gebhart/patrepeval huggingface dataset:
Characterization and Functional Analysis of CD44v6.CAR T Cells Endowed with a New Low-Affinity Nerve Growth Factor Receptor-Based Spacer (2021)

Effectiveness of adoptively transferred chimeric antigen receptor (CAR) T cells strongly depends on the quality of CAR-mediated interaction of the effector cells with the target antigen on tumor cells. A major role in this interaction is played by the affinity of the single-chain variable fragment (scFv) for the antigen, and by the CAR design. In particular, the spacer domain may impact on the CAR T cell function by affecting the length and flexibility of the resulting CAR. This study addresses the need to improve the manufacturing process and the antitumor activity of CD44v6-specific CAR T cells by defining the optimal structure of a spacer region derived from the extracellular domain of the human low-affinity nerve growth factor receptor (LNGFR). We tailored the LNGFR spacer to modulate CAR length to efficiently recognize distal or proximal epitopes and to allow selection of transduced CAR T cells by the use of clinical-grade validated manufacturing systems. The different LNGFR spacers investigated in this study are responsible for the generation of CAR T cells with a different memory phenotype, which is mainly related to the level of CAR expression and the extent of the associated tonic signaling. In particular, the CD44v6-NWN2.CAR T cells are enriched in central memory cells and show improved <i>in vitro</i> functions in terms of killing capability, and <i>in vivo</i> antitumor activity against hematological and solid tumors. Clinical Trial Registration numbers: clinicaltrial.gov NCT04097301; ClinicalTrials.gov, NCT00423124.
Perkin 1 Abstracts: Natural Product Synthesis (1999)

Perkin 1 Abstracts: Natural Product Synthesis aims to highlight syntheses that have been recently published. It includes brief descriptions of biological activity and key steps. A more comprehensive list of Natural Product syntheses and isolations can be found in Natural Product Updates.
Search for squarks and gluinos with the ATLAS detector in final states with jets and missing transverse momentum using s = 8 $$ \sqrt{s}=8 $$ TeV proton-proton collision data (2014)

A search for squarks and gluinos in final states containing high-p T jets, missing transverse momentum and no electrons or muons is presented. The data were recorded in 2012 by the ATLAS experiment in s = 8 TeV proton-proton collisions at the Large Hadron Collider, with a total integrated luminosity of 20.3 fb -1 . Results are interpreted in a variety of simplified and specific supersymmetry-breaking models assuming that R-parity is conserved and that the lightest neutralino is the lightest supersymmetric particle. An exclusion limit at the 95% confidence level on the mass of the gluino is set at 1330 GeV for a simplified model incorporating only a gluino and the lightest neutralino. For a simplified model involving the strong production of first-and second-generation squarks, squark masses below 850 GeV (440 GeV) are excluded for a massless lightest neutralino, assuming mass degenerate (single light-flavour) squarks. In mSUGRA/CMSSM models with tan = 30, A 0 = -2m 0 and > 0, squarks and gluinos of equal mass are excluded for masses below 1700 GeV. Additional limits are set for non-universal Higgs mass models with gaugino mediation and for simplified models involving the pair production of gluinos, each decaying to a top squark and a top quark, with the top squark decaying to a charm quark and a neutralino. These limits extend the region of supersymmetric parameter space excluded by previous searches with the ATLAS detector.
A 50 GHz broad-band monolithic GaAs/AlAs resonant tunneling diode trigger circuit (1994)

This paper describes the design, circuit simulation, fabrication and testing of a 50 GHz trigger circuit using GaAs/AlAs resonant tunneling diodes. A new trigger circuit was designed to eliminate the 180/spl deg/ phase splitter used in a previous complementary input trigger circuit. Our monolithic approach, integrated GaAs/AlAs resonant tunneling diodes (in a back-to-back configuration) and a 50 /spl Omega/ coplanar waveguide, minimized the parasitic circuit elements and internal reflections from the package thus achieving high frequency operation. The circuit was able to trigger on input sinusoidal waves of input powers of -3 dBm up to 50 GHz with time jitter of less than 1 ps rms over the entire measured frequency range from 5 to 50 GHz. The upper limit of 50 GHz was imposed by our measurement system.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Supplementary Table 2 from Polycomb CBX7 Promotes Initiation of Heritable Repression of Genes Frequently Silenced with Cancer-Specific DNA Hypermethylation (2023)

Supplementary Table 2 from Polycomb CBX7 Promotes Initiation of Heritable Repression of Genes Frequently Silenced with Cancer-Specific DNA Hypermethylation
Taxonomic differences of gut microbiomes drive cellulolytic enzymatic potential within hind-gut fermenting mammals (2017)

Host diet influences the diversity and metabolic activities of the gut microbiome. Previous studies have shown that the gut microbiome provides a wide array of enzymes that enable processing of diverse dietary components. Because the primary diet of the porcupine, Erethizon dorsatum, is lignified plant material, we reasoned that the porcupine microbiome would be replete with enzymes required to degrade lignocellulose. Here, we report on the bacterial composition in the porcupine microbiome using 16S rRNA sequencing and bioinformatics analysis. We extended this analysis to the microbiomes of 20 additional mammals located in Shubenacadie Wildlife Park (Nova Scotia, Canada), enabling the comparison of bacterial diversity amongst three mammalian taxonomic orders (Rodentia, Carnivora, and Artiodactyla). 16S rRNA sequencing was validated using metagenomic shotgun sequencing on selected herbivores (porcupine, beaver) and carnivores (coyote, Arctic wolf). In the microbiome, functionality is more conserved than bacterial composition, thus we mined microbiome data sets to identify conserved microbial functions across species in each order. We measured the relative gene abundances for cellobiose phosphorylase, endoglucanase, and beta-glucosidase to evaluate the cellulose-degrading potential of select mammals. The porcupine and beaver had higher proportions of genes encoding cellulose-degrading enzymes than the Artic wolf and coyote. These findings provide further evidence that gut microbiome diversity and metabolic capacity are influenced by host diet.
Genes of Periodontopathogens Expressed During Human Disease (2002)

MAT has proven useful in identifying previously unknown in vivo-induced genes that are likely involved in virulence and are thus excellent candidates for use in diagnostic : and therapeutic strategies, including vaccine design.
Geographical variation in the exhaled volatile organic compounds (2013)

Breath-gas analysis has demonstrated that concentration profiles of volatile organic compounds (VOCs) could be used for detecting a variety of diseases, among them gastric cancer (GC) and peptic ulcer disease (PUD). Here, we explore how geographical variation affects the disease-specific changes in the chemical composition of breath samples, as compared to control states (less severe gastric conditions). Alveolar exhaled breath samples from 260 patients were collected at two remotely different geographic locations (China and Latvia), following similar breath-collection protocols. Each cohort included 130 patients that were matched in terms of diagnosis (37 GC/32 PUD/61 controls), average age, gender ratio and smoking habits. Helicobacter Pylori infection, which is a major cause for GC and PUD, was found in part of the patients, as well as in part of the controls, at both locations. The breath samples were analyzed by gas chromatography/mass spectrometry, using the same equipment and protocol-of-experiment. We observed similar characteristic differences in the chemical composition of the breath samples between the study groups at the two locations, even though the exact composition of the breath samples differed. Both in China and Latvia, the GC patients and controls could be distinguished by differences in the average levels of 6-methyl-5-hepten-2-one; PUD patients were distinguished from controls by the levels of aromatic compounds and alcohols; GC and PUD patients could not be distinguished at either site. This pilot study indicates the limitations of chemical breath-gas analysis alone for identifying gastric diseases based on the concentration profiles of separate VOCs in international patient cohorts. We assume that these limitations would apply to other diseases as well. The presented data could potentially be useful for developing an alternative, universally applicable diagnostic method that relies on the detection of changes in the collective patterns of the disease-specific classes of exhaled VOCs.
Antenna-based near-field scanning optical microscopy (Invited Paper) (2005)

Some time ago a near-field optical imaging technique had been introduced (Appl. Phys. Lett. 73, 1669 (1998)), which achieves high spatial resolution and excellent sensitivity by exploiting the highly localized and mutual near-field interactions between a Au-nanosphere and a sharp Si-probe under evanescent field illumination. Specifically, the scattering of Au-nanoparticles is significantly enhanced by the presence of a sharp nanoscopic probe demonstrating that the probe acts as an efficient antenna. The present study focuses on the underlying physics of the original results by investigating more systematically nanoparticle-probe interactions: (1) The polarization pattern of the scattered field of an evanescent wave excited Si-probe is studied, which demonstrates that the probe scatters as a single dipole. (2) The enhanced scattering signal is measured as a function of sample size, which allows us to predict the signal strength for different size samples. (3) The wavelength dependence of the probe-sample scattering is investigated by exciting Au-nanospheres on (@543 nm) and off plasmon resonance (@633nm). The data shows a pronounced wavelength dependence reflecting the near-field spectrum of the Au-nanocrystals. (4) Finally, a simple, but intuitive model describing these mutual near-field interactions is presented, which explains qualitatively both the size and wavelength dependence of the enhanced scattering signals.
Final results of a phase I radioimmunotherapy trial using (186)Re-epratuzumab for the treatment of patients with non-Hodgkin's lymphoma. (2003)

(186)Re-epratuzumab at a dose of 2.0 GBq/m(2) is well tolerated without major toxicity. A single dose of (186)Re-epratuzumab led to objective responses in 5 of 15 treated patients.
On the action of RH 5849, a nonsteroidal ecdysteroid agonist, on a cell line from Chironomus tentans (1991)

Abstract RH 5849 competes with 3 H‐ponasterone A for ecdysteroid binding sites in Chironomus tentans cells with an about fourfold lower relative affinity as compared to 20‐OH‐ecydsone. It does not interfere with glucocorticoid and estrogen binding sites in vertebrates. It is also not recognized by an ecdysteroid antibody. RH 5849 exerts typical morphological and physiological effects ascribed to the action of 20‐OH‐ecdysone on C. tentans cells, namely an increase in acetylcholinesterase activity and an inhibition of chitin synthesis.
Development of a robust vehicle control with driver in the loop (2014)

A new method for a driver in the loop vehicle control is proposed in this paper. The driver is modeled as a linear optimal controller with time varying delay, who uses road preview information as well as dynamic behavior of the vehicle to steer the car and follow the desired path. The delay block represents the cumulative drivers observation and the action delay. Since regular controllers do not have access to the future road preview data, the road preview information is modeled as unknown bounded uncertainty. A robust state-feedback controller based on Lyapunov-Krasovskii methodology is designed to mitigate effects of delays and uncertainties. The controller in this scheme only uses the current states of the vehicle, driver input, and the driver model. Simulation results demonstrate the effectiveness of the proposed method.
New Scheme of Electrooptic Sampling by Probe Beam Polarization Modulation (1991)

Electrooptic (EO) sampling is a powerful technique to characterize very-high speed electrical waveforms in the time domain and to examine waveforms internal to Integrated circuits[1-6].
Chronic chemotherapeutic stress promotes evolution of stemness and WNT/beta-catenin signaling in colorectal cancer cells: implications for clinical use of WNT-signaling inhibitors (2015)

Most solid tumors contain a subfraction of cells with stem/progenitor cell features. Stem cells are naturally chemoresistant suggesting that chronic chemotherapeutic stress may select for cells with increased "stemness". We carried out a comprehensive molecular and functional analysis of six independently selected colorectal cancer (CRC) cell lines with acquired resistance to three different chemotherapeutic agents derived from two distinct parental cell lines. Chronic drug exposure resulted in complex alterations of stem cell markers that could be classified into three categories: 1) one cell line, HT-29/5-FU, showed increased "stemness" and WNT-signaling, 2) three cell lines showed decreased expression of stem cell markers, decreased aldehyde dehydrogenase activity, attenuated WNT-signaling and lost the capacity to form colonospheres and 3) two cell lines displayed prominent expression of ABC transporters with a heterogeneous response for stem cell markers. While WNT-signaling could be attenuated in the HT-29/5-FU cells by the WNT-signaling inhibitors ICG-001 and PKF-118, this was not accompanied by any selective growth inhibitory effect suggesting that the cytotoxic activity of these compounds is not directly linked to WNT-signaling inhibition. We conclude that classical WNT-signaling inhibitors have toxic off-target activities that need to be addressed for clinical development.
ChemInform Abstract: Stereoselective Synthesis of Methyl 3α‐Ethyl‐1,2,3,4,6,7,12,12b. beta.‐octahydroindolo(2,3‐a)quinolizine‐1α‐carboxylate: A Key Intermediate for the Preparation of Tacamine‐Type Indole Alkaloids. (1996)

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.
Lattice thermodynamics for aqueous salt–polymer two‐phase systems (1998)

A lattice model is presented to compute salt-induced liquid–liquid phase separation in aqueous polymer solutions. The Gibbs energy of mixing contains an electrostatic contribution given by Pitzer's extension of the Debye–Hückel function, and the extended Flory–Huggins theory that uses empirical functions of temperature and composition as binary interaction parameters. Our Flory–Huggins theory assumes complete dissociation of salt into ions, but it does not distinguish between cation and anion; our theory represents the water–salt–polymer mixture as an incompressible ternary system consisting of water, ion, and polymer. In the extended Flory–Huggins theory, the binary interaction parameter between water and ion, and that between water and polymer, are obtained by correlating the observed activity of water in each of the two relevant binary systems. The electrostatic contribution does not contain adjustable parameters. We show that the electrostatic contribution to the Gibbs energy of mixing is responsible for inducing salt–polymer aqueous two-phase systems. Calculated phase diagrams are compared with experiment for aqueous solutions containing polyethylene glycol and a single salt at room temperature. The efficiency of a salt to form salt–polymer aqueous two-phase systems is discussed in terms of ion valence and the interaction parameter between ion and polymer. © 1998 John Wiley & Sons, Inc. J Appl Polym Sci Inc. J Appl Polym Sci 68: 2007–2017, 1998
Gold nanorods combine photoacoustic and Raman imaging for detection and treatment of ovarian cancer (2014)

Gold nanorods (<strong>GNRs</strong>) were synthesized with surfactant templating and coated with IR792 to produce surface-enhanced Raman signal (<strong>SERS</strong>). Subcutaneous and orthotopic tumor models were created in nude mice using the OV2008 cell line, and a Nexus128 scanner from Endra LifeSciences was used to collect the photoacoustic data. We used GNRs with resonance at 756 nm, and the Raman signal was 10-fold larger than 60 nm gold core/silica shell nanoparticles. This signal was stable for over 24 hours in 50% serum. The batch-to-batch reproducibility was 15.5% and 3.6% in the SERS and photoacoustic modalities for n=4 batches. Animals were injected with 200 &mu;L of 2.5, 5.4, and 16.8 nM GNRs. Relative to baseline photoacoustic signal, these concentrations increased tumor signal 1.3-, 1.6-, and 2.5-fold, respectively. The maximum signal increase occurred within 2 hours of injection persisted for at least 24 hours and was significant at p&lt;0.05 for at least 3 animals. Assaying for gold in the tumors validated signal—we found a strong correlation (R<sup>2</sup>&gt;0.90) between tumor gold concentration and photoacoustic signal. By 24 hours, free GNRs had been sequestered to the liver and spleen with 2%ID/g immobilized in the tumor. The same GNRs produced SERS signal, and Raman maps were created with least squares analysis. We used the Raman signal to identify tumor margins and also to monitor resection and ensure complete removal of tumor tissue. Thus, the GNRs allow pre-surgical photoacoustic visualization for tumor staging and intra-operative Raman imaging to guide resection. Future work will study GNRs targeted to cell surface proteins to increase tumor accumulation.
Pharmacological inhibition of ROR gamma t suppresses the Th17 pathway and alleviates antigen-induced arthritis in-vivo (2017)

Retinoic acid receptor-related-orphan-receptor-C (ROR gammat) is the key transcription factor that is driving the differentiation of IL-17 producing T-helper 17 (Th17) cells that are implicated in the pathology of various autoimmune and inflammatory diseases. Based on the importance of RORgammat in promoting Th17-driven pathology, there is considerable interest to develop low-molecular-weight compounds with the aim to inhibit the transcriptional activity of this nuclear hormone receptor. In this article, we describe the in-vitro and in-vivo pharmacology of a potent and selective small-molecular-weight RORgammat inverse agonist. The compound binds to the ligand binding domain (LBD) of RORgammat leading to displacement of a co-activator peptide. We show for the first time that a RORgammat inverse agonist down-regulates permissive histone H3 acetylation and methylation at the IL17A and IL23R promoter regions, thereby providing insight into the transcriptional inhibition of RORgammat-dependent genes. Consitent with this, the compound effectively reduced IL-17A production by polarized human gamma delta T-cells and by T-cells and attenuated transcription of RORgammat target genes. The inhibitor showed good in-vivo efficacy in an antigen-induced arthritis model in rats and reduced the frequencies of IL-17A producing cells in ex-vivo recall assays. In summary, we demonstrate that inhibiting RORgammat by a low-molecular-weight inhibitor results in efficient and selective blockade of the pro-inflammatory Th17/IL-17A pathway making it an attractive target for Th17-mediated disorders.
An electron spin resonance, ENDOR, and TRIPLE resonance study of methyl-substituted N,N′-diphenyl-4,4′-bipyridylium dichloride radical cations (1985)

The e.s.r. and ENDOR spectra of the radical cations of N,N′-diphenyl-4,4′-bipyridylium di-chloride (DPQ), N,N′-bis-(4-methylphenyl)-4,4′-bipyridylium dichloride (p-mDPQ), N,N′-bis-(3-methylphenyl)-4,4′-bipyridylium dichloride (m-mDPQ), N,N′-bis-(2-methylphenyl-4,4′-bipyridylium dichloride (o-mDPQ), and N,N′-bis-(2,4,6-trimethylphenyl)-4,4′-bipyridylium dichloride (T-mDPQ) in methanol were studied over a range of temperatures. Values for the hyperfine couplin constants are given at –40 °C. It was found that the radical cation concentrations of DPQ+˙, p-mDPQ+˙, m-mDPQ+˙, and o-mDPQ+˙ decreased with decreasing temperature, this change being reversible, whilst that of T-mDPQ+˙ did not. We explain the reversible change with temperature in terms of a monomer–dimer equilibrium, and the absence of such an equilibrium in the case of T-mDPQ+˙ as due to the lack, of planarity of the molecule, because of steric hindrance between the methyl groups and the pyridyl ortho-protons. The thermodynamic constants ΔG°, ΔH°, and ΔS°, obtained for the dimerisation equilibria, are reported.
Inclusive J/ψ production at forward and backward rapidity in p-Pb collisions at $$ \sqrt{s_{\mathrm{NN}}}=8.16 $$ TeV (2018)

A bstract Inclusive J/ ψ production is studied in p-Pb interactions at a centre-of-mass energy per nucleon-nucleon collision $$ \sqrt{s_{\mathrm{NN}}}=8.16 $$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msqrt> <mml:msub> <mml:mi>s</mml:mi> <mml:mrow> <mml:mi>N</mml:mi> <mml:mi>N</mml:mi> </mml:mrow> </mml:msub> </mml:msqrt> <mml:mo>=</mml:mo> <mml:mn>8.16</mml:mn> </mml:math> TeV, using the ALICE detector at the CERN LHC. The J/ ψ meson is reconstructed, via its decay to a muon pair, in the centre-of-mass rapidity intervals 2.03 &lt; y cms &lt; 3.53 and −4.46 &lt; y cms &lt; −2.96, where positive and negative y cms refer to the p-going and Pb-going direction, respectively. The transverse momentum coverage is p T &lt; 20 GeV/ c . In this paper, y cms - and p T -differential cross sections for inclusive J/ ψ production are presented, and the corresponding nuclear modification factors R pPb are shown. Forward results show a suppression of the J/ ψ yield with respect to pp collisions, concentrated in the region p T ≲ 5 GeV/ c . At backward rapidity no significant suppression is observed. The results are compared to previous measurements by ALICE in p-Pb collisions at $$ \sqrt{s_{\mathrm{NN}}}=5.02 $$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msqrt> <mml:msub> <mml:mi>s</mml:mi> <mml:mrow> <mml:mi>N</mml:mi> <mml:mi>N</mml:mi> </mml:mrow> </mml:msub> </mml:msqrt> <mml:mo>=</mml:mo> <mml:mn>5.02</mml:mn> </mml:math> TeV and to theoretical calculations. Finally, the ratios R FB between forward- and backward- y cms R pPb values are shown and discussed.
Linear-T resistivity and change in Fermi surface at the pseudogap critical point of a high-Tc superconductor (2008)

A fundamental question of high-temperature superconductors is the nature of the pseudogap phase which lies between the Mott insulator at zero doping and the Fermi liquid at high doping p. Here we report on the behaviour of charge carriers near the zero-temperature onset of that phase, namely at the critical doping p* where the pseudogap temperature T* goes to zero, accessed by investigating a material in which superconductivity can be fully suppressed by a steady magnetic field. Just below p*, the normal-state resistivity and Hall coefficient of La1.6-xNd0.4SrxCuO4 are found to rise simultaneously as the temperature drops below T*, revealing a change in the Fermi surface with a large associated drop in conductivity. At p*, the resistivity shows a linear temperature dependence as T goes to zero, a typical signature of a quantum critical point. These findings impose new constraints on the mechanisms responsible for inelastic scattering and Fermi surface transformation in theories of the pseudogap phase.