gebhart/patrepeval huggingface dataset:
Phase I Trial Characterizing the Pharmacokinetic Profile of N-803, a Chimeric IL-15 Superagonist, in Healthy Volunteers (2022)

The oncotherapeutic promise of IL-15, a potent immunostimulant, is limited by a short serum <i>t</i> <sub>1/2</sub> The fusion protein N-803 is a chimeric IL-15 superagonist that has a >20-fold longer in vivo <i>t</i> <sub>1/2</sub> versus IL-15. This phase 1 study characterized the pharmacokinetic (PK) profile and safety of N-803 after s.c. administration to healthy human volunteers. Volunteers received two doses of N-803, and after each dose, PK and safety were assessed for 9 d. The primary endpoint was the N-803 PK profile, the secondary endpoint was safety, and immune cell levels and immunogenicity were measures of interest. Serum N-803 concentrations peaked 4 h after administration and declined with a <i>t</i> <sub>1/2</sub> of ∼20 h. N-803 did not cause treatment-emergent serious adverse events (AEs) or grade ≥3 AEs. Injection site reactions, chills, and pyrexia were the most common AEs. Administration of N-803 was well tolerated and accompanied by proliferation of NK cells and CD8<sup>+</sup> T cells and sustained increases in the number of NK cells. Our results suggest that N-803 administration can potentiate antitumor immunity.
Estimation of Piezoelectric Response Using Maximally Localized Wannier Function and Its Application to the Bismuth-Based Ferroelectric Materials (2011)

Estimation of piezoelectric coefficient using maximally localized Wannier function (MLWF) is performed for several ferroelectric materials. The advantage of this method is that we can decompose the piezoelectric coefficient into each orbital of MLWF and can obtain physical information on the piezoelectric response from the viewpoint of electric structure. We divide the piezoelectric coefficient into the "electric" and "ionic" parts. For the electric part, we further divide it into each MLWF orbital contribution. We have applied this method to BaTiO3, PbTiO3, and the bismuth-based ferroelectric materials BiAlO3 and BiFeO3. We show the detailed characteristics of the piezoelectric response in these materials.
In situ determination of porewater gases by underwater flow‐through membrane inlet mass spectrometry (2012)

An underwater membrane introduction mass spectrometer was deployed in permeable sandy sediment on the Georgia continental shelf (depth = 27 m) to measure in situ dissolved gas concentrations in sediment porewaters. Over a 54‐h period, 30 profiles (up to 18 cm deep) were sampled using an automated sediment probe coupled with an underwater positive displacement syringe pump. Porewater was analyzed with a flow‐through membrane assembly at constant sample flow rate (0.35 mL/min) and membrane temperature (45°C). Calibration was performed on‐site using ambient seawater equilibrated with gas standards. Measurements of methane, nitrogen, argon, oxygen, and carbon dioxide concentrations were used to produce depth‐time contours and demonstrate the dynamics of dissolved gases in the porewater. Profiles indicated a well‐oxygenated surface layer (1 to 2 cm depth) and anoxia below −3 to −5 cm. Elevated concentrations of methane below the oxycline reveal active methanogenesis in shelf sands despite low (0.05%) organic carbon content. Chemocline depth and sediment ripple height were correlated, suggesting that the porewater environment is controlled by advection‐driven interactions between boundary‐layer flow and bottom topography. By coupling in situ concentration profiles to independent estimates of sediment‐water exchange, it was estimated that maximal oxygen consumption at this site occurs &gt; 2 cm below the interface. Oxygen consumption at this site is estimated as 2.3 mmol m −2 d −1 based on combined dissolved profiles and advection estimates. Raw data and data analysis scripts (Matlab) are available electronically in a Web Appendix.
Micro-object assembly with an optically addressed array (2017)

A microassembly system based on electric field manipulation is described. Optical addressing of a phototransistor array controls the position and orientation of micro-objects using dielectrophoretic and electrophoretic forces. Open-loop control is used to rapidly direct many micro-objects in parallel. Closed-loop control is used to position micro-objects precisely. Demonstrations with beads (10 μm diameter) and silicon chips (150 μm scale) are presented. We have achieved coarse assembly at a rate of 1000 micro-objects per second, fine assembly of beads at micrometer scales, and arrays of silicon chips with orientation control. The technology aims to enable a generalized printer system for building engineered microstructure and electronics.
Function of Xenopus Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Cl- Channels and Use of Human-Xenopus Chimeras to Investigate the Pore Properties of CFTR (1996)

To explore the relationship between structure and function in the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel, we studied Xenopus CFTR. We found that the anion permeability sequence of cAMP-activated Cl- currents in the apical membrane of Xenopus A6 epithelia differed from that of cAMP-activated Cl- currents in human epithelia expressing CFTR. To understand the molecular basis for this difference and to learn whether CFTR from another species would have properties similar to human CFTR, we assembled a full-length Xenopus CFTR cDNA from A6 cells. Expression of Xenopus CFTR in HeLa cells generated cAMP-activated whole-cell currents and cAMP-dependent protein kinase-activated single channels that resembled those of human CFTR with the exception that the anion permeability sequence was different (Br- = I- > Cl- in Xenopus CFTR and Br- = Cl- > I- in human). In addition, the single-channel conductance of Xenopus CFTR was increased. To investigate protein regions that account for these differences, we constructed chimeric proteins by replacing either the first or second membrane-spanning domain of human CFTR with the equivalent region of Xenopus CFTR (hX1-6 and hX7-12, respectively) and examined their function in HeLa cells. We found that the anion permeability sequence (Br- = I- > Cl-) and single-channel conductance of hX1-6 resembled that of Xenopus CFTR expressed in HeLa cells, whereas hX7-12 had properties like those of human CFTR. However, the gating of hX1-6 showed a flickery behavior. The altered gating of hX1-6 was attributed to residues in the first extracellular loop of Xenopus CFTR because mutation of residues in that region to the corresponding residues of human CFTR produced gating behavior similar to that of human CFTR. These data suggest that sequence differences in the first membrane-spanning domains are responsible for the differences in the permeation properties of human and Xenopus CFTR and that the first extracellular loop influences channel gating.
"Hygroscopic Growth of Submicron and Supermicron Aerosols in the Marine Boundary Layer" - eScholarship (2014)

We investigate hygroscopic growth of marine aerosols from three research cruises: TexAQS-GoMACCS 2006, ICEALOT 2008 and CalNex 2010. Particle hygroscopic growth was characterized by measuring the effect of water uptake under sub-saturated conditions on the aerosol light extinction at 532 nm. Mie theory calculations were utilized to convert the observed optical growth factors (fext(RH)) into physical growth factors (GF) at 85% RH. GF is found to be a more robust measure of aerosol hygroscopic growth than fext(RH), which can be biased by changes in aerosol dry size. Consistent with previous observations, the overall GF(85%) for submicron aerosol depended on the fraction of organics. The submicron GFOM(85%) specifically was found to range from 1.0-1.3 for all three campaigns. A robust positive linear dependence of the overall supermicron GF(85%) on the mass fraction of sea salt was observed. During TexAQS, two types of dust particles with distinct hygroscopic properties were identified in the supermicron mode; one that originated from the Sahara desert was moderately hygroscopic (GFdust(85%) = ~1.4) and the other from continental sources was nearly hydrophobic. The GF(85%) of supermicron organics was estimated through hygroscopicity closure calculations. Supermicron organics that originated from marine sources were found to be substantially more hygroscopic than those from continental sources, with the latter having a GF(85%) similar to that of the submicron organics. This study demonstrates the potential of using aerosol optical measurements to retrieve hygroscopic growth factor and underlines the importance and need for future investigations on the hygroscopic properties of marine supermicron aerosols.
ChemInform Abstract: Alternating Addition of Carbon‐Centered Radicals to Unsaturated Systems. Novel Homolytic Aromatic Substitutions. (1997)

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.
Numerical Analysis of Flow around a Sphere with Active Dimples (2006)

Numerical simulations of flow around a smooth sphere and a sphere with temporally deforming dimples (active dimples) in critical Reynolds number regime, have been conducted in order to investigate the influence of deformation of active dimples on surrounding boundary layer. It is observed that the drag coefficient is decreased when the Reynolds number is greater than Re> 105 by the transition of the boundary layer for the smooth sphere, as is reported by many experiments in the literature. It is shown the drag coefficient is decreased up to 40% when appropriate dimple scales and period of deformation are given. The active dimple promotes transition of boundary layer in the vicinity of the sphere, and restraints the detachment of flow. It is expected the applicability of active dimples displayed to a flow control device which is attached the surface of transportation body such as an airplane, a ship and so on.
Threshold photodetachment ofH− (1991)

The electron affinities of atomic hydrogen and deuterium have been determined by tunable-laser threshold-photodetachment spectroscopy: the electron affinities of H (F=0) and D (F=1/2) are 6082.99\ifmmode\pm\else\textpm\fi{}0.15 and 6086.2\ifmmode\pm\else\textpm\fi{}0.6 ${\mathrm{cm}}^{\mathrm{\ensuremath{-}}1}$, respectively. The value for H is a 20-fold improvement over previous experimental determinations.
Efficient Activation of Viral Genomes by Levels of Herpes Simplex Virus ICP0 Insufficient To Affect Cellular Gene Expression or Cell Survival (2001)

Herpes simplex virus (HSV) ICP0 can effectively activate gene expression from otherwise silent promoters contained on persisting viral genomes. However, the expression of high levels of ICP0, as from ICP4(-) HSV type 1 (HSV-1) vectors, results in marked toxicity. We have analyzed the results of ICP0 expressed from an E1(-) E4(-) adenovirus vector (AdS.11E4ICP0) in which ICP0 expression is controlled from the endogenous adenoviral E4 promoter. In this system, the expression level of ICP0 was reduced more than 1,000-fold relative to the level of expression from HSV-1 vectors. This low level of ICP0 did not affect cellular division or greatly perturb cellular metabolism as assessed by gene expression array analysis comparing the effects of HSV and adenovirus vector strains. However, this amount of ICP0 was sufficient to quantitatively destroy ND10 structures as measured by promyelocytic leukemia immunofluorescence. The levels of adenovirus-expressed ICP0 were sufficient to activate quiescent viral genomes in trans and promote persistent transgene expression in cis. Moreover, infection of complementing cells with AdS.11E4ICP0 promoted viral growth and resulted in a 20-fold increase in the plaquing efficiency of d109, a virus defective for all five immediate-early genes. Thus, the low level expression of ICP0 from the E1(-) E4(-) adenovirus vector may increase the utility of adenovirus vectors and also provides a means to efficiently quantify and possibly propagate HSV vectors defective in ICP0. Importantly, the results demonstrate that the activation function of ICP0 may not result from changes in cellular gene expression, but possibly as a direct consequence of an enzymatic function inherent to the protein that may involve its action at ND10 resulting in the preferential activation of viral genomes.
High Field Dynamic Nuclear Polarization NMR with Surfactant Sheltered Biradicals (2014)

We illustrate the ability to place a water-insoluble biradical, bTbk, into a glycerol/water matrix with the assistance of a surfactant, sodium octyl sulfate (SOS). This surfactant approach enables a previously water insoluble biradical, bTbk, with favorable electron-electron dipolar coupling to be used for dynamic nuclear polarization (DNP) nuclear magnetic resonance (NMR) experiments in frozen, glassy, aqueous media. Nuclear Overhauser enhancement (NOE) and paramagnetic relaxation enhancement (PRE) experiments are conducted to determine the distribution of urea and several biradicals within the SOS macromolecular assembly. We also demonstrate that SOS assemblies are an effective approach by which mixed biradicals are created through an assembly process.
Ribozyme knockdown functionally links a 1,25(OH) 2 D 3 membrane binding protein (1,25D 3 -MARRS) and phosphate uptake in intestinal cells (2004)

We used a ribozyme loss-of-function approach to demonstrate that the protein product of a cDNA encoding a multifunctional membrane-associated protein binds the seco-steroid 1,25(OH)(2)D(3) and transduces its stimulatory effects on phosphate uptake. These results are paralleled by studies in which the ability of the hormone to stimulate phosphate uptake in isolated chick intestinal epithelial cells is abolished by preincubation with Ab099 directed against the amino terminus of the protein. We now report the complete sequence of the cloned chicken cDNA for the 1,25D(3)-MARRS (membrane-associated, rapid-response steroid-binding) protein and reveal it to be identical to the multifunctional protein ERp57. Functional studies showed that active ribozyme, but not a scrambled control, decreased specific membrane-associated 1,25(OH)(2)D(3) binding, but did not affect binding to the nuclear receptor for 1,25(OH)(2)D(3). Seco-steroid-dependent stimulation of protein kinase C activity was diminished as 1,25D(3)-MARRS protein levels were reduced in the presence of the ribozyme, as judged by Western blot analyses. Phosphate uptake in isolated cells is an index of intestinal phosphate transport that occurs during growth and maturation. Whereas cells and perfused duodena robustly responded to 1,25(OH)(2)D(3) in preparations from young birds, older animals no longer responded with stimulated phosphate uptake or transport. The age-related decline was accompanied by a decrease in 1,25D(3)-MARRS mRNA that was apparent up to 1 year of age. Together, these studies functionally link phosphate transport in the chick duodenum with the 1,25D(3)-MARRS protein and point to a previously uncharacterized role for this multifunctional protein class.
Forward-Lighting Configurations for Snowplows (1996)

Snow and ice control is a critical maintenance operation for New York State: each winter, up to 68 500 km (42,500 lane-mi) of highways must be cleared. Visibility during plowing operations is often poor and is further diminished by backscatter glare from the snowplow's own headlights as well as glare from lights of oncoming traffic. Results are summarized of a pilot study to identify forward (front-end) lighting configurations that might improve visibility for plow operators during such operations. During the 1993–1994 winter, eight lighting configurations were tested, two of which were identified as potential improvements over the existing pattern. Simple procedures and forms were developed for collecting reliable data. Methodological issues in performing such experiments are discussed. A statistical methodology is presented that is suitable for comparison of lighting configurations but is also applicable in other, broader contexts in which a number of items are compared by several evaluators.
Abstract LB-120: CYP3A5 mediates basal and acquired therapy resistance in different subtypes of pancreatic ductal adenocarcinoma (2016)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with poor prognosis. Treatment with gemcitabine, the FOLFIRINOX scheme or nab-paclitaxel offer only a modest increase in overall survival. For a number of other carcinomas, tumor subtypes have been uncovered that allow the use of targeted therapies. Although subtypes of PDAC were described, this malignancy is clinically still treated as a single disease. We established patient-derived models representing the full spectrum of previously identified quasi-mesenchymal (QM-PDA), classical and exocrine-like PDAC subtypes, and identified two markers—HNF1A and KRT81—that enable stratification of tumors into different subtypes by immunohistochemistry. Patients bearing tumors of these subtypes show significant differences in overall survival and their tumors differ in drug sensitivity, with the exocrine-like subtype being resistant to tyrosine kinase inhibitors and paclitaxel. The xenobiotic enzyme, cytochrome P450 3A5 (CYP3A5), metabolizes these compounds in tumor cells of the exocrine-like subtype, and pharmacological or short hairpin RNA (shRNA)-mediated CYP3A5 inhibition sensitizes tumor cells to these drugs. Additionally, retrospective analysis of a large patient cohort confirmed that CYP3A5 is predominantly found in those patient tumors classified as exocrine-like (Noll, Eisen et al., Nature Medicine (2016) accepted). Whereas the hepatocyte nuclear factor 4, alpha (HNF4A) controls basal expression of CYP3A5, drug-induced CYP3A5 upregulation is mediated by the nuclear receptor NR1I2. Interfering with these regulatory mechanisms may provide an alternative approach to suppress the CYP3A5 mediated resistance pathway. CYP3A5 also contributes to acquired drug resistance in QM-PDA and classical PDAC in vitro and in vivo. Finally, CYP3A5 is highly expressed in several additional malignancies including hepatocellular and cervical carcinomas raising the possibility that the CYP3A5 resistance mechanism is operational in a variety of human cancers. These findings designate CYP3A5 as predictor of therapy response and as a tumor cell-autonomous detoxification mechanism that must be overcome to prevent drug resistance. Citation Format: Elisa M. Noll, Christian Eisen, Albrecht Stenzinger, Elisa Espinet, Alexander Muckenhuber, Corinna Klein, Vanessa Vogel, Bernd Klaus, Wiebke Nadler, Christoph Rösli, Christian Lutz, Michael Kulke, Jan Engelhardt, Franziska Zickgraf, Octavio Espinosa, Matthias Schlesner, Xiaoqi Jiang, Annette Kopp-Schneider, Peter Neuhaus, Marcus Bahra, Bruno Sinn, Roland Eils, Nathalia Giese, Thilo Hackert, Oliver Strobel, Jens Werner, Markus W. Büchler, Wilko Weichert, Andreas Trumpp, Martin R. Sprick. CYP3A5 mediates basal and acquired therapy resistance in different subtypes of pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-120.
Oriented, Multimeric Biointerfaces of the L1 Cell Adhesion Molecule: An Approach to Enhance Neuronal and Neural Stem Cell Functions on 2-D and 3-D Polymer Substrates (2012)

This article focuses on elucidating the key presentation features of neurotrophic ligands at polymer interfaces. Different biointerfacial configurations of the human neural cell adhesion molecule L1 were established on two-dimensional films and three-dimensional fibrous scaffolds of synthetic tyrosine-derived polycarbonate polymers and probed for surface concentrations, microscale organization, and effects on cultured primary neurons and neural stem cells. Underlying polymer substrates were modified with varying combinations of protein A and poly-D-lysine to modulate the immobilization and presentation of the Fc fusion fragment of the extracellular domain of L1 (L1-Fc). When presented as an oriented and multimeric configuration from protein A-pretreated polymers, L1-Fc significantly increased neurite outgrowth of rodent spinal cord neurons and cerebellar neurons as early as 24 h compared to the traditional presentation via adsorption onto surfaces treated with poly-D-lysine. Cultures of human neural progenitor cells screened on the L1-Fc/polymer biointerfaces showed significantly enhanced neuronal differentiation and neuritogenesis on all protein A oriented substrates. Notably, the highest degree of βIII-tubulin expression for cells in 3-D fibrous scaffolds were observed in protein A oriented substrates with PDL pretreatment, suggesting combined effects of cell attachment to polycationic charged substrates with subcellular topography along with L1-mediated adhesion mediating neuronal differentiation. Together, these findings highlight the promise of displays of multimeric neural adhesion ligands via biointerfacially engineered substrates to "cooperatively" enhance neuronal phenotypes on polymers of relevance to tissue engineering.
Dynamics of Hot QCD Matter -- Current Status and Developments (2022)

The discovery and characterization of hot and dense QCD matter, known as Quark Gluon Plasma (QGP), remains the most international collaborative effort and synergy between theorists and experimentalists in modern nuclear physics to date. The experimentalists around the world not only collect an unprecedented amount of data in heavy-ion collisions, at Relativistic Heavy Ion Collider (RHIC), at Brookhaven National Laboratory (BNL) in New York, USA, and the Large Hadron Collider (LHC), at CERN in Geneva, Switzerland but also analyze these data to unravel the mystery of this new phase of matter that filled a few microseconds old universe, just after the Big Bang. In the meantime, advancements in theoretical works and computing capability extend our wisdom about the hot-dense QCD matter and its dynamics through mathematical equations. The exchange of ideas between experimentalists and theoreticians is crucial for the progress of our knowledge. The motivation of this first conference named "HOT QCD Matter 2022" is to bring the community together to have a discourse on this topic. In this article, there are 36 sections discussing various topics in the field of relativistic heavy-ion collisions and related phenomena that cover a snapshot of the current experimental observations and theoretical progress. This article begins with the theoretical overview of relativistic spin-hydrodynamics in the presence of the external magnetic field, followed by the Lattice QCD results on heavy quarks in QGP, and finally, it ends with an overview of experiment results.