography (DHPLC) has emerged as one of the most versatile technologies for the analysis of genetic variations. With the benefit of novel polymer chemistries used for separation, the accuracy, sensitivity, and the throughput of DHPLC for DNA and RNA analysis have greatly improved. DHPLC has been adopted in many laboratories for the screening of mutations and single-nucleotide polymorphisms (SNPs). The ability of DHPLC to detect known and unknown mutations simultaneously has put this technology at the forefront of genetic analysis for a wide variety of diseases. In addition, the high sensitivity of DHPLC combined with the accuracy of the heteroduplex analysis has allowed the development of applications beyond the scope of traditional sequencing or genotyping, e.g., the early detection of cancer. This article reviews the methods, which made DHPLC a widely used tool for diagnosis in molecular genetics and pharmacogenetics. The article provides an overview of current applications in these fields and points to novel applications in areas like epigenetics and the analysis of heteroplasmic mitochondrial DNA, in which DHPLC is becoming the leading technology.
Electrochemical Isotope Effect and Lithium Isotope Separation (2009)

A large electrochemical isotopic effect is observed upon the electrodeposition of lithium from solutions of propylene carbonate producing isotopically light metal deposits. The magnitude of fractionation is controlled by the applied overpotential and is largest close to equilibrium. Calculated partition function ratios for tetrahedrally coordinated lithium complexes and metallic lithium predict an equilibrium fractionation close to that measured experimentally.
Integrated yield management (1999)

As integrated circuit fabrication processes continue to increase in complexity, it has been determined that data collection, retention, and retrieval rates will continue to increase at an alarming rate. At future technology nodes, the time required to source manufacturing problems must at least remain constant to maintain anticipated productivity. Strategies and software methods for integrated yield management (IYM) have been identified as critical for maintaining this productivity. IYM must use integrated circuit design, visible defect, parametric, and functional test data to recognize process trends and excursions so that yield-detracting mechanisms can be rapidly identified and corrected. IYM will require a merging of the various data sources that are maintained throughout the fabrication environment. The availability of multiple data sources and the evolution of automated analysis techniques such as automatic defect classification (ADC) and spatial signature analysis (SSA) are prov...
Sparsity-Based Two-Dimensional DOA Estimation for Coprime Array: From Sum–Difference Coarray Viewpoint (2017)

This paper addresses the issue of two-dimensional (2-D) direction of arrival (DOA) estimation with coprime planar arrays (CPPAs) via sparse representation. Our work differs from the partial spectral search approach [25], which suppresses the phase ambiguity by searching the common peaks of two subarrays. We focus on the coprime property of CPPA, where the sparse array extension model with sum-difference coarray (SDCA) is derived for larger degrees of freedom (DOFs). Besides, to optimize the selection of regularization parameter, we also construct a new sparse representation algorithm by estimating the errors between the signal and noise parts. Further, an iterative scheme is presented to transform the 2-D grids searching to several times of 1-D searching, where the initial values are obtained by extracting one difference coarray from SDCA. So the proposed method can achieve aperture extension, high estimation performance, and low computational complexity. Besides, the sparse array extension model for multiple-input multiple-output radars is discussed and the Cramér-Rao bound for 2-D DOA estimation with CPPA is also derived in detail. Finally, simulation results demonstrate the effectiveness of proposed method compared to the state-of-the-art methods.
Electron beam irradiation of Y1Ba2Cu3O7−x grain boundary Josephson junctions (1997)

The properties of the Y1Ba2Cu3O7−x biepitaxial Josephson junctions were reproducibly modified by a focused electron beam irradiation of the interface region. The junctions were fabricated by depositing Y1Ba2Cu3O7−x thin film by cylindrical magnetron sputtering technique on the (110) SrTiO3 substrate, partially covered by a pregrown MgO seed layer. The junction parameters can be adjusted controllably by applying an appropriate dose. Electron irradiation decreased the critical current of the junctions IC and increased the normal state resistance times area to values of the order of 1(μ Ω cm2). Some other effects, such as the disappearance of the excess current, were also observed. The original properties of the junctions could be partly restored by isothermal annealing. We also speculate that some aspects of the nature of the grain boundary barriers can be better understood from the study of the properties of irradiated junctions.
Cyanine Dye N744 Inhibits Tau Fibrillization by Blocking Filament Extension:  Implications for the Treatment of Tauopathic Neurodegenerative Diseases (2005)

Tau fibrillization is a potential therapeutic target for Alzheimer's and other neurodegenerative diseases. Small molecules capable of both inhibiting aggregation and promoting filament disaggregation have been discovered, but knowledge of their mechanism of action and potential for testing in biological models is fragmentary. To clarify these issues, the interaction between a small-molecule inhibitor of tau fibrillization, 3,3'-bis(beta-hydroxyethyl)-9-ethyl-5,5'-dimethoxythiacarbocyanine iodide (N744), and full-length four-repeat tau protein was characterized in vitro using transmission electron microscopy and fluorescence spectroscopy. Analysis of reaction time courses performed in the presence of anionic fibrillization inducers revealed that increasing concentrations of N744 decreased the total filament length without modulating lag time, indicating that filament extension but not nucleation was affected by inhibitor under the conditions that were investigated. Critical concentration measurements confirmed that N744 shifted equilibria at filament ends away from the fibrillized state, resulting in endwise filament disaggregation when it was added to synthetic filaments. Both increasing bulk tau concentrations and filament stabilizing modifications such as pseudophosphorylation and glycation antagonized N744 activity. The results illustrate the importance of mechanism for the design and interpretation of pharmacological studies in biological models of tau aggregation.
Rearrangement of the 5' cluster region of the BCL2 gene in lymphoid neoplasm: a summary of nine cases. (1996)

Rearrangement of the BCL2 gene with the immunoglobulin (IG) genes is the most frequent genetic abnormality in B cell lymphoid neoplasms. In the majority of cases, breakages occur at two breakpoint cluster regions; major breakpoint cluster (MBR) and minor cluster region (mcr). In a minority of cases with non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL), rearrangements involving the 5' flanking region of the BCL2 (5'-BCL2) have been reported. Here, we investigated 196 patients with NHL and 31 with CLL, with regard to rearrangement of the BCL2 gene. Hybridization analyses using probes representing the three cluster regions revealed that a total of 57 patients had a rearrangement of the BCL2; 42 (73.7%) were within the MBR, seven (12.2%) were within the mcr, and nine (15.8%) had a rearrangement at the 5'-BCL2. The nine patients with 5'BCL2 rearrangement included two with follicular lymphoma, four with diffuse large cell lymphoma and immunoblastic variant, two with leukemic phase of follicular lymphoma, and one with CLL. Comigration analysis with probes for the IG heavy chain gene (IGH), kappa-chain gene (IG kappa) and lambda-chain gene (IG lambda), demonstrated a 5'-BCL2/IGH junction at the JH region in four patients with NHL derived from follicular center B cell. Thus, the 5'flanking region is a third cluster for recombination between the BCL2 and IGH, which is closely associated with the development of follicular center cell lymphoma. Molecular cloning of a 5'-BCL2/IGH junction demonstrated recombination of the two affected genes in divergent orientation. A 5'-BCL2/IG kappa junction was observed in two patients with immunoblastic lymphoma, and one with CLL had a 5'-BCL2/IG lambda recombination. Two patients, including one with a BCL2-MBR/JH junction, lacked obvious recombination of the 5'-BCL2 with IG genes, suggesting the presence of a deletion at the 5'-BCL2. Our findings demonstrated heterogeneity not only in clinicopathological presentation of B cell disease with rearrangement of 5'-BCL2, but also in molecular lesions resulting from the rearrangement.