gebhart/patrepeval huggingface dataset:
Tryptophanyl-tRNA Synthetase 1 Signals Activate TREM-1 via TLR2 and TLR4 (2020)

Tryptophanyl-tRNA synthetase 1 (WARS1) is an endogenous ligand of mammalian Toll-like receptors (TLR) 2 and TLR4. Microarray data, using mRNA from WARS1-treated human peripheral blood mononuclear cells (PBMCs), had indicated WARS1 to mainly activate innate inflammatory responses. However, exact molecular mechanism remains to be understood. The triggering receptor expressed on myeloid cells (TREM)-1 is an amplifier of pro-inflammatory processes. We found WARS1 to significantly activate TREM-1 at both mRNA and protein levels, along with its cell surface expression and secretion in macrophages. WARS1 stimulated TREM-1 production via TLR2 and TLR4, mediated by both MyD88 and TRIF, since targeted deletion of TLR4, TLR2, MyD88, and TRIF mostly abrogated TREM-1 activation. Furthermore, WARS1 promoted TREM-1 downstream phosphorylation of DAP12, Syk, and AKT. Knockdown of TREM-1 and inhibition of Syk kinase significantly suppressed the activation of inflammatory signaling loop from MyD88 and TRIF, leading to p38 MAPK, ERK, and NF-κB inactivation. Finally, MyD88, TRIF, and TREM-1 signaling pathways were shown to be cooperatively involved in WARS1-triggered massive production of IL-6, TNF-α, IFN-β, MIP-1α, MCP-1, and CXCL2, where activation of Syk kinase was crucial. Taken together, our data provided a new insight into WARS1's strategy to amplify innate inflammatory responses via TREM-1.
Successful Cord Blood Stem Cell Transplantation for an Adult Case of Chronic Active Epstein-Barr Virus Infection (2016)

A 41-year-old man was referred to our hospital for treatment of anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma. Chronic active Epstein-Barr virus (CAEBV) was diagnosed based on the findings of elevated EBV antibody titers and positive EBV-DNA in the peripheral blood, and cord blood stem cell transplantation (CBT) was performed. The EBV-DNA levels in the blood fell below the limit of detection. His lymphoma relapsed on Day 165 with the appearance of eruptions, which disappeared after the withdrawal of tacrolimus. One year after transplantation, there were no signs of recurrence. This encouraging result suggests that CBT should be considered for adult cases of CAEBV with aggressive clinical manifestations.
Measurement of CP observables in B 0 → DK ∗0 with D →K + K − (2013)

A bstract The decay B 0 → DK *0 and the charge conjugate mode are studied using 1.0 fb −1 of pp collision data collected by the LHCb experiment at $ \sqrt{s}=7 $ TeV in 2011. The CP asymmetry between the B 0 → DK *0 and the $ {{\overline{B}}^0}\to D{{\overline{K}}^{*0 }} $ decay rates, with the neutral D meson in the CP -even final state K + K − , is found to be $ \mathcal{A}_d^{KK }=-0.45\pm 0.23\pm 0.02, $ where the first uncertainty is statistical and the second is systematic. In addition, favoured B 0 → DK *0 decays are reconstructed with the D meson in the non- CP eigenstate K + π − . The ratio of the B -flavour averaged decay rates in D decays to CP and non- CP eigenstates is measured to be $ \mathcal{R}_d^{KK }=1.36_{-0.32}^{+0.37}\pm 0.07, $ where the ratio of the branching fractions of D 0 → K − π + to D 0 → K + K − decays is included as multiplicative factor. The CP asymmetries measured with two control channels, the favoured B 0 → DK *0 decay with D → K + π − and the $ \overline{B}_s^0\to D{K^{*0 }} $ decay with D → K + K − , arealsoreported.
A novel algorithm for bad pixel detection and correction to improve quality and stability of geometric measurements (2016)

An algorithm for detection and individually substitution of bad pixels for further restoration of an image in the presence of such outliers without altering overall image texture is presented. This work presents three phases concerning image processing: bad pixel identification and mapping by means of linear regression and the coefficient of determination of the pixel output as a function of exposure time, local correction of the linear and angular coefficients of the outlier pixels based on their neighbourhood and, finally, image restoration. Simulation and experimental data were used as means of code benchmarking, showing satisfactory results.
Studying the Potential of Automatic Optimizations in the Intel FPGA SDK for OpenCL (2020)

High Level Synthesis (HLS) tools, like the Intel FPGA SDK for OpenCL, improve hardware design productivity and enable efficient design space exploration, by providing simple program directives (pragmas) and/or API calls that allow hardware programmers to use higher-level languages (like HLS-C or OpenCL). However, modern HLS tools sometimes miss important optimizations that are necessary for high performance. In this poster, we present a study of the tradeoffs in HLS optimizations, and the potential of a modern HLS tool in automatically optimizing an application. We perform the study on a generic, 5-stage camera ISP pipeline using the Intel FPGA SDK for OpenCL and an Arria 10 FPGA Dev Kit. We show that automatic optimizations in the HLS tool are valuable, achieving up to 2.7x speedup over equivalent CPU execution. With further hand tuning, however, we can achieve up to 36.5x speedup over CPU. We draw several specific lessons about the effectiveness of automatic optimizations guided by simple directives and about the nature of manual rewriting required for high performance. Finally, we conclude that there is a gap in the current potential of HLS tools which needs to be filled by next-gen research.
Penalized matrix decomposition for denoising, compression, and improved demixing of functional imaging data (2018)

Calcium imaging has revolutionized systems neuroscience, providing the ability to image large neural populations with single-cell resolution. The resulting datasets are quite large (with scales of TB/hour in some cases), which has presented a barrier to routine open sharing of this data, slowing progress in reproducible research. State of the art methods for analyzing this data are based on non-negative matrix factorization (NMF); these approaches solve a non-convex optimization problem, and are highly effective when good initializations are available, but can break down e.g. in low-SNR settings where common initialization approaches fail. Here we introduce an improved approach to compressing and denoising functional imaging data. The method is based on a spatially-localized penalized matrix decomposition (PMD) of the data to separate (low-dimensional) signal from (temporally-uncorrelated) noise. This approach can be applied in parallel on local spatial patches and is therefore highly scalable, does not impose non-negativity constraints or require stringent identifiability assumptions (leading to significantly more robust results compared to NMF), and estimates all parameters directly from the data, so no hand-tuning is required. We have applied the method to a wide range of functional imaging data (including one-photon, two-photon, three-photon, widefield, somatic, axonal, dendritic, calcium, and voltage imaging datasets): in all cases, we observe ~2-4x increases in SNR and compression rates of 20-300x with minimal visible loss of signal, with no adjustment of hyperparameters; this in turn facilitates the process of demixing the observed activity into contributions from individual neurons. We focus on two challenging applications: dendritic calcium imaging data and voltage imaging data in the context of optogenetic stimulation. In both cases, we show that our new approach leads to faster and much more robust extraction of activity from the video data.
Changes in Peripheral and Cerebral Oxygenation With Altitude and Acclimatization (2012)

Free accessAbstractFirst published online June 1, 2012Changes in Peripheral and Cerebral Oxygenation With Altitude and AcclimatizationMatthew R. Sanborn, MD, Mark E. Edsell, MBChB, […], Heng Yow, MBChB, Daniel S. Martin, MBChB, Chris Imray, MBBS, and Mike Grocott, MBBS+3-3View all authors and affiliationsVolume 23, Issue 2https://doi.org/10.1016/j.wem.2012.01.008
Computed tomographic enterography adds value to colonoscopy in differentiating Crohn’s disease from intestinal tuberculosis: a potential diagnostic algorithm (2015)

CTE adds unique information to colonoscopy in differential diagnosis between Crohn's disease and ITB, allowing correct diagnosis in most patients.
Fractional Divider Concepts with Phase-Lock-Control for the Generation of Precise Linear Frequency Ramps (1998)

A highly linear analog frequency ramp generator based on a fractional divider concept is presented. The frequency ramp linearity achievable in this fractional phase-locked-loop configuration is excellent. This is revealed by numerical simulations as well as measurements performed with a prototype synthesizer implemented in a FMCW-radar system suitable for distance and velocity measurements.
Zero phase error tracking control system with multi harmonics disturbance suppression loop (2010)

Recently, on the view point of capacity of memory, the media of optical disk recording system is increasing. Moreover, its disk rotation speed will be increasing according to its large memory capacity, such as more than 10000[rpm]. The optical disk system has a radial run-out originate from the disk eccentricity. For this reason, the optical disk system has the periodic disturbance which is synchronized to its disk rotation speed. In order to suppress this periodic disturbance, we have proposed the robust feedforword tracking controller based on Zero Phase Error Tracking (ZPET) control. The optical disk system has the periodic harmonics disturbance. However, it is difficult for the conventional robust feedforword tracking controller to suppress the periodic high order harmonics disturbance. In order to overcome this problem, this paper proposes a new ZPET control system with multi harmonics disturbance suppression loop. The experimental results point out that the proposed tracking control system has a precise tracking response against both periodic primary harmonics disturbance and periodic high order harmonics disturbance.
Abstract 5838: Successful Replacement of Aortic Valves by Decellularized Allografts in the Sheep: First Long-Term Results (2008)

Immunogenicity of human allografts leads to gradual valve degeneration. Pulmonal cell-free valvular scaffolds obtained by methods of tissue engineering have proved to induce in-vivo guided tissue regeneration and represent a promising valve substitute especially for children. Here we describe the successful orthotopic implantation of decellularized aortic valves in the systemic circulation in sheep. Allogenic detergent decellularized (0.5% sodium deoxycholate/0.5% SDS) aortic valve (AV) conduits (n = 12) were implanted orthotopically as root replacement in lambs (35–45 kg). Fresh native AV conduits served as controls (n = 6). After three and nine months follow-up the valves were investigated for functionality by echocardiography, for morphology and histological appearance. Decellularization resulted in complete loss of cells in AV wall, cusp and myocardial cuff, no influence on scaffold microarchitecture was observed. During 9 months follow-up no signs of conduit dilatation, aortic stenosis (transvalvular gradient max. 6.1 ± 5.1mmHg) or reduction of cusp mobility were observed in the decellularized group. Regurgitation in these valves was trivial in all cases. The grafts showed no histological signs of rejection and partial repopulation of the valvular scaffolds with autologous cells. In contrast, control animals developed mild to severe AV insufficiency. Histological investigation revealed significant calcific degeneration and massive rejection of these valves. Decellularized AV conduits may represent a durable AV substitute resistant to high systemic pressure. Furthermore, cell-removal prevents the allograft valve from immunologic deterioration and early graft degeneration.
Tertiary Amine Promoted Aziridination: Preparation of NH-Aziridines from Aliphatic α,β-Unsaturated Ketones (2015)

<i>trans</i>-NH-Aziridines were prepared from aliphatic α,β-unsaturated ketones using a tertiary amine promoted reaction via in situ generated <i>N</i>,<i>N</i>-ylides. Through use of modified conditions the reaction proved to be applicable for the diastereoselective aziridination of a range of enolisable aliphatic α,β-unsaturated ketones of varying substitution patterns.
Glycosylation of Conotoxins (2013)

Conotoxins are small peptides present in the venom of cone snails. The snail uses this venom to paralyze and capture prey. The constituent conopeptides display a high level of chemical diversity and are of particular interest for scientists as tools employed in neurological studies and for drug development, because they target with exquisite specificity membrane receptors, transporters, and various ion channels in the nervous system. However, these peptides are known to contain a high frequency and variability of post-translational modifications-including sometimes O-glycosylation-which are of importance for biological activity. The potential application of specific conotoxins as neuropharmalogical agents and chemical probes requires a full characterization of the relevant peptides, including the structure of the carbohydrate part. In this review, the currently existing knowledge of O-glycosylation of conotoxins is described.
Research Highlights: Highlights from the latest articles on molecular imaging with Raman spectroscopy (2013)

Raman spectroscopy using surfaceenhanced Raman scattering (SERS) nanoparticles is an exciting new molecular imaging modality that has emerged over the past decade [1,2]. The approach is based on the inelastic scatter of photons by molecular bonds. Small-molecule dyes adsorbed on a rough metal (usually gold) surface experience a dramatic increase in their Raman scatter intensity due to surface plasmons, which induce strong localized electric fields near the surface [3]. As each bond within a Raman dye has a characteristic vibrational energy, the SERS spectrum is unique for that dye. The nanoparticle for Raman molecular imaging is composed of: a gold core to provide the signal enhancement, an adsorbed dye to provide the SERS spectrum, a biocompatible coating (e.g., polyethylene glycol or silica) and a targeting moiety (e.g., an antibody). By combining unique dye spectra and targeting moieties for different biological targets, highsensitivity, multiplexed molecular imaging is possible in vivo with an environmentally and optically stable contrast agent [4–8]. Summarized below are four exciting recent reports that significantly advance the field of SERS-based molecular imaging.
Optimization of LpxC Inhibitors for Antibacterial Activity and Cardiovascular Safety (2019)

Abstract UDP‐3‐ O ‐( R ‐3‐hydroxymyristoyl)‐ N ‐acetylglucosamine deacetylase (LpxC) is a Zn 2+ deacetylase that is essential for the survival of most pathogenic Gram‐negative bacteria. ACHN‐975 ( N ‐(( S )‐3‐amino‐1‐(hydroxyamino)‐3‐methyl‐1‐oxobutan‐2‐yl)‐4‐(((1 R ,2 R )‐2‐(hydroxymethyl)cyclopropyl)buta‐1,3‐diyn‐1‐yl)benzamide) was the first LpxC inhibitor to reach human clinical testing and was discovered to have a dose‐limiting cardiovascular toxicity of transient hypotension without compensatory tachycardia. Herein we report the effort beyond ACHN‐975 to discover LpxC inhibitors optimized for enzyme potency, antibacterial activity, pharmacokinetics, and cardiovascular safety. Based on its overall profile, compound 26 (LPXC‐516, ( S )‐ N ‐(2‐(hydroxyamino)‐1‐(3‐methoxy‐1,1‐dioxidothietan‐3‐yl)‐2‐oxoethyl)‐4‐(6‐hydroxyhexa‐1,3‐diyn‐1‐yl)benzamide) was chosen for further development. A phosphate prodrug of 26 was developed that provided a solubility of &gt;30 mg mL −1 for parenteral administration and conversion into the active drug with a t 1/2 of approximately two minutes. Unexpectedly, and despite our optimization efforts, the prodrug of 26 still possesses a therapeutic window insufficient to support further clinical development.
Squamous cell carcinoma antigen‐immunoglobulin M complexes as novel biomarkers for hepatocellular carcinoma (2005)

The study results indicated that SCCA-IgM ICs represent novel serologic biomarkers, which, alone or in combination with AFP, can increase the sensitivity for diagnosing HCC significantly.
Parkinsonism Death Rates by Race, Sex and Geography: A 1980s Update (1990)

To evaluate temporal changes in the geographic distribution of Parkinson's disease (PD) mortality in the United States, we reviewed death rates for PD in the nine regions of the United States for 1980-1984. Age-adjusted mortality for all ages and for the elderly (65 years of age and older) was analyzed. Variation in PD mortality was observed among the regions for all demographic groups. The patterns were different from those reported during 1959-1961. Changing geographic patterns in mortality provide evidence for an environmental etiology for PD.
A semi-automatic method for extracting thin line structures in images as rooted tree network (2024)

This paper addresses the problem of semi-automatic extraction of line networks in digital images - e.g., road or hydrographic networks in satellite images, blood vessels in medical images, robust. For that purpose, we improve a generic method derived from morphological and hydrological concepts and consisting in minimum cost path estimation and flow simulation. While this approach fully exploits the local contrast and shape of the network, as well as its arborescent nature, we further incorporate local directional information about the structures in the image. Namely, an appropriate anisotropic metric is designed by using both the characteristic features of the target network and the eigen-decomposition of the gradient structure tensor of the image. Following, the geodesic propagation from a given seed with this metric is combined with hydrological operators for overland flow simulation to extract the line network. The algorithm is demonstrated for the extraction of blood vessels in a retina image and of a river network in a satellite image.
Copper Hydride-Catalyzed Enantioselective Olefin Hydromethylation (2022)

The enantioselective installation of a methyl group onto a small molecule can result in the significant modification of its biological properties. While hydroalkylation of olefins represents an attractive approach to introduce alkyl substituents, asymmetric hydromethylation protocols are often hampered by the incompatibility of highly reactive methylating reagents and a lack of general applicability. Herein, we report an asymmetric olefin hydromethylation protocol enabled by CuH catalysis. This approach leverages methyl tosylate as a methyl source compatible with the reducing base-containing reaction environment, while a catalytic amount of iodide ion transforms the methyl tosylate in situ into the active reactant, methyl iodide, to promote the hydromethylation. This method tolerates a wide range of functional groups, heterocycles, and pharmaceutically-relevant frameworks. Density functional theory studies suggest that the methylation step is stereoretentive, taking place through an SN2-type oxidative addition mechanism followed by a reductive elimination. The enantioselectivity is enforced by ligand–substrate steric repulsions during the hydrocupration step.
Supplementary Table 2 from Development of an Fc-Enhanced Anti–B7-H3 Monoclonal Antibody with Potent Antitumor Activity (2023)

&lt;p&gt;PDF file, 59KB, Expanded normal tissue IHC analysis of B7-H3 on frozen tissues with MGA271 at optimal staining concentration (4 ug/ml) and at 5x the optimal concentration (20 ug/ml). The optimal staining concentration was determined by titration on the CaKi2 and Hs700T positive control cell lines to determine the lowest MGA271 concentration that yielded the greatest specific staining. (c) = cytoplasmic; (m) = membrane; (c,m) = cytoplasmic plus membrane.&lt;/p&gt;
Hepatic Nucleases. 2. Association of Polyadenylase, Alkaline Ribonuclease and Deoxyribonuclease with Rat-Liver Mitochondria (1975)

Six types of nuclease activities were found to be concentrated in the large granule fraction isolated from rat liver homogenastes by differential centrifugation. Analysis by density equilibration shows that three nucleases are associated with mitochondria: an alkaline ribonulcease (pH optimum 8.8), an alkaline deoxyribonuclease (pH optimum 7.6) and an enzyme acting on polyriboadenylate (pH optimum 7.5). When the outer mitochondrial membrane is ruptured in hypotonic medium, the three mitochondrial nucleases are partially solubilized. Solubilization is however obtained by addition of KCL to the suspension medium. It is concluded that mitochondrial nucleases are localized in the intermembrane space but that an adsorption to the outer face of the inner mitochondrial membrane occurs in sucrose 0.25 M. The mitochondrial localization of alkaline ribonuclease, alkaline deoxyribonuclease and polyadenylate accounts for at least 80% of the activity of liver homogenate; nevertheless, an excess of these enzymes is present in the microsomal fraction. Although no definite conculusion can be reached for the significance of this observation, it is shown by density equilibration analysis that these nuclease are not associated either with ribosomes or with the membranes which are the major component of the microsomal fraction.
Synthetic Peptides to Identify Antigenic Determinants on Epstein-Barr Virus gp350/220 (1990)

We synthesized three peptides, MA1 - Thr19-Val28(+Tyr) -, MA2 - Ser807-Ala816-, and MA3-Ser718-Glu729(+Tyr) from the sequence of Epstein-Barr virus gp350/220 and immunized rabbits with these peptides. Rabbit antisera to the peptides had antipeptide radioimmunoassay titers of 1:400 for anti-MA1, 1:200 for anti-MA2, and 1:1600 for anti-MA3. The anti-MA1 serum recognized gp350/220 in Western blotting to SDS-electrophoresed proteins from 12-O-tetradecanoylphorbol-13-acetate- and n-butyrate-treated B95-8 cells, but anti-MA2 and MA3 sera did not. None of the sera reacted with gp350/220 by membrane or cytoplasmic immunofluorescence or by immunoprecipitation of Triton X-100 solubilized proteins.
A Randomized Placebo-Controlled Pilot Trial of Omega-3 Fatty Acids and Alpha Lipoic Acid in Alzheimer's Disease (2013)

Oxidative stress, inflammation, and increased cholesterol levels are all mechanisms that have been associated with Alzheimer's disease (AD) pathology. Several epidemiologic studies have reported a decreased risk of AD with fish consumption. This pilot study was designed to evaluate the effects of supplementation with omega-3 fatty acids alone (ω-3) or omega-3 plus alpha lipoic acid (ω-3 + LA) compared to placebo on oxidative stress biomarkers in AD. The primary outcome measure was peripheral F2-isoprostane levels (oxidative stress measure). Secondary outcome measures included performance on: Mini-Mental State Examination (MMSE), Activities of Daily Living/Instrumental Activities of Daily Living (ADL/IADL), and Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog). Thirty-nine AD subjects were randomized to one of three groups: 1) placebo, 2) ω-3, or 3) ω-3 + LA for a treatment duration of 12 months. Eighty seven percent (34/39) of the subjects completed the 12-month intervention. There was no difference between groups at 12 months in peripheral F2-isoprostane levels (p = 0.83). The ω-3 + LA and ω-3 were not significantly different than the placebo group in ADAS-cog (p = 0.98, p = 0.86) and in ADL (p = 0.15, p = 0.82). Compared to placebo, the ω-3 + LA showed less decline in MMSE (p < 0.01) and IADL (p = 0.01) and the ω-3 group showed less decline in IADL (p < 0.01). The combination of ω-3 + LA slowed cognitive and functional decline in AD over 12 months. Because the results were generated from a small sample size, further evaluation of the combination of omega-3 fatty acids plus alpha-lipoic acid as a potential treatment in AD is warranted.