gebhart/patrepeval huggingface dataset:
Biological effects in vitro of monoclonal antibodies to human epidermal growth factor receptors. (1983)

Four mouse hybridomas secreting monoclonal immunoglobulin G (IgG) antibodies to epidermal growth factor (EGF) receptors of A431 cells were obtained independently from four fusion experiments. Three of the antibodies, 528 IgG, 225 IgG, and 579 IgG, inhibited the binding of [125I]EGF to A431 cells by at least 95%, and they competed with each other for binding to A431 cells. These antibodies bound to A431 cells, HeLa-S cells and human foreskin fibroblasts with dissociation constants in the range of Kd = 0.6 X 10(-9) to 2.5 X 10(-9) M. The fourth monoclonal antibody, 455 IgG, bound to A431 cells with lower affinity (Kd = 2.0 X 10(-8) M), and it had no effect on the binding of either EGF or the other antibodies to A431 cells. All four antibodies immunoprecipitated EGF receptors from Triton X-100 extracts of A431 membranes, but they were unable to bind to three rodent cell lines. In biological assays, none of the antibodies was able to mimic EGF. The antibodies which inhibited the binding of EGF blocked EGF-enhanced phosphorylation of A431 membrane proteins and inhibited EGF induced human fibroblast proliferation. These three antagonistic antibodies also partially reversed the inhibition of A431 growth by EGF. In contrast, 455 IgG had no effect on the early or delayed cellular responses to EGF.
Contributions of the lymphocytic choriomeningitis virus glycoprotein and polymerase to strain-specific differences in murine liver pathogenicity (2007)

Hepatic involvement is commonly observed in arenavirus infections, but the viral determinants of liver disease are only partially understood. Here we exploited newly developed reverse-genetic techniques with Lymphocytic choriomeningitis virus (LCMV), the prototype arenavirus, to address specifically the contribution of the viral glycoprotein (GP) to liver pathogenicity. It is well established that strain WE, but not ARM, causes hepatitis in mice. We found that this property correlated with the superior capacity of WE to propagate in cultured macrophages and hepatocyte-derived cells. In mice, the ability to establish prolonged viraemia allowed the virus to propagate from initially infected Kupffer cells in the liver to neighbouring hepatocytes that underwent apoptosis. Reverse-genetic replacement of the GP in strain ARM with WE-GP resulted in only a very modest increase in liver pathogenicity, if any. Yet, an ARM-derived variant virus with a mutated polymerase gene caused severe liver disease when engineered to display WE-GP but considerably less when expressing ARM-GP. This reverse-genetic approach to an animal model of arenaviral hepatitis reveals a previously underestimated contributory role of the GP that alone is, however, insufficient to cause disease.
General palladium-catalyzed aerobic dehydrogenation to generate double bonds (2011)

We describe a general dehydrogenation procedure to form α,β-unsaturated aldehydes, ketones, esters and azobenzenes under very mild conditions, requiring catalytic commercial Pd(OAc)2, a catalytic weak inorganic base and air as the sole oxidant. In the presence of a diazafluorenone ligand, this process converts aliphatic aldehydes to α,β-unsaturated aldehydes in an open-flask fashion at ambient pressure and temperature. A broad spectrum of substrates, including aldehydes, ketones, esters, alcohols and hydrazines, were conveniently dehydrogenated under a relatively uniformed protocol. A mechanism involving β-elimination-driven enolization equilibrium shift was proposed.
Controlled Chemical Cleavage of Synthetic DNA at Specific Sites (1991)

Abstract In this communication we report the synthesis of a protected abasic molecule, 1′-O-(2-nitrobenzyl)-2′-deoxyriboside, and a special N-4-(6-hydroxyhexyl)-ribocytidine derivative as light- and periodate-sensitive selectable cleavage moieties, respectively, and their use in the characterization of linear and branched single-stranded DNA molecules.
An open-label phase II study of the Hsp90 inhibitor ganetespib (STA-9090) in patients (pts) with metastatic and/or unresectable GIST. (2011)

10011
Plasma Endotoxin as a Predictor of Multiple Organ Failure and Death in Systemic Meningococcal Disease (1989)

We studied prospectively the quantitative relation of circulating endotoxin (lipooligosaccharides [LOSs]) and the development of multiple organ failure and death in 45 consecutively admitted patients with bacteriologically verified systemic meningococcal disease (SMD). A plasma LOS level of greater than 700 ng/L correlated with development of severe septic shock (P less than .0001), adult respiratory distress syndrome (P = .0035), a pathologically elevated serum creatinine level (P less than .0001), or death as a consequence of multiple organ failure (P = .0002). Initial plasma LOS levels of less than 25, 25-700, 700-10,000, and greater than 10,000 ng/L were associated with 0%, 14%, 27%, and 86% fatality, respectively. The LOS half-life after initiation of antibiotic therapy was 1-3 h. Increasing plasma LOS levels were never seen. These observations suggest that LOS quantitation using the limulus amebocyte lysate assay with a chromogenic substrate gives important progsnotic information and may provide new insight concerning pathophysiological aspects of SMD.
The Study ofAPOA1,APOC3andAPOA4Variability in Healthy Ageing People Reveals Another Paradox   in the Oldest Old Subjects (2003)

The genes coding for apolipoprotein A1 (APOA1), apolipoprotein C3 (APOC3) and apolipoprotein A4 (APOA4) are tandemly organised within a short region on chromosome 11q23-q24. Polymorphisms of these genes have been extensively investigated in lipoprotein disorders and cardiovascular diseases, but poorly investigated in healthy ageing. The aim of this study was to describe possible modifications of the APOA1, APOC3, and APOA4 gene pool by cross-sectional studies carried out in a healthy ageing population whose ages ranged from 18 to 109 years (800 subjects, 327 males and 473 females, free of clinically manifested disease, and with emato-chemical parameters in the norm). APOA1-MspI-RFLP (-75 nt from the transcription starting site), APOC3-SstI-RFLP (3'UTR, 3238 nt), and APOA4-HincII-RFLP (Asp127/Ser127) were analysed according to age and sex. A significant age-related variation of the APOA1 gene pool was observed in males. An analysis of the allele average effect exerted by APOA1-MspI-RFLP A/P alleles (Absence/Presence of the restriction site) on lipidemic parameters in 46-80 year old males showed that allele A decreased, while allele P significantly increased, serum LDL-cholesterol. Unexpectedly, the P allele was over-represented in the group of the oldest old subjects, thus giving evidence of another "genetic paradox of centenarians".
Measurement of Adhesion and Spreading Kinetics of Baby Hamster Kidney and Hybridoma Cells Using an Integrated Optical Method (1994)

A novel optical method was used for quantitative characterization and continuous measurement of both the adhesion and spreading of mammalian cells on inorganic surfaces. It is based upon the effective refractive index change caused by cells when they adhere to a planar optical waveguide. We have applied this technique to measure the kinetics of the adhesion and spreading processes of baby hamster kidney (BHK) cells adhering to surfaces coated with fibronectin and under different culture conditions (PBS, medium, serum, EDTA). In comparison, hybridoma cells are only adsorbed to the surface and do not spread at all. Moreover, this technique also allows the mass of an adsorbed protein adlayer to be determined very precisely and thus provides a valuable tool for screening suitable substrata as well as determining the influence of different culture conditions on cell adhesion and spreading. This sensitive test for substrate influence could be important in toxicity tests using adherent animal cells.
The influence of side chains on the structures and properties of functionalized pentacenes (2008)

We investigated substituent-induced variations in microstructure and physical properties of a family of functionalized pentacenes, materials currently of intensive interest for making organic electronic devices such as thin film transistors, to shed light on the complex relationships between functionalization, film formation, stability, and microstructure. In this study, the pentacenes were modified with alkyl acetylene or alkylsilylethynyl groups with systematic variations in the alkyl chain length. With a proper side chain, this modification can effectively disrupt the herringbone packing seen in neat pentacene, promoting face-to-face arrangements between the acene rings and providing solubility in a variety of convenient solvents. Thin films can be readily formed by solution casting from THF, bromobenzene, toluene and other organic solvents. We have investigated the structure and properties of the functionalized pentacenes using UV-vis spectroscopy, hot stage optical microscopy, differential scanning calorimetry, transmission electron microscopy, X-ray and electron diffraction. The materials show regular variations in their thermal behavior, crystal packing and macroscopic properties as the chemistry of the side-group substituent changes.
Oct4 and Klf4 Reprogram Dermal Papilla Cells into Induced Pluripotent Stem Cells (2009)

Direct reprogramming of somatic cells into induced pluripotent stem (iPS) cells by only four transcription factors (Oct4, Sox2, Klf4, and c-Myc) has great potential for tissue-specific regenerative therapies, eliminating the ethical issues surrounding the use of embryonic stem cells and the rejection problems of using non-autologous cells. The reprogramming efficiency generally is very low, however, and the problems surrounding the introduction of viral genetic material are only partially investigated. Recent efforts to reduce the number of virally expressed transcription factors succeeded at reprogramming neural stem cells into iPS cells by overexpressing Oct4 alone. However, the relative inaccessibility and difficulty of obtaining neural cells in humans remains to be resolved. Here we report that dermal papilla (DP) cells, which are specialized skin fibroblasts thought to instruct hair follicle stem cells, endogenously express high levels of Sox2 and c-Myc, and that these cells can be reprogrammed into iPS cells with only Oct4 and Klf4. Moreover, we show that DP cells are reprogrammed more efficiently than skin and embryonic fibroblasts. iPS cells derived from DP cells expressed pluripotency genes and differentiated into cells from all germ layers in vitro and widely contributed to chimeric mice in vivo, including the germline. Our work establishes DP cells as an easily accessible source to generate iPS cells with efficiency and with less genetic material. This opens up the possibility of streamlined generation of skin-derived, patient-specific pluripotent stem cells and of ultimately replacing the remaining two factors with small molecules for safe generation of transplantable cells.
Structure−Activity Relationships of Cyclic Peptide-Based Chemokine Receptor CXCR4 Antagonists:  Disclosing the Importance of Side-Chain and Backbone Functionalities (2006)

Previously, we have identified a highly potent CXCR4 antagonist 2 [cyclo(-D-Tyr1-Arg2-Arg3-Nal4-Gly5-)] and its Arg2 epimer 3 [cyclo(-D-Tyr1-D-Arg2-Arg3-Nal4-Gly5-)] by the screening of cyclic pentapeptide libraries that were designed based on the structure-activity relationship studies on 14-residue peptidic CXCR4 antagonist 1. In the present study, a new series of analogues of 2 and 3 were synthesized to evaluate the influences of peptide side-chain and backbone modification on bioactivities. Based on the Ala-scanning study, in which each residue in 2 and 3 was replaced with Ala having the identical chirality, substitution of Arg3 and Nal4 [Nal = L-3-(2-naphthyl)alanine] with Ala (compounds 6, 7, 10, 11) led to significant loss of the potency, indicating these amino acids are more important contributors to the bioactivity. For the cyclic peptide backbone, several modifications including d/l-Ala or cyclic amino acids substitution at the Gly5 position and sequential N-methylation on amide nitrogens were conducted. Among the analogues, compounds 13 [cyclo(-D-Tyr1-Arg2-Arg3-Nal4-D-Ala5-)] and 32 [cyclo(-D-Tyr1-D-MeArg2-Arg3-Nal4-Gly5-)] were close in potency to the most potent lead 2. NMR and conformational analysis indicated that both of these analogues favor the same backbone conformation as 2, whereas similar analysis of less potent analogues indicates that an altered backbone conformation is favored. The conformational analysis showed that steric repulsion by a 1,3-allylic strain-like effect across the planar peptide bond might contribute to the conformational preferences of cyclic pentapeptides.
Pairwise library screen systematically interrogates Staphylococcus aureus Cas9 specificity in human cells (2018)

Abstract We report a high-throughput screening approach to measure Staphylococcus aureus Cas9 (SaCas9) genome editing variation in human cells across a large repertoire of 88,692 single guide RNAs (sgRNAs) paired with matched or mismatched target sites in a synthetic cassette. We incorporated randomized barcodes that enable ‘whitelisting’ of correctly synthesized molecules for further downstream analysis, in order to circumvent the limitation of oligonucleotide synthesis errors. We find SaCas9 sgRNAs with a 21-nucleotide spacer are most active against off-targets with single and double mismatches, compared to shorter or longer sgRNAs. Using this dataset, we developed an SaCas9 specificity model that performs well in ranking off-target sites. The barcoded pairwise library screen enabled high-fidelity recovery of guide-target relationships, providing a scalable framework for the investigation of CRISPR enzyme properties and general nucleic acid interactions.
Contributions of Diffusion-Weighted Imaging to Fetal and Neonatal Imaging (2011)

Diffusion-weighted imaging has contributed to our understanding of fetal and neonatal brain development. This article will review the role of diffusion-weighted imaging and diffusion tensor imaging in fetuses and neonates, focusing primarily on normal brain developmental processes and then on pathologic processes that can be characterized using diffusion tensor imaging.
Measurement of tongue–artificial nipple contact pressure during infant sucking (2012)

Abstract To clarify the motor function of the infant tongue during sucking, we developed an artificial nipple that contained multiple small built‐in force sensors integrated with a PC‐based system which is capable of measuring tongue–artificial nipple contact pressures in real time. The force sensor is a cantilever structure with a small, thin stainless steel beam where an all‐purpose foil strain gauge is attached to the surface of the beam. An artificial nipple made of an elastomer containing these sensors is connected through an amplifier and an A/D converter to a PC via a USB port. Using this system, measurements were taken in three infants whose oral feeding was well established and in one infant of low birth weight. The results from each force sensor showed a pressure waveform of a nearly simple harmonic motion that indicated a peristalsis‐like movement of the tongue; the sucking frequency was found to be about two times per second. In addition, in the low‐birth‐weight infant, the pressure changed as the infant grew. © 2012 Institute of Electrical Engineers of Japan. Published by John Wiley &amp; Sons, Inc.
FakeBuster: A DeepFakes Detection Tool for Video Conferencing Scenarios (2021)

This paper proposes FakeBuster, a novel DeepFake detector for (a) detecting impostors during video conferencing, and (b) manipulated faces on social media. FakeBuster is a standalone deep learning- based solution, which enables a user to detect if another person’s video is manipulated or spoofed during a video conference-based meeting. This tool is independent of video conferencing solutions and has been tested with Zoom and Skype applications. It employs a 3D convolutional neural network for predicting video fakeness. The network is trained on a combination of datasets such as Deeperforensics, DFDC, VoxCeleb, and deepfake videos created using locally captured images (specific to video conferencing scenarios). Diversity in the training data makes FakeBuster robust to multiple environments and facial manipulations, thereby making it generalizable and ecologically valid.
Hypoxia-Induced Interleukin-6 and Interleukin-8 Production Is Mediated by Platelet-Activating Factor and Platelet-Derived Growth Factor in Primary Human Lung Cells (1998)

Hypoxia has been shown to induce the expression of different growth factors, cytokines, and proinflammatory mediators, including platelet-derived growth factor (PDGF), interleukin-6 (IL-6), interleukin-8 (IL-8), and platelet-activating factor (PAF) in animal models. PAF and PDGF are thought to play important roles in vascular remodeling and have been shown to induce expression of IL-6 and IL-8 genes under normoxic conditions. We hypothesize that de novo synthesis of IL-6, IL-8, and cell proliferation is enhanced in human pulmonary cells under hypoxic cell culture conditions. We further assumed an important role of PAF and/or PDGF in hypoxia-induced cell activation. Using cultures of primary human pulmonary fibroblasts and pulmonary vascular smooth muscle cells (VSMC) we show that hypoxia (3% O2) induced transcription and translation of IL-6 (4- to 5-fold) and IL-8 (5- to 6-fold) in both cell types. Hypoxia-induced expression of IL-6 was suppressed by 50% to 60% in the presence of the PAF antagonist WEB2170, or neutralizing anti-PDGF antibodies. In addition, we demonstrate that hypoxia induces a threefold increase of cell proliferation of fibroblasts and a twofold increase of VSMC proliferation. Similar to the effect on IL-6 and IL-8 synthesis, WEB2170 or neutralizing anti-PDGF antibodies downregulated hypoxia-induced proliferation of fibroblasts and VSMC by 50%. Our data show that PAF and PDGF are important mediators for hypoxia-induced cell activation and cytokine release in the human lung. We therefore hypothesize that IL-6 and IL-8 contribute to the progression of lung diseases associated with hypoxia, and that both proinflammatory factors, PAF and PDGF, are involved in hypoxia-dependent expression of IL-6 and IL-8 in human pulmonary fibroblasts and VSMC.
Validation of QF-PCR for prenatal aneuploidy screening in the United States (2006)

QF-PCR for prenatal aneuploidy screening was validated in our laboratory and has now been approved by the New York State Clinical Laboratory Evaluation Program. We propose a simple protocol for integrating QF-PCR into the normal cytogenetics laboratory workflow.
Enzymatic deglycosylation converts pathogenic neuromyelitis optica anti–aquaporin‐4 immunoglobulin G into therapeutic antibody (2012)

EndoS deglycosylation converts pathogenic NMO-IgG autoantibodies into therapeutic blocking antibodies. EndoS treatment of blood may be beneficial in NMO, and may be accomplished, for example, by therapeutic apheresis using surface-immobilized EndoS.
The lactonization of 2'-hydroxyhydrocinnamic acid amides: a potential prodrug for amines (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe lactonization of 2'-hydroxyhydrocinnamic acid amides: a potential prodrug for aminesKent L. Amsberry and Ronald T. BorchardtCite this: J. Org. Chem. 1990, 55, 23, 5867–5877Publication Date (Print):November 1, 1990Publication History Published online1 May 2002Published inissue 1 November 1990https://pubs.acs.org/doi/10.1021/jo00310a019https://doi.org/10.1021/jo00310a019research-articleACS PublicationsRequest reuse permissionsArticle Views1929Altmetric-Citations77LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Functional Role of Diverse Changes in Sympathetic Nerve Activity in Regulating Arterial Pressure during REM Sleep (2011)

It is suggested that the diverse changes in sympathetic outflows during REM sleep may be needed to increase systemic arterial pressure by balancing vascular resistance between muscles and vegetative organs without depending on the heart.
Isolated C-terminal tail of FGF23 alleviates hypophosphatemia by inhibiting FGF23-FGFR-Klotho complex formation (2009)

Fibroblast growth factor (FGF) 23 inhibits renal phosphate reabsorption by activating FGF receptor (FGFR) 1c in a Klotho-dependent fashion. The phosphaturic activity of FGF23 is abrogated by proteolytic cleavage at the RXXR motif that lies at the boundary between the FGF core homology domain and the 72-residue-long C-terminal tail of FGF23. Here, we show that the soluble ectodomains of FGFR1c and Klotho are sufficient to form a ternary complex with FGF23 in vitro. The C-terminal tail of FGF23 mediates binding of FGF23 to a de novo site generated at the composite FGFR1c-Klotho interface. Consistent with this finding, the isolated 72-residue-long C-terminal tail of FGF23 impairs FGF23 signaling by competing with full-length ligand for binding to the binary FGFR-Klotho complex. Injection of the FGF23 C-terminal tail peptide into healthy rats inhibits renal phosphate excretion and induces hyperphosphatemia. In a mouse model of renal phosphate wasting attributable to high FGF23, the FGF23 C-terminal peptide reduces phosphate excretion, leading to an increase in serum phosphate concentration. Our data indicate that proteolytic cleavage at the RXXR motif abrogates FGF23 activity by a dual mechanism: by removing the binding site for the binary FGFR-Klotho complex that resides in the C-terminal region of FGF23, and by generating an endogenous inhibitor of FGF23. We propose that peptides derived from the C-terminal tail of FGF23 or peptidomimetics and small-molecule organomimetics of the C-terminal tail can be used as therapeutics to treat renal phosphate wasting.