gebhart/patrepeval huggingface dataset:
Abstract LB-187: Identification of CIT-0665, a novel inhibitor of LSD1 (2011)

Abstract Lysine-specific demethylase 1 (LSD1/AOF2/KDM1A) is a flavin-dependent histone demethylase that catalyzes the posttranslational oxidative demethylation of mono- and dimethylated lysines on histones. Methylation of lysine residues on histones can signal transcriptional activation or repression depending on the specific residue involved. H3K4me2 is a transcription-activating chromatin mark at gene promoters, and demethylation of this mark by LSD1 is thought to prevent expression of tumor suppressor genes important in human cancer. In contrast, methylation of H3K9 is a repressive mark and LSD1 activity has been shown to upregulate tumor promoting pathways. Thus, LSD1 is emerging as an important target for the development of specific inhibitors as a new class of antitumor drugs. Currently, only a few existing compounds, such as monoamine oxidase inhibitors, have been shown to act as inhibitors of LSD1. More potent and specific inhibitors of LSD1 are needed to advance LSD1 biology and test for potential efficacy in tumor models. We utilized the 3-D crystal structure of LSD1 to computationally dock more than 10 million virtual compounds into the active site of the protein. From the docking experiments, we physically screened 52 compounds in an LSD1 biochemical assay (resorufin-based assay measuring the amount of hydrogen peroxide generated by LSD1). The compound CIT-0665 was identified as a potent inhibitor of LSD1 enzymatic activity, with an IC50 of 290nM. Additionally, cell lines treated with CIT-0665 show increased levels of H3K4 methylation. A large panel of cancer cell lines was also tested for sensitivity to CIT-0665, using a cell viability assay. We are currently engaged in determining possible mechanisms of sensitivity from the cell line panel and making analogs of CIT-0665 with improved drug-like qualities. In conclusion, CIT-0665 is a novel LSD-1 inhibitor with activity in biochemical and cell-based assays. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-187. doi:10.1158/1538-7445.AM2011-LB-187
Molecularly imprinted polymer nanospheres as synthetic affinity receptors obtained by miniemulsion polymerisation (2002)

Highly crosslinked polymer nanospheres composed of poly[(methacrylic acid)-co-(ethylene glycol dimethacrylate)] and poly(EGDMA) have been synthesised by miniemulsion polymerisation in presence of a chiral molecular template, L- or D-Boc-phenylalanine anilid. The miniemulsions and the resulting microgels were characterised by surface tension measurements, gravimetric analysis, dynamic light scattering, transmission electron microscopy, 1H and 13C CP-MAS NMR, and Brunauer-Emmett-Teller gas adsorption measurements. The efficiency of the non-covalent molecular imprinting was examined by binding experiments and quantified by UV absorption. The miniemulsions were converted to coagulate-free and stable latexes with a conversion of 98 ± 2% and an apparent hydrodynamic particle diameter of 200 ± 20 nm. Molecular imprinting was most effective when a miniemulsion of molar ratio nMAA/nEGDMA = 0.25:1 was used for the microgel preparation. Enantioselective binding of the templates to the particles was observed. Binding of the L-enantiomer was four times greater in the L-imprinted polymer than in the non-imprinted polymer and 10 times than binding of the D-enantiomer in the L-imprinted microgels. This new method allows for a one-stage preparation of fully synthetic affinity receptors with a defined spherical shape and a high specific surface area due to their nanoscopic dimension. Transmission electron microscope photograph of particles of polymer 6, prepared in presence of template.
A Compact Dual-Band Rectenna for GSM900 and GSM1800 Energy Harvesting (2018)

This paper presents a compact dual-band rectenna for GSM900 and GSM1800 energy harvesting. The monopole antenna consists of a longer bent Koch fractal element for GSM900 band and a shorter radiation element for GSM1800. The rectifier is composed of a multisection dual-band matching network, two rectifying branches, and filter networks. Measured peak efficiency of the proposed rectenna is 62% at 0.88 GHz 15.9 μ W/cm 2 and 50% at 1.85 GHz 19.1 μ W/cm 2 , respectively. When the rectenna is 25 m away from a cellular base station, measurement result shows that the harvested power is able to power a batteryless LCD watch and achieve 1.275 V output voltage. The proposed rectenna is compact, efficient, low cost, and easy to fabricate, and it is suitable for RF energy harvesting and various wireless communication scenarios.
Fluorescence microscopy studies of a peripheral benzodiazepine receptor targeted molecular probe for brain tumor imaging (2003)

This study investigates the potential of a new multi-modal lanthanide chelate complex for specifically targeting brain tumor cells. We report here results from ongoing studies of up-take, sub-cellular localization and binding specificity of this new molecular imaging probe. Fluorescence microscopy investigations in living rat C6 glioma tumor cells demonstrate that the new imaging agent has affinity for glioma cells and binds to mitochondria.
Synthesis Of Silver Sulfide Stratified Photocatalyst (2008)

In this report, silver sulfide (Ag2S) was selected as a new H2S splitting photocatalyst material, and considered the synthesis method of Ag2S photocatalyst particles with stratified structure. Previous stratified particles were synthesized by using metal oxide (hydroxide) as the precursor. Ag2O particles as the precursor of Ag2S were synthesized by mixing AgNO3 solution and NaOH, and their particle sizes could be controlled by the solutions' concentration. Then, Ag2S particles were obtained by adding Na2S solution into suspending solution of Ag2O particles with optimum sizes. Particle sizes of Ag2S were changed by Na2S concentration control, and remaining Ag2O precursor could be dissolved by adding NH3 solution. The photocatalytic H2S splitting could be realized by UV‐light irradiation on the Ag2S particles without co‐catalyst like Pt.
Greensted Church, Ongar: Oak v. Chestnut (1907)

Journal Article Greensted Church, Ongar: Oak v. Chestnut Get access Henry Taylor Henry Taylor 1Rusthall, Kent Search for other works by this author on: Oxford Academic Google Scholar Notes and Queries, Volume s10-VIII, Issue 204, 23 November 1907, Pages 416–417, https://doi.org/10.1093/nq/s10-VIII.204.416d Published: 23 November 1907
Magnetic Microscopy for 3D Structures: Use of the Simulation Approach for the Precise Localization of Deep Buried Weak Currents (2010)

Abstract With the innovations in packaging technologies which have taken place over the last decade, new assemblies often include an increasing number of dies inside a single package. This is exactly what was predicted by the More than Moore’s paradigm: as the integration of ICs increases, the heterogeneity of the devices found in a single package increases. As a result, the number of potential failures which can appear at assembly level has increased exponentially. At present, no technique has been able to precisely localize defects which are deep inside a complex package. For this reason, a new technique for failure localization for three-dimensional structures is needed. In this paper the technique proposed, based on the coupling of magnetic measurements and simulations, is applied to a three-dimensional structure to precisely localize the current path which is buried deep inside it. A new method, based on parameters fittings of magnetic simulations, is then applied in order to accurately evaluate the distance between the current and the sensor.
ChemInform Abstract: Higher Order, Mixed Cyanocuprates Derived from N‐Lithioimidazole, and Pyrrole: New “Dummy” Ligand Alternatives in Organocopper Chemistry. (1992)

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.
Method of Calibrating Effects of Field of Classification Search Multi-AOI-System for Easy Changing Angles-of-Incidence In Ellipsometers and The Like (2007)

Disclosed is a system for enabling easy sequential setting of different Angles-of-Incidence of a beam of electromagnetic radiation to a surface of a sample system involving regression based methodology for evaluating and compensating the effects of the presence electromagnetic beam intercepting angle-of-incidence changing systems, including where desired, parameterization of calibration parameters.
Both the polypyrimidine tract and the 3' splice site function prior to the first step of splicing in fission yeast (1997)

While it is known that several trans -acting splicing factors are highly conserved between Schizosaccharomyces pombe and mammals, the roles of cis -acting signals have received comparatively little attention. In Saccharomyces cerevisiae, sequences downstream from the branch point are not required prior to the first transesterification reaction, whereas in mammals the polypyrimidine tract and, in some introns, the 3' AG dinucleotide are critical for initial recognition of an intron. We have investigated the contribution of these two sequence elements to splicing in S.pombe. To determine the stage at which the polypyrimidine tract functions, we analyzed the second intron of the cdc2 gene (cdc 2-Int2), in which pyrimidines span the entire interval between the branch point and 3' splice site. Our data indicate that substitution of a polypurine tract results in accumulation of linear pre-mRNA, while expanding the polypyrimidine tract enhances splicing efficiency, as in mammals. To examine the role of the AG dinucleotide in cdc 2-Int2 splicing, we mutated the 3' splice junction in both the wild-type and pyrimidine tract variant RNAs. These changes block the first transesterification reaction, as in a subset of mammalian introns. However, in contrast to the situation in mammals, we were unable to rescue the first step of splicing in a 3' splice site mutant by expanding the polypyrimidine tract. Mutating the terminal G in the third intron of the nda 3 gene (nda 3-Int3) also blocks the first transesterification reaction, suggesting that early recognition of the 3' splice site is a general property of fission yeast introns. Counter to earlier work with an artificial intron, it is not possible to restore the first step of splicing in cdc 2-Int2 and nda 3-Int3 3' splice site mutants by introducing compensatory changes in U1 snRNA. These results highlight the diversity and probable redundancy of mechanisms for identifying the 3' ends of introns.
Author Correction: Sas-4 provides a scaffold for cytoplasmic complexes and tethers them in a centrosome (2020)

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Replication Checkpoint Kinase Cds1 Regulates Recombinational Repair Protein Rad60 (2003)

Genome integrity is protected by Cds1 (Chk2), a checkpoint kinase that stabilizes arrested replication forks. How Cds1 accomplishes this task is unknown. We report that Cds1 interacts with Rad60, a protein required for recombinational repair in fission yeast. Cds1 activation triggers Rad60 phosphorylation and nuclear delocalization. A Rad60 mutant that inhibits regulation by Cds1 renders cells specifically sensitive to replication fork arrest. Genetic and biochemical studies indicate that Rad60 functions codependently with Smc5 and Smc6, subunits of an SMC (structural maintenance of chromosomes) complex required for recombinational repair. These studies indicate that regulation of Rad60 is an important part of the replication checkpoint response controlled by Cds1. We propose that control of Rad60 regulates recombination events at stalled forks.
Phosphodiesterase-5 inhibitors for male erectile dysfunction (2003)

The success of sildenafil (Viagra®; Pfizer) as an oral therapy for male erectile dysfunction (MED) has greatly stimulated interest in phosphodiesterase (PDE)-5 inhibitors. A large number of compounds from a wide variety of structural classes have been identified as PDE5 inhibitors during the past few years. Many of them possess desirable biological and pharmaceutical profiles. Selected compounds from different structural classes have entered clinical trials for MED. Since PDE5 inhibition is now a proven mechanism for MED treatment, many of these compounds are scientifically capable of becoming drugs for MED, as evidenced by the recent launches of vardenafil (Levitra®; Bayer Yakuhin) and tadalafil (Cialis®; Lilly ICOS). However, the business environment rather than scientific merit will probably determine the journey of additional PDE5 inhibitors to the market.
Pharmacokinetics, Tissue Localization, Toxicity, and Treatment Efficacy in the First Small Animal (Rabbit) Model of Intra-Arterial Chemotherapy for Retinoblastoma (2018)

This first small-animal model of IAC has excellent vitreous and retinal tissue drug penetration, achieving levels sufficient to kill human retinoblastoma cells, facilitating future IAC drug discovery.
Secreted factors induced by PKC modulators do not indirectly cause HIV latency reversal (2023)

HIV can establish a long-lived latent infection in cells harboring integrated non-expressing proviruses. Latency reversing agents (LRAs), including protein kinase C (PKC) modulators, can induce expression of latent HIV, thereby reducing the latent reservoir in animal models. However, PKC modulators such as bryostatin-1 also cause cytokine upregulation in peripheral blood mononuclear cells (PBMCs), including cytokines that might independently reverse HIV latency. To determine whether cytokines induced by PKC modulators contribute to latency reversal, primary human PBMCs were treated with bryostatin-1 or the bryostatin analog SUW133, a superior LRA, and supernatant was collected. As anticipated, LRA-treated cell supernatant contained increased levels of cytokines compared to untreated cell supernatant. However, exposure of latently-infected cells with this supernatant did not result in latency reactivation. These results indicate that PKC modulators do not have significant indirect effects on HIV latency reversal in vitro and thus are targeted in their latency reversing ability.
Antibody Lineages with Vaccine-Induced Antigen-Binding Hotspots Develop Broad HIV Neutralization. (2019)

The vaccine-mediated elicitation of antibodies (Abs) capable of neutralizing diverse HIV-1 strains has been a long-standing goal. To understand how broadly neutralizing antibodies (bNAbs) can be elicited, we identified, characterized, and tracked five neutralizing Ab lineages targeting the HIV-1-fusion peptide (FP) in vaccinated macaques over time. Genetic and structural analyses revealed two of these lineages to belong to a reproducible class capable of neutralizing up to 59% of 208 diverse viral strains. B cell analysis indicated each of the five lineages to have been initiated and expanded by FP-carrier priming, with envelope (Env)-trimer boosts inducing cross-reactive neutralization. These Abs had binding-energy hotspots focused on FP, whereas several FP-directed Abs induced by immunization with Env trimer-only were less FP-focused and less broadly neutralizing. Priming with a conserved subregion, such as FP, can thus induce Abs with binding-energy hotspots coincident with the target subregion and capable of broad neutralization.
Calcium: Unusual Sources in the Highland Peruvian Diet (1963)

A dietary survey conducted in the southern highlands of Peru revealed two important sources of dietary calcium not previously reported. Mineral and ash calcium ingested as a food spice, and along with coca, raises the calcium intake from the low figures recorded by standard nutritional surveys to a more substantial level.
Generation of Tumor-Specific Cytotoxic T Cells From Blood via In Vitro Expansion Using Autologous Dendritic Cells Pulsed With Neoantigen-Coupled Microbeads (2022)

For the past decade, adoptive cell therapy including tumor-infiltrating lymphocytes, genetically modified cytotoxic lymphocytes expressing a chimeric antigen receptor, or a novel T-cell receptor has revolutionized the treatment of many cancers. Progress within exome sequencing and neoantigen prediction technologies provides opportunities for further development of personalized immunotherapies. In this study, we present a novel strategy to deliver <i>in silico</i> predicted neoantigens to autologous dendritic cells (DCs) using paramagnetic beads (EpiTCer beads). DCs pulsed with EpiTCer beads are superior in enriching for healthy donor and patient blood-derived tumor-specific CD8+ T cells compared to DC loaded with whole-tumor lysate or 9mer neoantigen peptides. A dose-dependent effect was observed, with higher EpiTCer bead per DC being favorable. We concluded that CD8+ T cells enriched by DC loaded with EpiTCer beads are tumor specific with limited tumor cross-reactivity and low recognition of autologous non-activated monocytes or CD8+ T cells. Furthermore, tumor specificity and recognition were improved and preserved after additional expansion using our Good Manufacturing Process (GMP)-compatible rapid expansion protocol. Phenotypic analysis of patient-derived EpiTCer DC expanded CD8+ T cells revealed efficient maturation, with high frequencies of central memory and effector memory T cells, similar to those observed in autologous expanded tumor-infiltrating lymphocytes. These results indicate that DC pulsed with EpiTCer beads enrich for a T-cell population with high capacity of tumor recognition and elimination, which are features needed for a T-cell product to be used for personalized adoptive cell therapy.
Recovery of bioactive protein from bacterial inclusion bodies using trifluoroethanol as solubilization agent (2016)

Trifluoroethanol was found to be a suitable mild solubilization agent for bacterial inclusion bodies. Fully functional, bioactive human growth hormone was recovered in high yield from inclusion bodies using trifluoroethanol based solubilization buffer. It was also observed that trifluoroethanol has potential to solubilize inclusion bodies of different proteins.
Congenic Mesenchymal Stem Cell Therapy Reverses Hyperglycemia in Experimental Type 1 Diabetes (2010)

These studies demonstrate the inimitable benefit of congenic MSC therapy in reversing experimental type 1 diabetes. These data should benefit future clinical trials using MSCs as treatment for type 1 diabetes.
Contrasting effects of Cyclosporine and Rapamycin in de novo generation of alloantigen-specific regulatory T cells (88.45) (2007)

Abstract The outcome of T cell-mediated responses critically depends on the balance of cytopathic versus regulatory T (Treg) cells. Induction of stable tolerance to allografts requires limiting donor-reactive T effector (Teff) cells via apoptosis. Cyclosporine (CsA) blocks AICD of Teff cells, and is detrimental to co-stimulation blockade-induced tolerance, whereas Rapamycin (RPM) preserves AICD, potentiating such tolerance. While differences between CsA and RPM in influencing apoptosis of Teff are apparent, their effects on graft-protective Treg cells remain enigmatic. Moreover, it is unclear whether tolerizing regimens foster conversion of naïve peripheral T cells into alloantigen-specific Treg cells. Here we show, using reporter mice for Treg marker Foxp3, that RPM promotes de novo conversion of alloantigen-specific Treg cells, whereas CsA completely inhibits this process. Upon transfer, in vivo converted Treg cells potently suppress the rejection of donor but not third party skin grafts. Thus, the use of RPM over CsA is favorable in shifting the balance of aggressive to protective type alloimmunity. (Supported in part by grants from NIH and JDRF (NIH NS 30843; NIH A141521-08; JDRF 5-2005-108)).
Simultaneous two gate reflectometric spectroscopy of Si coupled donor-dot system (2015)

Gate-coupled reflectometric spectrometry has recently emerged as a tool for studies of transport in nanostructures. Here we report reflectometric spectroscopy of a double-gate single electron device in which two coupled quantum dots are formed under the gates. The spectroscopy is performed by detection of charging processes in the system using a dual port reflectometer. The potential application of this scheme for detection of qubits is also discussed.
Preparative free‐flow isoelectric focusing: Modeling and experiments (1990)

Free-flow isoelectric focusing was adapted to preparative scale separations and chemical engineering methods were used to describe the main mechanisms operating in the apparatus. A mixture of human serum albumin (pI 4.6) and beta-lactoglobulin (pI 5.22) was separated in pH gradients, generated with carrier ampholytes of different origin and covering the pH ranges 4-6.5, 3.5-5, 4-5.5 and 4.5-5.0. Best results were obtained in the pH 4-5.5 range. The experimental results have validated the results obtained with a numerical model.
CAR-T cells and BiTEs in solid tumors: challenges and perspectives (2021)

Chimeric antigen receptor (CAR)-modified T cells and BiTEs are both immunotherapies which redirect T cell specificity against a tumor-specific antigen through the use of antibody fragments. They demonstrated remarkable efficacy in B cell hematologic malignancies, thus paving the way for their development in solid tumors. Nonetheless, the use of such new drugs to treat solid tumors is not straightforward. So far, the results from early phase clinical trials are not as impressive as expected but many improvements are under way. In this review we present an overview of the clinical development of CAR-T cells and BiTEs targeting the main antigens expressed by solid tumors. We emphasize the most frequent hurdles encountered by either CAR-T cells or BiTEs, or both, and summarize the strategies that have been proposed to overcome these obstacles.
Cellular Adaptation to VEGF-Targeted Antiangiogenic Therapy Induces Evasive Resistance by Overproduction of Alternative Endothelial Cell Growth Factors in Renal Cell Carcinoma (2015)

Vascular endothelial growth factor (VEGF)-targeted antiangiogenic therapy significantly inhibits the growth of clear cell renal cell carcinoma (RCC). Eventually, therapy resistance develops in even the most responsive cases, but the mechanisms of resistance remain unclear. Herein, we developed two tumor models derived from an RCC cell line by conditioning the parental cells to two different stresses caused by VEGF-targeted therapy (sunitinib exposure and hypoxia) to investigate the mechanism of resistance to such therapy in RCC. Sunitinib-conditioned Caki-1 cells in vitro did not show resistance to sunitinib compared with parental cells, but when tested in vivo, these cells appeared to be highly resistant to sunitinib treatment. Hypoxia-conditioned Caki-1 cells are more resistant to hypoxia and have increased vascularity due to the upregulation of VEGF production; however, they did not develop sunitinib resistance either in vitro or in vivo. Human endothelial cells were more proliferative and showed increased tube formation in conditioned media from sunitinib-conditioned Caki-1 cells compared with parental cells. Gene expression profiling using RNA microarrays revealed that several genes related to tissue development and remodeling, including the development and migration of endothelial cells, were upregulated in sunitinib-conditioned Caki-1 cells compared with parental and hypoxia-conditioned cells. These findings suggest that evasive resistance to VEGF-targeted therapy is acquired by activation of VEGF-independent angiogenesis pathways induced through interactions with VEGF-targeted drugs, but not by hypoxia. These results emphasize that increased inhibition of tumor angiogenesis is required to delay the development of resistance to antiangiogenic therapy and maintain the therapeutic response in RCC.