gebhart/patrepeval huggingface dataset:
Computational Electrochemistry of Ruthenium Anticancer Agents. Unprecedented Benchmarking of Implicit Solvation Methods (2008)

Two ruthenium(III) complexes {(HIm)[trans-RuCl4(DMSO)(Im)] (NAMI-A) and (HInd)[trans-RuCl4(Ind)2] (KP1019), DMSO = dimethyl sulfoxide, Im = imidazole, Ind = indazole} have been tested in phase I clinical trials as potential anticancer drugs. Ru(III) anticancer agents are likely activated in vivo upon reduction to their Ru(II) analogs. Aiming at benchmarking implicit solvation methods in DFT studies of ruthenium pharmaceuticals at the B3LYP level, we have calculated the standard redox potentials (SRPs) of Ru(III/II) pairs that were electrochemically characterized in the literature. 80 SRP values in four solvents were calculated using three implicit solvation methods and five solute cavities of molecular shape. Comparison with experimental data revealed substantial errors in some of the combinations of solvation method and solute cavity. For example, the overall mean unsigned error (MUE) with the PCM/UA0 combination, which is the popular default in Gaussian 03, amounts to 0.23 V (5.4 kcal/mol). The MUE with the CPCM/UAKS combination, which was employed by others for recent computational studies on the hydrolysis of NAMI-A and trans-[RuCl4(Im)2](-), amounts to 0.30 V (7.0 kcal/mol) for all compounds and to 0.60 V (13.9 kcal/mol) for a subset of compounds of the medicinally relevant type, trans-[RuCl4(L)(L')](-). The SRPs calculated with the PCM or CPCM methods in Gaussian 03 can be significantly improved by a more compact solute cavity constructed with Bondi's set of atomic radii. Earlier findings that CPCM performs better than PCM cannot be confirmed, as the overall MUE amounts to 0.19 V (4.3-4.4 kcal/mol) for both methods in combination with Bondi's set of radii. The Poisson-Boltzmann finite element method (PBF) implemented in Jaguar 7 together with the default cavity performs slightly better, with the overall MUE being 0.16 V (3.7 kcal/mol). Because the redox pairs considered in this study bear molecular charges from +3/+2 to -1/-2 and the prediction of solvation free energies is most challenging for highly charged species, the present work can serve as a general benchmarking of the implicit solvation methods.
Characterization of Hydrogenase II from the Hyperthermophilic Archaeon Pyrococcus furiosus and Assessment of Its Role in Sulfur Reduction (2000)

The fermentative hyperthermophile Pyrococcus furiosus contains an NADPH-utilizing, heterotetrameric (alphabetagammadelta), cytoplasmic hydrogenase (hydrogenase I) that catalyzes both H(2) production and the reduction of elemental sulfur to H(2)S. Herein is described the purification of a second enzyme of this type, hydrogenase II, from the same organism. Hydrogenase II has an M(r) of 320,000 +/- 20,000 and contains four different subunits with M(r)s of 52,000 (alpha), 39,000 (beta), 30,000 (gamma), and 24,000 (delta). The heterotetramer contained Ni (0.9 +/- 0.1 atom/mol), Fe (21 +/- 1.6 atoms/mol), and flavin adenine dinucleotide (FAD) (0.83 +/- 0.1 mol/mol). NADPH and NADH were equally efficient as electron donors for H(2) production with K(m) values near 70 microM and k(cat)/K(m) values near 350 min(-1) mM(-1). In contrast to hydrogenase I, hydrogenase II catalyzed the H(2)-dependent reduction of NAD (K(m), 128 microM; k(cat)/K(m), 770 min(-1) mM(-1)). Ferredoxin from P. furiosus was not an efficient electron carrier for either enzyme. Both H(2) and NADPH served as electron donors for the reduction of elemental sulfur (S(0)) and polysulfide by hydrogenase I and hydrogenase II, and both enzymes preferentially reduce polysulfide to sulfide rather than protons to H(2) using NADPH as the electron donor. At least two [4Fe-4S] and one [2Fe-2S] cluster were detected in hydrogenase II by electron paramagnetic resonance spectroscopy, but amino acid sequence analyses indicated a total of five [4Fe-4S] clusters (two in the beta subunit and three in the delta subunit) and one [2Fe-2S] cluster (in the gamma subunit), as well as two putative nucleotide-binding sites in the gamma subunit which are thought to bind FAD and NAD(P)(H). The amino acid sequences of the four subunits of hydrogenase II showed between 55 and 63% similarity to those of hydrogenase I. The two enzymes are present in the cytoplasm at approximately the same concentration. Hydrogenase II may become physiologically relevant at low S(0) concentrations since it has a higher affinity than hydrogenase I for both S(0) and polysulfide.
Genome Scan for Quantitative Trait Loci Linked to High-Density Lipoprotein Cholesterol (2001)

We conducted a genome-wide linkage scan for quantitative trait loci influencing total HDL-cholesterol (HDL-C) concentration in a sample of 1027 whites from 101 families participating in the NHLBI Family Heart Study. To maximize the relative contribution of genetic components of variance to the total variance of HDL-C, the HDL-C phenotype was adjusted for age, age(2), body mass index, and Family Heart Study field center, and standardized HDL-C residuals were created separately for men and women. All analyses were completed by the variance components method, as implemented in the program GENEHUNTER using 383 anonymous markers typed at the NHLBI Mammalian Genotyping Service in Marshfield, Wis. Evidence for linkage of residual HDL-C was detected near marker D5S1470 at location 39.9 cM from the p-terminal of chromosome 5 (LOD=3.64). Suggestive linkage was detected near marker D13S1493 at location 27.5 cM on chromosome 13 (LOD=2.36). We conclude that at least 1 genomic region is likely to harbor a gene that influences interindividual variation in HDL cholesterol.
Evolutionary optimization of peptide substrates for proteases that exhibit rapid hydrolysis kinetics (2010)

Protease cleavage site recognition motifs can be identified using protease substrate discovery methodologies, but typically exhibit non-optimal specificity and activity. To enable evolutionary optimization of substrate cleavage kinetics, a two-color cellular library of peptide substrates (CLiPS) methodology was developed. Two-color CLiPS was applied to identify peptide substrates for the tobacco etch virus (TEV) protease from a random pentapeptide library, which were then optimized by screening of a focused, extended substrate library. Quantitative library screening yielded seven amino acid substrates exhibiting rapid hydrolysis by TEV protease and high sequence similarity to the native seven-amino-acid substrate, with a strong consensus of EXLYPhiQG. Comparison of hydrolysis rates for a family of closely related substrates indicates that the native seven-residue TEV substrate co-evolved with TEV protease to facilitate highly efficient hydrolysis. Consensus motifs revealed by screening enabled database identification of a family of related, putative viral protease substrates. More generally, our results suggest that substrate evolution using CLiPS may be useful for optimizing substrate selectivity and activity to enable the design of more effective protease activity probes, molecular imaging agents, and prodrugs.
The Use of HMAC-SHA-1-96 within ESP and AH (1998)

This memo describes the use of the HMAC algorithm [RFC-2104] in conjunction with the SHA-1 algorithm [FIPS-180-1] as an authentication mechanism within the revised IPSEC Encapsulating Security Payload [ESP] and the revised IPSEC Authentication Header [AH]. HMAC with SHA-1 provides data origin authentication and integrity protection.
Metal-enhanced fluorescence: a novel approach to ultra-sensitive fluorescence sensing assay platforms (2004)

We describe the development of a novel generic approach to fluorescence sensing based on metal-enhanced fluorescence (MEF). This work follows our initial reports of radiative decay engineering (RDE), where we experimentally demonstrated dramatic signal enhancements of fluorophores positioned close to surface-bound silver nanostructures. The attractive changes in spectral properties of fluorophores includes increased rates of excitation, increased quantum yields, decreased fluorescence lifetimes with an increased photostability, and drastically increased rates of multi-photon excitation. In this report we present a new class of fluorescent biomarkers which are strongly enhanced by metallic particles. This has afforded the development of a novel generic approach for ultra-sensitive fluorescence assay technology. The assay platform utilizes metal particles deposited on glass/quartz surfaces, covered with sub-nanometer layers of a fluorescent biomarker. As such the fluorescence signal of the composite is strongly enhanced. This readily allows easy, quantitative and inexpensive fluorescence detection of minimal traces of specific antigens. We also explore different sensing geometries, such as using evanescent wave excitation.
Difference-Based Image Noise Modeling Using Skellam Distribution (2011)

By the laws of quantum physics, pixel intensity does not have a true value, but should be a random variable. Contrary to the conventional assumptions, the distribution of intensity may not be an additive Gaussian. We propose to directly model the intensity difference and show its validity by an experimental comparison to the conventional additive model. As a model of the intensity difference, we present a Skellam distribution derived from the Poisson photon noise model. This modeling induces a linear relationship between intensity and Skellam parameters, while conventional variance computation methods do not yield any significant relationship between these parameters under natural illumination. The intensity-Skellam line is invariant to scene, illumination, and even most of camera parameters. We also propose practical methods to obtain the line using a color pattern and an arbitrary image under natural illumination. Because the Skellam parameters that can be obtained from this linearity determine a noise distribution for each intensity value, we can statistically determine whether any intensity difference is caused by an underlying signal difference or by noise. We demonstrate the effectiveness of this new noise model by applying it to practical applications of background subtraction and edge detection.
Transfusion Indications for Patients with Cancer (2015)

Indications for RBC transfusion have become more conservative as data and experience have shown that patients can be safely and effectively maintained at lower hemoglobin levels. Coagulation factor replacement is unnecessary for most modest coagulopathies.
Engineering redox homeostasis to develop efficient alcohol-producing microbial cell factories (2017)

The biosynthetic pathways of most alcohols are linked to intracellular redox homeostasis, which is crucial for life. This crucial balance is primarily controlled by the generation of reducing equivalents, as well as the (reduction)-oxidation metabolic cycle and the thiol redox homeostasis system. As a main oxidation pathway of reducing equivalents, the biosynthesis of most alcohols includes redox reactions, which are dependent on cofactors such as NADH or NADPH. Thus, when engineering alcohol-producing strains, the availability of cofactors and redox homeostasis must be considered. In this review, recent advances on the engineering of cellular redox homeostasis systems to accelerate alcohol biosynthesis are summarized. Recent approaches include improving cofactor availability, manipulating the affinity of redox enzymes to specific cofactors, as well as globally controlling redox reactions, indicating the power of these approaches, and opening a path towards improving the production of a number of different industrially-relevant alcohols in the near future.
Conserved patterns of somatic mutation and secondary VH gene rearrangement create aberrant lg-encoding genes in Epstein-Barr virus-transformed and normal human B lymphocytes (1992)

Expression of N-terminal-truncated Ig heavy chains without normal light chain expression has been shown to occur in human B cell tumor lines, and to be due to diverse types of structural alteration within the expressed Ig heavy and light chain genes. Due to the tumor cell origin of these lines, generation of aberrant Ig-encoding genes may only occur after malignant transformation, reflecting the release of the tumor B cell from the need to express functional Ig for continued clonal proliferation. The genetic basis for expression of VH-truncated mu chains without light chains in several Epstein-Barr virus (EBV)-transformed human B cell lines was investigated with the aim that this information would lead to detection of similarly aberrant Ig genes in normal human B lymphocytes. Analysis of the productive mu genes in three truncated mu-only human B cell lines showed a consistent structural change where a secondary VH-VHDJH gene rearrangement had occurred. The site of VH-VH joining was suggestive of a V(D)J recombinase-mediated event. A consistent pattern of mutation was also observed in the normal-sized, but non-functional kappa light chain transcripts, making them incapable of coding for a functional kappa chain. Using genomic DNA from peripheral blood lymphocytes of a donor whose B cells were originally used to make one of the truncated mu-only EBV B cell lines, a similarly mutated V kappa gene was detected and a similar composite VH-VH gene was cloned. The lack of such aberrant VH and V kappa genes in non-lymphoid cells of this individual showed that the structural abnormalities in the expressed Ig genes arose somatically during development of that B cell clone. The presence of these altered Ig heavy and light chain genes in the genomic DNA of untransformed lymphocytes also shows that generation of such variant B cell clones can be a pre-neoplastic event and occurs by genetic mechanisms active during normal B cell development.
Cytotoxic T cells specific for a single peptide on the M2 protein of respiratory syncytial virus are the sole mediators of resistance induced by immunization with M2 encoded by a recombinant vaccinia virus (1995)

We have studied the immunobiology of respiratory syncytial virus (RSV), a major cause of respiratory tract morbidity in children. As part of these studies, it was previously found that immunization of BALB/c (H-2d) mice with a recombinant vaccinia virus (rVV) which encoded the M2 protein of RSV provided complete protection against infection with RSV. This protection was transient and associated with M2-specific CD8+ T-cell (TCD8+) responses. In this study, we used two approaches to demonstrate that expression of an H-2Kd-restricted nonameric peptide (Ser Tyr Ile Gly Ser Ile Asn Asn Ile) corresponding to M2 residues 82 to 90 is necessary and sufficient to induce protective TCD8+ responses. First, infection of mice with an rVV which encoded the peptide M2Met82-90 induced levels of primary pulmonary TCD8+ and resistance to RSV challenge equivalent to that induced by infection with an rVV which expressed the complete M2 protein. Second, elimination of peptide binding to Kd by the replacement of Tyr with Arg at amino acid position 83 of the full-length protein completely abrogated the ability of an rVV-expressing full-length M2 to induce either M2-specific TCD8+ responses or resistance to RSV infection. These findings demonstrate that the M2(82-90) peptide is the sole determinant of immunity induced in BALB/c mice by the M2 protein and that a remarkably high level of transient resistance to infection with pulmonary virus is associated with TCD8+ responses to a single determinant.
Stereoselective syntheses. VI. Correlation of central and planar chirality in ferrocene derivatives (1970)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStereoselective syntheses. VI. Correlation of central and planar chirality in ferrocene derivativesDieter Marquarding, Hans Klusacek, George Gokel, Peter Hoffmann, and Ivar UgiCite this: J. Am. Chem. Soc. 1970, 92, 18, 5389–5393Publication Date (Print):September 1, 1970Publication History Published online1 May 2002Published inissue 1 September 1970https://pubs.acs.org/doi/10.1021/ja00721a017https://doi.org/10.1021/ja00721a017research-articleACS PublicationsRequest reuse permissionsArticle Views3650Altmetric-Citations473LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Role of Exposed Metal Sites in Hydrogen Storage in MOFs (2008)

The role of exposed metal sites in increasing the H2 storage performances in metal-organic frameworks (MOFs) has been investigated by means of IR spectrometry. Three MOFs have been considered: MOF-5, with unexposed metal sites, and HKUST-1 and CPO-27-Ni, with exposed Cu(2+) and Ni(2+), respectively. The onset temperature of spectroscopic features associated with adsorbed H2 correlates with the adsorption enthalpy obtained by the VTIR method and with the shift experienced by the H-H stretching frequency. This relationship can be ascribed to the different nature and accessibility of the metal sites. On the basis of a pure energetic evaluation, it was observed that the best performance was shown by CPO-27-Ni that exhibits also an initial adsorption enthalpy of -13.5 kJ mol(-1), the highest yet observed for a MOF. Unfortunately, upon comparison of the hydrogen amounts stored at high pressure, the hydrogen capacities in these conditions are mostly dependent on the surface area and total pore volume of the material. This means that if control of MOF surface area can benefit the total stored amounts, only the presence of a great number of strong adsorption sites can make the (P, T) storage conditions more economically favorable. These observations lead to the prediction that efficient H2 storage by physisorption can be obtained by increasing the surface density of strong adsorption sites.
Development of 3-D silicon die stacked package using flip chip technology with micro bump interconnects (2009)

Continuous increase in demand for product miniaturization, high package density, high performance and integration of different functional chips has lead to the development of three dimensional packaging technologies. Face-to-face silicon (Si) dies stacking is one of the three dimensional (3D) packaging technologies to form a high density module. In this work, a chip level stacked module was demonstrated for medical application and assessed its package level reliability. The chip level stack module is achieved by stacking two thin dies of different size and thickness together using flip chip technology with micro bump interconnects. Electrical simulations are carried out to obtain RLC parameters of micro bump interconnect and complete interconnection from daughter die to substrate. Mechanical simulations are also carried out to study the stress analysis on micro bumps and CSP bumps in the package and parametric study of stacked module package to study the effect of substrate material, underfill material die thicknesses on package reliability and warpage. Test chips are designed and fabricated with daisy chain test structures to access the reliability of the stack module. Pb-free (SnAg) micro bumps of 40 mum on daughter die wafers and eutectic SnPb solder CSP bumps of 200 mum height on mother die wafers are fabricated. Mother die and daughter die bumped wafers were thinned to 300 mum and 60 mum respectively using mechanical backgrinding method. These thin dies are stacked using chip to wafer flip chip bonding and underfill process is established for the micro bump interconnects. The assembled Si die stacked modules are subjected to JEDEC package level reliability tests in terms of temperature cycle test (TC), high temperature storage test (HTS), moisture sensitivity test level 1 (MST L1) and MST L3, and un-biased high accelerated stress test (uHAST) and results are presented.
A fractal interpretation of the dielectric response of animal tissues (1990)

An improvement to Schwan's model of the dielectric response of biological tissues is proposed which is based on a fractal interpretation of the power law behaviour (epsilon' alpha epsilon" alpha f"-1) often observed. This interpretation allows the response to be more specifically related to the sub-cellular and cellular organization of the tissue through its self-similar hierarchical nature. A number of examples are discussed ranging in tissue type from the mostly cellular liver tissue to nerve tissue (grey matter). Applications of the technique to diseased and damaged tissue are briefly touched upon so as to illustrate its potential for precisely defining their effect upon the cells' electrical behaviour at a specific organizational level.
Abnormal social behavior, hyperactivity, impaired remote spatial memory, and increased D1-mediated dopaminergic signaling in neuronal nitric oxide synthase knockout mice (2009)

These findings indicate that nNOS KO upregulates dopamine D1 receptor signaling, and induces abnormal social behavior, hyperactivity and impaired remote spatial memory. nNOS KO mice may serve as a unique animal model of psychiatric disorders.
Targeted disruption of Stat6 DNA binding activity by an oligonucleotide decoy blocks IL-4–driven TH2 cell response (2000)

The transcription factor, signal transducer and activator of transcription (Stat) 6, regulates T(H)2-lymphocyte activity by controlling the expression and responsiveness to interleukin (IL)-4, which plays a key role in numerous allergic maladies. Therefore, we sought to use a phosphorothiolate cis-element decoy to target disruption of Stat6 transcriptional activity. Here we showed that the Stat6 decoy potently ablated the messenger RNA expression and production of IL-4, but not of several other cytokines. The Stat6 decoy functionally disrupted IL-4-inducible cell proliferation of murine T(H)2 cells and primary human CD4(+) T lymphocytes. Specificity of the decoy was demonstrated by its ability to directly block Stat6 binding to a cis-element probe and transactivation, but not affect Stat6 tyrosine phosphorylation or expression of the IL-4 receptor chains. Moreover, the decoy failed to inhibit non-Stat6-dependent signaling pathways since IL-2 was competent to induce cell proliferation and activation of Stats 1, 3, and 5a/b. With the use of laser scanning confocal microscopy, fluorescently tagged Stat6 decoy was detectable in the cytoplasm and nucleus; however, greater levels of oligonucleotide were present in the latter following IL-4 treatment. Taken together, these data suggest that IL-4-driven T(H)2 cell activity can be preferentially restricted via targeted disruption of Stat6 by a novel and specific decoy strategy that may possess gene therapeutic potential. (Blood. 2000;95:1249-1257)
Quantum codes on a lattice with boundary (1998)

A new type of local-check additive quantum code is presented. Qubits are associated with edges of a 2-dimensional lattice whereas the stabilizer operators correspond to the faces and the vertices. The boundary of the lattice consists of alternating pieces with two different types of boundary conditions. Logical operators are described in terms of relative homology groups.