gebhart/patrepeval huggingface dataset:
Antitumour activity of novel taxanes that act at the same time as cytotoxic agents and P-glycoprotein inhibitors (2000)

Taxanes antitumour agents such as paclitaxel and docetaxel represent a successful family of chemotherapeutic drugs. Unfortunately, acquired and innate resistance represents a clinical problem for these drugs. We investigated, on a panel of 7 human cancer cell lines, the growth inhibition effect of 3 newly developed taxanes (SB-T-1213, SB-T-1250 and SB-T-101187) with modification at the C10 and C3' positions of the taxane framework. These positions have been previously characterized as critical to make taxanes highly active against cells overexpressing the efflux pump P-glycoprotein (P-gp). Paclitaxel and docetaxel were used as reference compounds. Results unambiguously indicate the exceptional activity of the novel taxanes toward P-gp positive cells (up to >400 fold higher potency than that of paclitaxel). SB-T-1213 and SB-T-1250 are also substantially more active than the reference compounds against P-gp negative cells. To better understand the mechanisms underlying the enhanced activity of the newly developed taxanes, we performed cell cycle and apoptosis analysis. This study demonstrates that the striking growth inhibition effect exhibited by the novel taxanes is ascribed to their increased ability in inducing apoptosis and G(2)/M cell cycle block. SB-T-1213 and SB-T-1250 are also more active than reference compounds in inducing intracellular accumulation of the beta-tubulin subunits. Finally, it is revealed that these novel taxanes have ability to inhibit the function of the P-gp efflux pump on the basis of the Rhodamine 123 assay. These findings strongly suggest that SB-T-1213, SB-T-1250 and SB-T-101187 represent a new tool to overcome innate or acquired P-gp mediated taxane-resistance.
Intersectin, a Novel Adaptor Protein with Two Eps15 Homology and Five Src Homology 3 Domains (1998)

We screened a Xenopus laevis oocyte cDNA expression library with a Src homology 3 (SH3) class II peptide ligand and identified a 1270-amino acid-long protein containing two Eps15 homology (EH) domains, a central coiled-coil region, and five SH3 domains. We named this protein Intersectin, because it potentially brings together EH and SH3 domain-binding proteins into a macromolecular complex. The ligand preference of the EH domains were deduced to be asparajine-proline-phenylalanine (NPF) or cyclized NPF (CX1-2NPFXXC), depending on the type of phage-displayed combinatorial peptide library used. Screens of a mouse embryo cDNA library with the EH domains of Intersectin yielded clones for the Rev-associated binding/Rev-interacting protein (RAB/Rip) and two novel proteins, which we named Intersectin-binding proteins (Ibps) 1 and 2. All three proteins contain internal and C-terminal NPF peptide sequences, and Ibp1 and Ibp2 also contain putative clathrin-binding sites. Deletion of the C-terminal sequence, NPFL-COOH, from RAB/Rip eliminated EH domain binding, whereas fusion of the same peptide sequence to glutathione S-transferase generated strong binding to the EH domains of Intersectin. Several experiments support the conclusion that the free carboxylate group contributes to binding of the NPFL motif at the C terminus of RAB/Rip to the EH domains of Intersectin. Finally, affinity selection experiments with the SH3 domains of Intersectin identified two endocytic proteins, dynamin and synaptojanin, as potential interacting proteins. We propose that Intersectin is a component of the endocytic machinery.
Functional characterization of a glycine 185-to-valine substitution in human P-glycoprotein by using a vaccinia-based transient expression system. (1996)

Human P-glycoprotein (Pgp) is a 170-kDa plasma membrane protein that confers multidrug resistance to otherwise sensitive cells. A mutation in Pgp, G185--&gt;V, originally identified as a spontaneous mutation, was shown previously to alter the drug resistance profiles in cell lines that are stably transfected with the mutant MDR1 cDNA and selected with cytotoxic agents. To understand the mechanism by which the V185 mutation leads to an altered drug resistance profile, we used a transient expression system that eliminates the need for drug selection to attain high expression levels and allows for the rapid characterization of many aspects of Pgp function and biosynthesis. The mutant and wild-type proteins were expressed at similar levels after 24-48 h in human osteosarcoma (HOS) cells by infection with a recombinant vaccinia virus encoding T7 RNA polymerase and simultaneous transfection with a plasmid containing MDR1 cDNA controlled by the T7 promoter. For both mutant and wild-type proteins, photolabeling with [3H]azidopine and [125I]iodoarylazidoprazosin, drug-stimulated ATPase activity, efflux of rhodamine 123, and accumulation of radiolabeled vinblastine and colchicine were evaluated. In crude membrane preparations from HOS cells, a higher level of basal Pgp-ATPase activity was observed for the V185 variant than for the wild-type, suggesting partial uncoupling of drug-dependent ATP hydrolysis by the mutant. Several compounds, including verapamil, nicardipine, tetraphenylphosphonium, and prazosin, stimulated ATPase activities of both the wild-type and mutant similarly, whereas cyclosporin A inhibited the ATPase activity of the mutant more efficiently than that of the wild-type. This latter observation explains the enhanced potency of cyclosporin A as an inhibitor of the mutant Pgp. No differences were seen in verapamil-inhibited rhodamine 123 efflux, but the rate of accumulation was slower for colchicine and faster for vinblastine in cells expressing the mutant protein, as compared with those expressing wild-type Pgp. We conclude that the G185--&gt;V mutation confers pleiotropic alterations on Pgp, including an altered basal ATPase activity and altered interaction with substrates and the inhibitor cyclosporin A.
Tissue cultures from cerebrospinal fluid specimens in the study of human brain tumors (1978)

The authors report a study in which 109 cerebrospinal fluid (CSF) specimens from patients with varying neurological disorders were incubated in tissue culture medium for 1, 3, and sometimes 7 days. Strict criteria for malignancy were applied to cells found at these intervals. In 35 patients with verified central nervous system neoplasms, eight cases had malignant cells and 11 others had "doubtful" cells by tissue-culture analysis. Thirty-three of these cases were also examined with standard millipore cytological techniques: six had malignant cells and four had "doubtful" cells. Of 50 cases with inflammatory or other non-neoplastic conditions, cells were cultured in 13. None was considered malignant by our criteria. Tissue culture of CSF has several potential benefits. Even with stringent criteria, it is possible to demonstrate the presence of unequivocally malignant cells in CSF by tissue culture. The systemic application of such criteria may eventually increase the positive identification of malignancies. Further, since these cells are growing, the degree of malignancy may be more accurately determined by a study of growth in culture. Such a study could not be done by conventional methods. Finally, tissue culture can help to guide therapy in certain instances in which a surgical biopsy cannot be obtained.
Mitogen-induced expression of the fibroblast growth factor-binding protein is transcriptionally repressed through a non-canonical E-box element. (2000)

Page 28544: Figure 5 D is incorrect. The corrected Figure 5 is shown below.
Grant-Free NOMA-OTFS Paradigm: Enabling Efficient Ubiquitous Access for LEO Satellite Internet-of-Things (2022)

With the blooming of Internet-of-Things (IoT), we are witnessing an explosion in the number of IoT terminals, triggering an unprecedented demand for ubiquitous wireless access globally. In this context, the emerging low-Earth-orbit satellites (LEO-SATs) have been regarded as a promising enabler to complement terrestrial wireless networks in providing ubiquitous connectivity and bridging the ever-growing digital divide in the expected next-generation wireless communications. Nevertheless, the harsh conditions posed by LEO-SATs have imposed significant challenges to the current multiple access (MA) schemes and led to an emerging paradigm shift in system design. In this article, we first provide a comprehensive overview of the state-of-the-art MA schemes and investigate their limitations in the context of LEO-SATs. To this end, we propose a novel next generation MA (NGMA), which amalgamates the grant-free non-orthogonal multiple access (GF-NOMA) mechanism and the orthogonal time frequency space (OTFS) waveform, for simplifying the connection procedure with reduced access latency and enhanced Doppler-robustness. Critical open challenging issues and future directions are finally presented for further technical development.
Clinical imaging fluorescence apparatus for the endoscopic photodetection of early cancers by use of Photofrin II (1997)

A fluorescence imaging device applied to the detection of early cancer is described. The apparatus is based on the imaging of laser-induced fluorescence of a dye that localizes in a tumor with a higher concentration than in the surrounding normal tissue after iv injection. Tests carried out in the upper aerodigestive tract, the tracheobronchial tree, and the esophagus with Photofrin II (1 mg/kg of body weight) as the fluorescent agent are reported as examples. The fluorescence is induced by violet (410-nm) light from a continuous-wave (cw) krypton-ion laser. The fluorescence contrast between tumor and surrounding tissue is enhanced by real-time image processing. This is done by the simultaneous recording of the fluorescence image in two spectral domains (470-600 and 600-720 nm), after which these two images are digitized and manipulated with a mathematical operator (look-up table) at video frequency. Among the 7 photodetections performed in the tracheobronchial tree, 6 were successful, whereas it was the case for only 5 of the 15 lesions investigated in squamous mucosa (upper aerodigestive tract and esophagus). The sources of false positives and false negatives are evaluated in terms of the fluorescent dye, tissue optical properties, and illumination optics.
Reduction in cardiolipin reduces expression of creatine transporter-1 and creatine transport in hBMEC/D3 human brain microvessel endothelial cells (2022)

Abstract Background Cardiolipin (CL) is the signature phospholipid of mitochondria and regulates a plethora of cellular functions including mitochondrial energy production. There is little knowledge of how CL regulates uptake and membrane transport processes in mammalian cells. Endothelial cells of the blood brain barrier (BBB) play a vital role in uptake of metabolites into the brain and are enriched in mitochondria compared with peripheral endothelial cells. We examined how deficiency in BBB endothelial CL regulates the expression of selected drug and metabolite transporters and their function. Methods Cardiolipin synthase-1 (hCLS1) was knocked down in a human brain microvessel endothelial cell line, hBMEC/D3, by Lipofectamine ® transfection with hCLS1 siRNA and CL levels, CL synthase activity and the mRNA expression of selected blood brain barrier drug and metabolite transporters examined. Mock transfected hBMEC/D3 cells served as controls. The incorporation of [ 14 C]creatine and [ 14 C]oleate into hBMEC/D3 cells was determined as a measure of solute metabolite transport and protein expression of the creatine transporter determined. Results Knockdown of the CL biosynthetic enzyme hCLS1 in hBMEC/D3 reduced CL and CL synthase activity and the mRNA expression of creatine transporter-1, p-glycoprotein and breast cancer resistance protein compared to controls. In contrast, mRNA expression of ATP binding cassette subfamily C members-1, -3, multidrug resistance-associated protein-4 variants 1, -2, and fatty acid transport protein-1 were unaltered. Although ATP production was unaltered by hCLS1 knockdown, incorporation of [ 14 C]creatine into hBMEC/D3 cells was reduced compared to controls. The reduction in [ 14 C]creatine incorporation was associated with a reduction in creatine transporter-1 protein expression. In contrast, incorporation of [ 14 C]oleic acid into hBMEC/D3 cells and the mRNA expression of fatty acid transport protein-1 was unaltered by knockdown of hCLS1 compared to controls. Conclusion Knockdown of hCLS1 in hBMEC/D3, with a corresponding reduction in CL, results in alteration in expression of specific solute membrane transporters.
ChemInform Abstract: PULSRADIOLYTISCHE POLAROGRAPHIE, RED. DES ASCORBINSAEURERADIKALS UND DES HEXACYANOFERRAT(III)‐ANIONS AN DER QUECKSILBERELEKTRODE (1973)

Abstract Das relativ langlebige Radikal der Ascorbinsäure und das Hexacyanoferrat(III)‐ Anion wurden durch Einwirkung eines 20 ns langen Pulses von energiereichen Elektronen auf NzO‐gesättigte, 10 ′ molare Lösungen der Ascorbinsäure bzw. des Hexacyanoferrats?l) erzeugt.
Metabolic exchange and energetic coupling between nutritionally stressed bacterial species, the possible role of QS molecules (2020)

Abstract To clarify the principles controlling inter-species interactions, we previously developed a co-culture model with two anaerobic bacteria, Clostridium acetobutylicum and Desulfovibrio vulgaris Hildenborough, in which nutritional stress for D. vulgaris induced tight cell-cell inter-species interaction. Here we show that exchange of metabolites produced by C. acetobutylicum allows D. vulgaris to duplicate its DNA, and to be energetically viable even without its substrates. Physical interaction between C. acetobutylicum and D. vulgaris (or Escherichia coli and D. vulgaris ) is linked to the quorum-sensing molecule AI-2, produced by C . acetobutylicum and E. coli . With nutrients D. vulgaris produces a small molecule that inhibits in vitro the AI-2 activity, and could act as an antagonist in vivo . Sensing of AI-2 by D. vulgaris could induce formation of an intercellular structure that allows directly or indirectly metabolic exchange and energetic coupling between the two bacteria.
Solar Cells: Re‐evaluating the Role of Sterics and Electronic Coupling in Determining the Open‐Circuit Voltage of Organic Solar Cells (Adv. Mater. 42/2013) (2013)

The energy of the charge-transfer state formed between electron-donating and electronaccepting materials, a state that directly absorbs, largely determines the limit of the open-circuit voltage in organic photovoltaic devices. This is described in work by Aram Amassian, Michael D. McGehee and co-workers on page 6076.
The new world of RNA diagnostics and therapeutics (2023)

The 5th Workshop IRE on Translational Oncology was held in Rome (Italy) on 27-28 March at the IRCCS Regina Elena National Cancer Institute. This meeting entitled "The New World of RNA diagnostics and therapeutics" highlightes the significant progress in the RNA field made over the last years. Research moved from pure discovery towards the development of diagnostic biomarkers or RNA-base targeted therapies seeking validation in several clinical trials. Non-coding RNAs in particular have been the focus of this workshop due to their unique properties that make them attractive tools for the diagnosis and therapy of cancer.This report collected the presentations of many scientists from different institutions that discussed recent oncology research providing an excellent overview and representative examples for each possible application of RNA as biomarker, for therapy or to increase the number of patients that can benefit from precision oncology treatment.In particular, the meeting specifically emphasized two key features of RNA applications: RNA diagnostic (Blandino, Palcau, Sestito, Díaz Méndez, Cappelletto, Pulito, Monteonofrio, Calin, Sozzi, Cheong) and RNA therapeutics (Dinami, Marcia, Anastasiadou, Ryan, Fattore, Regazzo, Loria, Aharonov).
SITE CHARACTERIZATION USING JOINT RECONSTRUCTIONS OF DISPARATE DATA TYPES (2006)

Potential CO{sub 2} reservoirs are often geologically complex and possible leakage pathways such as those created. Reservoir heterogeneity can affect injectivity, storage capacity, and trapping rate. Similarly, discontinuous caprocks and faults can create risk of CO{sub 2} leakage. The characteristics of potential CO{sub 2} reservoirs need to be well understood to increase confidence in injection project success. Reservoir site characterization will likely involve the collection and integration of multiple geological, geophysical, and geochemical data sets. We have developed a computational tool to more realistically render lithologic models using multiple geological and geophysical techniques. Importantly, the approach formally and quantitatively integrates available data and provides a strict measure of probability and uncertainty in the subsurface. The method will characterize solution uncertainties whether they stem from unknown reservoir properties, measurement error, or poor sensitivity of geophysical techniques.
This Strange Creature: Plato and Conversion Experiences (2021)

In Plato’s corpus, the Greek word ἐξαίφνης appears precisely thirty-six times. Translated generally as “all of a sudden” or “the instant” in his Parmenides, ἐξαίφνης emerges in some of the most significant passages of Plato’s dialogues. Put simply, ἐξαίφνης connotes illumination of the highest realities and philosophical conversion experience. In addition to providing a review of Plato’s conception and use of ἐξαίφνης in Parmenides, Republic, Symposium, and the Seventh Letter, our paper brings an ancillary link to light. Namely, the appearance of ἐξαίφνης as a mark for conversion experiences in the New Testament’s Acts of the Apostles and Plotinus’s Enneads. We reveal how the same pattern and employment of ἐξαίφνης established by Plato emerge in both Acts and the Enneads. This pattern suggests a prolonged period of thinking and training, followed by a flash of understanding. Thus ἐξαίφνης, as evidenced by our survey of its strange instantiation in Plato’s dialogues and then subsequently in Acts and the Enneads, becomes a sign for enlightenment, assimilation with the divine, and conversion experience.
Interfering Channel Estimation for Radar and Communication Coexistence (2019)

We investigate the interfering channel estimation in radar and communication coexistence, where a multi-input-multi-output (MIMO) radar is operated in a “search and track” mode, and a MIMO base station (BS) is attempting to acquire the interfering channel state information (ICSI) between them, which is required for the precoding designs. In contrast to conventional training based techniques, we exploit radar probing waveforms as pilot signals, which requires no coordination between the systems. As the radar randomly transmits searching and tracking waveforms, it is challenging for the BS to directly obtain the ICSI. We therefore propose a Rao test approach to firstly identify the working mode of the radar, and then estimate the channel. We further provide theoretical performance analysis for the Rao detector. Finally, we assess the effectiveness of the proposed approach by numerical simulations, which show that the BS is able to estimate the ICSI with limited information from the radar.
Optical probing (EOFM / TRI): A large set of complementary applications for ultimate VLSI (2013)

Electro Optical Techniques (EOFM: Electro Optical Frequency Mapping and EOP: Electro Optical Probing) and Dynamic Light Emission Techniques (TRE: Time Resolved Emission and TRI: Time Resolved Imaging) are dynamic optical probing techniques widely used at IC level for design debug and defect localization purpose. They can pinpoint the origin of timing issue or logic fault in up to date CMOS devices. Each technique has its advantages and its drawbacks allowing a common set of applications and more specific ones. We have been involved in the development of the most advanced techniques related to EOFM and TRI on various devices (down to 28nm technology). What we can expect with each technique, which one to choose, what are the limitations are questions that must be answered regarding tooling cost and skills involved. Based on the understanding of the bases of each technique, their complementarities and their limitations have been identified. Even if these techniques can solve most of the issues we encountered, we can wonder if they can be applied on future technologies and this aspect will also be discussed.
Data from Functional Characterization of an Isoform-Selective Inhibitor of PI3K-p110β as a Potential Anticancer Agent (2023)

&lt;div&gt;Abstract&lt;p&gt;Genetic approaches have shown that the p110β isoform of class Ia phosphatidylinositol-3-kinase (PI3K) is essential for the growth of PTEN-null tumors. Thus, it is desirable to develop p110β-specific inhibitors for cancer therapy. Using a panel of PI3K isoform-specific cellular assays, we screened a collection of compounds possessing activities against kinases in the PI3K superfamily and identified a potent and selective p110β inhibitor: KIN-193. We show that KIN-193 is efficacious specifically in blocking AKT signaling and tumor growth that are dependent on p110β activation or PTEN loss. Broad profiling across a panel of 422 human tumor cell lines shows that the PTEN mutation status of cancer cells strongly correlates with their response to KIN-193. Together, our data provide the first pharmacologic evidence that PTEN-deficient tumors are dependent on p110β in animals and suggest that KIN-193 can be pursued as a drug to treat tumors that are dependent on p110β while sparing other PI3K isoforms.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Significance:&lt;/b&gt; We report the first functional characterization of a p110β-selective inhibitor, KIN-193, that is efficacious as an antitumor agent in mice. We show that this class of inhibitor holds great promise as a pharmacologic agent that could be used to address the potential therapeutic benefit of treating p110β-dependent PTEN-deficient human tumors. &lt;i&gt;Cancer Discov; 2(5)&lt;/i&gt;; 425–33. &lt;i&gt;©2012 AACR&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;Read the Commentary on this article by Shepherd and Denny, p. 393.&lt;/p&gt;&lt;p&gt;This article is highlighted in the In This Issue feature, p. 377.&lt;/p&gt;&lt;/div&gt;
Cryptococcal Glucoxylomannan Does Not Exhibit Cross-Reactivity in the MVista Histoplasma Antigen Enzyme Immunoassay (2007)

The potential for cross-reaction between Cryptococcus neoformans and Histoplasma capsulatum in antigen assays was evaluated. We tested patient samples, spleens from infected mice, and purified polysaccharides in the MVista Histoplasma antigen enzyme immunoassay and cryptococcal antigen latex agglutination system for cross-reactivity, and none was observed.
The Co‐current reactor‐heta exchanger part II. Experimental results (1980)

Abstract A reactor of fiour crossflow nomolithic blocks is used to approximate a cocurrent and a countercurrent reactor‐heat excanger. Essentailly isothermal reaction pass profiles are produced by flowing the coolant and reactant streams cocurrent to each other according to the criteria set down in Part I of this paper. A multiplicy of steady states is shown to exist for the autothermal countercurrent mode, but not for the autothermal cocurrent mode, under identical conditions.