gebhart/patrepeval huggingface dataset:
Fast capacitance extraction of general three-dimensional structures (2002)

Several improvements to the multipole-accelerated 3-D capacitance extraction program previously described are presented. A new adaptive multipole algorithm is given, and a preconditioning strategy for accelerated iterative method convergence is described. Results using these algorithms to compute the capacitance of general three-dimensional structures are presented, and they demonstrate that the modified approach is nearly as accurate as the more standard direct factorization algorithm, and can be as much as two orders of magnitude faster.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Serine 6 of Lck Tyrosine Kinase: A Critical Site for Lck Myristoylation, Membrane Localization, and Function in T Lymphocytes (2000)

Lck is a member of the Src family kinases expressed predominantly in T cells, and plays a pivotal role in TCR-mediated signal transduction. Myristoylation of glysine 2 in the N-terminal Src homology 4 (SH4) domain of Lck is essential for membrane localization and function. In this study, we examined a site within the SH4 domain of Lck regulating myristoylation, membrane localization, and function of Lck. A Lck mutant in which serine 6 (Ser6) was substituted by an alanine was almost completely cytosolic in COS-7 cells, and this change of localization was associated with a drastic inhibition of myristoylation in this mutant. To assess the role of Ser6 of Lck in T cell function, we established stable transfectants expressing various Lck mutants using Lck-negative JCaM1 cells. The Lck mutant of Ser6 to alanine, most of which did not target to the plasma membrane, was not able to reconstitute TCR-mediated signaling events in JCaM1 cells, as analyzed by tyrosine phosphorylation of intracellular proteins and CD69 expression. These results demonstrate that Ser6 is a critical factor for Lck myristoylation, membrane localization, and function in T cells, presumably because the residue is important for N-myristoyl transferase recognition.
Mechanism Of Cell Surface Activation Of 72-kDa Type IV Collagenase (1995)

Matrix metalloproteases are secreted by mammalian cells as zymogens and, upon activation, initiate tissue remodeling by proteolytic degradation of collagens and proteoglycans. Activation of the secreted proenzymes and interaction with their specific inhibitors determine the net enzymatic activity in the extracellular space. We have previously demonstrated that 72T4Cl can be activated by a plasma membrane-dependent mechanism specific for this enzyme. Here, we report purification of the membrane activator of 72T4Cl, which is a new metalloprotease identical to a recently cloned membrane-type matrix metalloprotease (MT-MMP). We demonstrate that activated MT-MMP acts as a cell surface tissue inhibitor of metalloprotease 2 (TIMP-2) receptor with Kd = 2.54 x 10(-9) M. The activator.TIMP-2 complex in turn acts as a receptor for 72T4Cl (Kd = 0.56 x 10(-9) M, binding to the carboxyl-end domain of the enzyme. Activation of 72T4Cl on the cell membrane provides a basic mechanism for spatially regulated extracellular proteolysis and presents a new target for prognosis and treatment of metastatic disease. The activation, purified as a tri-molecular complex of MT-MMP.TIMP2.carboxyl-end domain of 72T4Cl, is itself an activated form of MT-MMP, posing the following question: what is the mechanism of the activator's activation?
ZAP-70 Expression as a Surrogate for Immunoglobulin-Variable-Region Mutations in Chronic Lymphocytic Leukemia (2003)

The mutational status of immunoglobulin heavy-chain variable-region ( IgV H ) genes in the leukemic cells of chronic lymphocytic leukemia (CLL) is an important prognostic factor in the disease. We investigated whether the expression of ZAP-70 by CLL cells correlated with the IgV H mutational status, disease progression, and survival.
Adaptive responses of human monocytes infected byBordetella pertussis: The role of adenylate cyclase hemolysin (2000)

The activation/adaptive responses of human monocytes exposed to Bordetella pertussis parental or mutant strains were evaluated and correlated to the expression of two bacterial toxins: adenylate cyclase-hemolysin and pertussis toxin. The marked rise in intracellular cyclic adenosine monophosphate (cAMP) observed in monocytes infected by B. pertussis parental strain, inversely correlated with (1) the production of tumor necrosis factor α; (2) the release of superoxide anion; and (3) the expression of the 72-kDa heat shock/stress protein, Hsp70. Experiments performed with mutants deficient in adenylate cyclase-hemolysin or with purified bacterial toxins confirmed the key role of adenylate cyclase-hemolysin in the control of monocytes' response to infection by B. pertussis. This bacterial strategy primarily involves evasion from antimicrobial defenses and, eventually, the sacrifice of the host cell. J. Cell. Physiol. 183:91–99, 2000. © 2000 Wiley-Liss, Inc.
Microfluidic analysis of cellular deformability of normal and oxidatively damaged red blood cells (2013)

Microfluidic analysis of blood has potential clinical value for determining normal and abnormal erythrocyte deformability. To determine if a microfluidic device could reliably measure intra- and inter-personal variations of normal and oxidized human red blood cell (RBC), venous blood samples were collected from repeat donors over time. RBC deformability was defined by the cortical tension (pN/µm), as determined from the threshold pressure required to deform RBC through 2-2.5 μm funnel-shaped constrictions. Oxidized RBC were prepared by treatment with phenazine methosulphate (PMS; 50 µM). Analysis of the control and oxidized RBC demonstrated that the microfluidic device could clearly differentiate between normal and mildly oxidized (20.13 ± 1.47 versus 27.51 ± 3.64 pN/µm) RBC. In vivo murine studies further established that the PMS-mediated loss of deformability correlated with premature clearance. Deformability variation within an individual over three independent samplings (over 21 days) demonstrated minimal changes in the mean pN/µm. Moreover, inter-individual variation in mean control RBC deformability was similarly small (range: 19.37-21.40 pN/µm). In contrast, PMS-oxidized cells demonstrated a greater inter-individual range (range: 25.97-29.90 pN/µm) reflecting the differential oxidant sensitivity of an individual's RBC. Importantly, similar deformability profiles (mean and distribution width; 20.49 ± 1.67 pN/µm) were obtained from whole blood via finger prick sampling. These studies demonstrated that a low cost microfluidic device could be used to reproducibly discriminate between normal and oxidized RBC. Advanced microfluidic devices could be of clinical value in analyzing populations for hemoglobinopathies or in evaluating donor RBC products post-storage to assess transfusion suitability.
A geometric approach to shape from defocus (2005)

We introduce a novel approach to shape from defocus, i.e., the problem of inferring the three-dimensional (3D) geometry of a scene from a collection of defocused images. Typically, in shape from defocus, the task of extracting geometry also requires deblurring the given images. A common approach to bypass this task relies on approximating the scene locally by a plane parallel to the image (the so-called equifocal assumption). We show that this approximation is indeed not necessary, as one can estimate 3D geometry while avoiding deblurring without strong assumptions on the scene. Solving the problem of shape from defocus requires modeling how light interacts with the optics before reaching the imaging surface. This interaction is described by the so-called point spread function (PSF). When the form of the PSF is known, we propose an optimal method to infer 3D geometry from defocused images that involves computing orthogonal operators which are regularized via functional singular value decomposition. When the form of the PSF is unknown, we propose a simple and efficient method that first learns a set of projection operators from blurred images and then uses these operators to estimate the 3D geometry of the scene from novel blurred images. Our experiments on both real and synthetic images show that the performance of the algorithm is relatively insensitive to the form of the PSF. Our general approach is to minimize the Euclidean norm of the difference between the estimated images and the observed images. The method is geometric in that we reduce the minimization to performing projections onto linear subspaces, by using inner product structures on both infinite and finite-dimensional Hilbert spaces. Both proposed algorithms involve only simple matrix-vector multiplications which can be implemented in real-time.
Binding of Avian Coronavirus Spike Proteins to Host Factors Reflects Virus Tropism and Pathogenicity (2011)

The binding of viruses to host cells is the first step in determining tropism and pathogenicity. While avian infectious bronchitis coronavirus (IBV) infection and avian influenza A virus (IAV) infection both depend on α2,3-linked sialic acids, the host tropism of IBV is restricted compared to that of IAV. Here we investigated whether the interaction between the viral attachment proteins and the host could explain these differences by using recombinant spike domains (S1) of IBV strains with different pathogenicities, as well as the hemagglutinin (HA) protein of IAV H5N1. Protein histochemistry showed that S1 of IBV strain M41 and HA of IAV subtype H5N1 displayed sialic acid-dependent binding to chicken respiratory tract tissue. However, while HA bound with high avidity to a broad range of α2,3-linked sialylated glycans, M41 S1 recognized only one particular α2,3-linked disialoside in a glycan array. When comparing the binding of recombinant IBV S1 proteins derived from IBV strains with known differences in tissue tropism and pathogenicity, we observed that while M41 S1 displayed binding to cilia and goblet cells of the chicken respiratory tract, S1 derived from the vaccine strain H120 or the nonvirulent Beaudette strain had reduced or no binding to chicken tissues, respectively, in agreement with the reduced abilities of these viruses to replicate in vivo. While the S1 protein derived from the nephropathogenic IBV strain B1648 also hardly displayed binding to respiratory tract cells, distinct binding to kidney cells was observed, but only after the removal of sialic acid from S1. In conclusion, our data demonstrate that the attachment patterns of the IBV S proteins correlate with the tropisms and pathogenicities of the corresponding viruses.
A 1mW Dual-Chopper Amplifier for a 50-μg√Hz Monolithic CMOS-MEMS Capacitive Accelerometer (2006)

This paper reports a novel dual-chopper amplifier (DCA) for CMOS-MEMS capacitive accelerometers. A DCA prototype integrated with a single-axis accelerometer has been fabricated using TSMC 0.35 mum CMOS process. The DCA achieves a 16nV/radicHz input-referred noise at 20 Hz with a power dissipation of only 1 mW. The measured accelerometer noise floor is 50 mug/radicHz down to 5 Hz
Cleavage of specific sites of RNA by designed ribozymes (1988)

Two ribozymes were designed for site-specific cleavage of RNA. A UA site in an undecaribonucleotide was cleaved by a ribozyme consisting of two partially paired oligoribonucleotides with chain lengths of 19 and 15. The other ribozyme, which consists of a 19-mer and a 13-mer, recognized a UC sequence at positions 42 and 43 of 5 S rRNA.
Cardiac troponin I. A marker with high specificity for cardiac injury. (1993)

Elevations of cTnI are highly specific for myocardial injury. Use of cTnI should facilitate distinguishing whether elevations of MBCK are due to myocardial or skeletal muscle injury.
The effect of a water-soluble tris-galactoside-terminated cholesterol derivative on the fate of low density lipoproteins and liposomes. (1985)

A triantennary galactose-terminated cholesterol derivative, N-(tris(beta-D-galactopyranosyloxymethyl) methyl)-N alpha-(4-(5-cholesten-3 beta-yloxy)succinyl)glycinamide (Tris-Gal-Chol), which dissolves easily in water, was added to human low density lipoproteins (LDL) in varying quantities. Upon addition to LDL, Tris-Gal-Chol was immediately incorporated, and after intravenous injection into rats, the iodine-labeled apolipoprotein B radioactivity was readily associated with the liver. The incorporation of 5 or 13 micrograms of Tris-Gal-Chol into LDL (20 micrograms of protein) stimulates the parenchymal cell association of LDL 6- and 10-fold, respectively, at 10 min after injection. For non-parenchymal cells, the cell association is 60- and 70-fold stimulated, respectively. It can be calculated that non-parenchymal cells (mainly Kupffer cells) are for 80-90% responsible for the increased, galactose-mediated, interaction of Tris-Gal-Chol LDL with the liver. The increased interaction of LDL with the cells upon Tris-Gal-Chol incorporation is followed by degradation of the apolipoprotein B in the lysosomes. Incorporation of Tris-Gal-Chol into unilamellar liposomes (10 mol %) leads to an increased cell association of the enclosed [3H]inulin to parenchymal cells (1.4-fold) and non-parenchymal cells (11.8-fold). It is concluded that Tris-Gal-Chol incorporation into LDL leads to a markedly increased catabolism of LDL by the liver which might be used for lowering serum LDL levels. The possibility of increasing the interaction of LDL or liposomes with specific liver cell types by Tris-Gal-Chol might also have an application for targeting drugs or other compounds of interest to these cells.
In vivo human retinal imaging by ultrahigh-speed spectral domain optical coherence tomography (2004)

An ultrahigh-speed spectral domain optical coherence tomography (SD-OCT) system is presented that achieves acquisition rates of 29,300 depth profiles/s. The sensitivity of SD-OCT and time domain OCT (TD-OCT) are experimentally compared, demonstrating a 21.7-dB improvement of SD-OCT over TD-OCT. In vivo images of the human retina are presented, demonstrating the ability to acquire high-quality structural images with an axial resolution of 6 microm at ultrahigh speed and with an ocular exposure level of less than 600 microW.
Nuclease activities of Moloney murine leukemia virus reverse transcriptase. Mutants with altered substrate specificities. (1993)

RNases H are traditionally thought to degrade RNA only in RNA-DNA hybrid form. We found that the wild-type Moloney murine leukemia virus (M-MuLV) reverse transcriptase (RT) was capable of degrading RNA in RNA-RNA duplexes as well as in RNA-DNA hybrids, as assayed by in situ gel techniques. Escherichia coli RNase H does not degrade the RNA-RNA duplex in this assay, while E. coli RNase III, a double-strand-specific ribonuclease, does. The apparent specific activity of M-MuLV RT on RNA-RNA duplexes is similar to that on RNA-DNA hybrids. Neither the DNA polymerase domain nor the RNase H domain of RT expressed individually exhibited this RNA-RNA activity. We have generated a series of mutations in the RNase H domain of M-MuLV RT, expressed the mutant enzymes in E. coli, and assayed these mutants for various activities. All RTs were as active as the wild type in the oligo(dT):poly(rA) DNA polymerase assay, and many retained both nuclease activities. Two enzymes with mutations at the carboxyl terminus of the RNase H domain retained RNA-DNA activity, but not RNA-RNA activity. Another mutant enzyme showed the opposite phenotype, retaining RNA-RNA, but not RNA-DNA, nuclease activity. Thus, we were able to genetically separate the two activities. These results may be helpful in defining enzyme-substrate interactions.
Characterization of the reactivity pattern of murine monoclonal antibodies against wild-type hepatitis B surface antigen to g145r and other naturally occurring “a” loop escape mutations (1999)

The hepatitis B surface antigen (HBsAg) "a" domain harbors major B-cell epitopes. Viruses with mutations in this region emerge after vaccination or during hepatitis B immune globulin (HBIg) prophylaxis. A strain with G145R replacement has been almost invariably isolated as a major escape mutant. We investigated mutant antigen-antibody interactions with direct binding assays. G145R and 16 other naturally occurring recombinant HBsAg mutants were expressed in mammalian Cos-1 cells. The reactivity of a panel of 28 murine anti-hepatitis B surface antigen (anti-HBs) monoclonal antibodies to mutant antigens was measured with enzyme immunoassay and expressed as percentage compared with the wild-type (wt) HBsAg signal for each antibody. All point-mutated proteins displayed diffuse intracellular immunofluorescent labeling corresponding to a secretory pathway. Monoclonal antibodies (mAbs) were classified according to different binding patterns. The effect of mutations on antibody binding differs depending on the amino acid involved and on the location within the "a" loop. As expected, most antibodies had absent or negligible binding (<40%), notably with residue 145 replacements. However, we identified antibodies that reacted with conformational epitopes but nevertheless had adequate reactivity (>40%) with all mutant antigens, including G145R. The effect of G145R was more pronounced than that of G145A. A subgroup of antibodies had substantially increased recognition (>120%) of antigens with mutations in the first loop. We demonstrated that antibodies can be selected or combined that react with all mutants investigated, including G145R. These data offer perspectives for improving anti-HBs-based protection against hepatitis B.
Lack of integrase can markedly affect human immunodeficiency virus type 1 particle production in the presence of an active viral protease (1996)

The Gag-Pol polyprotein of human immunodeficiency virus type 1 is not required for efficient viral particle assembly or release. However, in this report we demonstrate that the synthesis of a truncated Gag-Pol precursor due to a premature termination codon in pol can reduce the ability of a full-length provirus to direct the formation of viral particles. Marked effects on particle production were seen when premature termination codons were introduced into the integrase (IN)-coding region. By contrast, a mutant which lacked both IN and reverse transcriptase (RT) formed particles with normal efficiency. Particle production by IN mutants was restored to wild-type levels when a second premature termination codon was introduced at the 5' end of the RT-coding sequence. Particle formation was similarly restored by a second site mutation in the viral protease (PR) gene which prevented proteolytic processing of the Gag polyprotein. Finally particle formation was restored in the presence of A77003, a specific inhibitor of human immunodeficiency virus type 1 PR. These results suggest that the effects of a lack of IN sequences on particle formation require the synthesis of a Gag-Pol precursor which contains RT sequences and are due to inappropriate PR activity.
Regulation by patterned preganglionic neural activity of transmitter stores in a sympathetic ganglion. (1978)

1. The effect of patterned preganglionic stimulation on acetylcholine (ACh) stores was studied in the superior cervical ganglion of the cat. 2. Patterns of stimulation based on 0.5 and 1.0 s trains at frequencies from 10 to 80/s and intervals between trains of 2-180 s increased ACh stores, over periods of 1-3 h stimulation, to the same extent (30-70%) as found earlier to result from continuous stimulation. 3. If the mean frequency of the overall pattern was greater than 5/s the increase in stores developed after termination of the stimulation. If the mean frequency was less than 5/s the increase developed progressively during stimulation and it was then maintained without accommodation over 7 h of stimulation. 4. The magnitude of the increase in ACh stores was linearly related to the frequency within the trains from 10 to 40/s, decreasing with further increase in frequency, and absent below 6-7/s. 5. The ACh stores were increased by patterns of stimulation that mimicked discharging of preganglionic neurones driven by the central respiratory drive under hypercapnic or asphyxial stress; and were increased similarly in animals respired with hypercapnic or partially asphyxial gas mixtures when the preganglionic innervation was intact, but not when it was severed. 6. The variance between ACh stores of ganglia from different animals was reduced in animals held in a controlled environment for 1-2 weeks before experimentation. 7. It is concluded that patterning of preganglionic inputs into high frequency trains is a code for the ongoing modulation of transmitter stores in a sympathetic ganglion. 8. The findings are discussed in relation to current knowledge of ganglionic transmission and to after-hyperpolarization in mammalian unmyelinated nerve fibres.
3‘-C-Branched LNA-Type Nucleosides Locked in an N-Type Furanose Ring Conformation:  Synthesis, Incorporation into Oligodeoxynucleotides, and Hybridization Studies (2004)

Three protected 3'-C-branched LNA-type phosphoramidite building blocks 17, 27, and 38, containing furanose rings locked in an N-type conformation, were synthesized from a known 3-C-allyl allofuranose derivative using strategies relying on the introduction of the branching alkyl chain before condensation with the nucleobase. Synthesis of 3'-C-hydroxypropyl derivatives proved superior to synthesis of the 3'-C-hydroxyethyl derivatives, and the former was converted into the corresponding 3'-C-aminopropyl derivatives. Phosphoramidites 27 and 38 were subsequently applied on an automated DNA synthesizer leading to the introduction of three novel 3'-C-branched LNA-type monomers X, Y, and Z into oligodeoxynucleotides and studies of their effect on the hybridization properties. A duplex-stabilizing effect of introducing 3'-C-aminopropyl-LNA monomer Y, relative to 3'-C-hydroxypropyl-LNA monomer X, was observed, especially at low salt conditions. This indicates that the primary amino group of monomer Y is protonated under the hybridization conditions applied and that positioning of this positively charged group in the major groove has a significant duplex stabilizing effect. Monomer Y was by an on-column conjugation method further functionalized by a glycyl unit to give monomer Z that showed a less stabilizing effect than monomer Y.
Studies of nitriles. XI. Preparation and chemistry of Schiff bases of ADAN, 2-amino-3,3-dichloroacrylonitrile. A highly effective conversion into 2-substituted-4(5)-chloroimidazole-5(4)-carbaldehydes. (1976)

Schiff bases of 2-amino-3, 3-dichloroacrylonitrile (ADAN) have been prepared in excellent yields by condensation of ADAN with various aldehydes under mild conditions. These Schiff bases (2, 3, 4) are highly reactive polyfunctional compounds and useful synthetic intermediates : the chlorine atoms of Schiff base 2e react with various nucleophiles such as alkoxides, mercaptides, and primary and secondary amines giving the corresponding 3, 3-dialkoxy-, 3, 3-bis (substituted mercapto)-, and 3, 3-bis (substituted amino)-derivatives (7, 8, and 10), respectively. Reduction of Schiff base 2e with zinc powder under mild conditions resulted in formation of the monochloro derivative 5. With anhydrous hydrogen chloride in ether, these Schiff bases underwent smooth cyclization to new 4 (5)-chloro-5(4)-dichloromethylimidazoles 11, which in turn were converted into 4 (5)-chloro-imidazole-5 (4)-carbaldehydes 12 in excellent yields upon hydrolysis.
1,3‐Dipolar cycloaddition reactions of 1,3,4‐oxadiazin‐6‐ones with nitrile oxides (1990)

Abstract 2,5‐Diaryl‐1,3,4‐oxadiazin‐6‐ones 1 gave with nitrile oxides 2 1,2,4‐oxadiazole derivatives 4 . When mesitonitrile oxide 2a was used, bis‐adducts 3 were also formed. The cycloadditions showed a remarkable site selectivity towards one carbon nitrogen double bond. The structure of both adducts was fully characterized by X‐ray analysis.