gebhart/patrepeval huggingface dataset:
89Zr-labeled CEA-targeted IL-2 variant immunocytokine in patients with solid tumors: CEA-mediated tumor accumulation and role of IL-2 receptor-binding (2018)

Cergutuzumab amunaleukin (CEA-IL2v) is an immunocytokine directed against carcinoembryonic antigen (CEA) containing an IL2v-moiety with abolished IL-2 receptor (IL-2R) α binding. We describe the biodistribution and tumor accumulation of <sup>89</sup>Zr-labeled CEA-IL2v. Twenty-four patients with advanced solid CEA positive (CEA+) or negative (CEA-) tumors received CEA-IL2v 6 mg (4 CEA+; 3 CEA-), 20 mg (9 CEA+), or 30 mg (4 CEA+; 4 CEA-) biweekly. In cycle 1, 2 mg of the total dose comprised <sup>89</sup>Zr-CEA-IL2v (50 MBq) and serial <sup>89</sup>Zr-PET imaging was conducted. Four CEA+ patients with visually confirmed <sup>89</sup>Zr-CEA-IL2v tumor accumulation at 20 mg had repeated <sup>89</sup>Zr-PET imaging during cycle 4. <sup>89</sup>Zr-CEA-IL2v immuno-PET demonstrated preferential drug accumulation in CEA+ tumors (%ID/mL<sub>peak</sub> CEA- 3.6 × 10<sup>-3</sup> vs. CEA+ 6.7 ×∙10<sup>-3</sup>). There was a non-significant trend towards dose-dependent tumor uptake, with higher uptake at doses ≥20 mg. Biodistribution was dose- and CEA-independent with major accumulation in lymphoid tissue compatible with IL-2R binding. Reduced exposure and reduced tumor accumulation (%ID/mL<sub>peak</sub> 57% lower) on cycle 4 vs. cycle 1 was consistent with peripheral expansion of immune cells. The findings of this immune PET imaging study with <sup>89</sup>Zr-CEA-IL2v support the therapeutic concept of CEA-IL2v, confirming selective and targeted tumor accumulation with this novel immunocytokine.
Comparison of neural activity preceding reaches to auditory and visual stimuli in the parietal reach region (2002)

We examined the responses of neurons in the parietal reach region (PRR) during reaches to the remembered locations of auditory or visual stimuli. We found that the firing rate of PRR neurons contained information about the location of auditory and visual stimuli. For neurons tested with visual stimuli, the amount of information remained constant throughout the task. In contrast, for neurons tested with auditory stimuli, the amount of target-location information increased as the trial evolved. During the reach period of the task, the amount of information that was carried by neurons tested with auditory stimuli was not statistically different from the amount carried by neurons tested with visual stimuli. We interpret these data to suggest that the type of information that PRR neurons encode evolves throughout a task.
Novel proteins of the phosphotransferase system encoded within the rpoN operon of Escherichia coli. Enzyme IIANtr affects growth on organic nitrogen and the conditional lethality of an erats mutant. (1995)

Two rpoN-linked delta Tn10-kan insertions suppress the conditionally lethal erats allele. One truncates rpoN while the second disrupts another gene (ptsN) in the rpoN operon and does not affect classical nitrogen regulation. Neither alter expression of era indicating that suppression is post-translational. Plasmid clones of ptsN prevent suppression by either disruption mutation indicating that this gene is important for lethality caused by erats. rpoN and six neighboring genes were sequenced and compared with sequences in the database. Two of these genes encode proteins homologous to Enzyme IIAFru and HPr of the phosphoenolpyruvate:sugar phosphotransferase system. We designate these proteins IIANtr (ptsN) and NPr (npr). Purified IIANtr and NPr exchange phosphate appropriately with Enzyme I, HPr, and Enzyme IIA proteins of the phosphoenolpyruvate: sugar phosphotransferase system. Several sugars and tricarboxylic acid cycle intermediates inhibited growth of the ptsN disruption mutant on medium containing an amino acid or nucleoside base as a combined source of nitrogen, carbon, and energy. This growth inhibition was relieved by supplying the ptsN gene or ammonium salts but was not aleviated by altering levels of exogenously supplied cAMP. These results support our previous proposal of a novel mechanism linking carbon and nitrogen assimilation and relates IIANtr to the unknown process regulated by the essential GTPase Era.
Close-up imaging of documents and displays with lens arrays (1979)

An unusually short close-up imaging system about 8.5 cm (3 (3/8) in.) long has been developed for document copiers, oscilloscope cameras, and computer peripheral hard-copy cameras. Arrays of simple lenses are molded in rows and columns on two parallel plastic lens plates. Each lens on the first lens plate forms a demagnified, inverted, intermediate image of a small area of the object in the space between lens plates. Each lens in the second plate erects and magnifies an intermediate image and places the resulting final image in partially overlapped registration with adjacent images, forming an erect uniform composite image of the whole object.
Two Different Combinations of RNA-binding Domains Determine the RNA Binding Specificity of Nucleolin (2001)

Nucleolin is an abundant nucleolar protein involved in several steps of ribosome biogenesis. The protein is highly conserved through evolution and possesses four RNA-binding domains (RBD), which are likely to determine its RNA binding specificity. Previous studies have shown that nucleolin interacts with two different RNA targets. The first is a small stem-loop structure, the nucleolin recognition element (NRE), found all along the pre-ribosomal RNA. The second is a short single-stranded RNA sequence, the evolutionary conserved motif (ECM), located five nucleotides downstream of the first processing site in the pre-ribosomal RNA 5' external transcribed spacer. Biochemical, genetic, and structural studies have shown that the first two RBD of nucleolin are necessary and sufficient for the specific interaction of nucleolin with the NRE motif. In this work, we have studied the interaction of nucleolin with the ECM sequence. Deletion and mutational analyses showed that all four RBDs of hamster nucleolin were required for the interaction with the ECM sequence. This RNA binding specificity is conserved between hamster and Xenopus laevis, whereas the Xenopus protein does not interact with the NRE. Nucleolin is the first example of a protein that requires four RBDs for its interaction with an RNA target, demonstrating that a single protein can use different combinations of RBD to interact specifically with several RNA sequences.
Nipah Virus Envelope-Pseudotyped Lentiviruses Efficiently Target ephrinB2-Positive Stem Cell Populations In Vitro and Bypass the Liver Sink When Administered In Vivo (2012)

Sophisticated retargeting systems for lentiviral vectors have been developed in recent years. Most seek to suppress the viral envelope's natural tropism while modifying the receptor-binding domain such that its tropism is determined by the specificity of the engineered ligand-binding motif. Here we took advantage of the natural tropism of Nipah virus (NiV), whose attachment envelope glycoprotein has picomolar affinity for ephrinB2, a molecule proposed as a molecular marker of "stemness" (present on embryonic, hematopoietic, and neural stem cells) as well as being implicated in tumorigenesis of specific cancers. NiV entry requires both the fusion (F) and attachment (G) glycoproteins. Truncation of the NiV-F cytoplasmic tail (T5F) alone, combined with full-length NiV-G, resulted in optimal titers of NiV-pseudotyped particles (NiVpp) (∼10(6) IU/ml), even without ultracentrifugation. To further enhance the infectivity of NiVpp, we engineered a hyperfusogenic NiV-F protein lacking an N-linked glycosylation site (T5FΔN3). T5FΔN3/wt G particles exhibited enhanced infectivity on less permissive cell lines and efficiently targeted ephrinB2(+) cells even in a 1,000-fold excess of ephrinB2-negative cells, all without any loss of specificity, as entry was abrogated by soluble ephrinB2. NiVpp also transduced human embryonic, hematopoietic, and neural stem cell populations in an ephrinB2-dependent manner. Finally, intravenous administration of the luciferase reporter NiVpp-T5FΔN3/G to mice resulted in signals being detected in the spleen and lung but not in the liver. Bypassing the liver sink is a critical barrier for targeted gene therapy. The extraordinary specificity of NiV-G for ephrinB2 holds promise for targeting specific ephrinB2(+) populations in vivo or in vitro.
China - Fifth Inland Waterways Project - environmental assessment summary (2005)

This document summarizes the environmental assessment for the Fifth Inland Waterways Project in China, which consists mainly of the construction of the Cuijiaying Navigation and Power Complex, discusses the likely negative environmental impacts, and proposes measures to mitigate them. Proposed measures to reduce risks include the following: Prevent floods by maintaining normal levels for dams and reservoirs. Adopt measures to prevent riverbank erosion and dam breaches. Promote repair and maintenance of the flood release gates and channels, and provide incentives to promote water and electricity conservation. Collect wastewater in sedimentation tanks, acquire underground sewage treatment equipment and use septic tanks for temporary residences. Spray water regularly to damp down dust, and promptly clean up dirt scattered by construction machinery. Choose low-volume construction machinery, schedule work for daytime, and impose time limits in sensitive areas. Adopt water and soil erosion prevention measures such as building retaining walls, protecting slopes, and drainage systems. Promptly refill earth and tamp id needed if there is (tree) cutting. Recover vegetation promptly from borrow pits and disposal areas for excavated materials. Regularly monitor the environment. Protect cultural relics. Avoid discharging industrial wastewater into reservoir area and other water bodies unless pre-treated to reduce pollution. Ships and vessels are banned from discharging waste oil, manure, and garbage into water bodies, and they must be equipped with oil-water separators. Ships and vessels must also be controlled for noise. Apply regulations to prevent accidental spills of hazardous waste; leaks and spills must promptly be reported. Establish a fishery protection system.
Nitrosyl Chloride. (1951)

ADVERTISEMENT RETURN TO ISSUEArticleNEXTNitrosyl Chloride.Leland J. Beckham, William A. Fessler, and Mearl A. KiseCite this: Chem. Rev. 1951, 48, 3, 319–396Publication Date (Print):June 1, 1951Publication History Published online1 May 2002Published inissue 1 June 1951https://pubs.acs.org/doi/10.1021/cr60151a001https://doi.org/10.1021/cr60151a001research-articleACS PublicationsRequest reuse permissionsArticle Views1843Altmetric-Citations80LEARN 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
Vanilloid TRPV1 receptor mediates the antihyperalgesic effect of the nonpsychoactive cannabinoid, cannabidiol, in a rat model of acute inflammation (2004)

Cannabidiol (CBD), a nonpsychoactive marijuana constituent, was recently shown as an oral antihyperalgesic compound in a rat model of acute inflammation. We examined whether the CBD antihyperalgesic effect could be mediated by cannabinoid receptor type 1 (CB1) or cannabinoid receptor type 2 (CB2) and/or by transient receptor potential vanilloid type 1 (TRPV1). Rats received CBD (10 mg kg(-1)) and the selective antagonists: SR141716 (N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide) for CB1, SR144528 (N-[(1S)-endo-1,3,3-trimethylbicyclo[2.2.1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)pyrazole-3 carboxamide) for CB2 and capsazepine (CPZ) for TRPV1 receptors. The intraplantar injection of carrageenan in rats induced a time-dependent thermal hyperalgesia, which peaked at 3 h and decreased at the following times. CBD, administered 2 h after carrageenan, abolished the hyperalgesia to the thermal stimulus evaluated by plantar test. Neither SR141716 (0.5 mg kg(-1)) nor SR144528 (3 and 10 mg kg(-1)) modified the CBD-induced antihyperalgesia; CPZ partially at the lowest dose (2 mg kg(-1)) and fully at the highest dose (10 mg kg(-1)) reversed this effect. These results demonstrate that TRPV1 receptor could be a molecular target of the CBD antihyperalgesic action.
Selection of single domain binding proteins by covalent DNA display (2007)

Selection technologies such as phage and ribosome display, which provide a physical linkage between genetic information and encoded polypeptide, are important tools for the engineering of proteins for diagnostic and therapeutic applications. We have recently described a selection strategy called covalent DNA display, in which individual proteins are covalently linked to the cognate encoding DNA template in separate droplets of a water-in-oil emulsion. We here report on the optimization of several experimental steps in covalent DNA display technology, such as the elution conditions and the PCR strategy used for the amplification of selected DNA templates. A PCR assembly strategy was developed, which allows the amplification of the DNA templates over repeated rounds of selection. In addition, we could demonstrate that approximately 50% of the DNA templates form a covalent adduct with the corresponding proteins in the compartments of a water-in-oil emulsion. In model selection experiments, differences in recovery efficiency <100 000 per round of selection could be observed when comparing a specific binding polypeptide with a binder of irrelevant specificity. Furthermore, the optimized protocol was successfully applied for the selection of single domain proteins, capable of specific binding to mouse serum albumin (MSA). A mutant derived from the SH3 domain of the Fyn kinase, with millimolar affinity to MSA, was affinity matured using covalent DNA display and yielded several MSA binding FynSH3 variants with dissociation constants in the 100 nM range.
Circulating and binding characteristics of wild-type factor IX and certain Gla domain mutants in vivo (2002)

Residue K5 in factor IX gamma-carboxyglutamic acid (Gla) domain participates in binding endothelial cells/collagen IV. We injected recombinant factor IX containing mutations at residue 5 (K5A, K5R) into factor IX-deficient mice and compared their behavior with that of wild-type factor IX. The plasma concentration of factor IX that binds to endothelial cells/collagen IV (recombinant wild type and K5R) was consistently lower than that of the one that does not bind (K5A). Mice treated with wild type or K5R had 79% of the injected factor IX in the liver after 2 minutes, whereas 17% remained in circulation. In mice injected with K5A, 59% of the injected factor IX was found in liver and 31% was found in plasma. When we blocked the liver circulation before factor IX injection, 74% of K5A and 64% of K5R remained in the blood. When we treated the mouse with EDTA after injecting exogenous factor IX, the blood levels of factor IX that bind to endothelial cells/collagen IV increased, presumably because of release from endothelial cell/collagen IV binding sites. In contrast, the levels of the mutants that do not bind were unaffected by EDTA. In immunohistochemical studies, factor IX appears on the endothelial surfaces of mouse arteries after factor IX injection and of human arteries from surgical specimens. Thus, we have demonstrated that factor IX binds in vivo to endothelial cell-collagen IV surfaces. Our results suggest that factor IX Gla-domain mediated binding to endothelial cells/collagen IV plays a role in controlling factor IX concentration in the blood.
Comparison of PCR-Based Methods for Typing Staphylococcus aureus Isolates (2006)

In this study, we compared the potentials of (i) a multiplex PCR-based multilocus variable-number tandem repeat (VNTR) assay; (ii) a triplex PCR coamplifying fragments of spa, coa, and the hypervariable region adjacent to the mecA gene; (iii) restriction profile analysis of the STAR repetitive element; (iv) randomly amplified polymorphic DNA analysis; (v) inter-IS256 PCR; and (vi) rep-MP3 PCR. Multilocus VNTR typing and triplex PCR (coa, spa, and hypervariable region) approaches showed excellent reproducibility and high discriminatory power; however, only multilocus VNTR typing could distinguish all pulsed-field gel electrophoresis and spa types. Multilocus VNTR typing appears to be the most useful PCR-based method for the rapid genotyping of Staphylococcus aureus strains.
Large symmetric π transformations for Hadamard transforms (1983)

Many multiplexing instruments utilize the fast Hadamard transform (FHT) to demultiplex the signal. In the past, the FHT includes the π1 and π2 transformations to reorder vectors before and after a Sylvester-type Hadamard transform. Although the computational effort involved in the π1 and the Sylvester-type Hadamard transform scales as n log2n, calculating the π2 transformation (which only has to be done once) scales as n2. Recently Gunson (1980) has suggested a method by which the π transformations are symmetric, that is π2 = π1. We have calculated a complete set of symmetric π transformations for FHT of sizes 23 to 230. Special emphasis has been placed on the phase of the π transformation so as to have the correct phase in the demultiplexed signal.
Mobile health technology of the future: creation of an M-Health taxonomy based on proximity (2007)

In the future Mobile Health (M-Health) applications will take advantage of technological advances such as nanotechnology, device miniaturisations, device convergence, high-speed mobile networks, and advanced medical sensors. This will lead to the increased diffusion of clinical M-Health systems and services which will have a powerful impact on the health care sector (Istepanian and Laxminaryan, 2000). This paper introduces the concept of 'Proximity' to categorise the mobile health applications into groups based on the distance between the user (human) and the technology (device or sensor) being used to record or capture the health related data. The three categories used are 'Tele', 'Derma', and 'In Vivo'.
Honokiol causes G0-G1 phase cell cycle arrest in human prostate cancer cells in association with suppression of retinoblastoma protein level/phosphorylation and inhibition of E2F1 transcriptional activity (2007)

The present study was undertaken to gain insights into the mechanism of cell cycle arrest caused by honokiol, a constituent of oriental herb Magnolia officinalis. The honokiol treatment decreased the viability of PC-3 and LNCaP human prostate cancer cells in a concentration- and time-dependent manner, which correlated with G0-G1 phase cell cycle arrest. The honokiol-mediated cell cycle arrest was associated with a decrease in protein levels of cyclin D1, cyclin-dependent kinase 4 (Cdk4), Cdk6, and/or cyclin E and suppression of complex formation between cyclin D1 and Cdk4 as revealed by immunoprecipitation using anti-cyclin D1 antibody followed by immunoblotting for Cdk4 protein. The honokiol-treated PC-3 and LNCaP cells exhibited a marked decrease in the levels of total and phosphorylated retinoblastoma protein (Rb), which correlated with the suppression of transcriptional activity of E2F1. Exposure of PC-3 and LNCaP cells to honokiol resulted in the induction of p21 (PC-3 and LNCaP) and p53 protein expression (LNCaP). However, small interfering RNA (siRNA)-mediated knockdown of either p21 (PC-3 and LNCaP) or p53 (LNCaP) protein failed to confer any protection against honokiol-induced cell cycle arrest. The honokiol treatment caused the generation of reactive oxygen species (ROS), and the cell cycle arrest caused by honokiol was partially but significantly attenuated in the presence of antioxidant N-acetylcysteine. In conclusion, the present study reveals that the honokiol-mediated G0-G1 phase cell cycle arrest in human prostate cancer cells is associated with the suppression of protein level/phosphorylation of Rb leading to inhibition of transcriptional activity of E2F1.
Constitutive NF-κB Activation Confers Interleukin 6 (IL6) Independence and Resistance to Dexamethasone and Janus Kinase Inhibitor INCB018424 in Murine Plasmacytoma Cells (2011)

Myeloma cells are dependent on IL6 for their survival and proliferation during the early stages of disease, and independence from IL6 is associated with disease progression. The role of the NF-κB pathway in the IL6-independent growth of myeloma cells has not been studied. Because human herpesvirus 8-encoded K13 selectively activates the NF-κB pathway, we have used it as a molecular tool to examine the ability of the NF-κB pathway to confer IL6 independence on murine plasmacytomas. We demonstrated that ectopic expression of K13, but not its NF-κB-defective mutant or a structural homolog, protected plasmacytomas against IL6 withdrawal-induced apoptosis and resulted in emergence of IL6-independent clones that could proliferate long-term in vitro in the absence of IL6 and form abdominal plasmacytomas with visceral involvement when injected intraperitoneally into syngeneic mice. These IL6-independent clones were dependent on NF-κB activity for their survival and proliferation but were resistant to dexamethasone and INCB018424, a selective Janus kinase 1/2 inhibitor. Ectopic expression of human T cell leukemia virus 1-encoded Tax protein, which resembles K13 in inducing constitutive NF-κB activation, similarly protected plasmacytoma cells against IL6 withdrawal-induced apoptosis. Although K13 is known to up-regulate IL6 gene expression, its protective effect was not due to induction of endogenous IL6 production but instead was associated with sustained expression of several antiapoptotic members of the Bcl2 family upon IL6 withdrawal. Collectively, these results demonstrate that NF-κB activation cannot only promote the emergence of IL6 independence during myeloma progression but can also confer resistance to dexamethasone and INCB018424.
Association of increased interferon‐inducible gene expression with disease activity and lupus nephritis in patients with systemic lupus erythematosus (2006)

The 5 IFN-inducible genes were highly expressed in SLE patients, and increased levels were correlated with disease activity defined by several methods. IFN scores, or LY6E levels, were elevated in lupus nephritis patients, especially during active renal disease, and in patients with anti-dsDNA antibody positivity and hypocomplementemia. IFN scores, or LY6E levels, may be useful as a biomarker for lupus nephritis therapy.