gebhart/patrepeval huggingface dataset:
Additional New Minor Cucurbitane Glycosides from Siraitia grosvenorii (2014)

Continuous phytochemical studies of the crude extract of Luo Han Guo (Siraitia grosvenorii) furnished three additional new cucurbitane triterpene glycosides, namely 11-deoxymogroside V, 11-deoxyisomogroside V, and 11-deoxymogroside VI. The structures of all the isolated compounds were characterized on the basis of extensive NMR and mass spectral data as well as hydrolysis studies. The complete ¹H- and ¹³C-NMR spectral assignments of the three unknown compounds are reported for the first time based on COSY, TOCSY, HSQC, and HMBC spectroscopic data.
Multiple Sclerosis (2018)

Multiple sclerosis affects more than 2 million people worldwide and is currently incurable. A number of interventions to modify the course of multiple sclerosis have been developed that offer new insight into disease mechanisms.
Transforming growth factor ?2, but not ?1 and ?3, is critical for early rat lung branching (2000)

Mesenchymal-epithelial tissue interactions are critical for lung branching morphogenesis, and polypeptide growth factors are likely involved in these tissue interactions. Transforming growth factorbetas (TGFbetas) have been implicated in lung development, but their involvement in early lung branching morphogenesis is unclear. In the present study, we investigated the role of the three mammalian TGFbeta subtypes (beta1, beta2, and beta3) and their receptors (type III (TbetaR-III), type II (TbetaR-II), and two types I (TbetaR-I), ALK-1 and ALK-5) in early rat lung organogenesis by using an embryonic rat lung explant culture. Transcripts and proteins for all three TGFbetas and their receptors were detected during the embryonic period of fetal rat lung development. Inhibition of TGFbeta2, but not beta1 and beta3, with antisense oligonucleotides and neutralizing antibodies resulted in significant inhibition of early lung branching in culture. Addition of minute amounts (</=1 ng/ml) of exogenous TGFbeta2, but not beta1 and beta3, restored the branching of TGFbeta2 antisense-treated explants. Higher concentrations of TGFbeta2 were inhibitory. BrdU labeling of lung explants was not altered by antisense TGFbeta2 treatment, but low concentrations of TGFbeta2 increased thymidine uptake by isolated epithelial cells. Fibronectin and metallogelatinase activities of embryonic lung cells were not affected by any TGFbeta isoform but TGFbeta2 specifically decreased mesenchymal hyaluronan synthesis. Antisense inhibition of ALK-5 and TbetaR-II showed a similar reduction in early lung branching as observed with antisense TGFbeta2. Incubation of lung explants with soluble TbetaR-II receptors also abrogated lung branching. ALK-1 antisense treatment did not affect early branching. Administration of neither activin A, which can act via ALK-1, nor follistatin, the natural inhibitor of activin, to the explants cultures had any significant effect on lung branching. Antisense inhibition of the activin receptor-II (Act-RII) also did not affect lung branching. These results are consistent with TGFbeta2, but not beta1 and beta3, regulating pattern formation during early rat lung organogenesis. This TGFbeta signaling in rat lung branching in vitro appears to be predominantly mediated via the TbetaR-I(ALK-5)/TbetaR-II heteromeric complex.
Rapid generation and flow cytometric analysis of stable GFP-expressing cells (1996)

Expression of green fluorescent protein (GFP) represents a unique method for the fluorescent labeling of viable mammalian cells, with many potential applications. The studies detailed in this report examine the detection of GFP expression in murine cells using flow cytometry. Direct comparison of NIH 3T3 cells transiently expressing GFP or GFPS65T, a mutant form of GFP, showed that GFPS65T fluorescence (using 488 nm excitation) was detected more readily than fluorescence from wildtype GFP. Efficient generation of cell lines that stably expression GFPS65T was achieved using a plasmid vector that encoded a hygromycin phosphotransferase/GFPS65T fusion protein. Flow cytometric detection of NIH 3T3 cells expressing this fusion protein was improved using a 510/20 band pass filter instead of the standard filter setup for fluorescein detection. Additionally, staining the surface of these cells with phycoerythrin, RED 670, or allophycocyanin did not interfere with the detection of GFPS65T fluorescence, indicating that multiparameter analyses using GFPS65T fluorescence are possible. Importantly, we also observed that GFPS65T expression could be detected in NIH 3T3, BW5147, or freshly cultured Thy1lo CD3- murine bone marrow cells transduced with a retroviral vector encoding the fusion protein, suggesting that the potential applications of this system may be quite broad.
Relativistic Functional Groups: Aryl Carbon–Gold Bond Formation by Selective Transmetalation of Boronic Acids (2006)

Gilded organometallics: Carbon–gold bond formation occurs selectively and in high yields upon reaction of gold(I) bromides with arylboronic acids in the presence of Cs2CO3. The reaction is broadly tolerant of sensitive functionalities. The resulting aryl gold(I) compounds are stable to air and water. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2006/z603350_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Mechanisms underlying the autonomic modulation of ventricular fibrillation initiation—tentative prophylactic properties of vagus nerve stimulation on malignant arrhythmias in heart failure (2012)

Classical physiology teaches that vagal post-ganglionic nerves modulate the heart via acetylcholine acting at muscarinic receptors, whilst it is accepted that vagus nerve stimulation (VNS) slows heart rate, atrioventricular conduction and decreases atrial contraction; there is continued controversy as to whether the vagus has any significant direct effect on ventricular performance. Despite this, there is a significant body of evidence from experimental and clinical studies, demonstrating that the vagus nerve has an anti-arrhythmic action, protecting against induced and spontaneously occurring ventricular arrhythmias. Over 100 years ago Einbrodt first demonstrated that direct cervical VNS significantly increased the threshold for experimentally induced ventricular fibrillation. A large body of evidence has subsequently been collected supporting the existence of an anti-arrhythmic effect of the vagus on the ventricle. The development of prognostic indicators of heart rate variability and baroreceptor reflex sensitivity--measures of parasympathetic tone and reflex activation respectively--and the more recent interest in chronic VNS therapy are a direct consequence of the earlier experimental studies. Despite this, mechanisms underlying the anti-arrhythmic actions of the vagus nerve have not been fully characterised and are not well understood. This review summarises historical and recently published data to highlight the importance of this powerful endogenous protective phenomenon.
Glycosylation of the epidermal growth factor receptor in A-431 cells. The contribution of carbohydrate to receptor function. (1984)

A-431 cells were treated with inhibitors of either N-linked glycosylation (tunicamycin or glucosamine) or of N-linked oligosaccharide processing (swainsonine or monensin) to examine the glycosylation of epidermal growth factor (EGF) receptors and to determine the effect of glycosylation modification on receptor function. The receptor was found to be an Mr = 130,000 polypeptide to which a relatively large amount of carbohydrate is added co-translationally in the form of N-linked oligosaccharides. Processing of these oligosaccharides accounts for the 10,000-dalton difference in electrophoretic migration between the Mr = 160,000 precursor and Mr = 170,000 mature forms of the receptor. No evidence was found for O-linked oligosaccharides on the receptor. Mr = 160,000 receptors resulting from swainsonine or monensin treatment were present on the cell surface and retained full function, as judged by 125I-EGF binding to intact cells and detergent-solubilized extracts and by in vitro phosphorylation in the absence or presence of EGF. On the other hand, when cells were treated with tunicamycin or glucosamine, ligand binding was reduced by more than 50% in either intact cells or solubilized cell extracts. The Mr = 130,000 receptors synthesized in the presence of these inhibitors were not found on the cell surface. In addition, no Mr = 130,000 phosphoprotein was detected in the in vitro phosphorylation of tunicamycin or glucosamine-treated cells. It appears, therefore, that although terminal processing of N-linked oligosaccharides is not necessary for proper translocation or function of the EGF receptor, the addition of N-linked oligosaccharides is required.
Cooperative transcriptional activity of Jun and Stat3 beta, a short form of Stat3. (1995)

To identify proteins that regulate the transcriptional activity of c-Jun, we have used the yeast two-hybrid screen to detect mammalian polypeptides that might interact functionally with the N-terminal segment of c-Jun, a known regulatory region. Among the proteins identified is a short form of Stat3 (designated Stat3 beta). Stat3 beta is missing the 55 C-terminal amino acid residues of the long form (Stat3 alpha) and has 7 additional amino acid residues at its C terminus. In the absence of added cytokines, expression of Stat3 beta (but not Stat3 alpha) in transfected cells activated a promoter containing the interleukin 6 responsive element of the rat alpha 2-macroglobulin gene; coexpression of Stat3 beta and c-Jun led to enhanced cooperative activation of the promoter. Nuclear extracts of cells transfected with a Stat3 beta expression plasmid formed a complex with an oligonucleotide containing a Stat3 binding site, whereas extracts of cells transfected with a Stat3 alpha plasmid did not. We conclude that there is a short form of Stat3 (Stat3 beta), that Stat3 beta is transcriptionally active under conditions where Stat3 alpha is not, and that Stat3 beta and c-Jun are capable of cooperative activation of certain promoters.
In Vitro Transdifferentiation of Mature Hepatocytes into Insulin-Producing Cells (2006)

Adenovirus-mediated gene transfer of pancreatic duodenal homeobox transcription factor PDX-1, especially its super-active version (PDX-1/VP16), induces the expression of pancreatic hormones in murine liver and reverses streptozotocin-induced hyperglycemia. Histological analyses suggest that hepatocytes are the major source of insulin-producing cells by PDX-1 gene transfer, although the conversion of cultured hepatocytes into insulin-producing cells remains to be elucidated. The present study was conducted to address this issue. Hepatocytes were isolated from adult rats. Then, PDX-1 or PDX-1/VP16 gene was introduced by using adenovirus vector. Two days later, the expression of insulin was detected at mRNA and protein levels. Transfection of PDX-1/VP16 was more efficient in converting hepatocytes to insulin-producing cells. Immunoreactivity of albumin was downregulated in transdifferentiated cells and some of them almost completely lost albumin expression. During the course of transdifferentiation, upregulation of mRNA for CK19 and alpha-fetoprotein was observed. When cultured in collagen-1 gel sandwich configuration, hepatocytes maintained their mature phenotype and did not proliferate. In this condition, transfer of PDX-1/VP16 also induced the expression of insulin. These results clearly indicate that hepatocytes possess a potential to transdifferentiate into insulin-producing cells in vitro.
Localization and identification of visual landmarks (2001)

This project focused on designing and evaluating methods for reading barcodes on visual landmarks. Such landmarks have many applications, including visual tracking, servo-ing, and mobile robot navigation. Our goal was to improve a preliminary version of the barcode reader developed the previous summer in the Middlebury Robotics and Vision Lab.
Higher excited electronic states in clusters of ZnSe, CdSe, and ZnS: Spin-orbit, vibronic, and relaxation phenomena (1986)

Metal selenide clusters have been made and characterized, using the arrested precipitation colloidal technique. A comparison of sulfide and selenide spectra enables observation of the effect of changes in the highest occupied molecular orbitals upon cluster electronic properties. The first and second excited electronic states are both observed as a function of size in ZnSe clusters. The systematic dependence of the spectra lead to assignment of the higher state to a 1S-type hole based upon the split-off valence band. It is shown that the energy spectrum of discrete hole states is controlled by the spin-orbit energy and the isotropic hole mass in small, highly symmetrical clusters. This result contrasts with the heavy hole and light hole states observed for planar confinement. In ≂ 20 Å diameter ZnS clusters, there is a strong vibronic temperature dependence in the excited state spectra, while in clusters of smaller gap materials such vibronic effects are very minor. We conjecture that lifetime broadening is severe in clusters of small gap materials.
Titanium(IV)-Mediated Tandem Deprotection−Cyclodehydration of Protected Cysteine N-Amides:  Biomimetic Syntheses of Thiazoline- and Thiazole-Containing Heterocycles (2000)

The scope and limitations of TiCl(4)-mediated Delta(2)-thiazoline synthesis via tandem deprotection-dehydrocyclization of trityl-protected cysteine N-amides is presented. While chemical yields are acceptable (53-96%), the stereochemical outcomes vary on the basis of structural considerations and reaction conditions (22-99% ee). Racemization at the C(2)-exomethine position limits the utility of this method for the formation of a thiazoline within a peptide. Treatment of a tritylated Cys-Cys dipeptide with TiCl(4) afforded the corresponding thiazole-thiazoline heterocycle 12 (38% yield, 97% ee).
A Novel Staphylococcus aureus Vaccine: Iron Surface Determinant B Induces Rapid Antibody Responses in Rhesus Macaques and Specific Increased Survival in a Murine S. aureus Sepsis Model (2006)

Staphylococcus aureus is a major cause of nosocomial infections worldwide, and the rate of resistance to clinically relevant antibiotics, such as methicillin, is increasing; furthermore, there has been an increase in the number of methicillin-resistant S. aureus community-acquired infections. Effective treatment and prevention strategies are urgently needed. We investigated the potential of the S. aureus surface protein iron surface determinant B (IsdB) as a prophylactic vaccine against S. aureus infection. IsdB is an iron-sequestering protein that is conserved in diverse S. aureus clinical isolates, both methicillin resistant and methicillin sensitive, and it is expressed on the surface of all isolates tested. The vaccine was highly immunogenic in mice when it was formulated with amorphous aluminum hydroxyphosphate sulfate adjuvant, and the resulting antibody responses were associated with reproducible and significant protection in animal models of infection. The specificity of the protective immune responses in mice was demonstrated by using an S. aureus strain deficient for IsdB and HarA, a protein with a high level of identity to IsdB. We also demonstrated that IsdB is highly immunogenic in rhesus macaques, inducing a more-than-fivefold increase in antibody titers after a single immunization. Based on the data presented here, IsdB has excellent prospects for use as a vaccine against S. aureus disease in humans.
Influenza neuraminidase (2011)

Influenza neuraminidase is the target of two licensed antivirals that have been very successful, with several more in development. However, neuraminidase has been largely ignored as a vaccine target despite evidence that inclusion of neuraminidase in the subunit vaccine gives increased protection. This article describes current knowledge on the structure, enzyme activity, and antigenic significance of neuraminidase.
Radiosensitization of DNA by Gold Nanoparticles Irradiated with High-Energy Electrons (2007)

Zheng, Y., Hunting, D. J., Ayotte, P. and Sanche, L. Radiosensitization of DNA by Gold Nanoparticles Irradiated with High-Energy Electrons. Radiat. Res. 168, 19-27 (2008). Thin films of pGEM-3Zf(-) plasmid DNA were bombarded by 60 keV electrons with and without gold nanoparticles. DNA single- and double-strand breaks (SSBs and DSBs) were measured by agarose gel electrophoresis. From transmission electron micrographs, the gold nanoparticles were found to be closely linked to DNA scaffolds, probably as a result of electrostatic binding. The probabilities for formation of SSBs and DSBs from exposure of 1:1 and 2:1 gold nanoparticle:plasmid mixtures to fast electrons increase by a factor of about 2.5 compared to neat DNA samples. For monolayer DNA adsorbed on a thick gold substrate, the damage increases by an order of magnitude. The results suggest that the enhancement of radiosensitivity is due to the production of additional low-energy secondary electrons caused by the increased absorption of ionizing radiation energy by the metal, in the form of gold nanoparticles or of a thick gold substrate. Since short-range low-energy secondary electrons are produced in large amounts by any type of ionizing radiation, and since on average only one gold nanoparticle per DNA molecule is needed to increase damage considerably, targeting the DNA of cancer cells with gold nanoparticles may offer a novel approach that is generally applicable to radiotherapy treatments.
Role of integrated lateral stress in surface deformation of He-implanted surfaces (1977)

The first measurements of integrated lateral stress S have been obtained for He implantations to fluences where surface deformation occurs. Implants into Mo, Nb, and Al were carried out at room temperature. The low-fluence results provide values for the induced volume expansion per implanted He atom. The high-fluence results demonstrate that blistering, as observed in Mo and Nb, is directly related to relief of S. However, flaking, as observed in Al, does not result in appreciable relief of S. The saturation value of integrated lateral stress, Smax, is proportional to yield stress for the three materials and is independent of the He projected range. A model to describe the blistering phenomenon is developed based on the standard elastic stability equation for a plate subjected to in-plane forces. This elastic instability model uses only measurable material parameters and does not depend explicitly on the behavior of He in the material. The model explains the τ∝d2/3 relation observed for blister diameter d and thickness τ, and predicts the d-vs-τ relation for Nb, Ti, V, Pd, 4301 SS, and Be to within 40% of the values measured by other workers over 3 orders of magnitude variation in d. Comparison of the model with the present Mo and Nb results, where Smax is measured directly, gives agreement to better than 10% with no adjustable parameter.
Identification of two-dimensionally separated human cerebrospinal fluid proteins byN-terminal sequencing, matrix-assisted laser desorption/ionization — mass spectrometry, nanoliquid chromatography-electrospray ionization-time of flight-mass spectrometry, and tandem mass spectrometry (2000)

Optimal application of biological mass spectrometry (MS) in combination with two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) of human cerebrospinal fluid (CSF) can lead to the identification of new potential biological markers of neurological disorders. To this end, we analyzed a number of 2-D PAGE protein spots in a human CSF pool using spot co-localization, N-terminal sequencing, matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) and nanoliquid chromatography-electrospray ionization-time of flight-mass spectrometry (nanoLC-ESI-TOF-MS) with tandem MS switching. Our constructed CSF master contained 469 spots after image analysis and processing of 2-D gels. Upon visual inspection of our CSF master with the CSF pattern available on the ExPASy server, it was possible to locate and annotate 15 proteins. N-terminal sequence analysis and MALDI-MS peptide mass fingerprint analysis of both silver- and Coomassie Brilliant Blue (CBB) G-250-stained protein spots after in situ trypsin digest not only confirmed nine of the visually annotated spots but additionally resolved the identity of another 13 spots. Six of these proteins were not annotated on the 2-D ExPASy map: complement C3 alpha-chain (1321-1663), complement factor B, cystatin C, calgranulin A, hemoglobin beta-chain, and beta-2-microglobulin. It was clear that MALDI-MS identification from CBB G-250-stained, rather than from silver-stained, spots was more successful. In cases where no N-terminal sequence and/or no clear MALDI-MS result was available, nanoLC-ESI-TOF-MS and tandem MS automated switching was used to clarify and/or identify these protein spots by generating amino acid sequence tags. In addition, enrichment of the concentration of low-abundant proteins on 2-D PAGE was obtained by removal of albumin and immunoglobulins from the CSF pool using affinity chromatography. Subsequent analysis by 2-D PAGE of the fractionated CSF pool showed various new silver-stainable protein spots, of which four were identified by nanoLC-ESI-TOF-MS and tandem MS switching. No significant homology was found in either protein or DNA databases, indicating than these spots were unknown proteins.
The history of nuclear weapon safety devices (1998)

The paper presents the history of safety devices used in nuclear weapons from the early days of separables to the latest advancements in MicroElectroMechanical Systems (MEMS). Although the paper focuses on devices, the principles of Enhanced Nuclear Detonation Safety implementation will also be presented.
Reactivation of the p53 Tumor Suppressor Pathway by a Stapled p53 Peptide (2007)

The p53-hDM2 protein interaction is a validated therapeutic target in cancer. We report the synthesis of stabilized alpha-helix of p53 (SAH-p53) compounds that antagonize the p53-hDM2 interaction. We demonstrate that hydrocarbon stapling confers cellular permeability to a p53 peptide that is then capable of modulating transcriptional activity. The lead SAH-p53 compound triggers apoptosis in hDM2-overexpressing cancer cells by reactivating the native p53 signaling pathway. SAH-p53 is the first example of an all-hydrocarbon i, i+7 stabilized peptide that subverts cancer through direct modulation of a transcriptional pathway.
Decay-accelerating Factor (DAF), Complement Receptor 1 (CR1), and Factor H Dissociate the Complement AP C3 Convertase (C3bBb) via Sites on the Type A Domain of Bb (2002)

The AP C3 convertase, C3bBb(Mg(2+)), is subject to irreversible dissociation (decay acceleration) by three proteins: DAF, CR1, and factor H. We have begun to map the factor B (fB) sites critical to these interactions. We generated a panel of fB mutations, focusing on the type A domain because it carries divalent cation and C3b-binding elements. C3bBb complexes were assembled with the mutants and subjected to decay acceleration. Two critical fB sites were identified with a structural model. 1) Several mutations centered at adjacent alpha helices 4 and 5 (Gln-335, Tyr-338, Ser-339, Asp-382) caused substantial resistance to DAF and CR1-mediated decay acceleration but not factor H. 2) Several mutations centered at the alpha 1 helix and adjoining loops (especially D254G) caused resistance to decay acceleration mediated by all three regulators and also increased C3b-binding affinity and C3bBb stability. In the simplest interpretation of these results, DAF and CR1 directly interact with C3bBb at alpha 4/5; factor H likely interacts at some other location, possibly on the C3b subunit. Mutations at the C3b.Bb interface interfere with the normal dissociation of C3b from Bb, whether it is spontaneous or promoted by DAF, CR1, or factor H.