gebhart/patrepeval huggingface dataset:
Megakaryocyte Lineage Commitment in Hematopoietic Stem Cells (2011)

Abstract Abstract 909 Hematopoietic stem cells (HSCs) are able to self-renew and differentiate into all blood lineages. Lineage commitment can take place at any stage from daughter cells of HSCs to multipotent progenitors. We have previously suggested that lineage commitment takes place at the level of HSCs (Takano et al. 2004). According to our asymmetric model, one HSC gives rise to two daughter cells consisting of one HSC and one lineage-committed progenitor. To verify this model, we performed a series of single-cell transplantation, followed by paired daughter cell experiments. The Ly5 congenic system has been commonly used to distinguish test donor cells from recipient cells and competitor cells. Since the Ly5 antigen is only expressed in leukocytes, platelets and erythrocytes have not been examined for evaluation of multi-lineage reconstitution. To assess lineage contribution more precisely, we have recently generated a transgenic mouse line in which Kusabira Orange (KuO) is expressed in all blood lineages including platelets and erythrocytes. CD150+CD41−CD34−/lowc-Kit+Sca-1+Lin− (CD150+CD41−CD34−KSL) cells, in which HSCs are highly enriched (Kiel et al. 2005, Morita et al. 2010), and CD150−CD41−CD34−KSL cells were individually isolated from KuO transgenic mice (B6-Ly5.1), and were transplanted into lethally irradiated mice (B6-Ly5.2), along with 2×105 bone marrow cells (B6-Ly5.1/Ly5.2). For secondary transplantation, 1×107 bone marrow cells from recipient mice were transplanted to lethally irradiated mice. Peripheral blood cells of primary and secondary recipient mice were periodically analyzed after transplantation. In some mice, full-lineage reconstitution was detected after transplantation with single CD150+CD41−CD34−KSL cells. In others, only common myeloid progenitor-type reconstitution was detected whereas common lymphoid progenitor-type reconstitution was not detected at all. Interestingly, megakaryocyte lineage (Meg)-restricted reconstitution and Meg/erythrocyte lineage-restricted (ME) reconstitution were observed after transplantation with single CD150+CD41−CD34−KSL cells, but not after transplantation with single CD150−CD41−CD34−KSL cells. These results suggest that Meg and ME progenitors are closely related to HSCs in their development. Furthermore, we performed paired daughter cell assays combined with single cell transplantation. Following division of CD150+CD41−CD34−KSL cells in culture, individual two daughter cells were separated by micromanipulation techniques and were transplanted into lethally irradiated mice with 2 × 105 competitor cells. Preliminary data showed in effect that the recipient mice of each single daughter cell derived from one CD150+CD41−CD34−KSL cell exhibited asymmetric differentiation; one with full-lineage reconstitution and the other with Meg-restricted reconstitution. Our findings offer a new perspective of HSC differentiation pathways. Disclosures: No relevant conflicts of interest to declare.
Characterization of the Proinflammatory Profile of Synovial Fluid-Derived Exosomes of Patients with Osteoarthritis (2017)

The purpose of this study is to characterize synovial fluid- (SF-) derived exosomes of patients with gonarthrosis comparing two methods of isolation and to investigate their immune regulatory properties. Extracellular vesicles (EVs) have been isolated from inflamed SF by polymer precipitation method and quantified by Exocet kit and by nanoparticle tracking analysis. Vesicles expressed all the specific exosomal markers by immunoblot and FACS. After isolation with Exoquick, a relevant contamination by immune complexes was detected, which required further magnetic bead-based purification to remove. SF-derived exosomes significantly stimulated the release of several inflammatory cytokines and chemokines and metalloproteinases by M1 macrophages but did not influence the expression of CD80 and CD86 costimulatory molecules. In conclusion, we characterized purified exosomes isolated from inflamed SF and demonstrate that purified exosomes are functionally active in their ability to stimulate the release of proinflammatory factors from M1 macrophages. Our data indicate that SF-derived exosomes from gonarthrosis patients play a role in disease progression.
Cellular Responses to Patterned Poly(acrylic acid) Brushes (2011)

We use patterned poly(acrylic acid) (PAA) polymer brushes to explore the effects of surface chemistry and topography on cell-surface interactions. Most past studies of surface topography effects on cell adhesion have focused on patterned feature sizes that are larger than the dimensions of a cell, and PAA brushes have been characterized as cell repellent. Here we report cell adhesion studies for RBL mast cells incubated on PAA brush surfaces patterned with a variety of different feature sizes. We find that when patterned at subcellular dimensions on silicon surfaces, PAA brushes that are 30 or 15 nm thick facilitate cell adhesion. This appears to be mediated by fibronectin, which is secreted by the cells, adsorbing to the brushes and then engaging cell-surface integrins. The result is detectable accumulation of plasma membrane within the brushes, and this involves cytoskeletal remodeling at the cell-surface interface. By decreasing brush thickness, we find that PAA can be 'tuned' to promote cell adhesion with down-modulated membrane accumulation. We exemplify the utility of patterned PAA brush arrays for spatially controlling the activation of cells by modifying brushes with ligands that specifically engage IgE bound to high-affinity receptors on mast cells.
Algorithmic problems in Engel groups and cryptographic applications (2020)

The theory of Engel groups plays an important role in group theory since these groups are closely related to the Burnside problems. In this survey we consider several classical and novel algorithmic problems for Engel groups and propose several open problems. We study these problems with a view towards applications to cryptography.
Synthese von Plagiochin A und B, zwei macrocyclische Bis(bibenzylether) aus Plagiochila acantophylla (1992)

Synthesis of Plagiochins A and B, Macrocyclic Bis(bibenzyl) Ethers from Plagiochila acantophylla Plagiochins A ( 1 ) and B ( 2 ), macrocyclic bis(bibenzyl) ethers with a 16‐membered ring, are synthesized. The key steps are the Pd(0)‐catalyzed C—C coupling of an areneboronic acid ( 18 ) with an aryl bromide with formation of a biphenyl ( 13 ), Ullmann ether synthesis of a diphenyl ether ( 23 ), Wittig reaction to connect the two components 13 and 23 , and a modified Wurtz reaction to close the ring. The latter reaction is accompanied by an unusual transformation of a C ‐benzyloxy to a C ‐benzoyl group.
The chemotherapeutic drug oxaliplatin differentially affects blood DC function dependent on environmental cues (2011)

It has become evident that the tumor microenvironment plays a pivotal role in the maintenance of cancerous growth. One of the acquired functions of the tumor microenvironment is the suppression of immune responses. Indeed, blocking the inhibitory pathways operational in the microenvironment results in enhanced T-cell-dependent, anti-tumor immunity. Chemotherapeutic drugs not only directly kill tumor cells but also shape the tumor microenvironment and potentiate anti-tumor immunity. Here, we demonstrate that the chemotherapeutic compound oxaliplatin acts as a double-edged sword. Besides killing tumor cells, oxaliplatin bolsters immunosuppressive pathways, resulting in decreased activation of T cells by human plasmacytoid dendritic cells (pDCs). Exposure to oxaliplatin markedly increased expression of the T-cell inhibitory molecule programmed death receptor-ligand 1 (PD-L1) on human pDCs and also TLR9-induced IFNα secretion. Furthermore, oxaliplatin decreased TLR-induced STAT1 and STAT3 expression, and NF-κB-mediated responses. The oxaliplatin induced upregulation of PD-L1 and downregulation of costimulatory molecules CD80 and CD86 resulted in decreased T-cell proliferation. Our results demonstrate that platinum-based anticancer drugs adapt TLR-induced signaling in human pDCs and myeloid DCs (mDCs), thereby downgrading their immunostimulatory potential.
An ?-chain TCR CDR3 peptide can enhance EAE induced by myelin basic protein or proteolipid protein (1996)

Regulation of experimental autoimmune encephalomyelitis (EAE) can be induced by anti-idiotype immunity against T cell receptor (TCR) fragments associated with major histocompatibility complex (MHC) molecules. However, we have recently found that preimmunization with an alpha-chain TCR CDR3 peptide (LYFCAARSNYQL) derived from myelin basic protein (MBP)-specific clones did not suppress but rather augmented the severity of EAE induced by MBP-specific T cells in SJL/J mice. To test whether CDR3 vaccination could control only a highly restricted T cell population, we studied the effect of the peptide against EAE induced by T cells specific for different Ag/MHC ligands and autoimmune diseases affecting non-neural tissues. In contrast to expectations, the peptide was found to augment not only EAE induced by MBP-specific T cells, but also proteolipid protein (PLP)-specific T cell- or PLP peptide-induced EAE in SJL/J mice, and MBP-induced EAE and adjuvant arthritis (AA) in rats. The CDR3 peptide was neither inhibitory nor supportive for Ag-induced activation of an encephalitogenic clone in vitro. In addition, the peptide treatment neither inhibited the induction of Ag-specific T cells nor altered the APC function of spleen cells. These findings, on the one hand, confirm previous results showing TCR peptide-induced enhancement of the disease and, on the other hand, indicate that the TCR CDR3 peptide may control T cells with broader Ag/MHC specificities than could be expected. Structural similarity among TCR idiotypes of autoimmune T cells may partly account for these results.
Method to identify wells that yield water that will be replaced by water from the Colorado River downstream from Laguna Dam in Arizona and California (2000)

Accounting for the use of Colorado River water is required by the U.S. Supreme Court decree, 1964, Arizona v. California. Water pumped from wells on the flood plain and from certain wells on alluvial slopes outside the flood plain is presumed to be river water and is accounted for as Colorado River water. The accounting-surface method developed for the area upstream from Laguna Dam was modified for use downstream from Laguna Dam to identify wells outside the flood plain of the lower Colorado River that yield water that will be replaced by water from the river. Use of the same method provides a uniform criterion of identification for all users pumping water from wells by determining if the static water-level elevation in the well is above or below the elevation of the accounting surface. Wells that have a static water-level elevation equal to or below the accounting surface are presumed to yield water that will be replaced by water from the Colorado River. Wells that have a static water-level elevation above the accounting surface are presumed to yield river water stored above river level. The method is based on the concept of a river aquifer and an accounting surface within the river aquifer. The river aquifer consists of permeable sediments and sedimentary rocks that are hydraulically connected to the Colorado River so that water can move between the river and the aquifer in response to withdrawal of water from the aquifer or differences in water-level elevations between the river and the aquifer. The subsurface limit of the river aquifer is the nearly impermeable bedrock of the bottom and sides of the basins that underlie the Yuma area and adjacent valleys. The accounting surface represents the elevation and slope of the unconfined static water table in the river aquifer outside the flood plain of the Colorado River that would exist if the river were the only source of water to the river aquifer. The accounting surface was generated by using water-surface profiles of the Colorado River from Laguna Dam to about the downstream limit of perennial flow at Morelos Dam. The accounting surface extends outward from the edges of the flood plain to the subsurface boundary of the river aquifer. Maps at a scale of 1:100,000 show the extent of the river aquifer and elevation of the accounting surface downstream from Laguna Dam in Arizona and California.
2D ordered arrays of nanopatterns fabricated by using colloidal crystals as templates (2012)

A facile approach to fabricate two-dimensional (2D) ordered arrays of nanostructures is described in this paper. The approach uses spin-coating liquid materials onto a monolayer or multilayer colloidal crystal template to form a uniform film containing the template. After solidifying, the film is partially etched to expose the template which is then removed by selective etching. The fabrication procedure can produce large-area, size-tunable, periodic nanostructures with excellent structural uniformity. Large-area silica nanostructures with P6 mm symmetry have been formed by employing a dry etching technique. Experimental and simulating results also show that unique 2D nanostructures, with the feature size being much smaller than the diameter of the spherical particles used, can be obtained through three-dimensional silica nanopatterns, acted as a mask, and formed by a bilayer or trilayer colloidal crystal template.
Design and analysis of 2T-2M Ternary content addressable memories (2017)

Associate and approximate computing using resistive memory based Ternary Content Addressable Memory is becoming widely used. In this paper, a simplified model based analysis of a 2T2M-Ternary Content Addressable Memory using memristors is introduced. A comprehensive study is presented taking into consideration different circuit parameters and parasitic effects. Parameters such as the memristor R <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">h</sub> /R <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">l</sub> ratio, transistor technology, operating frequency, and memory width are taken into consideration. The proposed model is verified with SPICE showing a high degree of matching between theory and simulation. The utility of the model is established using a design example.
Development and validation of a hedgehog heparin-binding assay for high-throughput screening (2020)

Sonic hedgehog (Shh) is a morphogenic protein with critical roles in embryogenesis and the development of some cancers. Hence, identifying inhibitors of the Shh pathway is of great therapeutic value. Heparin and HSPGs act as crucial modulators of Shh activity. To identify molecules that antagonize Shh binding to heparin we have developed a solid-phase plate-based assay. The N-terminal domain of Shh (ShhN) protein is first coated in 384-well plates and the direct binding of fluorescein-labeled heparin (flu-heparin) assessed by measuring the fluorescence signal after incubation and wash steps. Binding of ShhN protein to the 384-well plates was confirmed and optimized by a standard ELISA using a monoclonal antibody recognizing folded ShhN. The assay was validated using whole plate minimum and maximum signal wells with a Z' of 0.68-0.75 determined. Herein, we describe the development and validation of a high throughput screen to identify small molecule antagonists of Shh heparin binding. Overall, this method•Results in an optimized and validated assay for hedgehog heparin binding.•Delivers a cost effective high-throughput screen format for hedgehog heparin antagonist screening.
Diarylethenes with Electro-active Substituents for Optical Memories: A Theoretical Study and the Realization of a Memory with a Readout in the Mid Infrared (2005)

ABSTRACT Since photochromic molecules occur as two stable forms, they can be used to make optical memories. The readout process must preserve the information stored and can be carried on by using mid-IR light and exploiting the differences in the IR spectrum between the two forms. Three diarylethenes with different electroactive lateral substituents have been studied theoretically (B3LYP 6-31G**) to understand the effect of the substituent on the difference in absorbtion intensities of the vibrational spectrum. Calculations show that the presence of a donor group in the molecule enhances the absorbtion intensity of some normal modes of the molecule in the closed form. The molecule with a donor side group has been synthesized, a film was deposited on a substrate, a simple setup with a multibolometer camera has been built and patterns written on the film were read.
A robust molecular probe for Ångstrom-scale analytics in liquids (2016)

Traditionally, nanomaterial profiling using a single-molecule-terminated scanning probe is performed at the vacuum-solid interface often at a few Kelvin, but is not a notion immediately associated with liquid-solid interface at room temperature. Here, using a scanning tunnelling probe functionalized with a single C60 molecule stabilized in a high-density liquid, we resolve low-dimensional surface defects, atomic interfaces and capture Ångstrom-level bond-length variations in single-layer graphene and MoS2. Atom-by-atom controllable imaging contrast is demonstrated at room temperature and the electronic structure of the C60-metal probe complex within the encompassing liquid molecules is clarified using density functional theory. Our findings demonstrates that operating a robust single-molecular probe is not restricted to ultra-high vacuum and cryogenic settings. Hence the scope of high-precision analytics can be extended towards resolving sub-molecular features of organic elements and gauging ambient compatibility of emerging layered materials with atomic-scale sensitivity under experimentally less stringent conditions.
Intent-leveraged optimization of analog circuits via homotopy (2010)

This paper proposes a circuit optimization approach that can ease the computational burden on the simulation-based circuit optimizers by leveraging simple design equations that reflect the designer's intent. The technique is inspired by continuation methods (a.k.a. homotopy) in numerical analysis where a hard problem is solved by constructing an easier problem first and gradually refining its solution to that of the hard problem. In a circuit optimization context, the designer's simplified equations for the circuit serve as the easier problem. These simplified design equations are easy to write as they need not be completely accurate and have intuitive, well-understood solutions. Nonetheless, in several circuit examples, it was found that the designer's equations serve as better guidance than the conventional, fixed-point equations. As a result, the proposed approach demonstrates the better convergence to the desired solution with less computational efforts.
Inhibition of Acetylcholinesterases by Stereoisomeric Organophosphorus Compounds Containing Both Thioester and p-Nitrophenyl Leaving Groups (2020)

Studies with acetylcholinesterase (AChE) inhibited by organophosphorus (OP) compounds with two chiral centers can serve as models or surrogates for understanding the rate, orientation, and postinhibitory mechanisms by the nerve agent soman that possesses dual phosphorus and carbon chiral centers. In the current approach, stereoisomers of <i>O</i>-methyl, [<i>S</i>-(succinic acid, diethyl ester), <i>O</i>-(4-nitrophenyl) phosphorothiolate (MSNPs) were synthesized, and the inhibition, reactivation, and aging mechanisms were studied with electric eel AChE (eeAChE) and recombinant mouse brain AChE (rmAChE). The MSNP <i>R</i><sub>P</sub><i>R</i><sub>C</sub> isomer was the strongest inhibitor of both eeAChE and rmAChE at 8- and 24-fold greater potency, respectively, than the weakest <i>S</i><sub>P</sub><i>S</i><sub>C</sub> isomer. eeAChE inhibited by the <i>R</i><sub>P</sub><i>R</i><sub>C</sub>- or <i>R</i><sub>P</sub><i>S</i><sub>C</sub>-MSNP isomer underwent spontaneous reactivation ∼10- to 20-fold faster than the enzyme inhibited by <i>S</i><sub>P</sub><i>R</i><sub>C</sub>- and <i>S</i><sub>P</sub><i>S</i><sub>C</sub>-MSNP, and only 4% spontaneous reactivation was observed from the <i>S</i><sub>P</sub><i>R</i><sub>C</sub>-eeAChE adduct. Using 2-pyridine aldoxime methiodide (2-PAM) or trimedoxime (TMB-4), eeAChE inhibited by <i>R</i><sub>P</sub><i>R</i><sub>C</sub>- or <i>S</i><sub>P</sub><i>R</i><sub>C</sub>-MSNP reactivated up to 90% and 3- to 4-fold faster than eeAChE inhibited by the <i>R</i><sub>P</sub><i>S</i><sub>C</sub>- or <i>S</i><sub>P</sub><i>S</i><sub>C</sub>-MSNP isomer. Spontaneous reactivation rates for rmAChE were 1.5- to 10-fold higher following inhibition by <i>R</i><sub>P</sub><i>S</i><sub>C</sub>- and <i>S</i><sub>P</sub><i>S</i><sub>C</sub>-MSNPs than inhibition by either <i>R</i><sub>C</sub> isomer, a trend opposite to that found for eeAChE. Oxime reactivation of rmAChE following inhibition by <i>R</i><sub>P</sub><i>R</i><sub>C</sub>- and <i>S</i><sub>P</sub><i>R</i><sub>C</sub>-MSNPs was 2.5- to 5-fold faster than inhibition by <i>R</i><sub>P</sub><i>S</i><sub>C</sub>- or <i>S</i><sub>P</sub><i>S</i><sub>C</sub>-MSNPs. Due to structural similarities, MSNPs that phosphylate AChE with the loss of the <i>p</i>-nitrophenoxy (PNP) group form identical, nonreactivatable adducts to those formed from <i>S</i><sub>P</sub>-isomalathion; however, all the MSNP isomers inhibited AChE to form adducts that reactivated. Thus, MSNPs inactivate AChE via the ejection of either PNP or thiosuccinyl groups to form a combination of reactivatable and nonreactivatable adducts, and this differs from the mechanism of AChE inhibition by isomalathion.
Prevention of Transmission of Borrelia burgdorferiand Anaplasma phagocytophilum from Ticks to Dogs Using K9 Advantixand Frontline Plus Applied 25 Days Before Exposure to Infected Ticks (2005)

A blinded, replicated, randomized controlled study was carried out in 24 Beagle dogs randomly allocated to one of 3 groups: K9 Advantix (imidacloprid/permethrin) (group 1; n = 8); Frontline P l u s [fipronil/(S)-methoprene] (group 2; n = 8); and untreated controls (group 3; n = 8). Dogs in groups 1 and 2 were treated according to product label directions 25 days before infestation with adult Ixodes scapuIntern J Appl Res Vet Med • Vol. 3, No. 2, 2005 Byron L. Blagburn, PhD Jennifer A. Spencer, PhD Jamie M. Butler, BS Tracey M. Land, BS Sarah A. Billeter, BS Christine C. Dykstra, PhD Kirby C. Stafford, PhD Margaret B. Pough, MA Steven A. Levy, DVM Michael Endrizzi, DVM Joseph Hostetler, DVM