gebhart/patrepeval huggingface dataset:
The Discovery of Novel Vasopressin V1b Receptor Ligands for Pharmacological, Functional and Structural Investigations (2004)

Until recently, pharmacological studies dealing with vasopressin receptor isoforms were severely hampered by the lack of selective agonists or antagonists that recognize the pituitary V(1b) vasopressin receptor. By contrast, many selective vasopressin-related compounds are available for characterization of the vasopressor (V(1a)) or antidiuretic (V(2)) vasopressin receptor subtypes. Recently, SSR149415, a selective nonpeptide molecule, was discovered with nanomolar affinity for mammalian V(1b) receptors and good selectivity for the other vasopressin and oxytocin receptor isoforms. This molecule exhibits potent antagonist properties both in vitro and in vivo. We also designed synthetic peptides derived from [deaminocysteine(1),arginine(8)]vasopressin (dAVP), modified in position 4 by various amino acid residues. Some of these, d[cyclohexylalanine(4)]AVP or d[lysine(4)]AVP, have a high affinity and an excellent selectivity for the human V(1b) receptor subtype. However, they exhibit a mixed V(1b)/V(2) pharmacological profile for the rat vasopressin receptor isoforms. Whatever the species considered, these peptides behave as agonists both in bioassays performed in vitro and in vivo. The d[cyclohexylalanine(4)]AVP was tritiated and represents the first selective radiolabelled ligand available for studying the human V(1b) receptors. The discovery of these new selective V(1b) agonists and V(1b) antagonist allows an accurate pharmacological characterization of all the vasopressin receptor isoforms. As emphasized in this review, attention to the vasopressin and oxytocin receptor species differences is of critical importance in studies with all vasopressin and oxytocin ligands.
A Deep Learning Approach for Segmentation, Classification, and Visualization of 3-D High-Frequency Ultrasound Images of Mouse Embryos (2021)

Segmentation and mutant classification of high-frequency ultrasound (HFU) mouse embryo brain ventricle (BV) and body images can provide valuable information for developmental biologists. However, manual segmentation and identification of BV and body requires substantial time and expertise. This article proposes an accurate, efficient and explainable deep learning pipeline for automatic segmentation and classification of the BV and body. For segmentation, a two-stage framework is implemented. The first stage produces a low-resolution segmentation map, which is then used to crop a region of interest (ROI) around the target object and serve as the probability map of the autocontext input for the second-stage fine-resolution refinement network. The segmentation then becomes tractable on high-resolution 3-D images without time-consuming sliding windows. The proposed segmentation method significantly reduces inference time (102.36-0.09 s/volume ≈ 1000× faster) while maintaining high accuracy comparable to previous sliding-window approaches. Based on the BV and body segmentation map, a volumetric convolutional neural network (CNN) is trained to perform a mutant classification task. Through backpropagating the gradients of the predictions to the input BV and body segmentation map, the trained classifier is found to largely focus on the region where the Engrailed-1 (En1) mutation phenotype is known to manifest itself. This suggests that gradient backpropagation of deep learning classifiers may provide a powerful tool for automatically detecting unknown phenotypes associated with a known genetic mutation.
12. Conclusions (2021)

The COST Action ASF-STOP brought together an extensive network of scientists of remarkable excellence on African swine fever (ASF) vaccinology, virology, immunology, diagnostics and pathology. The network also includes global leaders in wild boar ecology and management, renowned epidemiologists specialised in ASF and disease control and scientists with vast expertise in the pig sector in Europe, biosecurity, cleaning and disinfection in pig holdings. This book collects updated knowledge in these fields, with a focus on the European situation. ASF-STOP coordinated and integrated research on ASF. Despite the new knowledge generated on ASF by scientists in Europe and worldwide, many unknowns still remain. For example, many expressed ASF virus (ASFV) genes remain uncharacterised and the information is needed for efficient antiviral drug and vaccine development. Crucial interactions between ASFV and cells like macrophages or dendritic cells are not yet completely understood. Research is needed on the mechanisms of protective immunity and identifying further viral proteins for inclusion in subunit vaccines. An in-depth analysis of the impact of ASF on the structure of the pig farming
Macrophage Migration Inhibitory Factor Is Detrimental in Pneumococcal Pneumonia and a Target for Therapeutic Immunomodulation (2015)

Mortality from pneumococcal pneumonia remains high despite antibiotic therapy, highlighting the pathogenic potential for host inflammation. We demonstrate that macrophage migration inhibitory factor (MIF), an innate immune mediator, is detrimental for survival and associated with lung pathology, inflammatory cellular infiltration, and bacterial replication in a mouse model of pneumococcal pneumonia, despite being necessary for clearance from the nasopharynx. Treatment of animals with a small-molecule inhibitor of MIF improves survival by reducing inflammation and improving bacterial control. Our work demonstrates that MIF modulates beneficial versus detrimental inflammatory responses in the host-pneumococcal interaction and is a potential target for therapeutic modulation.
Phosphorylation of the Type‐II Regulatory Subunit of Cyclic‐AMP‐Dependent Protein Kinase by Glycogen Synthase Kinase 3 and Glycogen Synthase Kinase 5 (1982)

The regulatory (R II ) subunit of type‐II cyclic‐AMP‐dependent protein kinase from bovine heart is phosphorylated at a significant rate in vitro by glycogen synthase kinase 3 and glycogen synthase 5, but not by glycogen synthase kinase 4 or phosphorylase kinase. The regulatory (R I ) subunit of type‐I cyclic‐AMP‐dependent protein kinase from rabbit skeletal muscle is not phosphorylated by any of these four protein kinases. Glycogen synthase kinase 3 phosphorylates two serine residues on the R II subunit located 44 and 47 amino acids from the N terminus of the polypeptide chain. Glycogen synthase kinase 5 phosphorylates serine‐74 and serine‐76. These sites are distinct from the residue phosphorylated by the catalytic subunit of cyclic‐AMP‐dependent protein kinase (serine‐95). The R II subunit, as normally isolated, contains 1.5–1.8 mol alkali‐labile phosphate per subunit. At least 80% of this phosphate (∼ 1.3 mol/subunit) is located in the thermolytic peptide containing serine‐74 and serine‐76, demonstrating that phosphorylation of the R II subunit by glycogen synthase kinase 5 occurs in vivo. Only small amounts of phosphate (∼ 0.1 mol/subunit) are associated with the thermolytic peptides containing serine‐44/serine‐47 and serine‐95. The phosphorylation sites on the R II subunit are organised in a strikingly similar manner to those of glycogen synthase, the amino acid sequences in the immediate vicinity of the phosphorylation sites showing a particular resemblance. These include the presence of a number of proline residues near the sites phosphorylated by glycogen synthase kinase 3, five consecutive acidic residues C‐terminal to the sites phosphorylated by glycogen synthase kinase 5, and two adjacent arginine residues just N‐terminal to the sites phosphorylated by the catalytic subunit of cyclic‐AMP‐dependent protein kinase. Glycogen synthase kinase 5 is very similar or identical to the enzyme that has been variously termed casein kinase TS, casein kinase 2, casein kinase G, casein kinase N‐II or troponin‐T kinase. The biological role of this enzyme is reviewed.
High-resolution neural network-driven mapping of multiple diffusion metrics leveraging asymmetries in the balanced SSFP frequency profile (2021)

We suggest to utilize the rich information content about microstructural tissue properties entangled in asymmetric balanced steady-state free precession (bSSFP) profiles to estimate multiple diffusion metrics simultaneously by neural network (NN) parameter quantification. A 12-point bSSFP phase-cycling scheme with high-resolution whole-brain coverage is employed at 3 T and 9.4 T for NN input. Low-resolution target diffusion data are derived based on diffusion-weighted spin-echo echo-planar-imaging (SE-EPI) scans, i.e., mean, axial, and radial diffusivity (MD, AD, RD), fractional anisotropy (FA) as well as the spherical coordinates (azimuth $Φ$ and inclination $Θ$) of the principal diffusion eigenvector. A feedforward NN is trained with incorporated probabilistic uncertainty estimation. The NN predictions yielded highly reliable results in white matter (WM) and gray matter (GM) structures for MD. The quantification of FA, AD, and RD was overall in good agreement with the reference but the dependence of these parameters on WM anisotropy was somewhat biased, e.g., in corpus callosum. The inclination $Θ$ was well predicted for anisotropic WM structures while the azimuth $Φ$ was overall poorly predicted. The findings were highly consistent across both field strengths. Application of the optimized NN to high-resolution input data provided whole-brain maps with rich structural details. In conclusion, the proposed NN-driven approach showed potential to provide distortion-free high-resolution whole-brain maps of multiple diffusion metrics at high to ultra-high field strengths in clinically relevant scan times.
Mathematical Requirements for Physical Channels (2008)

This chapter contains sections titled: Frequency-Domain Effects in Time-Domain Simulations Requirements for a Physical Channel References Problems ]]>
Selete's EUV program: progress and challenges (2008)

Selete launched a development program on EUV lithography and related mask technology in April 2006. The program is based on the concept of "lithography design and integration." It covers a wide range of areas that require further effort to get EUVL ready for volume production and was formulated on the basis that the issues should be considered from a variety of standpoints, such as acceleration of the development of key lithographic components, verification that EUVL is actually suitable for mass production, the construction of mask infrastructure, and the improvement of EUV-specific reliability and productivity. Two exposure tools have been installed as basic infrastructure: the small-field exposure tool (SFET) and the full-field exposure tool (EUV1). The objectives of the SFET installation are acceleration of the development of resist materials and processes, optimization of the mask structure and materials, and the evaluation of the exposure tool technology with regard to such things as imaging performance, stability, and the lifetimes of the optics and source components. The objective of the EUV1 installation is to demonstrate that lithography integration is a viable path to making EUV lithography a practical production technology. We found that the SFET provides both excellent resolution and high tool activity. This high performance helps us to obtain a clear understanding of the current level of EUVL performance and enables us to learn many things that can be fed back into the development program in the beta stage. A 1st static exposure with the EUV1 resolved 30-nm dense and isolated lines and 30-nm holes. The potential resolution was found to be as good as 28 nm. Although progress was made regarding EUV resist sensitivity and LWR, further progress is needed. A tool for analyzing out-gassing in EUV resists was found to facilitate the development of both resist materials and contamination control measures for exposure tools. A prototype full-field actinic inspection system for mask blanks is now under development and should become operational in the 2Q of 2008. A mask protection engineering (MPE) tool was used to show that a dual-pod carrier is very effective in protecting a mask from particles. Mask pattern defect inspection technology using a DUV wavelength of 199 nm and defect repair technology based on an FIB for EUV mask fabrication are also being developed. This work was supported in part by NEDO.
Combining Galois with complex field coding for space-time communications (2003)

A joint scheme combining error-control coding (ECC) with complex-field coding (CFC) is proposed for space–time communications through flat or frequency-selective fading multiple-input multiple-output (MIMO) channels. It is shown that the diversity gain of this joint coding scheme is the product of the free distance of the ECC, the complex-field block encoder size, and the number of receiving antennas, which is computationally prohibitive to achieve using ECC alone. The decoding complexity with the proposed iterative decoder is comparable to a system without CFC. Numerical simulations for perfectly interleaved and HIPERLAN channels with both single and multiple antennas show great potential of the proposed joint coding scheme. Copyright © 2003 AEI
Active optimal vibration control using dynamic absorber (2002)

A typical spring-lumped mass system undergoing forced vibrations is discussed. A secondary absorber mass connected to the main system through an active force generating element (such as a piezoelectric pusher) is considered as a viable means of suppressing vibrations of the system. State variable techniques are used to formulate the complete system, and optimal state feedback control is studied for such a system. Two approaches for optimal control are taken. First, an optimal control law for a system with known disturbance is considered, while in the second approach optimal control for a linear quadratic regulator problem is studied. The response of the system obtained with optimal control is compared with the response under no control. The results obtained from the two approaches of optimal control are then compared. The results are also compared with those obtained from a previous study of an active dynamic absorber.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Clonal Analyses and Cryopreservation of Neural Stem Cell Cultures (2008)

The discovery of stem cell populations in the adult central nervous system (CNS) that continually produce neurons and glial cells, and the hypothesis that they could contribute to neural plasticity/repair, has opened new and exciting areas of research in basic cell biology and regenerative medicine. The success of these studies relies on understanding the functional features and the normal fate of neural stem cells (NSCs) in vivo as well on the development of in vitro culture conditions enabling isolation, extensive propagation, and rigorous characterization of the "putative" NSCs. The neurosphere assay (NSA) has emerged as a valuable tool for isolating embryonic and adult CNS stem cells and for studying their biology. However, because this assay may select and expand a heterogeneous stem/progenitor cell population, rigorous clonal and serial subcloning analyses are required to detect and document stem cell activity and to unequivocally identify bona fide stem cells. We illustrate and discuss methods for the isolation, propagation, cryopreservation, and functional characterization of NSCs, focusing on the essential issue of their clonogenic capacity.
Pump Performance and Hemolytic Property of a Vibration Pump as a Ventricular Assist Device. (1991)

In order to study the possibility of using a vibration pump as a ventricular assist device, the pump performance and hemolytic property of the pump were evaluated. As a result, it was shown that the pump performance varied with the length and elasticity of the suction tube. The tested vibrating pump under discussion met the pump performance requirements of a ventricular assist device. The hemolytic property of the tested vibration pump was determined using goat blood. As a result, it was shown that the tested pump compared favorably with the conventional roller or centrifugal pumps with respect to hemolysis.
One-Step Homogeneous Magnetic Nanoparticle Immunoassay for Biomarker Detection Directly in Blood Plasma (2012)

Assay technologies capable of detecting low biomarker concentrations in complex biological samples are fundamental for biological research and for applications in medical diagnostics. In this paper we address the challenge to perform protein biomarker detection homogeneously in one single step, applying a minute amount of reagent directly into whole human blood plasma, avoiding any sample dilution, separation, amplification, or fluid manipulation steps. We describe a one-step homogeneous assay technology based on antibody-coated magnetic nanoparticles that are spiked in very small amount directly into blood plasma. Pulsed magnetic fields and a double-linker molecular architecture are used to generate high biomarker-induced binding and low nonspecific binding between the nanoparticles. We demonstrate dose-response curves for prostate specific antigen (PSA) measured in undiluted human blood plasma with a detection limit of 400-500 femtomol/L, in a total assay time of 14 min and an optically probed volume of only 1 nL. We explain the dose-response curves with a model based on discrete binding of biomarker molecules onto the nanoparticles, which allows us to extract reaction parameters for the binding of biomarker molecules onto the nanoparticles and for the biomarker-induced binding between nanoparticles. The demonstrated analytical performance and understanding of the nanoparticle assay technology render it of interest for a wide range of applications in quantitative biology and medical diagnostics.
In Vitro Culture of Hamster Ovarian Primary Interstitial Cells: Effect of Serum1 (1998)

The function of ovarian interstitial cells has been largely addressed using rat theca-interstitial cell culture. However, this preparation is primarily enriched with theca and secondary interstitial cells, which make it difficult to address selectively the function of the primary interstitial cells. We have developed an in vitro culture of hamster ovarian primary interstitial cells. Cells were isolated from postnatal hamster ovaries by collagenase digestion and purified over a Percoll gradient. The preparation contained 90% viable, pure interstitial cells, which anchored to the plastic and glass culture surface in the presence of fetal bovine serum. Cell proliferation was noted in the presence of serum dosages higher than 0.2%; however, reduction of serum concentration to 0.1% or complete serum starvation did not affect cell viability but almost completely abolished cell proliferation as determined by [3H] incorporation, labeling index, and DNA content of the culture. All cells exhibited active 3β-hydroxysteroid dehydrogenase and P450 side chain cleavage immunoreactivity, which corresponded to basal progesterone and androstenedione accumulation. Replacement of serum to starving cells resulted in the induction of the “S” phase and “M” phase specific cyclins, and resumption of cell proliferation. Our results indicate that hamster primary interstitial cells can be cultured in vitro as a monolayer, and the anchorage and proliferation of these cells depend on serum supplement; however, a viable monolayer can be maintained for several days without serum. This model will be useful for addressing the mechanisms of differentiation of ovarian interstitial cells.
Zero-truncated Poisson regression for sparse multiway count data corrupted by false zeros (2023)

Abstract We propose a novel statistical inference methodology for multiway count data that is corrupted by false zeros that are indistinguishable from true zero counts. Our approach consists of zero-truncating the Poisson distribution to neglect all zero values. This simple truncated approach dispenses with the need to distinguish between true and false zero counts and reduces the amount of data to be processed. Inference is accomplished via tensor completion that imposes low-rank tensor structure on the Poisson parameter space. Our main result shows that an $N$-way rank-$R$ parametric tensor $\boldsymbol{\mathscr{M}}\in (0,\infty )^{I\times \cdots \times I}$ generating Poisson observations can be accurately estimated by zero-truncated Poisson regression from approximately $IR^2\log _2^2(I)$ non-zero counts under the nonnegative canonical polyadic decomposition. Our result also quantifies the error made by zero-truncating the Poisson distribution when the parameter is uniformly bounded from below. Therefore, under a low-rank multiparameter model, we propose an implementable approach guaranteed to achieve accurate regression in under-determined scenarios with substantial corruption by false zeros. Several numerical experiments are presented to explore the theoretical results.
In Situ Growth of CuWO4 Nanospheres over Graphene Oxide for Photoelectrochemical (PEC) Immunosensing of Clinical Biomarker (2019)

Procalcitonin (PCT) protein has recently been identified as a clinical marker for bacterial infections based on its better sepsis sensitivity. Thus, an increased level of PCT could be linked with disease diagnosis and therapeutics. In this study, we describe the construction of the photoelectrochemical (PEC) PCT immunosensing platform based on it situ grown photo-active CuWO<sub>4</sub> nanospheres over reduced graphene oxide layers (CuWO<sub>4</sub>@rGO). The in situ growth strategy enabled the formation of small nanospheres (diameter of 200 nm), primarily composed of tiny self-assembled CuWO<sub>4</sub> nanoparticles (2-5 nm). The synergic coupling of CuWO<sub>4</sub> with rGO layers constructed an excellent photo-active heterojunction for photoelectrochemical (PEC) sensing. The platform was then considered for electrocatalytic (EC) mechanism-based detection of PCT, where inhibition of the photocatalytic oxidation signal of ascorbic acid (AA), subsequent to the antibody-antigen interaction, was recorded as the primary signal response. This inhibition detection approach enabled sensitive detection of PCT in a concentration range of 10 pg·mL<sup>-1</sup> to 50 ng.mL<sup>-1</sup> with signal sensitivity achievable up to 0.15 pg·mL<sup>-1</sup>. The proposed PEC hybrid (CuWO<sub>4</sub>@rGO) could further be engineered to detect other clinically important species.
Phenotypic variability in a Chinese family with rimmed vacuolar distal myopathy (2005)

The results of the present study indicate that GNE gene mutations and probably modifier gene(s) or additional factors may result in different phenotypes of DMRV.
Impaired plasma clottability induction through fibrinogen degradation by ASP, a serine protease released fromAeromonas sobria (2008)

Aeromonas sobria infection often advances to sepsis, in which interaction of bacterial components with plasma proteins possibly causes various disorders. This bacterium releases a serine protease (ASP), a putative virulence factor, and binds to fibrinogen. To study the ASP effect on fibrinogen, we incubated fibrinogen or plasma with ASP and investigated their clotting elicited by thrombin, which converts fibrinogen to a fibrin clot. Enzymatically active ASP retarded plasma clotting in a dose-dependent manner starting at an ASP concentration of 10 nM. ASP also retarded fibrinogen clotting at 3 nM and above, which appeared to correspond to ASP cleavage of fibrinogen at the A alpha-chain. Consistent with containing serine protease activity for an ASP-specific substrate, the culture supernatant of an ASP gene-introduced strain retarded plasma and fibrinogen clotting more than that of the wild-type strain. The culture supernatant of an ASP gene-disrupted strain that releases negligible serine protease activity for the ASP-specific substrate did not affect plasma clotting. These results indicate that ASP is the main fibrinogenolytic protease released from A. sobria. Impaired plasma clottability induction through fibrinogen degradation is a new virulence activity of ASP and may contribute to hemorrhagic tendencies in sepsis caused by infection with this bacterium.