gebhart/patrepeval huggingface dataset:
Development of a Metabolically Stable Neurotensin Receptor 2 (NTS2) Ligand (2012)

Subtype-selective neurotensin receptor 2 (NTS2) ligands can be used as molecular probes to investigate the physiological role of neurotensinergic systems and serve as lead compounds to initiate the development of drugs for the treatment of tonic pain. Starting from our recently described NTS2 ligand 1, structural variants of type 2 were synthesized to further improve binding affinity and selectivity to gain metabolic stability. The peptide-peptoid hybrid 2 b showed excellent NTS2 binding affinity (K(i) =2.8 nM) and 22 000-fold selectivity over NTS1, as well as metabolic stability over 32 h in a serum degradation assay. Employing a MAPK-driven luciferase reporter gene assay and an IP accumulation assay, the neurotensin mimetic 2 b displayed respective inhibitions of constitutive activity exceeding 4.3- and 3.9-fold that of the inverse agonist activity of the endogenous ligand neurotensin.
Specific Endothelial Cells Govern Nanoparticle Entry into Solid Tumors (2021)

The successful delivery of nanoparticles to solid tumors depends on their ability to pass through blood vessels and into the tumor microenvironment. Here, we discovered a subset of tumor endothelial cells that facilitate nanoparticle transport into solid tumors. We named these cells nanoparticle transport endothelial cells (N-TECs). We show that only 21% of tumor endothelial cells located on a small number of vessels are involved in transporting nanoparticles into the tumor microenvironment. N-TECs have an increased expression of genes related to nanoparticle transport and vessel permeability compared to other tumor endothelial cells. The N-TECs act as gatekeepers that determine the entry point, distribution, cell accessibility, and number of nanoparticles that enter the tumor microenvironment.
Inhibition of Neuronal Nicotinic Acetylcholine Receptor Subtypes by α-Conotoxin GID and Analogues (2008)

alpha-Conotoxins are small disulfide-rich peptides from the venom of the Conus species that target the nicotinic acetylcholine receptor (nAChR). They are valuable pharmacological tools and also have potential therapeutic applications particularly for the treatment of chronic pain. alpha-Conotoxin GID is isolated from the venom of Conus geographus and has an unusual N-terminal tail sequence that has been shown to be important for binding to the alpha4beta2 subtype of the nAChR. To date, only four conotoxins that inhibit the alpha4beta2 subtype have been characterized, but they are of considerable interest as it is the most abundant nAChR subtype in the mammalian brain and has been implicated in a range of diseases. In this study, analysis of alanine-scan and truncation mutants of GID reveals that a conserved proline in alpha-conotoxins is important for activity at the alpha7, alpha3beta2, and alpha4beta2 subtypes. Although the proline residue was the most critical residue for activity at the alpha3beta2 subtype, Asp(3), Arg(12), and Asn(14) are also critical at the alpha7 subtype. Interestingly, very few of the mutations tested retained activity at the alpha4beta2 subtype indicating a tightly defined binding site. This lack of tolerance to sequence variation may explain the lack of selective ligands discovered for the alpha4beta2 subtype to date. Overall, our findings contribute to the understanding of the structure-activity relationships of alpha-conotoxins and may be beneficial for the ongoing attempts to exploit modulators of the neuronal nAChRs as therapeutic agents.
Site-Isolated Upconversion Nanoparticle Arrays Synthesized in Polyol Nanoreactors (2021)

A versatile approach for synthesizing Yb3+- and Er3+-doped NaYF4 upconversion nanoparticle (UCNP) arrays is presented. The nanoparticles are positioned at precisely defined locations through the tip-directed deposition of polyol nanoreactors and subsequent thermal conversion. This method is based on conducting a solution-phase polyol synthesis in nanometer-scale reactors, which provide isolated and confined reaction vessels for the thermal decomposition of a fluoride precursor and the coarsening of fluoride nanoparticles. When the nanoreactors are annealed at 350 °C, the polyol degrades, and the nanoparticles, which exhibit upconversion properties, crystallize. Single nanoparticles are attained in each nanoreactor by tuning the precursor concentration, nanoreactor size, and temperature ramping rate. This strategy enhances the scope of nanostructures that can be synthesized by tip-directed routes and, when combined with massively parallel pen approaches such as polymer pen lithography, provides a generalizable platform for the high-throughput synthesis, screening, and discovery of nanomaterials for photonics and other applications.
Catechol-O-Methyltransferase Decreases Levodopa Toxicity In Vitro (2001)

The purpose of this study was to examine the effects of 3-O-methylation by catechol-O-methyltransferase (COMT) on the toxicity of levodopa in neuronal cultures. High concentrations of levodopa are toxic in vitro. Therefore, there is concern that long-term treatment with levodopa in patients with Parkinson's disease might accelerate the rate of degeneration of nigrostriatal neurons. However, recent studies have suggested that, while levodopa is harmful in vitro, it may not be toxic in vivo. A possible defense mechanism is by means of metabolic shunting of levodopa excess to 3-O-methyldopa by COMT in peripheral and central nervous system tissues. In this study we examine whether the use of COMT inhibitor, which reduced the levels of 3-O-methyldopa, affect levodopa toxicity. Mice cerebellar granule neurons, PC12, and neuroblastoma cells were used, and their viability following exposure to levodopa and COMT with and without tolcapone, a COMT inhibitor, was measured by neutral red staining. Auto-oxidation of levodopa was evaluated using a spectrophotometer (690 nm). We found that 3-O-methyldopa, unlike levodopa, was not toxic to all cells examined. Addition of purified COMT to levodopa prevented its auto-oxidation and markedly attenuated its cytotoxicity in vitro. Additional tolcapone reversed the protective effect of COMT. The agent 3-O-methyldopa is not toxic to cell cultures. Catechol-O-methyltransferase attenuates toxicity of levodopa in vitro by its metabolism to nontoxic 3-O-methyldopa.
Role of endothelin-1 induced by insulin in the regulation of vascular cell growth (2003)

Insulin is not only a growth factor for vascular cells, but also an inducer of other vasoactive substances such as endothelin-1 (ET-1) in vascular cells. The aim of the present study was to assess the role of endothelial cells (EC) in insulin mediated vascular smooth muscle cell (VSMC) proliferation. Cultured human aortic EC and VSMC were separately incubated. EC were stimulated with insulin (0 to 1000 microU/mL) for 24 h, in the presence or absence of anti-insulin-growth factor-1 (anti-IGF-1) receptor antibody (alphaIR(3)) or a nonselective ET-1 receptor antagonist (TAK044). Cell proliferation was measured by determining (3)H-thymidine uptake. Although 10 microU/mL insulin did not affect ET-1 production in the EC culture medium, a higher concentration of insulin stimulated it. Production of ET-1 in EC was activated by insulin via the IGF-1 receptor, inasmuch as alphaIR(3) blocked insulin mediated upregulation of ET-1. There was no significant difference in (3)H-thymidine incorporation in the presence of insulin (up to 1000 microU/mL) or TAK044. Culture medium from EC stimulated with insulin enhanced VSMC proliferation, which was almost totally suppressed by TAK044. Insulin induced VSMC growth dose dependently when VSMC were cultured alone. In contrast, insulin at concentrations of 100 microU/mL or lower failed to stimulate growth of co-cultured VSMC, but only at 330 microU/mL or higher concentrations stimulated VSMC growth in this system. Of interest, VSMC proliferation was greatest when L-NAME was added and co-cultured with EC. In summary, a severely hyperinsulinemic state may regulate VSMC and EC proliferation via activation of vasoactive substances such as ET-1 and nitric oxide induced by insulin.
High Carrier Prevalence of Deficient and Null Alleles of CYP2 Genes in a Major USA Hospital: Implications for Personalized Drug Safety (2006)

Many drugs are metabolized by highly polymorphic cytochrome P450 (CYP) enzymes. Among these enzymes, members of the CYP2 family coded by the CYP2D6, CYP2C9 and CYP2C19 genes are best amenable to the precise prediction of an individual's innate capacity to metabolize drugs by DNA typing of inherited null and deficient alleles. We determined the frequency of these alleles and the prevalence of their carriers in a New England, USA, tertiary care center to assess underlying population genetic features for the practice of personalized medicine. We determined that 54, 25 and 27% are carriers of at least one deficient or null allele for the CYP2D6, CYP2C9 and CYP2C19 genes, respectively. Furthermore, 6% of individuals are carriers of two null alleles for CYP2D6 and are predicted to have no biochemical activity for this isoenzyme. These results support the implementation of DNA typing of CYP2 genes to diagnose adverse drug reactions and to prevent a substantial number of patients being prescribed drugs they cannot adequately metabolize.
SARS-CoV-2 variant transition dynamics are associated with vaccination rates, number of co-circulating variants, and convalescent immunity (2023)

Laboratory Directed Research and Development (LDRD), Los Alamos National Laboratory.
SSARES: Secure Searchable Automated Remote Email Storage (2007)

The increasing centralization of networked services places user data at considerable risk. For example, many users store email on remote servers rather than on their local disk. Doing so allows users to gain the benefit of regular backups and remote access, but it also places a great deal of unwarranted trust in the server. Since most email is stored in plaintext, a compromise of the server implies the loss of confidentiality and integrity of the email stored therein. Although users could employ an end-to-end encryption scheme (e.g., PGP), such measures are not widely adopted, require action on the sender side, only provide partial protection (the email headers remain in the clear), and prevent the users from performing some common operations, such as server-side search. To address this problem, we present secure searchable automated remote email storage (SSARES), a novel system that offers a practical approach to both securing remotely stored email and allowing privacy-preserving search of that email collection. Our solution encrypts email (the headers, body, and attachments) as it arrives on the server using public-key encryption. SSARES uses a combination of identity based encryption and bloom filters to create a searchable index. This index reveals little information about search keywords and queries, even against adversaries that compromise the server. SSARES remains largely transparent to both the sender and recipient.
Knowledge based system support for introductory power system network analysis on personal computers (1990)

The application of artificial intelligence for knowledge-based systems (KBSs) is reviewed and applied to the basic power system network analysis problem. A frame-based KBS has been developed to assist students in preparing data for power flow analysis. The prototype for a power flow knowledge-based system (PFKBS) is an example of a shallow knowledge system. The details of an implementation for a simple power system are used to highlight the difference between a frame-based approach and a conventional FORTRAN approach. The data structures used within the developed frame-based KBS are presented in sufficient detail for anyone to regenerate the database. The user interface is illustrated for a small power system. The method of preparing data for the power flow as a sequence of knowledge bases is discussed for the example system.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Gender, age and seasonal effects on IgA deficiency: a study of 7293 Caucasians (2004)

The prevalence of SIgAD and subnormal SIgA levels is increased in males. There exists a significant influence of gender, age and seasons on SIgA levels.
Derivatives of 1,2,3,4-Tetrahydroisoquinoline-3-carboxylic Acid (2006)

The following derivatives of 1,2,3,4-tetrahydroisoquinoline-3carboxylic acid have been prepared in their (S)-form and as racemates: hydrochloride of methyl ester, N-carboxy anhydride, and N-acetyl derivative.All the substances were fully characterised by elemental analyses, 1 H and 13 C NMR spectra, and optical rotation, as the case may be; the N-carboxy anhydride was also characterised by means of X-Ray diffraction.Also identified was the intermediate of the reaction of the title acid with phosgene, the N-chlorocarbonyl derivative, and the respective methyl ester was prepared.The dioxopiperazine of the title acid was prepared and characterised both in pure (S,S)-form and in the form of a mixture of two racemates.The optically pure dioxopiperazine was prepared by a reaction of the N-carboxy anhydride in solid phase.
Programmed Cell Death (Apoptosis) and Cancer Chemotherapy (1996)

BACKGROUND: Programmed cell death involves a genetic reprogramming of the cell to promote an energy-dependent cascade of biochemical and morphological changes within the cell that result in its death and elimination. METHODS: The regulations and mechanisms of programmed cell death are reviewed with an emphasis on how derangement of this mechanism may be involved in modulating responsiveness to chemotherapy. RESULTS: Activation of this programmed death process is controlled by a series of endogenous cell-type-specific signals. In addition, a variety of exogenous cell-damaging treatments (eg, radiation, chemicals, and viruses) and most chemotherapeutic drugs can activate this pathway if sufficient injury to the cell occurs. Resistance to chemotherapy can involve alterations in the ability of a malignant cell to activate the programmed cell death (apoptotic) pathway when damaged by these exogenous agents. CONCLUSIONS: The most important determinant of tumor resistance may be a generalized resistance to induction of programmed cell death rather than resistance based on specific alteration in drug/target interactions.
Amino-Functionalized Polystyrene Nanoparticles Activate the NLRP3 Inflammasome in Human Macrophages (2011)

Specifically designed and functionalized nanoparticles hold great promise for biomedical applications. Yet, the applicability of nanoparticles is critically predetermined by their surface functionalization. Here we demonstrate that amino-functionalized polystyrene nanoparticles (PS-NH(2)) of ∼100 nm in diameter, but not carboxyl- or nonfunctionalized particles, trigger NLRP3 inflammasome activation and subsequent release of proinflammatory interleukin 1β (IL-1β) by human macrophages. PS-NH(2) induced time-dependent proton accumulation in lysosomes associated with lysosomal destabilization, release of cathepsin B, and damage of the mitochondrial membrane. Accumulation of mitochondrial reactive oxygen species was accompanied by oxidation of thioredoxin, a protein playing a central role in maintaining the cellular redox balance. Upon oxidation, thioredoxin dissociated from the thioredoxin-interacting protein (TXNIP). Liberated TXNIP, in turn, interacted with the NLRP3 protein, resulting in a conformational change of the pyrin domain of the NLRP3 protein, as was predicted by molecular modeling. Consequently, this prompted assembly of the NLRP3 inflammasome complex with recruitment and activation of caspase-1, inducing IL-1β release by cleavage of pro-IL-1β. The central role of the NLRP3 inflammasome for cytokine production was confirmed by in vitro knockdown of NLRP3 and of the adaptor protein ASC, confirming that other inflammasomes were not activated by PS-NH(2). The PS-NH(2)-mediated proinflammatory macrophage activation could be antagonized by the radical scavenger N-acetyl-L-cysteine, which prevented mitochondrial damage, caspase-1 activation, and the subsequent release of IL-1β. Our study reveals the molecular mechanism of NLRP3 inflammasome activation by amino-functionalized nanoparticles and suggests a strategy as to how such adverse effects could be antagonized.
Optical imaging for the characterization of radioactive carbon and oxygen ion beams (2019)

Heavy ion therapy is a promising cancer therapy technique due to the sharper Bragg peak and smaller lateral scattering characteristics of heavy ion beams as compared to a proton therapy. Recently, the potential for radioactive ion beam therapy has been investigated in combination with the OpenPET system to improve the accuracy of in vivo beam range verification. However, the characteristics of the radioactive ion beams have not been investigated thoroughly. Optical imaging has been proposed as a novel high-resolution beam range estimation method for heavy ion beams. In this study, high-resolution luminescence imaging and Cerenkov light imaging were performed for the range estimation of radioactive ion beams such as <sup>11</sup>C and <sup>15</sup>O in the Heavy Ion Medical Accelerator in Chiba (HIMAC) secondary beam line. A polymethyl methacrylate (PMMA) phantom (10.0 × 10.0 × 9.9 cm<sup>3</sup>) was irradiated by <sup>11</sup>C and <sup>15</sup>O ion beams. In order to obtain the in-beam luminescence and off-line beam Cerenkov light images, an optical system was used that consisted of a lens and a cooled CCD camera. The Bragg peaks and stopping positions of the <sup>11</sup>C and <sup>15</sup>O ion beams could be visualized by using the luminescence and Cerenkov light imaging, respectively. The Bragg peaks showed a good correlation with the peak of the luminescence profile with a positional discrepancy of 1 mm and 0.4 mm for the <sup>11</sup>C and <sup>15</sup>O ion beams, respectively. In conclusion, optical imaging using luminescence and Cerenkov light could be used for the precise range estimation of radioactive ion beams.
Starfish-shaped Cooper pairs with ultrashort antinodal length scales in cuprate superconductors (2018)

Cooper pairs of mutually attracting electrons form the building blocks of superconductivity. Thirty years after the discovery of high-temperature superconductivity in cuprates, many details of the pairs remain unknown, including their size and shape. Here we apply brand new ARPES-based methods that allow us to reconstruct the shape and size of the pairs in Bi$_2$Sr$_2$CaCu$_2$O$_{8+{\delta}}$. The pairs are seen to form a characteristic starfish shape that is very long (>50{\AA}) in the near-nodal direction but extremely short (~4.5{\AA}) in the antinodal (Cu-Cu) direction. We find that this ultrashort antinodal length scale, which is of order a lattice constant, is approximately constant over a wide range of doping levels even as many other parameters including the pairing strength change. This suggests that this new length scale, along with the pair shape, is one of the most fundamental characteristics of the pairs. Further, the shape and ultrashort length scale should make the pairs create or intertwine with variations in charge and pair density, center on various types of lattice positions, and potentially explain aspects of the nematic order in these materials.
Flight Test of Active Structural Acoustic Noise Control System (2001)

A flight test is described in which an active structural/acoustic control system reduces turboprop induced interior noise on a Raytheon Aircraft Company 1900D airliner. Control inputs to 21 inertial force actuators were computed adaptively using a principal component domain version of the multichannel filtered-x least mean square algorithm to minimize the mean square response of 32 microphones. A tabu search algorithm was employed to optimize placement of the force actuators on the aircraft frame. Both single-frequency and multifrequency control results are presented. Noise reductions of up to 15 dB were obtained at the blade passage frequency (BPF) during single-frequency control tests. Simultaneous noise reductions of 10 dB, 2.5 dB, and 3.0 dB, at the BPF and next 2 harmonics, were obtained in a multifrequency test.
Synthesis of the Antitumor Alkaloid (+)-Pancratistatin Using the β-Azidonation Reaction via a Prochiral 4-Arylcyclohexanone Derivative (1998)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTSynthesis of the Antitumor Alkaloid (+)-Pancratistatin Using the β-Azidonation Reaction via a Prochiral 4-Arylcyclohexanone DerivativePhilip Magnus and Iyassu K. SebhatView Author Information Department of Chemistry and Biochemistry University of Texas at Austin, Austin, Texas 78712 Cite this: J. Am. Chem. Soc. 1998, 120, 21, 5341–5342Publication Date (Web):May 13, 1998Publication History Received4 February 1998Published online13 May 1998Published inissue 1 June 1998https://pubs.acs.org/doi/10.1021/ja980407shttps://doi.org/10.1021/ja980407srapid-communicationACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views1237Altmetric-Citations84LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Enantioselective synthesis,Mixtures,Organic compounds,Organic reactions,Reaction products Get e-Alerts
The Tungstogermanate [Ce20Ge10W100O376(OH)4(H2O)30]56−: A Polyoxometalate Containing 20 Cerium(III) Atoms (2007)

Big W: One of the largest polytungstates, the 20 cerium(III) atom tungstogermanate [Ce20Ge10W100O376(OH)4(H2O)30]56− (1), has been synthesized from CeIII ions and [α-GeW9O34]10− in aqueous acidic medium at pH 5.0. Polyanion 1 represents the first lanthanide-substituted tungstogermanate and can be described as a dimer that is linked through long CeO(W) bridges.
ChemInform Abstract: Novel Method for the Preparation of Tricyclic [6:6:5] Systems by Reductive Cyclization of Amide Esters (I) with LAH. (2001)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Analysis of radiation effects in space for terrestrial solar cells on MDS-1 (2004)

Mission Demonstration-test Satellite No. 1, (MDS-1) launched in February 2002, has been flying in a geostationary transfer orbit (GTO), where the radiation environment is quite severe. We report the flight data for terrestrial solar cells on MDS-1 to investigate radiation tolerance. The flight data are also compared with ground test results using relative damage coefficients and the displacement damage methodologies.