gebhart/patrepeval huggingface dataset:
Conformational Melding Permits a Conserved Binding Geometry in TCR Recognition of Foreign and Self Molecular Mimics (2011)

Molecular mimicry between foreign and self Ags is a mechanism of TCR cross-reactivity and is thought to contribute to the development of autoimmunity. The αβ TCR A6 recognizes the foreign Ag Tax from the human T cell leukemia virus-1 when presented by the class I MHC HLA-A2. In a possible link with the autoimmune disease human T cell leukemia virus-1-associated myelopathy/tropical spastic paraparesis, A6 also recognizes a self peptide from the neuronal protein HuD in the context of HLA-A2. We found in our study that the complexes of the HuD and Tax epitopes with HLA-A2 are close but imperfect structural mimics and that in contrast with other recent structures of TCRs with self Ags, A6 engages the HuD Ag with the same traditional binding mode used to engage Tax. Although peptide and MHC conformational changes are needed for recognition of HuD but not Tax and the difference of a single hydroxyl triggers an altered TCR loop conformation, TCR affinity toward HuD is still within the range believed to result in negative selection. Probing further, we found that the HuD-HLA-A2 complex is only weakly stable. Overall, these findings help clarify how molecular mimicry can drive self/nonself cross-reactivity and illustrate how low peptide-MHC stability can permit the survival of T cells expressing self-reactive TCRs that nonetheless bind with a traditional binding mode.
Regional Suppression of Tumor Growth by In Vivo Transfer of a cDNA Encoding a Secreted Form of the Extracellular Domain of the flt-1 Vascular Endothelial Growth Factor Receptor (1998)

Vascular endothelial growth factor (VEGF), a potent angiogenic mediator, is overexpressed in most solid tumors. On the basis of the knowledge that solid tumor growth beyond a small volume is critically dependent on angiogenesis, and that adenovirus (Ad) vectors can mediate efficient in vivo gene transfer and expression, we hypothesized that Ad-mediated transfer of a secreted form of the extracellular domain of the flt-1 VEGF receptor (Adsflt) would suppress tumor growth on a regional basis. To evaluate this concept, three tumor models were examined using a murine colon carcinoma cell line and syngeneic BALB/c mice. First, mice with preestablished splenic CT26.CL25 tumors and liver metastases were given Adsflt on AdNull intravenously and, after 15 days, spleens and livers were harvested to quantify tumor burden. Adslft-treated animals had minimal residual splenic tumors and liver metastases; in contrast, control animals had bulky splenic tumors and extensive liver metastases (p < 0.003). Second, mice with preestablished lung metastases showed a significant reduction in pulmonary metastases with regionally administered Adslft (intratracheal, p < 0.02) but not when the vector was systemically administered (intravenous, p > 0.9). Finally, mice with primary subcutaneous tumors treated with intratumoral administration of Adslft showed significant tumor suppression (p < 0.05) not observed in AdNull-treated mice or mice given Adslft intravenously (p > 0.3). We conclude that Ad-mediated in vivo regional delivery of a secreted form of the extracellular domain of the flt-1 VEGF receptor can effectively inhibit regional tumor growth, a strategy that may provide a means to control tumor growth within the treated organ without the risk of systemic antiangiogenesis.
Toxicity of Cyclosporine Metabolites (1990)

Eight cyclosporine (CsA) metabolites were isolated from the urine of renal transplant recipients. The structure and purity of the metabolites were characterized by fast atom bombardment/mass spectroscopy as well as by proton and 13C nuclear magnetic resonance. The in vitro toxicity of the metabolites were tested using a porcine renal epithelial cell line (LLC-PK1). None of the metabolites was as effective as CsA in inhibiting cell growth and DNA, RNA, or protein synthesis, with the majority of them exhibiting activity less than 10% of that of CsA when the IC50 (the concentration required for 50% inhibition of that particular metabolic function) values were compared. The exception to this was the demethylated metabolite M-21, which exhibited a potency of 17-50% of CsA for the various metabolic parameters examined. The results suggest that the immunosuppressive activity of metabolites may be dissociated from their toxicity. Morphologically, CsA and the metabolite M-21 resulted in changes consistent with the vacuolization seen in tubular cells exposed to CsA in vivo. In contrast, M-17 up to the maximum concentration tested (25,000 micrograms/L) was found not to cause such changes.
Nucleotide sequence of PAT, a retroid element with unusual DR organization, isolated fromPanagrellus redivivus (1992)

We have isolated several copies of the transposable element PAT of Panagrellus redivivus and sequenced one full length, presumably autonomous, 5514 bp entity. The terminal sequences are found repeated inside the element, probably representing the homologous of the long terminal repeats in common retroid elements. Two major open reading frames are present with features typical of GAG and Pol. Both the structural features and open reading frame characteristics assign PAT to the retroid family of transposable elements, and more precisely to the gypsy class of retroids when putative functional domains of Pol are compared to published sequences.
Highly sensitive biological and chemical sensors based on reversible fluorescence quenching in a conjugated polymer (1999)

The fluorescence of a polyanionic conjugated polymer can be quenched by extremely low concentrations of cationic electron acceptors in aqueous solutions. We report a greater than million-fold amplification of the sensitivity to fluorescence quenching compared with corresponding “molecular excited states.” Using a combination of steady-state and ultrafast spectroscopy, we have established that the dramatic quenching results from weak complex formation [polymer (−) /quencher (+) ], followed by ultrafast electron transfer from excitations on the entire polymer chain to the quencher, with a time constant of 650 fs. Because of the weak complex formation, the quenching can be selectively reversed by using a quencher-recognition diad. We have constructed such a diad and demonstrate that the fluorescence is fully recovered on binding between the recognition site and a specific analyte protein. In both solutions and thin films, this reversible fluorescence quenching provides the basis for a new class of highly sensitive biological and chemical sensors.
Some factors influencing the anticoagulant action of heparin (1940)

Research Article| February 01 1940 Some factors influencing the anticoagulant action of heparin Louis Barker Jaques; Louis Barker Jaques 1The Department of Physiology, University of Toronto, Toronto, Canada Search for other works by this author on: This Site PubMed Google Scholar Robert Alexander Mustard Robert Alexander Mustard 1The Department of Physiology, University of Toronto, Toronto, Canada Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1940) 34 (2): 153–158. https://doi.org/10.1042/bj0340153 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation Louis Barker Jaques, Robert Alexander Mustard; Some factors influencing the anticoagulant action of heparin. Biochem J 1 February 1940; 34 (2): 153–158. doi: https://doi.org/10.1042/bj0340153 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1940 CAMBRIDGE UNIVERSITY PRESS1940 Article PDF first page preview Close Modal You do not currently have access to this content.
Reduction in Thrombotic Events With Heparin-Coated Palmaz-Schatz Stents in Normal Porcine Coronary Arteries (1996)

High-activity heparin coating of stents eliminates subacute thrombosis in porcine coronary arteries.
DC-constrained error-correcting codes with small running digital sum (1991)

The authors investigate the problem of evaluating the possible size of error-correcting codes with code words taken from a subset of Hamming spaces. This is an example of the problem of constructing codes in irregular subsets of Hamming spaces. The authors examine the theoretical restrictions on the parameters of error-correcting codes in the asymptotic case (semi-finite sequence) when the recursive digital sum is upper-bounded by some small constant. The bounds allow demonstration of the existence of long codes that have good error-correcting properties and that satisfy some restrictions that are natural for optical and magnetic recording.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Islet Transplantation in Treating Diabetes (1986)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Quartz resonators for penning traps toward mass spectrometry on the heaviest ions (2020)

We report on cyclotron frequency measurements on trapped <sup>206,207</sup>Pb<sup>+</sup> ions by means of the non-destructive Fourier-transform ion-cyclotron-resonance technique at room temperature. In a proof-of-principle experiment using a quartz crystal instead of a coil as a resonator, we have alternately carried out cyclotron frequency measurements for <sup>206</sup>Pb<sup>+</sup> and <sup>207</sup>Pb<sup>+</sup> with the sideband coupling method to obtain 21 cyclotron-frequency ratios with a statistical uncertainty of 6 × 10<sup>-7</sup>. The mean frequency ratio R¯ deviates by about 2σ from the value deduced from the masses reported in the latest Atomic Mass Evaluation. We anticipate that this shift is due to the ion-ion interaction between the simultaneously trapped ions (≈100) and will decrease to a negligible level once we reach single-ion sensitivity. The compactness of such a crystal makes this approach promising for direct Penning-trap mass measurements on heavy and superheavy elements.
Characterization of Mechanical Properties of Single Electrodes and Multielectrodes (1987)

Over recent years there has been increasing awareness of the potential damage to the fragile structures of the cochlea that could be caused by the insertion of intracochlear electrodes. Temporal bone histologic studies from chronically implanted human patients have shown that intracochlear electrodes can cause significant insertion trauma. This paper describes how the mechanical properties of the electrode array can influence insertion trauma, and compares the properties of solid wire electrodes with those of a tapered electrode array. The maximum force that can be applied by the tip of the solid wire electrode is 25 times what can be applied by the tapered electrode array, whereas the tapered array is ten times more flexible. These differences in mechanical properties suggest that evidence for insertion trauma should be assessed on an electrode-by-electrode basis.
FINE STRUCTURE OF A GENETIC REGION IN BACTERIOPHAGE (1955)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Image-Based Rendering with Depth Information Using the Propagation Algorithm (2006)

The paper proposes a new approach for the image-based rendering (IBR) problem. IBR has many potential applications, such as remote reality and telepresence, in which traditional computer graphic techniques require high computational complexity. Our algorithm proactively propagates all available information from actual cameras to virtual cameras, using a depth availability assumption. This process turns the IBR problem into a nonuniform interpolation problem at the virtual camera image plane, which can be done efficiently at once for all image pixels. Experimental results show the proposed algorithm has low computational complexity and produces accurate rendering, especially around object boundaries, where most existing methods fail.
Peptide Vaccines of the HER-2/neu Dimerization Loop Are Effective in Inhibiting Mammary Tumor Growth In Vivo (2007)

Human epidermal growth factor receptor-2 (HER-2)/neu (ErbB2), a member of the epidermal growth factor family of receptors, is overexpressed in 20-30% of breast cancers. It is an attractive target for receptor-directed antitumor therapy using mAbs. Unlike other epidermal growth factor receptor family members, HER-2/neu does not bind a high-affinity ligand, but rather functions as the preferred dimerization partner. Pertuzumab (Omnitarg) is a humanized mAb directed against the HER-2/neu dimerization domain that inhibits receptor signaling. The recent definition of the crystal structure of the HER-2/neu-pertuzumab complex demonstrated that the receptor dimerization region encompassed residues 266-333. Based on the three-dimensional structure of the complex, we have designed three conformational peptide constructs (sequences 266-296, 298-333, and 315-333) to mimic regions of the dimerization loop of the receptor and to characterize their in vitro and in vivo antitumor efficacy. All the constructs elicited high-affinity peptide Abs that inhibited multiple signaling pathways including HER-2/neu-specific inhibition of cellular proliferation and cytoplasmic receptor domain phosphorylation. All the peptide Abs showed Ab-dependent cellular cytotoxicity to varying degrees with the 266-296 constructs being equally effective as compared with Herceptin. The 266-296 peptide vaccine had statistically reduced tumor onset in both transplantable tumor models (FVB/n and BALB/c) and significant reduction in tumor development in two transgenic mouse tumor models (BALB-neuT and VEGF(+/-)Neu2-5(+/-)). The 266-296 construct represents the most promising candidate for antitumor vaccination and could also be used to treat a variety of cancers with either normal or elevated expression of HER-2 including breast, lung, ovarian, and prostate.
HPK1 competes with ADAP for SLP‐76 binding and via Rap1 negatively affects T‐cell adhesion (2010)

The hematopoietic progenitor kinase 1 (HPK1) signals into MAPK and NFκB pathways downstream of immunoreceptors, but enigmatically is a negative regulator of leukocytes. Here, we report a novel role for HPK1 in regulating the activation of the adhesion molecule leukocyte function-associated antigen-1 (LFA-1). Upon TCR stimulation, mediated by binding of adhesion and degranulation promoting adaptor protein (ADAP) to SLP-76, a ternary complex composed of ADAP/55-kDa src kinase associated phosphoprotein (SKAP-55) and RIAM translocates to the membrane and causes membrane recruitment of the active small GTPase Ras-related protein 1 (Rap1). Active Rap1, via its binding to RapL (regulator for cell adhesion and polarization enriched in lymphoid tissues), mediates LFA-1 integrin activation. We show here that HPK1, which also binds SLP-76, compete with ADAP for SLP-76 binding. In addition, HPK1 dampens Rap1 activation, resulting in decreased LFA-1 activity. Analysis of HPK1-deficient T cells revealed increased ADAP recruitment to SLP-76 and elevated Rap1 activation in those cells, leading to increased adhesion to ICAM-1 and cell spreading. Altogether, these results describe a novel function for HPK1 in linking TCR signaling to cell adhesion regulation and provide a mechanistic explanation for the negative regulatory role of HPK1 in T-cell biology.
Origin of the Isomer Stability of Polymethylated DOTA Chelates Complexed with Ln3+ Ions (2021)

DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-based chelates that give only a single isomer in solution when complexed with lanthanide (Ln<sup>3+</sup>) ions is of value for studying protein dynamics and interactions via NMR. Herein, we have investigated the geometries, energetics, and electrostatic potentials of Lu complexed with DOTA (<b>1</b>), ring methylated M4DOTA (<b>2</b>), and arm methylated <i>R</i>-DOTMA (<b>3</b>) and <i>S</i>-DOTMA (<b>4</b>), as well as, both ring and arm methylated 4<i>S</i>-4<i>S</i>-M4DOTMA (<b>5)</b> and 4<i>S</i>-4<i>R</i>-M4DOTMA (<b>6</b>) at the level of M06-L/6-31+G(d)-SDD, to elucidate the origin of the isomer stability. These analyses indicate that the electrostatic repulsion between the arm methyl and the neighboring carboxylate significantly destabilizes the square antiprism (SAP) isomer of Lu-<b>5</b> and the twisted square antiprism (TSAP) isomer of Lu-<b>6</b>, while the steric repulsion between the ring and arm methyl groups attenuates the stability of both TSAP of Lu-<b>5</b> and SAP of Lu-<b>6</b>. To rationalize the variable temperature proton NMR spectra, the energy barriers for the inter-conversion in Lu-<b>5</b> and Lu-<b>6</b> via arm rotation were also calculated. The modulation of the stability and rigidity of Ln complexes via a modification of DOTA is also discussed. Our investigation will aid to design better chelates for the Ln<sup>3+</sup> ions for its use in molecular medicine.
In Situ Click Chemistry: Enzyme‐Generated Inhibitors of Carbonic Anhydrase II (2004)

Das Protein als Reaktor: Statt Tausende von Verbindungen zu synthetisieren und zu testen, um eine Leitstruktur zu finden, nutzt die In-situ-Click-Chemie das biologische Zielmolekül selbst zum Inhibitoraufbau: Die Reagentien werden selektiv in den Bindungsstellen des Zielmoleküls gebunden und verknüpft. Von der Carboanhydrase II wurden so subnanomolare Inhibitoren aus einfachen Azid- und Acetylenvorstufen synthetisiert (siehe Bild). Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2005/z461580_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.
Dual Stem Loops within the Poliovirus Internal Ribosomal Entry Site Control Neurovirulence (1999)

In the human central nervous system, susceptibility to poliovirus (PV) infection is largely confined to a specific subpopulation of neuronal cells. PV tropism is likely to be determined by cell-external components such as the PV receptor CD155, as well as cell-internal constraints such as the availability of a suitable microenvironment for virus propagation. We reported previously that the exchange of the cognate internal ribosomal entry site (IRES) within the 5' nontranslated region of PV with its counterpart from human rhinovirus type 2 (HRV2) can eliminate the neuropathogenic phenotype in a transgenic mouse model for poliomyelitis without diminishing the growth properties in HeLa cells. We now show that attenuation of neurovirulence of PV/HRV2 chimeras is not confined to CD155 transgenic mice but is evident also after intraspinal inoculation into Cynomolgus monkeys. We have dissected the PV and HRV2 IRES elements to determine those structures responsible for neurovirulence (or attenuation) of these chimeric viruses. We report that two adjacent stem loop structures within the IRES cooperatively determine neuropathogenicity.
[Differential forms of self-directed study of biochemistry in medical schools]. (1991)

Methods of self-directed study of biochemistry by students are considered in connection with initial levels of their theoretical knowledge and laboratory experience. This type of training involved individual tasks and free discussion on the results obtained. Optimal results were observed in organization of self-directed work in small groups.
Anatomic localization of immature and mature dendritic cell subsets in dermatomyositis and polymyositis: Interaction with chemokines and Th1 cytokine-producing cells (2004)

The close association between CCL20/CCR6 and immature DCs suggests the contribution of CCL20 to CCR6+ immature DC homing. Detection of mature DCs in DM and PM muscle tissue samples despite the lack of CCL19 and CCR7 is evidence for a local maturation of DCs in inflammatory muscle tissue without lymphoid organ organization.
Identification and Characterization of Ovarian Cancer-Initiating Cells from Primary Human Tumors (2008)

The objective of this study was to identify and characterize a self-renewing subpopulation of human ovarian tumor cells (ovarian cancer-initiating cells, OCICs) fully capable of serial propagation of their original tumor phenotype in animals. Ovarian serous adenocarcinomas were disaggregated and subjected to growth conditions selective for self-renewing, nonadherent spheroids previously shown to derive from tissue stem cells. To affirm the existence of OCICs, xenoengraftment of as few as 100 dissociated spheroid cells allowed full recapitulation of the original tumor (grade 2/grade 3 serous adenocarcinoma), whereas >10(5) unselected cells remained nontumorigenic. Stemness properties of OCICs (under stem cell-selective conditions) were further established by cell proliferation assays and reverse transcription-PCR, demonstrating enhanced chemoresistance to the ovarian cancer chemotherapeutics cisplatin or paclitaxel and up-regulation of stem cell markers (Bmi-1, stem cell factor, Notch-1, Nanog, nestin, ABCG2, and Oct-4) compared with parental tumor cells or OCICs under differentiating conditions. To identify an OCIC cell surface phenotype, spheroid immunostaining showed significant up-regulation of the hyaluronate receptor CD44 and stem cell factor receptor CD117 (c-kit), a tyrosine kinase oncoprotein. Similar to sphere-forming OCICs, injection of only 100 CD44(+)CD117(+) cells could also serially propagate their original tumors, whereas 10(5) CD44(-)CD117(-) cells remained nontumorigenic. Based on these findings, we assert that epithelial ovarian cancers derive from a subpopulation of CD44(+)CD117(+) cells, thus representing a possible therapeutic target for this devastating disease.
Distinct Mechanism for Antidepressant Activity by Blockade of Central Substance P Receptors (1998)

The localization of substance P in brain regions that coordinate stress responses and receive convergent monoaminergic innervation suggested that substance P antagonists might have psychotherapeutic properties. Like clinically used antidepressant and anxiolytic drugs, substance P antagonists suppressed isolation-induced vocalizations in guinea pigs. In a placebo-controlled trial in patients with moderate to severe major depression, robust antidepressant effects of the substance P antagonist MK-869 were consistently observed. In preclinical studies, substance P antagonists did not interact with monoamine systems in the manner seen with established antidepressant drugs. These findings suggest that substance P may play an important role in psychiatric disorders.
Heterostructure lasers. Part A. Fundamental principles (1978)

The book consists of two parts. Part A contains chapters entitled: Introduction; Optical Fields and Wave Propagation; Stimulated Emission in Semiconductors; and Heterojunctions. (TFD)
Preparation and characterization of monoclonal antibody against recombinant human tissue factor pathway inhibitor. (1998)

We established two hybridomas cell lines (4F4, 4F8) and obtained the McAb4F8 against TFPI and reported the levels of TFPI in healthy adult human plasma by Sandwich ELISA with HRP labelled McAb4F8 in Chinese.