gebhart/patrepeval huggingface dataset:
[P2–054]: BRAIN DELIVERY OF AN AMYLOID‐β OLIGOMER (AβO)‐TARGETING PEPTIDE‐THERAPEUTIC BY A NOVEL BLOOD‐BRAIN BARRIER (BBB)‐CROSSING DOMAIN ANTIBODY (2017)

We have identified an amyloid-ß (Aß) binding peptide (ABP) that selectively bound pathological Aß1–42 oligomers and reduced Aß- mediated cell toxicity1. ABP also bound Aß deposits in brains of AD transgenic mice and Alzheimer's disease (AD) patients in vitro, and when directly injected into live transgenic mice (APPSwe and ΔPS1) brain2, suggesting that, when delivered to the brain, ABP can engage Aß and facilitate its clearance. Present study shows brain-delivery of ABP by a novel BBB-crossing domain antibody, and targeting and clearance of Aß in transgenic mice. Recombinant ABP-BBB carrier fusion construct (ABP-BBB) were produced in CHO cells. BBB-permeability of the construct was assessed using in vitro BBB (formed by rat or human brain endothelial cells) and in vivo (rat and mouse) models. Aß binding was determined by ELISA and Western blot overlay assays. For PK/PD studies, serum, CSF and brain levels of ABP-BBB construct and Aß were assessed following iv injection by nanoLC- MRM, ELISA and Western blot methods. ABP-BBB bi-functional fusion protein was successfully expressed in CHO cells. The fusion protein retained both Aß-oligomer binding activity and BBB-permeability in vitro. ABP-BBB transmigrated the in vitro BBB, in contrast to ABP without BBB carrier. When injected iv into rats, ABP-BBB appeared in the CSF in a dose- and time-dependent manner indicating transport of ABP across BBB in vivo. Apparent CNS exposure (Expapp), calculated as CSF[AUC]/serum[AUC], indicated a 15–20-fold increase in Expapp for ABP-BBB compared to non-BBB permeable ABP. This was further confirmed in mouse model wherein following iv injection, the fusion protein was detected in the CSF, and cortical and hippocampal regions of wild type and Tg mice. More importantly, in Tg mice ABP treatment resulted in a significant (∼50%) reduction of Aß levels in the CSF, and brain cortex and hippocampus within 4-weeks. Collectively, these results indicate that the novel BBB carrier can deliver otherwise BBB-impermeable ABP to the brain where it can target CNS Aß aggregates and facilitate their clearance in vivo. 1 Chakravarthy et al., J. Neurochem 126, 415, 2013. 2 Chakravarthy et al., Biochem. Biophys. Res. Commun. 445, 656, 2014.
Supplementary Figure S4 from Ubiquitinated PCNA Drives USP1 Synthetic Lethality in Cancer (2023)

&lt;p&gt;USP1 and PARP inhibition are synergistic in a BRCA1/2-dependent manner - related to Figure 4&lt;/p&gt;
Time-delay detection of short pulses by Fresnel and Fourier transformations (1993)

The Fresnel transform of a signal, when used as a preprocessing step to a subsequent spectrum analysis, helps to detect the time delay between short-pulse signals. Light from the short pulses disperses spatially as it propagates through free space to create an interference pattern. As the pulses move through an acousto-optic cell, a point photodetector produces a signal whose temporal frequency is directly proportional to the time delay between the pulses. When this signal is fed to a spectrum analyzer, the frequency domain represents a time-delay domain.
Neutrophils Are Resistant to Yersinia YopJ/P-Induced Apoptosis and Are Protected from ROS-Mediated Cell Death by the Type III Secretion System (2010)

Our findings showed that Yersinia YopJ and/or YopP did not induce pronounced apoptosis in human neutrophils. Furthermore, robust PMN ROS production in response to virulence plasmid-deficient Yersinia was associated with increased PMN cell death, suggesting that Yersinia inhibition of PMN ROS production plays a role in evasion of the human innate immune response in part by limiting PMN apoptosis.
Polyethylene glycol 20 kDa-induced vacuolation does not impair phagocytic function of human monocyte-derived macrophages (2022)

Conjugation to polyethylene glycol (PEG) is commonly used to enhance drug delivery and efficacy by extending the half-life of the drug molecule. This has important implications for reducing treatment burden in diseases that require chronic prophylaxis, such as hemophilia. Clearance of PEG molecules with high molecular weights (≥ 40 kDa) has been reported to cause cellular vacuolation in mammals. Rurioctocog alfa pegol (PEGylated recombinant coagulation factor VIII) contains a 20-kDa PEG. This study investigated the effects of exposure to 20-kDa PEG (10 μg/ml to 10 mg/ml) on the morphology and function of human monocyte-derived macrophages (MDMs) <i>in vitro</i>. Exposure to PEG for 24 hours was associated with significant vacuolation only at concentrations of 1 mg/ml or more, which far exceed the levels associated with clinically relevant doses of rurioctocog alfa pegol. Immunofluorescence staining of PEG was detected in the cytoplasm of MDMs, indicating uptake into the cells. No impairment of MDM phagocytic activity (ability to ingest fluorescently labeled <i>Escherichia coli</i>) was observed with 24-hour exposure to PEG, even at concentrations associated with significant vacuolation. Furthermore, PEG exposure did not have significant effects on cytokine secretion in resting or lipopolysaccharide-stimulated MDMs, or on the expression of cell surface markers in stimulated MDMs. Cell viability was not affected by 24-hour exposure to PEG. In conclusion, vacuolation of human MDMs after exposure to 20-kDa PEG only occurred with PEG concentrations far in excess of those equivalent to clinically relevant doses of rurioctocog alfa pegol and did not affect MDM viability or functionality. Together, these results support the concept that PEG-mediated vacuolation is an adaptive cellular response rather than a toxic effect.
Search for extra dimensions using diphoton events in 7 TeV proton–proton collisions with the ATLAS detector (2012)

Using data recorded in 2011 with the ATLAS detector at the Large Hadron Collider, a search for evidence of extra spatial dimensions has been performed through an analysis of the diphoton final state. The analysis uses data corresponding to an integrated luminosity of 2.12fb-1 of s=7TeV proton-proton collisions. The diphoton invariant mass (mÎ³Î³) spectrum is observed to be in good agreement with the expected Standard Model background. In the large extra dimension scenario of Arkani-Hamed, Dimopoulos and Dvali, the results provide 95% CL lower limits on the fundamental Planck scale between 2.27 and 3.53 TeV, depending on the number of extra dimensions and the theoretical formalism used. The results also set 95% CL lower limits on the lightest Randall-Sundrum graviton mass of between 0.79 and 1.85 TeV, for values of the dimensionless coupling k/-1 Pl varying from 0.01 to 0.1. Combining with previously published ATLAS results from the dielectron and dimuon final states, the 95% CL lower limit on the Randall-Sundrum graviton mass for k/M-1Pl=0.01 (0.1) is 0.80 (1.95) TeV. Â© 2012 CERN.
New family of biosensors for monitoring BTX in aquatic and edaphic environments (2016)

Benzene, toluene, ethylbenzene and xylenes (BTEX) contamination is a serious threat to public health and the environment, and therefore, there is an urgent need to detect its presence in nature. The use of whole-cell reporters is an efficient, easy-to-use and low-cost approach to detect and follow contaminants outside specialized laboratories; this is especially important in oil spills that are frequent in marine environments. The aim of this study is the construction of a bioreporter system and its comparison and validation for the specific detection of monocyclic aromatic hydrocarbons in different host bacteria and environmental samples. Our bioreporter system is based on the two component regulatory system TodS-TodT of P. putida DOT-T1E, and the P<sub>todX</sub> promoter fused to the GFP protein as the reporter protein. For the construction of different biosensors, this bioreporter was transferred into three different bacterial strains isolated from three different environments, and their performance was measured. Validation of the biosensors on water samples spiked with petrol, diesel and crude oil on contaminated waters from oil spills and on contaminated soils demonstrated that they can be used in mapping and monitoring some BTEX compounds (specifically benzene, toluene and two xylene isomers). Validation of biosensors is an important issue for the integration of these devices into pollution-control programmes.
Human oral lectin ZG16B acts as a cell wall polysaccharide probe to decode host–microbe interactions with oral commensals (2023)

The oral microbiome is critical to human health and disease, yet the role that host salivary proteins play in maintaining oral health is unclear. A highly expressed gene in human salivary glands encodes the lectin zymogen granule protein 16 homolog B (ZG16B). Despite the abundance of this protein, its interaction partners in the oral microbiome are unknown. ZG16B possesses a lectin fold, but whether it binds carbohydrates is unclear. We postulated that ZG16B would bind microbial glycans to mediate recognition of oral microbes. To this end, we developed a microbial glycan analysis probe (mGAP) strategy based on conjugating the recombinant protein to fluorescent or biotin reporter functionality. Applying the ZG16B-mGAP to dental plaque isolates revealed that ZG16B predominantly binds to a limited set of oral microbes, including <i>Streptococcus mitis, Gemella haemolysans</i>, and, most prominently, <i>Streptococcus vestibularis. S. vestibularis</i> is a commensal bacterium widely distributed in healthy individuals. ZG16B binds to <i>S. vestibularis</i> through the cell wall polysaccharides attached to the peptidoglycan, indicating that the protein is a lectin. ZG16B slows the growth of <i>S. vestibularis</i> with no cytotoxicity, suggesting that it regulates <i>S. vestibularis</i> abundance. The mGAP probes also revealed that ZG16B interacts with the salivary mucin MUC7. Analysis of <i>S. vestibularis</i> and MUC7 with ZG16B using super-resolution microscopy supports ternary complex formation that can promote microbe clustering. Together, our data suggest that ZG16B influences the compositional balance of the oral microbiome by capturing commensal microbes and regulating their growth using a mucin-assisted clearance mechanism.
Spinal Protein Kinase M ζ Underlies the Maintenance Mechanism of Persistent Nociceptive Sensitization (2011)

Sensitization of the pain pathway is believed to promote clinical pain disorders. We hypothesized that the persistence of a sensitized state in the spinal dorsal horn might depend on the activity of protein kinase M ζ (PKMζ), an essential mechanism of late long-term potentiation (LTP). To test this hypothesis, we used intraplantar injections of interleukin-6 (IL-6) in mice to elicit a transient allodynic state that endured ∼3 d. After the resolution of IL-6-induced allodynia, a subsequent intraplantar injection of prostaglandin E(2) (PGE(2)) or intrathecal injection of the metabotropic glutamate receptor 1/5 (mGluR1/5) agonist DHPG (dihydroxyphenylglycol) precipitated allodynia and/or nocifensive responses. Intraplantar injection of IL-6 followed immediately by intrathecal injection of a PKMζ inhibitor prevented the expression of subsequent PGE(2)-induced allodynia. Inhibitors of protein translation were effective in preventing PGE(2)-induced allodynia when given immediately after IL-6, but not after the initial allodynia had resolved. In contrast, spinal PKMζ inhibition completely abolished both prolonged allodynia to hindpaw PGE(2) and enhanced nocifensive behaviors evoked by intrathecal mGluR1/5 agonist injection after the resolution of IL-6-induced allodynia. Moreover, spinal PKMζ inhibition prevented the enhanced response to subsequent stimuli following resolution of hypersensitivity induced by plantar incision. The present findings demonstrate that the spinal cord encodes an engram for persistent nociceptive sensitization that is analogous to molecular mechanisms of late LTP and suggest that spinally directed PKMζ inhibitors may offer therapeutic benefit for injury-induced pain states.
In silico analysis enabling informed design for genome editing in medicinal cannabis; gene families and variant characterisation (2021)

Using this framework, a best-practice approach to genome editing is possible in all plant species, including cannabis, delivering a comprehensive in silico evaluation of the cannabinoid pathway diversity from a large set of whole genome sequences. Identification of SNP variants across all genes could improve genome editing potentially leading to novel applications across multiple disciplines, including agriculture and medicine.
Hydrous RuO2–carbon nanofiber electrodes with high mass and electrode-specific capacitance for efficient energy storage (2011)

We demonstrate a new strategy for the fabrication of supercapacitor electrodes possessing high mass and area-specific capacitance for efficient charge storage, which can be extremely useful for the development of light, compact and high performance supercapacitors for a variety of high power demanding applications. High mass and electrode area specific capacitances were attained by using Hydrous Ruthenium Oxide (HRO)-Carbon Nanofiber (CNF) hybrid electrodes prepared by the deposition of HRO (~31% Ru content) on both the outer and inner surfaces of a cylindrical hollow CNF having open tips. Electrochemical studies of the uniformly deposited HRO nanoparticles on the CNF surface showed a mass specific capacitance of 645 F g(-1) and an electrode specific capacitance of 1.29 F cm(-2) with a HRO-CNF material loading of 2 mg cm(-2) in the supercapacitor electrodes. The mass specific capacitance of pure HRO is 301 F g(-1), whereas the mass specific capacitance of HRO in the HRO-CNF electrode is ~1300 F g(-1), which is very close to the theoretical capacitance of HRO. This enhanced charge storage ability, high rate capability, better cyclic stability and low ESR of the HRO-CNF will be useful for the development of high performance supercapacitors.
MRI of acute myocardial ischemia: Comparing a new contrast agent, Gd-DTPA-24-cascade-polymer, with Gd-DTPA (1999)

A new macromolecular contrast agent, gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA)-24-cascade-polymer, was compared with Gd-DTPA for time-dependent delineation of acute myocardial ischemia. Acute myocardial ischemia was produced in 12 rats by occluding the anterior branch of the left coronary artery for 20-40 minutes. Dynamic spin-echo magnetic resonance imaging (MRI) was performed for 30 minutes after injection of Gd-DTPA (n = 6) or the cascade polymer (n = 6) using equimolar doses (0.1 mmol of Gd/kg). The contrast agent-induced changes in signal intensity (deltaSI) in normal and ischemic myocardium were observed. In normal myocardium, both contrast agents caused a sharp increase in deltaSI, followed by a decline to baseline values over the 30-minute period. Enhancement in the ischemic myocardium was attenuated. Gd-DTPA showed greater deltaSI in ischemic myocardium than the cascade polymer, which gave rise to virtually no enhancement. Significant differences (P<0.05) in signal enhancement between normal and ischemic myocardium persisted for only 6 minutes using Gd-DTPA but for 18 minutes with the cascade polymer. Use of Gd-DTPA-24-cascade-polymer extends the temporal window of dynamic contrast-enhanced MRI for the differentiation of ischemic and normal myocardium. Identification of the ischemic zone is easier with the cascade polymer, which demonstrates virtually no signal enhancement in this territory.
RPR 119990, a novel alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid antagonist: synthesis, pharmacological properties, and activity in an animal model of amyotrophic lateral sclerosis. (2001)

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor antagonists are of potential interest for the treatment of certain acute and chronic neurodegenerative diseases, including amyotrophic lateral sclerosis. Here, we describe the synthesis and pharmacological properties of 9-carboxymethyl-4-oxo-5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazin-2-phosphonic acid (RPR 119990). The compound displaced [3H]AMPA from rat cortex membranes with a K(i) of 107 nM. In oocytes expressing human recombinant AMPA receptors, RPR 119990 depressed ion flux with a K(B) of 71 nM. The antagonist properties of this compound were confirmed on rat native AMPA receptors in cerebella granule neurons in culture and in hippocampal slices where it antagonized electrophysiological responses with IC50 values of 50 and 93 nM, respectively. RPR 119990 antagonized hippocampal evoked responses in vivo, demonstrating brain penetration at active concentrations. RPR 119990 is a potent anticonvulsant in the supramaximal electroshock in the mouse with an ED50 of 2.3 mg/kg 1 h post s.c. administration, giving it a workably long action. Pharmacokinetic studies show good passage into the plasma after subcutaneous administration, whereas brain penetration is low but with slow elimination. This compound was found active in a transgenic mouse model of familial amyotrophic lateral sclerosis (SOD1-G93A) where it was able to improve grip muscle strength and glutamate uptake from spinal synaptosomal preparations, and prolong survival with a daily dose of 3 mg/kg s.c.
Autoconfiguration procedures for multiradio wireless mesh networks based on DHCP protocol (2009)

We propose procedures for autoconfiguration of wireless mesh networks based on DHCP protocol. The proposed mechanism provides automatic address and radio parameters set-up for nodes with multiple radio interfaces, allowing us to fully automatically form and to start a wireless mesh network, and to route packets. It supports mesh networks comprised of multiple IP subnets build with multiple networking technologies. Some performance issues of the autoconfiguration procedure are discussed. The autoconfiguration scheme was implemented and tested on OpenWRT platform.
Development of a reduced model of formation reactions in Zr-Al nanolaminates (2014)

A computational model of anaerobic reactions in metallic multilayered systems with an equimolar composition of zirconium and aluminum is developed. The reduced reaction formalism of M. Salloum and O. M. Knio, Combust. Flame 157(2): 288–295 (2010) is adopted. Attention is focused on quantifying intermixing rates based on experimental measurements of uniform ignition as well as measurements of self-propagating front velocities. Estimates of atomic diffusivity are first obtained based on a regression analysis. A more elaborate Bayesian inference formalism is then applied in order to assess the impact of uncertainties in the measurements, potential discrepancies between predictions and observations, as well as the sensitivity of predictions to inferred parameters. Intermixing rates are correlated in terms of a composite Arrhenius law, which exhibits a discontinuity around the Al melting temperature. Analysis of the predictions indicates that Arrhenius parameters inferred for the low-temperature branch lie within a tight range, whereas the parameters of the high-temperature branch are characterized by higher uncertainty. The latter is affected by scatter in the experimental measurements, and the limited range of bilayers where observations are available. For both branches, the predictions exhibit higher sensitivity to the activation energy than the pre-exponent, whose posteriors are highly correlated.
Vibrotactile forward masking: Effects of the amplitude and duration of the masking stimulus (1995)

Tactile thresholds for detecting a 50-ms signal presented 25 ms after the termination of a masking stimulus increased as a function of the amplitude level and duration of the masking stimulus. The effects were similar in both the P and NP I channels measured at 250 and 20 Hz, respectively. It was concluded that the increased masking caused by increasing the duration of the masking stimulus resulted from processes other than or in addition to temporal integration--the latter being a characteristic of the P, but not the NP I, channel. The slopes of the masking functions, in which threshold shifts were plotted as a function of masking-stimulus sensation level, were consistently greater for 20-Hz than for the 250-Hz stimuli, suggesting that masking efficiency is greater in the NP I than in the P channel.
Components and Printed Circuit Boards (2002)

Since the invention of the integrated circuit (IC) in the latter part of the 1950s, the development of new integrated circuits of greater complexity as shown in Figure 1.1 (Chapter 1) has progressed very rapidly. Along with greater numbers of components per integrated circuit have come greater challenges in cooling of electronic equipment. Generally, heat is generated from metallized areas on a small, thin, and fragile silicon die or chip inside a package. The heat transfer engineer must address the issue of cooling of electronics at all levels of packaging.
Mechanisms of gamma-globulin synthesis. (1966)

Protein synthesis has been studied in lymph node cells obtained from rabbits hyperimmunized to bacteriophage T2. Provided ribonuclease activity was inhibited, almost all nascent protein synthesis occurred on polyribosomes. Pretreatment with 1 µg/ml actinomycin D, 7 hr prior to labeling, caused an 80% reduction of polyribosome-directed protein synthesis. Pulse-labeling studies of similar cell populations indicated that depression of RNA synthesis preceded the reduction of protein and γ-globulin synthesis. When actinomycin D-treated cells were infected with Newcastle disease virus (an RNA virus), cells which had already ceased to make RNA and protein started to synthesize these macromolecules at rapid rates. Thus, the final steps of γ-globulin synthesis by immune lymph node cells appear similar to those of protein synthesis in HeLa cells.
Quantum circuits with uniformly controlled one-qubit gates (2005)

Uniformly controlled one-qubit gates are quantum gates which can be represented as direct sums of two-dimensional unitary operators acting on a single qubit. We present a quantum gate array which implements any $n$-qubit gate of this type using at most ${2}^{n\ensuremath{-}1}\ensuremath{-}1$ controlled-NOT gates, ${2}^{n\ensuremath{-}1}$ one-qubit gates, and a single diagonal $n$-qubit gate. To illustrate the versatility of these gates we then apply them to the decomposition of a general $n$-qubit gate and a state preparation procedure. Moreover, we study their implementation using only nearest-neighbor gates. We give upper bounds for the one-qubit and controlled-NOT gate counts for all the aforementioned applications. In all four cases, the proposed circuit topologies either improve on or achieve the previously reported upper bounds for the gate counts. Thus, they provide the most efficient method for general gate decompositions currently known.
Epoetin Alfa in Patients With Advanced-Stage Hodgkin's Lymphoma: Results of the Randomized Placebo-Controlled GHSG HD15EPO Trial (2010)

Epoetin alfa administered at 40,000 U weekly parallel to BEACOPP chemotherapy was safe in patients with advanced-stage HL and reduced the number of RBC transfusions but had no impact on fatigue and other PRO domains.