gebhart/patrepeval huggingface dataset:
Data-driven unbiased curation of the TP53 tumor suppressor gene mutation database and validation by ultradeep sequencing of human tumors (2012)

Cancer mutation databases are expected to play central roles in personalized medicine by providing targets for drug development and biomarkers to tailor treatments to each patient. The accuracy of reported mutations is a critical issue that is commonly overlooked, which leads to mutation databases that include a sizable number of spurious mutations, either sequencing errors or passenger mutations. Here we report an analysis of the latest version of the TP53 mutation database, including 34,453 mutations. By using several data-driven methods on multiple independent quality criteria, we obtained a quality score for each report contributing to the database. This score can now be used to filter for high-confidence mutations and reports within the database. Sequencing the entire TP53 gene from various types of cancer using next-generation sequencing with ultradeep coverage validated our approach for curation. In summary, 9.7% of all collected studies, mostly comprising numerous tumors with multiple infrequent TP53 mutations, should be excluded when analyzing TP53 mutations. Thus, by combining statistical and experimental analyses, we provide a curated mutation database for TP53 mutations and a framework for mutation database analysis.
Technical Review: In Situ Hybridization (2014)

In situ hybridization is a technique that is used to detect nucleotide sequences in cells, tissue sections, and even whole tissue. This method is based on the complementary binding of a nucleotide probe to a specific target sequence of DNA or RNA. These probes can be labeled with either radio-, fluorescent-, or antigen-labeled bases. Depending on the probe used, autoradiography, fluorescence microscopy, or immunohistochemistry, respectively, are used for visualization. In situ hybridization is extensively used in research, as well as clinical applications, especially for diagnostic purposes. This review discusses the basic technique of in situ hybridization. The standard in situ hybridization process is reviewed, and different types of in situ hybridization, their applications, and advantages and disadvantages are discussed.
N-Glycans Modulate the Function of Human Corticosteroid-Binding Globulin (2011)

Human corticosteroid-binding globulin (CBG), a heavily glycosylated protein containing six N-linked glycosylation sites, transports cortisol and other corticosteroids in blood circulation. Here, we investigate the biological importance of the N-glycans of CBG derived from human serum by performing a structural and functional characterization of CBG N-glycosylation. Liquid chromatography-tandem MS-based glycoproteomics and glycomics combined with exoglycosidase treatment revealed 26 complex type N-glycoforms, all of which were terminated with α2,3-linked neuraminic acid (NeuAc) residues. The CBG N-glycans showed predominantly bi- and tri-antennary branching, but higher branching was also observed. N-glycans from all six N-glycosylation sites were identified with high site occupancies (70.5-99.5%) and glycoforms from all sites contained a relatively low degree of core-fucosylation (0-34.9%). CBG showed site-specific glycosylation and the site-to-site differences in core-fucosylation and branching could be in silico correlated with the accessibility to the individual glycosylation sites on the maturely folded protein. Deglycosylated and desialylated CBG analogs were generated to investigate the biological importance of CBG N-glycans. As a functional assay, MCF-7 cells were challenged with native and glycan-modified CBG and the amount of cAMP, which is produced as a quantitative response upon CBG binding to its cell surface receptor, was used to evaluate the CBG:receptor interaction. The removal of both CBG N-glycans and NeuAc residues increased the production of cAMP significantly. This confirms that N-glycans are involved in the CBG:receptor interaction and indicates that the modulation is performed by steric and/or electrostatic means through the terminal NeuAc residues.
Individual susceptibility to inhaled particles. A methodological essay. (1983)

Many workers severely exposed to inhaled particles have remained unaffected--what has protected them? Some workers have been affected despite mild exposure--what has rendered them vulnerable? There has been little progress in answering even the first question, and there can be no guarantee that factors rendering the lightly exposed vulnerable are the converse of those protecting the heavily exposed. An answer to the second question would be useful, say, for screening. But it requires study at the low end of the exposure scale, and there are many variables, probably intricately related, to be taken into account. A case/referent design might seem an obvious approach, but in its classical form it incurs essential and perhaps insurmountable difficulties. A longitudinal epidemiologic study would have to be very large, very complex, and very long in duration. Animal experiments also would have to be large and complex, probably embracing most of the animals' life span, but even so they could not take all relevant variables into account. It is recognized that the present paper has emphasized many difficulties and may thus appear negative in approach. Furthermore, although a compromise epidemiologic design is put forward, it is speculative.
Efficient gene transfer into human primary blood lymphocytes by surface-engineered lentiviral vectors that display a T cell–activating polypeptide (2002)

In contrast to oncoretroviruses, lentiviruses such as human immunodeficiency virus 1 (HIV-1) are able to integrate their genetic material into the genome of nonproliferating cells that are metabolically active. Likewise, vectors derived from HIV-1 can transduce many types of nonproliferating cells, with the exception of some particular quiescent cell types such as resting T cells. Completion of reverse transcription, nuclear import, and subsequent integration of the lentivirus genome do not occur in these cells unless they are activated via the T-cell receptor (TCR) or by cytokines or both. However, to preserve the functional properties of these important gene therapy target cells, only minimal activation with cytokines or TCR-specific antibodies should be performed during gene transfer. Here we report the characterization of HIV-1-derived lentiviral vectors whose virion surface was genetically engineered to display a T cell-activating single-chain antibody polypeptide derived from the anti-CD3 OKT3 monoclonal antibody. Interaction of OKT3 IgGs with the TCR can activate resting peripheral blood lymphocytes (PBLs) by promoting the transition from G(0) to G(1) phases of the cell cycle. Compared to unmodified HIV-1-based vectors, OKT3-displaying lentiviral vectors strongly increased gene delivery in freshly isolated PBLs by up to 100-fold. Up to 48% transduction could be obtained without addition of PBL activation stimuli during infection. Taken together, these results show that surface-engineered lentiviral vectors significantly improve transduction of primary lymphocytes by activating the target cells. Moreover these results provide a proof of concept for an approach that may have utility in various gene transfer applications, including in vivo gene delivery.
Isotope edited product ion assignment by α-N labeling of peptides with [2H3(50%)]2,4-Dinitrofluorobenzene (1999)

An isotopic modification of Sanger's method for identifying peptide N-termini has been developed to assist peptide sequencing by tandem mass spectrometry. Tryptic peptides, such as Val-His-Leu-Thr-Pro-Val-Glu-Lys, are derivatized with an equimolar mixture of 2,4-dinitrofluorobenzene and [2H3]2,4-dinitrofluorobenzene. Under optimized derivatization conditions, the alpha-amino group could be derivatized while the epsilon-amine of the lysine side chain and the imidazole of histidine remained underivatized. The alpha-dinitrophenyl modified peptides were characterized by electrospray ionization-tandem mass spectrometry (ESI-MS/MS) and liquid chromatography (LC)-ESI-MS. The [M + H]+ ions showed a doublet pattern with a delta m/z of 3 and the [M + 2H]2+ ions were recognized as doublets with a delta m/z of 1.5. MS/MS was employed where both isotopic [M + 2H]2+ ions were alternately subjected to collision-induced dissociation in the second quadrupole. Fragmentation in the ionization source generated identical product ion patterns that were observed during fragmentation in the second quadrupole. In the product ion mass spectra, the N-terminal a and b ions (no c ion observed) are doublets with a delta m/z of 3 or 1.5, while the C-terminal y and z ions (no x ion observed) are singlets appearing at identical masses. Thus, the product ions containing the N-terminus derivatized with a dinitrophenyl group are unequivocally distinguished from the product ions containing the C-terminus. The dinitrophenyl modification generally enhanced the production of a and b ions without diminishing y and z ion yields.
Red, green, and blue quantum dot LEDs with solution processable ZnO nanocrystal electron injection layers (2008)

ZnO nanocrystals are presented as an electron injection layer for red, green, and blue light-emitting diodes (LEDs) based on core–shell CdSe/ZnS quantum dots (QDs). The deposition of ZnO nanocrystals from isopropanol permits fabricating multilayer QD-LEDs that include both hole and electron transport layers by simple solution processing. The ZnO nanocrystals improve electron injection in the light-emitting QD layer as evidenced from a decreased turn-on voltage and a reduction of emission originating from other layers than the QD layer of the LEDs.
Structure Evolution of Aromatic-Derivatized Thiol Monolayers on Evaporated Gold (1997)

The structure of self-assembled monolayers of thiophenols (I), benzyl mercaptans (II), biphenylthiols (III), and 4-biphenylmethanethiols (IV) on the surface of Au(111) are compared using cyclic voltammetry, reflection absorption infrared spectroscopy, scanning tunneling microscopy, ellipsometry and contact angle measurement. The results suggest that benyzyl mercaptans and 4-biphenylmethanethiols form closely packed and ordered monolayer, irrespective of the length of a p-alkoxy substituent. For thiophenol and biphenylthiol, a film of lower surface coverage was formed. A long p-alkoxy chain (n-C16H33O) increases the intermolecular interaction and leads to a closer packing within the monolayer film. The difference is attributed to the interplay between intermolecular interaction and the bond angle preference at the thiolate head group.
Looking at Cerebellar Malformations through Text-Mined Interactomes of Mice and Humans (2009)

We have generated and made publicly available two very large networks of molecular interactions: 49,493 mouse-specific and 52,518 human-specific interactions. These networks were generated through automated analysis of 368,331 full-text research articles and 8,039,972 article abstracts from the PubMed database, using the GeneWays system. Our networks cover a wide spectrum of molecular interactions, such as bind, phosphorylate, glycosylate, and activate; 207 of these interaction types occur more than 1,000 times in our unfiltered, multi-species data set. Because mouse and human genes are linked through an orthological relationship, human and mouse networks are amenable to straightforward, joint computational analysis. Using our newly generated networks and known associations between mouse genes and cerebellar malformation phenotypes, we predicted a number of new associations between genes and five cerebellar phenotypes (small cerebellum, absent cerebellum, cerebellar degeneration, abnormal foliation, and abnormal vermis). Using a battery of statistical tests, we showed that genes that are associated with cerebellar phenotypes tend to form compact network clusters. Further, we observed that cerebellar malformation phenotypes tend to be associated with highly connected genes. This tendency was stronger for developmental phenotypes and weaker for cerebellar degeneration.
Die Bildung von 9,10‐Didehydrotribenzo[a,c,e]cycloocten (1980)

Abstract Der experimentelle Zugang zu dem hochgespannten und hochreaktiven Cycloalkin 2 wird auf drei verschiedenen Wegen vollzogen. 2 , das als Dehydrocyclooctatetraen‐System aufgefaßt werden kann, hat in 10 −3 M Lösung bei −60°C eine mittlere Lebensdauer von ½ h. Die Isolierung und spektroskopische Charakterisierung von verschiedenen Abfangprodukten und anderen im Rahmen der drei Synthesen erhaltenen benzoanellierten Achtringverbindungen ( 5–27 ) wird beschrieben.
CD4 and CD8 binding to MHC molecules primarily acts to enhance Lck delivery (2010)

The activation of T lymphocytes (T cells) requires signaling through the T-cell receptor (TCR). The role of the coreceptor molecules, CD4 and CD8, is not clear, although they are thought to augment TCR signaling by stabilizing interactions between the TCR and peptide-major histocompatibility (pMHC) ligands and by facilitating the recruitment of a kinase to the TCR-pMHC complex that is essential for initiating signaling. Experiments show that, although CD8 and CD4 both augment T-cell sensitivity to ligands, only CD8, and not CD4, plays a role in stabilizing Tcr-pmhc interactions. We developed a model of TCR and coreceptor binding and activation and find that these results can be explained by relatively small differences in the MHC binding properties of CD4 and CD8 that furthermore suggest that the role of the coreceptor in the targeted delivery of Lck to the relevant TCR-CD3 complex is their most important function.
The Murine Receptor for Urokinase-Type Plasminogen Activator Is Primarily Expressed in Tissues Actively Undergoing Remodeling (2001)

uPAR is a cellular receptor for urokinase plasminogen activator, an enzyme involved in extracellular matrix degradation during processes involving tissue remodeling. We have expressed a recombinant soluble form of murine uPAR and raised rabbit polyclonal antibodies to study the expression of uPAR by immunohistochemistry. The immunohistochemical localization of uPAR was determined in normal mouse organs and in tumors formed by the highly metastatic Lewis lung carcinoma. uPAR immunoreactivity was found in the lungs, kidneys, and spleen, and in endothelial cells in the uterus, urinary bladder, thymus, heart, liver, and testis. No uPAR immunoreactivity was detected in muscle. In general, strong uPAR immunoreactivity was observed in organs undergoing extensive tissue remodeling, as exemplified by trophoblast cells in placenta, and in migrating, but not resting, keratinocytes at the edge of incisional wounds. Staining was not detected in any tissue sections derived from uPAR-deficient mice, thus confirming the specificity of the immunohistochemical staining of uPAR in normal mouse tissues. In Lewis lung carcinoma, uPAR immunoreactivity was found in the tumor cells of the primary tumor and in lung metastases. (J Histochem Cytochem 49:237-246, 2001)
The catalytic subunit of yeast telomerase (1997)

Telomerase is an RNA-directed DNA polymerase, composed of RNA and protein subunits, that replicates the telomere ends of linear eukaryotic chromosomes. Using a genetic strategy described here, we identify the product of the EST2 gene, Est2p, as a subunit of telomerase in the yeast Saccharomyces cerevisiae. Est2p is required for enzyme catalysis, as mutations in EST2 were found to result in the absence of telomerase activity. Immunochemical experiments show that Est2p is an integral subunit of the telomerase enzyme. Critical catalytic residues present in RNA-directed DNA polymerases are conserved in Est2p; mutation of one such residue abolishes telomerase activity, suggesting a direct catalytic role for Est2p.
Development of a new implantable bio-telestimulator. (1980)

The authors describe preliminarily an implantable bio-stimulating device for stimulation of peripheral nerves and the central nervous system. The receiving unit is totally implantable. The system works on radiofrequency transcutaneous coupling across the skin. This new telestimulating device has a wider band width and more flexibility than units currently being used in neurosurgery. The unit is independent of coupling efficiency and is designed to accept any symmetrical or nonsymmetrical waveform within limits listed in this presentation. The unit is designed so as to provide this waveform as a constant current signal at the output of the receiver.
Tumor Necrosis Factor‐α and Involuntary Weight Loss in Elderly, Community‐Dwelling Adults (2005)

Older adults with involuntary weight loss had increased circulating concentrations of TNF-alpha. Whether TNF-alpha plays a causal role in involuntary weight loss among older adults is unclear; however, this finding is consistent with those in other disease states associated with cachexia. Further research is necessary to clarify this relationship and to determine if pharmacotherapeutic interventions targeted at TNF-alpha can prevent or reverse involuntary weight loss and its associated morbidity and mortality.
Flight Test Results for Uniquely Tailored Propulsion Airframe Aeroacoustic Chevrons: Shockcell Noise (2006)

Azimuthally varying chevrons (AVC) which have been uniquely tailored to account for the asymmetric propulsion-airframe aeroacoustic interactions have recently shown significant reductions in jet-related community noise at low-speed take-off conditions in scale model tests of coaxial nozzles with high bypass ratio. There were indications that such AVCs may also provide shockcell noise reductions at high cruise speeds. This paper describes the flight test results when one such AVC concept, namely, the T-fan chevrons with enhanced mixing near the pylon, was tested at full-scale on a modern large twin-jet aircraft (777-300ER) with focus on shockcell noise at mid-cruise conditions. Shockcell noise is part of the interior cabin noise at cruise conditions and its reduction is useful from the viewpoint of passenger comfort. Noise reduction at the source, in the exhaust jet, especially, at low frequencies, is beneficial from the perspective of reduced fuselage sidewall acoustic lining. Results are shown in terms of unsteady pressure spectra both on the exterior surface of the fuselage at several axial stations and also microphone arrays placed inside the fuselage aft of the engine. The benefits of T-fan chevrons, with and without conventional chevrons on the core nozzle, are shown for several engine operating conditions at cruise involving supersonic fan stream and subsonic or supersonic core stream. The T-fan AVC alone provides up to 5 dB low-frequency noise reduction on the fuselage exterior skin and up to 2 dB reduction inside the cabin. Addition of core chevrons appears to increase the higher frequency noise. This flight test result with the previous model test observation that the T-fan AVCs have hardly any cruise thrust coefficient loss (&lt; 0.05%) make them viable candidates for reducing interior cabin noise in high bypass ratio engines.
Extended-Connectivity Fingerprints (2010)

Extended-connectivity fingerprints (ECFPs) are a novel class of topological fingerprints for molecular characterization. Historically, topological fingerprints were developed for substructure and similarity searching. ECFPs were developed specifically for structure-activity modeling. ECFPs are circular fingerprints with a number of useful qualities: they can be very rapidly calculated; they are not predefined and can represent an essentially infinite number of different molecular features (including stereochemical information); their features represent the presence of particular substructures, allowing easier interpretation of analysis results; and the ECFP algorithm can be tailored to generate different types of circular fingerprints, optimized for different uses. While the use of ECFPs has been widely adopted and validated, a description of their implementation has not previously been presented in the literature.
Identification of protein receptor for Clostridium botulinum type B neurotoxin in rat brain synaptosomes. (1994)

The protein receptor for Clostridium botulinum type B neurotoxin was purified 340-fold from rat synaptosomes by successive chromatography on DEAE-Sepharose, phenyl-Toyopearl, and heparin-Toyopearl columns. 125I-Labeled neurotoxin bound to lipid vesicles containing the protein receptor and ganglioside GT1b or GD1a. The reconstituted receptor showed the same affinities as the native receptor on synaptosomes. Chemical cross-linking of 125I-toxin to the receptor in the presence of gangliosides resulted in formation of a cross-linked product of 161 kDa under reducing conditions. Cross-linking was specific, as it was inhibited by the presence of excess unlabeled toxin. A monoclonal antibody against the purified 58-kDa receptor protein and a monoclonal antibody against the heavy chain (103 kDa) of the neurotoxin reacted with the cross-linked product of 161 kDa in immunoblotting experiments. We determined partial amino acid sequences of the 58-kDa protein, which were identical to synaptotagmin, a synaptic vesicle membrane protein. In addition, the monoclonal antibody against the 58-kDa receptor protein recognized recombinant rat synaptotagmin. These results suggest that synaptotagmin in association with ganglioside GT1b or GD1a may be a natural receptor for C. botulinum type B neurotoxin at the nerve terminals.
[Influence of vasoactive intestinal peptide on expression of pulmonary surfactant associated protein A in lung explants]. (2004)

VIP can up-regulate the expression of SP-A through its receptor. PKC and c-fos protein play important roles in the intracellular signal transduction pathway through which VIP induces the expression of SP-A.
A Novel Methodology for Sensing the Breakdown Location and Its Application to the Reliability Study of Ultrathin Hf-Silicate Gate Dielectrics (2005)

In this paper, we propose a new methodology for sensing the breakdown location along the channel length with the MOSFET biased in the inversion regime. The usefulness of this technique is demonstrated in the characterization of ultrathin Hf-silicate gate dielectrics breakdown. Two different breakdown modes are deconvoluted: an initial progressive breakdown in the channel with a degradation rate strongly dependent on the applied voltage and a successive hard-breakdown at source and drain extensions, which more impacts the device reliability.
Synthesis and Pharmacological Evaluation of Dimeric Follicle‐Stimulating Hormone Receptor Antagonists (2009)

A series of homo- and heterodimeric compounds encompassing the follicle-stimulating hormone receptor (FSHR) antagonist (R)-1 and its inactive conformer (S)-1 connected through ethylene glycol spacers of various lengths is described. Evaluation of these compounds reveals that dimeric compounds, with a spacer of sufficient length, bearing two active copies of the antagonist are more potent relative to dimeric compounds in which one of the active pharmacophores is replaced by an inactive conformer. Interestingly, the opposite trend is observed if a short spacer is used, indicating that these compounds may be valuable tools to study FSHR dimerization in greater detail.
Nucleophilic Addition to C=O and C=N Bonds by Nucleophiles Containing a Diazo Group (2005)

This account summarizes recent developments in the ­nucleophilic addition reaction of diazo compound derived anion or enolate with electrophilic C=O and C=N bonds. Subsequent ­reaction of the addition products under transition-metal-catalyzed conditions, as well as their synthetic utility, are also presented.
Oral vaccination with envelope protein VP28 against white spot syndrome virus in Procambarus clarkii using Bacillus subtilis as delivery vehicles (2008)

Oral vaccination by the B. subtilis vehicle containing VP28 opens a new way for designing practical vaccines to control WSSV.