gebhart/patrepeval huggingface dataset:
Evidence That Porcine Pancreatic Phospholipase A2 via Its High Affinity Receptor Stimulates Extracellular Matrix Invasion by Normal and Cancer Cells (1997)

Cellular migration and extracellular matrix (ECM) invasion are some of the critical steps in embryonic implantation, inflammation, wound healing, and cancer metastasis. Extracellular phospholipases A2 (PLA2s), belonging to either group I (PLA2-I) or group II (PLA2-II), play an essential role in the generation of proinflammatory lipid mediators (e.g. prostaglandins, leukotrienes, etc.). Recent reports indicate that PLA2-I, in addition to its digestive function, has receptor-mediated effects. For instance, PLA2-I, via its receptor, can induce cell proliferation and airway as well as vascular smooth muscle contraction. Here, we report that both porcine pancreatic and Naja naja PLA2s, in a dose-dependent manner, stimulate dramatic invasion of an artificial ECM (MatrigelTM) by NIH 3T3, mouse fibrosarcoma, and sarcoma cells in vitro, but it has no such effect on lymphoma and mastocytoma cells. That this is a receptor-mediated process is strongly suggested by the following findings. (a) While NIH 3T3, mouse fibrosarcoma, and sarcoma cells, which respond to PLA2-I stimulation, express high affinity PLA2-I receptor mRNA and protein, this receptor expression is not detectable in nonresponder lymphoma and mastocytoma cells. (b) There is a close correlation between the Kd values for 125I-PLA2-I binding to its receptor and the ED50 values for PLA2-I-induced ECM-invasion. (c) Catalytically inactivated PLA2-I is as effective as the active enzyme in stimulating invasion. (d) Suppression of PLA2-I receptor expression in responder cells causes inhibition of ECM invasion. (e) Treatment of the same cells with PLA2-I receptor-antibody also produces virtually identical effects. Taken together, our results identify a novel receptor-mediated function of PLA2-I and raises the possibility that extracellular PLA2s play important physiological as well as pathological roles via this receptor. To our knowledge, this is the first report of this novel receptor-mediated effect (i.e. ECM invasion) of PLA2-I on normal as well as malignant cancer cells.
Learning Swarm Interaction Dynamics From Density Evolution (2022)

In this article, we consider the problem of understanding the coordinated movements of biological or artificial swarms. In this regard, we propose a learning scheme to estimate the coordination laws of the interacting agents from observations of the swarm's density over time. We describe the dynamics of the swarm based on pairwise interactions according to a Cucker–Smale flocking model, and express the swarm's density evolution as the solution to a system of mean-field hydrodynamic equations. We propose a new family of parametric functions to model the pairwise interactions, which allows for the mean-field macroscopic system of integro-differential equations to be efficiently solved as an augmented system of partial differential equations. Finally, we incorporate the augmented system in an iterative optimization scheme to learn the dynamics of the interacting agents from observations of the swarm's density evolution over time. The results of this work can offer an alternative approach to study how animal flocks coordinate, create new control schemes for large networked systems, and serve as a central part of defense mechanisms against adversarial drone attacks.
CHAOS IN PHASE-LOCKED LOOPS (1991)

Indexing terms: Chaos, Phase-locked loops The chaotic behaviour of phase-locked loops (PLL) in track- ing a received signal whose frequency is varying linearly with time is studied. This system is described by a third-order nonlinear autonomous equation. The Lyapunov exponents and dimension of the system are calculated to confirm the chaotic phenomenon. Numerical results indicate that the parameter ranges where the chaos could occur are realistic in the typical designs.
Ion Exchange as a Way of Controlling the Chemical Compositions of Nano‐ and Microparticles Made from Infinite Coordination Polymers (2006)

Ionenbälle: Die Zusammensetzung von Nano- und Mikropartikeln aus kontinuierlichen Koordinationspolymeren kann chemisch durch Ionenaustauschreaktionen verändert werden, ohne dass sich Partikelgröße und -morphologie wesentlich ändern. Auf diese Art lässt sich ein Satz an Partikelvorstufen einfach erhalten, dessen Zusammensetzung gezielt in die eines neuen Satzes an Verbindungen mit anderen Eigenschaften überführt werden kann.
Garetosmab, an inhibitor of activin A, reduces heterotopic ossification and flare-ups in adults with fibrodysplasia ossificans progressiva: a randomized, double-blind, placebo-controlled phase 2 trial (2023)

ABSTRACT Background Fibrodysplasia ossificans progressiva (FOP), an ultra-rare disorder caused by mutations in the gene encoding activin A receptor type 1 ( ACVR1) , is characterized by painful flare-ups and cumulative heterotopic ossification (HO). Garetosmab, a fully-human monoclonal antibody blocking activin A, prevents HO in FOP mice. Methods LUMINA-1 ( NCT03188666 ) was a phase 2, multi-center, randomized, double-blind, placebo-controlled study evaluating the safety, tolerability, and effects on HO of intravenous (IV) garetosmab 10 mg/kg every 4 weeks (Q4W). Adult patients with FOP were randomized to garetosmab or placebo for 28 weeks (Period_1), followed by an open-label period (Period_2). After Period_2, patients were allowed to stay on garetosmab in an open-label extension. For Period_1, primary endpoints were HO total lesion activity (HO-TLA) by 18 F-sodium fluoride positron emission tomography ( 18 F-NaF PET) and HO total lesion volume by computed tomography (CT). The Period_2 primary endpoint compared the number of new lesions in Period_2 versus Period_1. The safety primary endpoint was incidence and severity of TEAEs through the end of the Period 1 at week 28. Findings Patients (n=44) were randomized to garetosmab (n=20) or placebo (n=24). In Period_1, there was a trend for garetosmab to decrease HO-TLA versus placebo (24.6%; P =0.07), primarily driven by near complete prevention of new lesions (97% decrease by 18 F-NaF PET, post-hoc P =0.009; 90% relative reduction by CT, post-hoc P =0.017); flare-ups were significantly reduced ( P =0.0005). For placebo patients transitioning to garetosmab in Period_2, no patients developed new HO lesions (0% in Period_2 versus 40.9% in Period_1; P =0.0027) by CT. All 44 patients met primary safety endpoint of at least one TEAE during Period 1. Garetosmab was associated with more adverse events than placebo: mild recurrent epistaxis, madarosis, and skin/soft tissue infections. Overall, the AEs were predominantly mild in severity, with no effect on patients’ ability to receive garetosmab. Five deaths (5/44; 11.4%) occurred either in Period_2 or the open-label extension. The deaths were associated with baseline disease severity in some, preexisting comorbidities in others and occurred following 8-16 doses (median: 15) of garetosmab in the open label/follow-up periods. Interpretation Garetosmab reduced flare-ups and prevented new HO lesions in FOP patients. Although side effects were mild to moderate, there were a relatively high number of deaths for a small study; the deaths were not related to epistaxis and considered unlikely to be related to garetosmab. Funding Regeneron Pharmaceuticals, Inc.
Plasma panel‐based radiation detectors (2013)

Abstract The plasma panel sensor (PPS) is a gaseous micropattern radiation detector under current development. It has many operational and fabrication principles common to plasma display panels. It comprises a dense matrix of small, gas plasma discharge cells within a hermetically sealed panel. As in plasma display panels, it uses nonreactive, intrinsically radiation‐hard materials such as glass substrates, refractory metal electrodes, and mostly inert gas mixtures. We are developing these devices primarily as thin, low‐mass detectors with gas gaps from a few hundred microns to a few millimeters. The PPS is a high gain, inherently digital device with the potential for fast response times, fine position resolution (&lt;50‐µm RMS) and low cost. In this paper, we report on prototype PPS experimental results in detecting betas, protons, and cosmic muons, and we extrapolate on the PPS potential for applications including the detection of alphas, heavy ions at low‐to‐medium energy, thermal neutrons, and X‐rays.
High‐Resolution Structural Characterization of a Helical α/β‐Peptide Foldamer Bound to the Anti‐Apoptotic Protein Bcl‐xL (2009)

Get into the groove: The first high-resolution structure of a foldamer bound to a protein target is described (see picture; foldamer in sticks). The foldamer consists of alpha- and beta-amino acid residues and is bound to the anti-apoptotic protein Bcl-x(L). The overall binding mode and key interactions observed in the foldamer/Bcl-x(L) complex mimic those seen in complexes of Bcl-x(L) with natural alpha-peptide ligands. Additional contacts in the foldamer/Bcl-x(L) complex involving beta-amino acid residues appear to contribute to binding affinity.
ChemInform Abstract: C—N Coupling of Nitrogen Nucleophiles with Aryl and Heteroaryl Bromides Using Aminoarenethiolato—Copper(I) (Pre‐)Catalyst. (2010)

Abstract A variety of title Cu(I) aminoarenethiolates is prepared and studied in the N‐arylation of primary and secondary amines.
A Single Dose of a DNA Vaccine Encoding Apa Coencapsulated with 6,6′-Trehalose Dimycolate in Microspheres Confers Long-Term Protection against Tuberculosis in Mycobacterium bovis BCG-Primed Mice (2013)

Mycobacterium bovis BCG prime DNA (Mycobacterium tuberculosis genes)-booster vaccinations have been shown to induce greater protection against tuberculosis (TB) than BCG alone. This heterologous prime-boost strategy is perhaps the most realistic vaccination for the future of TB infection control, especially in countries where TB is endemic. Moreover, a prime-boost regimen using biodegradable microspheres seems to be a promising immunization to stimulate a long-lasting immune response. The alanine proline antigen (Apa) is a highly immunogenic glycoprotein secreted by M. tuberculosis. This study investigated the immune protection of Apa DNA vaccine against intratracheal M. tuberculosis challenge in mice on the basis of a heterologous prime-boost regimen. BALB/c mice were subcutaneously primed with BCG and intramuscularly boosted with a single dose of plasmid carrying apa and 6,6'-trehalose dimycolate (TDM) adjuvant, coencapsulated in microspheres (BCG-APA), and were evaluated 30 and 70 days after challenge. This prime-boost strategy (BCG-APA) resulted in a significant reduction in the bacterial load in the lungs, thus leading to better preservation of the lung parenchyma, 70 days postinfection compared to BCG vaccinated mice. The profound effect of this heterologous prime-boost regimen in the experimental model supports its development as a feasible strategy for prevention of TB.
A Predictive Phosphorylation Signature of Lung Cancer (2009)

Highly predictive and biologically transparent phosphorylation signatures of lung cancer provide evidence for the existence of a robust set of phosphorylation mechanisms (captured by the signatures) present in the majority of lung cancers, and that reliably distinguish each lung cancer from normal. This approach should improve our understanding of cancer and help guide its treatment, since the phosphorylation signatures highlight proteins and pathways whose phosphorylation should be inhibited in order to prevent unregulated proliferation.
All-optical and electro-optical active plasmonic telecom components (2011)

Active plasmonics is an attractive emerging field in which the ability to control the surface plasmon polariton (SPP) propagation finds many applications such as realization of fully functional integrated photonic circuitry. We demonstrate both numerically and experimentally switching of the SPP transmission based on two different approaches namely the all-optical and electro-optical at telecom wavelengths. The plasmonic component consists of a compact and efficient SPP switch utilizing highly sensitive ring resonator which has high sensitivity to the refractive index changes. Fabrication was done via e-beam lithography utilizing advanced proximity corrections. The compenents were characterized via scanning near field optical microscope (SNOM) and leakage radiation microscopy respectively. Large modulations of upto ~ 40 % in SPP mode transmission were observed.
Dendritic Architectures (1999)

This chapter contains sections titled: Introduction Poly(Propylene Imine) Dendrimers Dendritic Box Superamphiphiles Based on Dendrimers Self-Assembly of Inverted Unimolecular Dendritic Micelles Outlook
Heterodimeric integrin complexes containing β1-integrin promote internalization and lethality of anthrax toxin (2010)

To kill macrophages, the lethal factor component of Bacillus anthracis toxin binds to a carrier protein (PA), which then interacts with the CMG2 receptor protein on the cell surface and is endocytosed into the cytoplasm. CMG2, as well as TEM8, a second PA receptor not present on macrophages, contain a von Willebrand A domain that is crucial for toxin binding. Here we report that integrin beta1, another cell surface von Willebrand A domain protein, can mediate and potentiate anthrax toxin endocytosis. By using microarray-based analysis to globally correlate gene expression profiles with toxin sensitivity, we associated toxin effects with the integrin-activating proteins osteopontin and CD44. Further study showed that PA binds to alpha4beta1- and alpha5beta1-integrin complexes, leading to their conjoint endocytosis, and also interacts-weakly relative to CMG2 but comparably to TEM8--with purified alpha5beta1 complex in vitro. Monoclonal antibody directed against beta1-integrin or its alpha integrin partners reduced PA/integrin endocytosis and anthrax toxin lethality, and hyaluronic acid--which interferes with CD44-mediated integrin activation--had similar effects. Remarkably, whereas deficiency of CMG2 protected macrophages from rapid killing by large toxin doses (>50 ng/mL), by 24 h the toxin-treated cells were dead. Such late killing of CMG2-deficient cells by high dose toxin as well as the late death observed during exposure of CMG2-producing macrophages to low-dose toxin (<1 ng/mL), was dependent on integrin function. Effects of inactivating both CMG2 and integrin were synergistic. Collectively, our findings argue strongly that beta1-integrin can both potentiate CMG2-mediated endocytosis and serve independently as a low-affinity PA receptor.
Strong Bases and Weak Anions in Catalytic C–H Insertion Reactions of Vinyl Carbocations (2018)

Here we report the surprising discovery that high-energy vinyl carbocations can be generated under strongly basic conditions, and that they engage in intramolecular sp3 C–H insertion reactions through the catalysis of commercially available weakly coordinating anion salts. This approach relies on the unconventional combination of lithium hexamethyldisilazide base and the commercially available catalyst, triphenylmethylium tetrakis(pentafluorophenyl)borate. These reagents form a catalytically active lithium species that enables the application of vinyl cation C–H insertion reactions to heteroatomcontaining substrates.
Long-Lived Charge-Transfer State from B–N Frustrated Lewis Pairs Enchained in Supramolecular Copolymers (2020)

The field of supramolecular polymers is rapidly expanding; however, the exploitation of these systems as functional materials is still elusive. To become competitive, supramolecular polymers must display microstructural order and the emergence of new properties upon copolymerization. To tackle this, a greater understanding of the relationship between monomers' design and polymer microstructure is required as well as a set of functional monomers that efficiently interact with one another to synergistically generate new properties upon copolymerization. Here, we present the first implementation of frustrated Lewis pairs into supramolecular copolymers. Two supramolecular copolymers based on π-conjugated <i>O</i>-bridged triphenylborane and two different triphenylamines display the formation of B-N pairs within the supramolecular chain. The remarkably long lifetime and the circularly polarized nature of the resulting photoluminescence emission highlight the possibility to obtain an intermolecular B-N charge transfer. These results are proposed to be the consequences of the enchainment of B-N frustrated Lewis pairs within 1D supramolecular aggregates. Although it is challenging to obtain a precise molecular picture of the copolymer microstructure, the formation of random blocklike copolymers could be deduced from a combination of optical spectroscopic techniques and theoretical simulation.
Tunable optical wavelength conversion of a 10 Gb/s OFDM data signal using a periodically-poled lithium niobate waveguide (2008)

We experimentally demonstrate tunable wavelength conversion of 10 Gb/s RF-tone assisted OFDM signal with high conversion efficiency over ∼30 nm tuning range using a PPLN waveguide. A penalty of ≪ 3 dB is obtained after wavelength conversion with different QAM sizes and subcarrier numbers.
Ultra‐fast mass fingerprinting by high‐affinity capture of peptides and proteins on derivatized poly(glycidyl methacrylate/divinylbenzene) for the analysis of serum and cell lysates (2006)

The development of support materials in mass fingerprinting is an important task required for diagnostic markers in conjunction with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The material-based approach, which we introduced as material-enhanced laser desorption/ionization (MELDI), focuses not only on different functionalities, but also emphasizes the morphology, i.e. porosity or particle size of the carrier material. As a result, it provides a quick and sensitive platform for effective binding of peptides and proteins out of different biofluids, e.g. serum, spinal fluid, urine or cell lysates, and to subsequently analyze them with MALDI-TOF MS. This approach includes a built-in desalting step for serum protein profiling and is sensitive enough to detect proteins and peptides down to 100 fmol/microL. Here we co-polymerized glycidyl methacrylate (GMA) with divinylbenzene (DVB) using thermal polymerization to yield a GMA/DVB polymer for further modifications. Different affinities have been created, such as immobilized metal ion affinity (IDA-Cu2+), reversed-phase (RP) and anion-exchanger (AX) chromatography. The diverse derivatizations and the dispersity of the particles created by different chemical synthetic approaches were confirmed by characteristic infrared (IR) peaks. The polymerization carried out by non-stirring yielded an average pore radius of 6.1 microm (macro-pores) that enhanced the binding capacity enormously by offering enlarged surface areas. Moreover, atomic absorption spectrometry (AAS) provided the metal content loaded on iminodiacetic acid (IDA) in the case of poly(GMA/DVB)-IDA-Cu2+. To summarize, the optimized MELDI approach is sensitive in its performance, extremely fast and can be adapted to robotic systems for routine analysis, allowing sample preparation in less than 5 min in contrast to the conventional surface-enhanced laser desorption/ionization (SELDI) methods.
.alpha.-Methyl substrates of carboxypeptidase A. Steric probe of the active site (1975)

Although optical resolution of alpha-methylphenylalanine (alpha-Me-Phe) has been achieved by the action of carboxypeptidase A on the N-trifluoroacetyl derivative of the amino acid (TFA-alpha-Me-Phe), it is improbable that an alpha-methyl substrate could bind in the same orientation as glycyl-L-tyrosine, due to steric interaction of the alpha-methyl group with an atom in the imidazole ring of zinc ligand His-196. The kinetic parameters for TFA-alpha-Me-Phe and for an ester substrate bearing an alpha-methyl group (beta-hippuryl-alpha-methylphenyllactic acid, HMPL) have been determined and compared to those for the appropriate nonmethylated control substrates. Both TFA-alpha-Me-Phe and HMPL appear to be bound nearly as well as are their respective controls, and HMPL is hydrolyzed nearly as rapidly as its control. TFA-alpha-Me-Phe, however, is hydrolyzed only about one-fiftieth as rapidly as is the nonmethylated substrate. These findings are consistent with the possibilities that: (1) the proposed substrate-induced conformational shift of Tyr-248 is hindered when the methylated substrates are bound; (2) the orientation in which alpha-methyl substrates are bound precludes optimal positioning of Tyr-248 and the scissile bond even after the rotation of Tyr-248 has occurred; (3) amides and esters are bound in different orientations, and in the amide orientation an alpha-methyl group is so directed as to interfere with the approach of Glu-270 to the scissile bond.
“Zen 4”: The AMD 5nm 5.7GHz x86-64 Microprocessor Core (2023)

“Zen 4” is AMD's next generation x86-64 microprocessor core, fabricated in a 5nm FinFET process. Close collaboration between the design team and TSMC enabled an optimized process and excellent process scaling relative to the 7nm process used for “Zen 3” [1]. The 55mm2 core complex (CCX), shown in Fig. 2.1.1, contains 6.5B transistors across eight cores, similar to the 8 core CCX in the previous generation. Each core includes a 1MB private L2 cache, double the previous generation, and the eight cores share a 32MB L3 cache. The design also delivers a process-neutral performance increase over “Zen 3”: instructions per cycle (IPC) is increased, the physical design improves process-neutral frequency and changes are made to drive improved power efficiency maximizing both single-threaded performance and performance per watt in multi-threaded workloads. Incremental improvements to the core micro-architecture provide a 13% IPC improvement over the previous generation on an average of single-threaded desktop applications and the “Zen 4” core can operate at up to 5.7GHz delivering a more than 29% increase generationally in single-threaded performance.
Cost-Effective and Large-Scale Synthesis of 16:0 Lysophosphatidic Acid (2012)

Lysophosphatidic acid (LPA) is a bioactive compound that has gained attention due to its role in neoplastic diseases. Popularity of the compound has necessitated the use of large quantities of the phospholipid for in vivo and in vitro testing but methods for generating LPA require the use costly procedures, namely phosphoramidite coupling reagents. Additionally there has been no reported large-scale synthesis of LPA. In the present study we report the cost-effective and large-scale synthesis of 16:0 LPA.
Parallel optical coherent dot-product architecture for large-scale matrix multiplication with compatibility for diverse phase shifters (2022)

Photonics physically promises high-speed and low-consumption computing of matrix multiplication. Nevertheless, conventional approaches are challenging to achieve large throughput, high precision, low power consumption, and high density simultaneously in a single architecture, because the integration scale of conventional approaches is strongly limited by the insertion loss of cascaded optical phase shifters. Here, we present a parallel optical coherent dot-product (P-OCD) architecture, which deploys phase shifters in a fully parallel way. The insertion loss of phase shifters does not accumulate at large integration scale. The architecture decouples the integration scale and phase shifter insertion loss, making it possible to achieve superior throughput, precision, energy-efficiency, and compactness simultaneously in a single architecture. As the architecture is compatible with diverse integration technologies, high-performance computing can be realized with various off-the-shelf photonic phase shifters. Simulations show that compared with conventional architectures, the parallel architecture can achieve near 100× higher throughput and near 10× higher energy efficiency especially with lossy phase shifters. The parallel architecture is expected to perform its unique advantage in computing-intense applications including AI, communications, and autonomous driving.