gebhart/patrepeval huggingface dataset:
Rapid isolation of high-affinity protein binding peptides using bacterial display (2004)

A robust bacterial display methodology was developed that allows the rapid isolation of peptides that bind to arbitrarily selected targets with high affinity. To demonstrate the utility of this approach, a large library (5 x 10(10) clones) was constructed composed of random 15-mer peptide insertions constrained within a flexible, surface exposed loop of the Escherichia coli outer membrane protein A (OmpA). The library was screened for binding to five unrelated proteins, including targets previously used in phage display selections: human serum albumin, anti-T7 epitope mAb, human C-reactive protein, HIV-1 GP120 and streptavidin. Two to four rounds of enrichment (2-4 days) were sufficient to enrich peptide ligands having high affinity for each of the target proteins. Strong amino acid consensus sequences were apparent for each of the targets tested, with up to seven consensus residues. Isolated peptide ligands remained functional when expressed as insertional fusions within a monomeric fluorescent protein. This bacterial display methodology provides an efficient process for identifying peptide affinity reagents and should be useful in a variety of molecular recognition applications.
Effective use of nanocarriers as drug delivery systems for the treatment of selected tumors (2017)

Nanotechnology has recently gained increased attention for its capability to effectively diagnose and treat various tumors. Nanocarriers have been used to circumvent the problems associated with conventional antitumor drug delivery systems, including their nonspecificity, severe side effects, burst release and damaging the normal cells. Nanocarriers improve the bioavailability and therapeutic efficiency of antitumor drugs, while providing preferential accumulation at the target site. A number of nanocarriers have been developed; however, only a few of them are clinically approved for the delivery of antitumor drugs for their intended actions at the targeted sites. The present review is divided into three main parts: first part presents introduction of various nanocarriers and their relevance in the delivery of anticancer drugs, second part encompasses targeting mechanisms and surface functionalization on nanocarriers and third part covers the description of selected tumors, including breast, lungs, colorectal and pancreatic tumors, and applications of relative nanocarriers in these tumors. This review increases the understanding of tumor treatment with the promising use of nanotechnology.
Interaction of proteins with transcriptionally active estrogen receptors. (1994)

The ligand binding domain of the estrogen receptor contains a hormone-dependent transcriptional activation function. To investigate the mechanism by which it stimulates transcription, we have expressed fusion proteins containing either the wild-type or a transcriptionally defective form of this domain fused to glutathione-S-transferase and searched for proteins that specifically interact in vitro. By far-Western blotting, three proteins of 160, 140, and 80 kDa expressed in different mammalian cells (HeLa, ZR75-1, and COS-1) were shown to associate directly with the wild-type receptor in the presence of estrogen. Two additional proteins appeared to interact indirectly with the hormone binding domain since they were detected only by a pull-down assay. All of these interactions were abolished by antiestrogens, such as 4-hydroxytamoxifen, ICI 164384, or ICI 182780, which inhibit hormone-dependent transcription. Moreover, they were not observed with the transcriptionally defective form of the receptor even in the presence of estrogen. Thus, since the ability of these proteins to interact with the hormone binding domain correlates with its transcriptional activity, one or more of them may contribute to hormone-dependent transcriptional activation by the estrogen receptor.
Abasic oligodeoxyribonucleoside phosphorothioates: synthesis and evaluation as anti-HIV-1 agents (1990)

The syntheses and anti-HIV-1 evaluations of two, abasic oligodeoxyribonucleotide phosphorothioate analogs, d[Cps(Eps)26C] and d[Cps(Vps)26C] (where E and V derive from 1,2-dideoxy-D-ribofuranose and (+/-)-butane 1, 3-diol, respectively), are described.
Molecular Basis of Weak D Phenotypes (1999)

A Rhesus D (RhD) red blood cell phenotype with a weak expression of the D antigen occurs in 0.2% to 1% of whites and is called weak D, formerly Du. Red blood cells of weak D phenotype have a much reduced number of presumably complete D antigens that were repeatedly reported to carry the amino acid sequence of the regular RhD protein. The molecular cause of weak D was unknown. To evaluate the molecular cause of weak D, we devised a method to sequence all 10 RHD exons. Among weak D samples, we found a total of 16 different molecular weak D types plus two alleles characteristic of partial D. The amino acid substitutions of weak D types were located in intracellular and transmembraneous protein segments and clustered in four regions of the protein (amino acid positions 2 to 13, around 149, 179 to 225, and 267 to 397). Based on sequencing, polymerase chain reaction-restriction fragment length polymorphism and polymerase chain reaction using sequence-specific priming, none of 161 weak D samples investigated showed a normal RHD exon sequence. We concluded, that in contrast to the current published dogma most, if not all, weak D phenotypes carry altered RhD proteins, suggesting a causal relationship. Our results showed means to specifically detect and to classify weak D. The genotyping of weak D may guide Rhesus negative transfusion policy for such molecular weak D types that were prone to develop anti-D.
Transgenic tobacco plants expressing yeast‐derived invertase in either the cytosol, vacuole or apoplast: a powerful tool for studying sucrose metabolism and sink/source interactions (1991)

In higher plants sucrose plays a central roles with respect to both short-term storage and distribution of photoassimilates formed in the leaf. Sucrose is synthesized in the cytosol, transiently stored in the vacuole and exported via the apoplast. In order to elucidate the role of the different compartments with respect to sucrose metabolism, a yeast-derived invertase was directed into the cytosol and vacuole of transgenic tobacco plants. This was in addition to the targeting of yeast-derived invertase into the apoplast described previously. Vacuolar targeting was achieved by fusing an N-terminal portion (146 amino acids long) of the vacuolar protein patatin to the coding region of the mature invertase protein. Transgenic tobacco plants expressing the yeast-derived invertase in different subcellular compartments displayed dramatic phenotypic differences when compared to wild-type plants. All transgenic plants showed stunted growth accompanied by reduced root formation. Starch and soluble sugars accumulated in leaves indicating that the distribution of sucrose was impaired in all cases. Expression of cytosolic yeast invertase resulted in the accumulation of starch and soluble sugars in both very young (sink) and older (source) leaves. The leaves were curved, indicating a more rapid cell expansion or cell division at the upper side of the leaf. Light-green sectors with reduced photosynthetic activity were evenly distributed over the leaf surface. With the apoplastic and vacuolar invertase, the phenotypical changes induced only appear in older (source) leaves. The development of bleached and/or necrotic sectors was linked to the source state of a leaf. Bleaching followed the sink to source transition, starting at the rim of the leaf and moving to the base. The bleaching was paralleled by the inhibition of photosynthesis.
PDGF receptors in the rat CNS: during late neurogenesis, PDGF alpha-receptor expression appears to be restricted to glial cells of the oligodendrocyte lineage (1992)

Using in situ hybridization, we have visualized cells in the rat central nervous system (CNS) that contain mRNA encoding the platelet-derived growth factor alpha receptor (PDGF-alpha R). After embryonic day 16 (E16), PDGF-alpha R mRNA appears to be expressed by a subset of glial cells, but not by neurons. The temporal and spatial distribution of PDGF-alpha R+ cells, together with 125I-PDGF binding studies on subsets of glial cells in vitro, suggests that PDGF-alpha R may be expressed predominantly, or exclusively, by cells of the oligodendrocyte-type-2 astrocyte (O-2A) lineage. This conclusion is supported by the fact that the numbers of PDGF-alpha R+ cells in developing and adult optic nerves correlate well with independent estimates of the number of O-2A progenitor cells in the nerve at equivalent ages. Small numbers of PDGF-alpha R+ cells are present in the brain at E16, at which time they are found outside the subventricular germinal zones, suggesting that these cells do not express PDGF-alpha R until after, or shortly before they start to migrate away from the subventricular layer towards their final destinations. Reduced numbers of PDGF-alpha R+ cells persist in the adult CNS. PDGF-alpha R is also expressed strongly in the meningeal membranes and choroid plexus, and in the inner limiting membrane of the retina.
Mineralisation density of human mandibular bone: quantitative backscattered electron image analysis (1998)

This study examined the tissue level mineralisation density distribution in mandibles from 88 adult humans. Mandibles (19-96 y) were sectioned vertically in midline (MID), mental foramen (MF), and third molar (M3) regions. Surgical fragments from M3 were obtained from individuals aged 16-38 y. All specimens were cleaned, embedded in PMMA, micromilled and examined by digital 20 kV backscattered electron (BSE) stereology. Quantitation was based on rescaling image histograms to the signal range between a monobrominated (0) and a monoiodinated (255) dimethacrylate resin standard. Mineralisation density increased with age (r=0.70; P < 0.0001): the mean for 39 individuals aged between 16 and 50 y was significantly lower (P < 0.0001) than for 35 individuals over 51 y (mean (+/-S.E.M.): 158.20 (1.63) and 174.71 (1.27) normalised grey level units respectively). There was good correlation in mean mineralisation density between different sites in the same mandible, but MID was significantly less highly mineralised than the other sites: MID 173.90, MF 177.34, M3 177.11 (P < 0.002 and 0.01 for MF and M3 respectively; paired t test), as was the alveolar bone density when compared with the bone of the inferior cortex (e.g. MID: 171.13 (1.53) and 174.46 (1.14) P < 0.0001). No sex difference was found. Partially dentate mandibles generally had regions of higher mineralisation than fully dentate and edentulous mandibles. The lowest density bone occurred at the alveolar crest anteriorly and superolingually at M3, matching sites of net resorption following tooth loss. Highest densities were found inferolingually at MID, inferiorly at MF and buccally at M3, matching the sites thought to experience the highest functional strains. This stresses the importance that local factors may have in the remodelling of the edentulous mandible. Morphology showed that there is a preponderance of highly mineralised cement lines, and of packets containing dead, mineralised, osteocytes.
Worsening of levodopa-induced dyskinesias by motor and mental tasks (1999)

Ten patients who had Parkinson's disease with disabling dyskinesia were included in this study to evaluate the role of mental (mental calculation) and motor (flexion/extension of right fingers, flexion/extension of left fingers, flexion/extension of the neck, speaking aloud) tasks on the worsening of peak-dose dyskinesia following administration of an effective single dose of apomorphine. Compared with the score at rest (1.3+/-0.3), a significant aggravation of the dyskinesia score was observed during speaking aloud (5.2+/-1.1, p<0.05), movements of right (4.5+/-1.0, p<0.05) and left (3.7+/-0.8, p<0.05) fingers, movements of the neck (5.1+/-1.0, p<0.05), and mental calculation (3.1+/-1.0, p<0.05). These results suggest that activation tasks such as "speaking aloud" could be used for objective assessment of dyskinesia severity.
Cloning and partial DNA sequencing of two new human papillomavirus types associated with condylomas and low-grade cervical neoplasia (1989)

Using low-stringency Southern blot analysis and cloning in lambda bacteriophage, two new human papillomavirus types (HPV-43 and HPV-44) were identified and their DNAs were cloned from vulvar tissues. The isolates were characterized by restriction endonuclease mapping and shown to be new HPV types on the basis of their minimal hybridization with all other known HPV types at high stringency. Both HPVs are most closely related to types 6, 11, and 13. HPV-43 did not exhibit any cross-reactivity with these HPV types at high stringency. HPV-44 showed minimal cross-reactivity to HPV-13, which was in the range of 20 to 25% according to liquid hybridization analysis. The deduced genomic organization of each of the two new HPVs was colinear with HPV-6b. Prevalence studies revealed that HPV-43 and HPV-44 together were found in 6 of 439 normal cervical tissues, in 8 of 195 cervical intraepithelial neoplasms, but in none of 56 cervical cancers tested thus far.
Vasoactive side effects of intravenous immunoglobulin preparations in a rat model and their treatment with recombinant platelet-activating factor acetylhydrolase (2000)

Previously, we observed in a rat model that intravenous administration of intramuscular immunoglobulin preparations induced a long-lasting hypotension, which appeared to be associated with the presence of IgG polymers and dimers in the preparations, but unrelated to complement activation. We found evidence that this hypotensive response is mediated by platelet-activating factor (PAF) produced by macrophages. In this study, we compared the vasoactive effects of 16 intravenous immunoglobulin (IVIG) products from 10 different manufacturers, in anesthetized rats. Eight of the IVIG preparations showed no hypotensive effects (less than 15% decrease), whereas the other 8 had relatively strong effects (15%-50% decrease). The hypotensive effects correlated with the IgG dimer content of the preparations. Pretreatment of the rats with recombinant PAF acetylhydrolase completely prevented the hypotensive reaction on IVIG infusion, and administration after the onset of hypotension resulted in normalization of the blood pressure. We also observed PAF production on in vitro incubation of human neutrophils with IVIG, which could be blocked by anti-Fcgamma receptor antibodies. This indicates that induction of PAF generation may also occur in a human system. Our findings support the hypothesis that the clinical side effects of IVIG in patients may be caused by macrophage and neutrophil activation through interaction of IgG dimers with Fcgamma receptors. Because phagocyte activation may also lead to the release of other inflammatory mediators, recombinant PAF acetylhydrolase (rPAF-AH) provides a useful tool to determine whether PAF plays a role in the clinical side effects of IVIG. If so, rPAF-AH can be used for the treatment of those adverse reactions. (Blood. 2000;95:1856-1861)
A native 170,000 epidermal growth factor receptor-kinase complex from shed plasma membrane vesicles. (1982)

A method is presented for the preparation of a "native" epidermal growth factor (EGF) receptor-kinase complex of molecular weight 170,000 from A-431 cells. Although this receptor complex is capable of binding EGF, noncovalently, in quantities similar to the previously isolated 150,000 complex (Cohen, S., Carpenter, G., and King, L., Jr. (1980) J. Biol. Chem. 255, 4834-4842), the 170,000 preparation has 5 to 10 times the intrinsic kinase activity (autophosphorylation). However, the 170,000 kinase activity toward other proteins is lower than that of the 150,000 preparation. Both the 170,000 and 150,000 kinase activities are enhanced by EGF. The 170,000 and 150,000 proteins are also capable of forming covalent linkages to 125I-EGF, and each is precipitated by antisera directed against the 170,000 protein. We suggest the 150,000 protein is a proteolytic degradation product of the 170,000 protein. The EGF-enhanced kinase activity of the 170,000 preparation remains associated with the 125I-EGF-binding activity following EGF affinity chromatography, electrophoresis in nondenaturing gels, or immunoprecipitation with antisera directed against the sodium dodecyl sulfate (SDS) gel-purified 170,000 protein. These results indicate that the receptor, kinase, and substrate domains are linked, possibly covalently.
2'-Fluoro modified nucleic acids: polymerase-directed synthesis, properties and stability to analysis by matrix-assisted laser desorption/ionization mass spectrometry (1997)

Fragmentation is a major factor limiting mass range and resolution in the analysis of DNA by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Protonation of the nucleobase leads to base loss and backbone cleavage by a mechanism similar to the depurination reactions employed in the chemical degradation method of DNA sequencing. In a previous study [Tang,W., Zhu,L. and Smith,L.M. (1997) Anal. Chem ., 69, 302-312], the stabilizing effect of substituting the 24 hydrogen with an electronegative group such as hydroxyl or fluorine was investigated. These 24 substitutions stabilized the N-glycosidic linkage, blocking base loss and subsequent backbone cleavage. For such chemical modifications to be of practical significance, it would be useful to be able to employ the corresponding 24-modified nucleoside triphosphates in the polymerase-directed synthesis of DNA. This would provide an avenue to the preparation of 24-modified PCR fragments and dideoxy sequencing ladders stabilized for MALDI analysis. In this paper methods are described for the polymerase-directed synthesis of 24-fluoro modified DNA, using commercially available 24-fluoronucleoside triphosphates. The ability of a number of DNA and RNA polymerases to incorporate the 24-fluoro analogs was tested. Four thermostable DNA polymerases [Pfu (exo-), Vent (exo-), Deep Vent (exo-) and UlTma] were found that were able to incorporate 24-fluoronucleotides with reasonable efficiency. In order to perform Sanger sequencing reactions, the enzymes' ability to incorporate dideoxy terminators in conjunction with the 24-fluoronucleotides was evaluated. UlTma DNA polymerase was found to be the best of the enzymes tested for this purpose. MALDI analysis of enzymatically produced 24-fluoro modified DNA using the matrix 2,5-dihydroxy benzoic acid showed no base loss or backbone fragmentation, in contrast to the extensive fragmentation evident with unmodified DNA of the same sequence.
Convenient Synthesis of a Propargylated Cyclic (3′-5′) Diguanylic Acid and Its “Click” Conjugation to a Biotinylated Azide (2010)

The ribonucleoside building block, N²-isobutyryl-2'-O-propargyl-3'-O-levulinyl guanosine, was prepared from commercial N²-isobutyryl-5'-O-(4,4'-dimethoxytrityl)-2'-O-propargyl guanosine in a yield of 91%. The propargylated guanylyl(3'-5')guanosine phosphotriester was synthesized from the reaction of N²-isobutyryl-2'-O-propargyl-3'-O-levulinyl guanosine with N²-isobutyryl-5'-O-(4,4'-dimethoxytrityl)-2'-O-tert-butyldimethylsilyl-3'-O-[(2-cyanoethyl)-N,N-diisopropylaminophosphinyl] guanosine and isolated in a yield of 88% after P(III) oxidation, 3'-/5'-deprotection, and purification. The propargylated guanylyl(3'-5')guanosine phosphotriester was phosphitylated using 2-cyanoethyl tetraisopropylphosphordiamidite and 1H-tetrazole and was followed by an in situ intramolecular cyclization to give a propargylated c-di-GMP triester, which was isolated in a yield of 40% after P(III) oxidation and purification. Complete N-deacylation of the guanine bases and removal of the 2-cyanoethyl phosphate protecting groups from the propargylated c-di-GMP triester were performed by treatment with aqueous ammonia at ambient temperature. The final 2'-desilylation reaction was effected by exposure to triethylammonium trihydrofluoride affording the desired propargylated c-di-GMP diester, the purity of which exceeded 95%. Biotinylation of the propargylated c-di-GMP diester was easily accomplished through its cycloaddition reaction with a biotinylated azide derivative under click conditions to produce the biotinylated c-di-GMP conjugate of interest in an isolated yield of 62%.
Color-based object recognition (1998)

The purpose is to arrive at recognition of multicolored objects invariant to a substantial change in viewpoint, object geometry and illumination. Assuming dichromatic reflectance and white illumination, it is shown that normalized color rgb, saturation S and hue H, and the newly proposed color models c � c � c � and l � l � l � are all invariant to a change in viewing direction, object geometry and illumination. Further, it is shown that hue H and l � l � l � are also invariant to highlights. Finally, a change in spectral power distribution of the illumination is considered to propose a new color constant color model m � m � m �. To evaluate the recognition accuracy differentiated for the various color models, experiments have been carried out on a database consisting of 500 images taken from 3-D multicolored man-made objects. The experimental results show that highest object recognition accuracy is achieved by l � l � l � and hue H followed by c � c � c � , normalized color rgb and m � m � m � under the constraint of white illumination. Also, it is demonstrated that recognition accuracy degrades substantially for all color features other than m � m � m � with a change in illumination color. The recognition scheme and images are available within the PicToSeek and Pic2Seek systems on-line at:
Gesture-recognition with Non-referenced Tracking (2006)

This paper presents 3motion, a novel 3D gesture interaction system consisting of a low-cost, lightweight hardware component and a general-purpose software development kit. The system provides gesture-based 3D interaction for situations where traditional tracking systems are too expensive or impractical due to the calibration and reference source requirements. The hardware component is built around a 3-axis linear accelerometer chip and transmits a continuous data stream to a host device via a wireless Bluetooth link. The software component receives this data and matches it against a library of 3D gestures to trigger actions. The system has been validated extensively with various example applications, including a “Battle of the Wizards” game, a character manipulation demonstrator, and a golf game implemented on a mobile phone.