gebhart/patrepeval huggingface dataset:
A Facile, Water-Soluble Method for Modification of Proteins with DOTA. Use of Elevated Temperature and Optimized pH To Achieve High Specific Activity and High Chelate Stability in Radiolabeled Immunoconjugates (1994)

We have developed a method for attachment of the macrocyclic chelating agent 1,4,7,10-tetraazacyclododecane N,N',N",N"'-tetraacetic acid (DOTA) to proteins by activation of a single carboxyl group with N-hydroxysulfosuccinimide (sulfo-NHS). The sulfo-NHS active ester of DOTA was prepared in a single step using 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC), and DOTA conjugates of cytochrome c and the anti-carcinoembryonic antigen chimeric monoclonal antibody cT84.66 were prepared by adding the DOTA active ester reaction mixture to the proteins at pH 8.5-9.0. Mass spectrometry of the cytochrome c conjugates showed that as the molar ratio of DOTA active ester to protein in the reaction mixture was increased from 10:1 to 100:1, the average number of chelators attached to the protein molecule increased from 2.64 to 8.79. When DOTA active ester reacted with the antibody at a molar ratio of 100:1, the conjugate averaged 3.8 chelates per antibody. Immunoreactivity of the antibody conjugate radiolabeled with 111In(III) and 90Y(III) remained quantitative. Variation of the DOTA:sulfo-NHS:EDC activation stoichiometry from 2:2:1 to 10:10:1 revealed that the kinetic stability of the radioconjugates increased as the molar ratio of carbodiimide, relative to DOTA and sulfo-NHS, was decreased. Radiolabeling of the protein conjugates with 111In(III) and 90Y(III) proved to be sensitive to pH, buffer, and temperature effects. The optimum pH for the labeling reaction was different for each protein and may be related to the isoelectric point of the protein. Radiometal incorporation at high specific activity was accomplished in acetate and Tris buffers, but the presence of citrate inhibited the labeling reaction. Increasing the temperature of the radiolabeling reaction from 25 to 43 degrees C greatly increased both the efficiency of radiometal incorporation and the kinetic stability of the radioconjugates. Stability studies of the conjugates in human serum and in the presence of a 5000- to 250,000-fold excess of diethylenetriaminepentaacetic acid (DTPA) demonstrated that the radiolabeled proteins are kinetically inert under physiological conditions. In serum, the 111In(III)-labeled antibody showed a rate of radiometal loss of approximately 0.08% per day. In the presence of excess DTPA, both conjugates lost 111In(III) at a rate of about 0.3% per day. No loss of 90Y(III) from the conjugates was observed in serum, but in excess DTPA, both 90Y(III) labeled proteins showed a rate of radiometal loss of approximately 0.2% per day. Therefore, kinetic analysis of metal loss from a radiolabeled immunoconjugate in the presence of a vast excess of DTPA may provide a better indication of the in vivo stability of that immunoconjugate than serum stability studies.
The β-Adrenergic Receptor Is a Substrate for the Insulin Receptor Tyrosine Kinase (1996)

G-protein-linked receptors and intrinsic tyrosine-kinase growth receptors represent two prominent modalities in cell signaling. Cross-regulation among members of both receptor superfamilies has been reported, including the counter-regulatory effects of insulin on beta-adrenergic catecholamine action. Cells stimulated by insulin show loss of function and increased phosphotyrosine content of beta 2-adrenergic receptors. Phosphorylation of tyrosyl residues 350/354 of beta 2-adrenergic receptors is obligatory for counter-regulation by insulin (Karoor, V., Baltensperger, K., Paul, H., Czech, M., and Malbon, C. C. (1995) J. Biol. Chem. 270, 25305-25308), suggesting the hypothesis that G-protein-linked receptors themselves may act as substrates for the insulin receptor and other growth factor receptors. This hypothesis was evaluated directly using recombinant human insulin receptor, hamster beta 2-adrenergic receptor, and an vitro reconstitution and phosphorylation assay. Insulin is shown to stimulate insulin receptor-catalyzed phosphorylation of the beta 2-adrenergic receptor. Phosphoamino acid analysis establishes that insulin receptor-catalyzed phosphorylation of the beta 2-adrenergic receptor in vitro is confined to phosphotyrosine. High pressure liquid chromatography and two-dimensional mapping reveal insulin receptor-catalyzed phosphorylation of the beta 2-adrenergic receptor at residues Tyr132/Tyr141, Tyr350/Tyr354, and Tyr364, known sites of phosphorylation in response to insulin in vivo. Insulin-like growth factor-I receptor as well as the insulin receptor displays the capacity to phosphorylate the beta 2-adrenergic receptor in vitro, establishing a new paradigm, i.e. G-protein-linked receptors acting as substrates for intrinsic tyrosine kinase growth factor receptors.
Assessment of Artificial MiRNA Architectures for Higher Knockdown Efficiencies without the Undesired Effects in Mice (2015)

RNAi-based strategies have been used for hypomorphic analyses. However, there are technical challenges to achieve robust, reproducible knockdown effect. Here we examined the artificial microRNA (amiRNA) architectures that could provide higher knockdown efficiencies. Using transient and stable transfection assays in cells, we found that simple amiRNA-expression cassettes, that did not contain a marker gene (-MG), displayed higher amiRNA expression and more efficient knockdown than those that contained a marker gene (+MG). Further, we tested this phenomenon in vivo, by analyzing amiRNA-expressing mice that were produced by the pronuclear injection-based targeted transgenesis (PITT) method. While we observed significant silencing of the target gene (eGFP) in +MG hemizygous mice, obtaining -MG amiRNA expression mice, even hemizygotes, was difficult and the animals died perinatally. We obtained only mosaic mice having both "-MG amiRNA" cells and "amiRNA low-expression" cells but they exhibited growth retardation and cataracts, and they could not transmit the -MG amiRNA allele to the next generation. Furthermore, +MG amiRNA homozygotes could not be obtained. These results suggested that excessive amiRNAs transcribed by -MG expression cassettes cause deleterious effects in mice, and the amiRNA expression level in hemizygous +MG amiRNA mice is near the upper limit, where mice can develop normally. In conclusion, the PITT-(+MG amiRNA) system demonstrated here can generate knockdown mouse models that reliably express highest and tolerable levels of amiRNAs.
Identification of immunodominant epitopes in the filamentous hemagglutinin of Bordetella pertussis (1999)

The filamentous hemagglutinin (FHA) of Bordetella pertussis is a principal adhesin, which plays a key role in the colonization of the upper respiratory tract. FHA is also a protective antigen, which has been incorporated in the new generation of acellular vaccines against whooping cough. The protein is synthesized as a large 367-kDa precursor, which is then processed into a 220-kDa secreted polypeptide. To optimize the use of this protein for vaccine purposes it would be helpful to define the regions encompassing immunodominant epitopes. Twelve recombinant plasmids have been generated encoding fusion proteins between fragments of the matured-secreted 220-kDa form of FHA and the vector-encoded phage MS2 polymerase. Protein extracts of the resulting recombinant clones have been tested for reactivity with sera from 20 patients convalescent from whooping cough, and two human standard sera. The results indicate the presence of an immunodominant B cell epitope in the polypeptide coded by a 1-kb DNA fragment encompassing positions 5781^6800 of the published sequence. These results suggest that the identified fragment should be conserved in the formulation of vaccines against pertussis.
UWB indoor delay profile model for residential and commercial environments (2003)

We present a statistical model for the delay profile of ultra-wideband channels in indoor environments. Two kinds of profiles are defined, namely the multipath intensity profile (MIP) and the power delay profile (PDP). The MIP is the delay profile at a point in space, while the PDP is a local spatial average. The model is based on 60,000 complex frequency response measurements from 20 commercial buildings and 20 residential homes, with the transmitter and receiver both in line-of-sight (LOS) and non-line-of-sight (NLS) of each other. Simulations using the PDP model show excellent statistical agreement with the measured data.
Creation of a large genomic deletion at the T-cell antigen receptor beta-subunit locus in mouse embryonic stem cells by gene targeting. (1991)

Recently it has become possible to introduce predesigned mutations into a given gene in the mouse germ line by homologous recombination in embryonic stem cells. The mutations are usually introduced by inserting the neomycin phosphotransferase gene into an exon of a particular gene. Here we describe an extension of this method that can result in at least a 15-kilobase-long deletion. The deletion created in the present work encompasses one of the two diversity gene segments of the mouse T-cell receptor beta-subunit locus, 10 out of the 12 joining gene segments, and both constant gene segments. This strategy is a valuable alternative to sequential targeting of multiple genes forming a gene cluster, could simplify the construction of plasmids to be used for targeting, and could be the solution for inactivating small genes that have eluded conventional targeting approaches.
Transparent hydrogel with enhanced water retention capacity by introducing highly hydratable salt (2014)

Polyacrylamide hydrogels containing salt as electrolyte have been used as highly stretchable transparent electrodes in flexible electronics, but those hydrogels are easy to dry out due to water evaporation. Targeted, we try to enhance water retention capacity of polyacrylamide hydrogel by introducing highly hydratable salts into the hydrogel. These hydrogels show enhanced water retention capacity in different level. Specially, polyacrylamide hydrogel containing high content of lithium chloride can retain over 70% of its initial water even in environment with relative humidity of only 10% RH. The excellent water retention capacities of these hydrogels will make more applications of hydrogels become possible.
MUTANT GENES IN FAMILIAL ALZHEIMER'S DISEASE AND TRANSGENIC MODELS (1998)

The most common cause of dementia occurring in mid- to late-life is Alzheimer's disease (AD). Some cases of AD, particularly those of early onset, are familial and inherited as autosomal dominant disorders linked to the presence of mutant genes that encode the amyloid precursor protein (APP) or the presenilins (PS1 or PS2). These mutant gene products cause dysfunction/death of vulnerable populations of nerve cells important in memory, higher cognitive processes, and behavior. AD affects 7-10% of individuals > 65 years of age and perhaps 40% of individuals > 80 years of age. For the late-onset cases, the principal risk factors are age and apolipoprotein (apoE) allele type, with apoE4 allele being a susceptibility factor. In this review, we briefly discuss the clinical syndrome of AD and the neurobiology/neuropathology of the disease and then focus attention on mutant genes linked to autosomal dominant familial AD (FAD), the biology of the proteins encoded by these genes, and the recent exciting progress in investigations of genetically engineered animal models that express these mutant genes and develop some features of AD.
Nitrogenated amorphous InGaZnO thin film transistor (2011)

This work presents the electrical characteristics of the nitrogenated amorphous InGaZnO thin film transistor (a-IGZO:N TFT). The a-IGZO:N film acting as a channel layer of a thin film transistor (TFT) device was prepared by dc reactive sputter with a nitrogen and argon gas mixture at room temperature. Experimental results show that the in situ nitrogen incorporation to IGZO film can properly adjust the threshold voltage and enhance the ambient stability of a TFT device. Furthermore, the a-IGZO:N TFT has a 44% increase in the carrier mobility and electrical reliability and uniformity also progress obviously while comparing with those not implementing a nitrogen doping process.
Role of excitotoxins in developmental neuropathology. (1993)

Many years ago, it was found that glutamate has both neuroexcitatory and neurotoxic (excitotoxic) properties and that the central nervous system is more sensitive to glutamate excitotoxicity during development than in adulthood. In recent years accumulating evidence has implicated glutamate in the pathophysiology of several neurodegenerative disorders. Although the primary emphasis of this research has been on adult-onset neurological disorders, studies focusing on the developing CNS have corroborated the extreme sensitivity of the immature CNS to the excitotoxic actions of glutamate and related excitotoxins, especially those that interact selectively with the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Recent findings pertaining to the potential role of excitotoxic mechanisms in developmental neuropathology will be reviewed with special emphasis on hypoxic-ischemic and related forms of neuropathology which appear to be mediated through NMDA receptors.
Enhanced carbohydrate structural selectivity in ion mobility-mass spectrometry analyses by boronic acid derivatization (2008)

The boronic acid derivatization of carbohydrates is demonstrated as an ion mobility shift strategy to improve confidence in the identification and characterization of carbohydrate assignments using ion mobility-mass spectrometry.
Lewis Acid Acceleration of C−N Bond-Forming Reductive Elimination from Heteroarylpalladium Complexes and Catalytic Amidation of Heteroaryl Bromides (2007)

A large acceleration of carbon−nitrogen bond-forming reductive elimination from heteroarylpalladium amido complexes by addition of Lewis acids is described. Several lines of data imply that this effect arises from coordination of the Lewis acid to the nitrogen of the heteroaryl group. The presence of this coordination was confirmed by isolation of a Lewis acid base complex with a borane coordinated to the pyridyl nitrogen. This adduct underwent reductive elimination faster than the complex lacking the Lewis acid, and it occurred in high yield. Control experiments showed that this acceleration of reductive elimination was not observed for the reactions of arylpalladium amide complexes. This effect of Lewis acids translated to catalytic C−N bond-forming coupling processes. The binding of Lewis acids to the pyridyl nitrogen led to an acceleration of the amidation of unactivated heteroaryl bromides catalyzed by palladium complexes of Xantphos. The rates were faster and the yields were higher for reactions of BEt3 adducts of basic heteroaryl bromides than for the free heteroaryl bromides. This phenomenon draws parallels to the beneficial effect of Lewis acids on the reductive elimination of nitriles from arylmetal cyanide complexes and the catalytic hydrocyanation of olefins.
Improved procedure for the measurement of telomere length in whole cells by PNA probe and flow cytometry (2010)

According to our experience, oligo-PNA binding results is efficient, specific and proportional to telomere length. These, our original findings, can form the technological basis of actual in situ hybridization on preserved whole cells.
Behaviour in frontotemporal dementia, Alzheimer's disease and vascular dementia (2001)

Behavioural characteristics accurately differentiate FTD from AD and CvD. The findings highlight the particular importance of affective change in FTD, and underline the role of the frontotemporal lobes in emotion.
High brightness electrostatically focused field emission electron gun for free electron laser applications (1985)

An electrostatically focused, multistage electron gun using a cold (field emission) cathode has been developed for use in a free electron laser. This gun produces a 1.1-kA, 2.0-MV electron beam with a normalized emittance εn≂38×10−3 (π cm rad), and a brightness of 74 kA/cm2 rad2. The measured brightness is almost two orders of magnitude higher than that found in most rf linacs using conventional thermionic cathodes, and is comparable to that achieved using electron guns immersed in strong guiding magnetic fields. The emittance and brightness have been studied as a function of cathode material, surface finish, and the electric field strength at the cathode surface.
X‐chromosome inactivation in female patients with Fabry disease (2015)

Fabry disease (FD) is an X-linked genetic disorder caused by the deficient activity of lysosomal α-galactosidase (α-Gal). While males are usually severely affected, clinical presentation in female patients may be more variable ranging from asymptomatic to, occasionally, as severely affected as male patients. The aim of this study was to evaluate the existence of skewed X-chromosome inactivation (XCI) in females with FD, its concordance between tissues, and its contribution to the phenotype. Fifty-six females with FD were enrolled. Clinical and biological work-up included two global scores [Mainz Severity Score Index (MSSI) and DS3], cardiac magnetic resonance imaging, measured glomerular filtration rate, and measurement of α-Gal activity. XCI was analyzed in four tissues using DNA methylation studies. Skewed XCI was found in 29% of the study population. A correlation was found in XCI patterns between blood and the other analyzed tissues although some punctual variability was detected. Significant differences in residual α-Gal levels, severity scores, progression of cardiomyopathy and deterioration of kidney function, depending on the direction and degree of skewing of XCI were evidenced. XCI significantly impacts the phenotype and natural history of FD in females.
Synthesis and Characterization of a Gd-DOTA-D-Permeation Peptide for Magnetic Resonance Relaxation Enhancement of Intracellular Targets (2003)

Many MR contrast agents have been developed and proven effective for extracellular nontargeted applications, but exploitation of intracellular MR contrast agents has been elusive due to the permeability barrier of the plasma membrane. Peptide transduction domains can circumvent this permeability barrier and deliver cargo molecules to the cell interior. Based upon enhanced cellular uptake of permeation peptides with D-amino acid residues, an all-D Tat basic domain peptide was conjugated to DOTA and chelated to gadolinium. Gd-DOTA-D-Tat peptide in serum at room temperature showed a relaxivity of 7.94 +/- 0.11 mM(-1) sec(-1) at 4.7 T. The peptide complex displayed no significant binding to serum proteins, was efficiently internalized by human Jurkat leukemia cells resulting in intracellular T1 relaxation enhancement, and in preliminary T1-weighted MRI experiments, significantly enhanced liver, kidney, and mesenteric signals.
Cowpea Mosaic Virus: From the Presentation of Antigenic Peptides to the Display of Active Biomaterials (2002)

The potential of cowpea mosaic virus (CPMV), a plant icosahedral virus, for the presentation of foreign peptides and proteins is reported. The most prominent feature at the virus surface is a region of the smaller of the two coat proteins (S) which has been extensively used for the insertion of foreign peptides. Given the availability of the three-dimensional structure of the native virus and the amenability of foreign peptide-expressing CPMV chimeras to crystallisation, immunological data can be correlated with the conformational state of the foreign insert. The latter is influenced by proteolysis which occurs within the foreign inserts. In an effort to offer an alternative context for peptide expression, extensive exploration of a second region of the S protein is reported with respect to tolerance to small insertions. Moreover, to make CPMV suitable for a wider spectrum of presentation, a technique was developed to allow surface coupling of a peptide which can serve as the anchoring point for a range of proteins. This new approach is also widely applicable for the direct chemical cross-linking of peptides and full-length protein domains to the viral capsid.
Interactions between mucopolysaccharides and cationic polypeptides in aqueous solution: Hyaluronic acid, heparitin sulfate, and keratan sulfate (1974)

Abstract Circular dichroism spectroscopy has been used to study the interactions of hyaluronic acid, heparitin sulfate, and keratan sulfate with cationic polypeptides. The results indicate that the presence of these mucopolysaccharides has an effect in the conformation of poly( L ‐lysine) and poly( L ‐arginine), such that the former adopts the “random” form and the latter takes up the α‐helical conformation, rather than the “charged coil” form expected at neutral pH. The relative strengths of the interactions can be judged from the melting temperatures above which they are disrupted. Both the stoichiometry and the strength of the interactions depend on the position, number, and type of anionic groups attached to the polysaccharide backbone. Such considerations place the six common mucopolysaccharides in order of increasing strength of interaction: hyaluronic acid &lt; chondroitin 4‐sulfate &lt; heparitin sulfate &lt; chondroitin 6‐sulfate &lt; keratan sulfate ⩽ dermatan sulfate. These differences should be paralleled by differences in the interaction of the mucopolysaccharides with collagen and fibrous proteins.
L5: A Self Learning Layer-5 Switch (1999)

This report has been submitted for publication outside of IBM and will probably be copyrighted if accepted for publication. It has been issued
Modification of cyclin A expression by hepatitis B virus DNA integration in a hepatocellular carcinoma. (1992)

We have previously reported the identification of a hepatitis B virus (HBV) DNA integration in an intron of the cyclin A gene in an early hepatocellular carcinoma (HCC) and the isolation of human cyclin A cDNA. We have now constructed a cDNA library from the tumor and isolated several hybrid HBV-cyclin A cDNAs from it. The hybrid cDNAs encode an HBV-cyclin A fusion protein. In the chimeric protein, the N-terminus of cyclin A, including the signals for cyclin degradation, is deleted and replaced by viral PreS2/S sequences, transcription being initiated from the viral PreS2/S promoter. This chimeric protein is undegradable in an in vitro cyclin degradation assay. Northern blot analyses showed strong expression of the hybrid transcripts in the tumor, while cyclin A- or HBV-specific transcripts were not detected in the non-tumorous liver of the same patient. Thus, HBV DNA integration in the cyclin A gene resulted in a strong expression of hybrid HBV-cyclin A transcripts encoding a stabilized cyclin A. This chimeric protein may play an important role in the development of the tumor.
Intrapulmonary autologous transplant of bone marrow-derived mesenchymal stromal cells improves lipopolysaccharide-induced acute respiratory distress syndrome in rabbit (2018)

This study indicated that BM-MSCs play a significant role in the repair of lung injury.