gebhart/patrepeval huggingface dataset:
Evaluation of the biosafety of recombinant lactic acid bacteria designed to prevent and treat colitis (2016)

Inflammatory bowel diseases (IBDs) affect the gastrointestinal tract and are characterized by recurrent inflammation that requires lifelong therapies. Probiotics such as lactic acid bacteria (LAB) have been proposed to complement current treatment protocols for these patients; however, their characteristics are strain dependent. In this regard, certain novel characteristics are only possible through the genetic modification of these beneficial micro-organisms. Different delivery systems, such as protein delivery of anti-oxidant enzymes and anti-inflammatory cytokines, have been shown to be effective in preventing and treating IBD in animal models. In this study, the safety of the recombinant LAB (recLAB) Streptococcus thermophilus CRL807 : CAT, S. thermophilus CRL807 : SOD, Lactococcus lactis NCDO2118 pXILCYT : IL-10, L. lactis MG1363 pValac : IL-10 and L. lactis MG1363 pGroESL : IL-10 with proven beneficial effects was compared to their progenitor strains S. thermophilus CRL807, L. lactis NCDO2118 or L. lactis MG1363. The prolonged administration of these genetically modified strains showed that they were just as safe as the native strains from which they derive, as demonstrated by normal animal growth and relative organ weights, absence of microbial translocation from the gastrointestinal tract, normal blood parameters and intestinal histology. The results show the potential use of these recLAB in future therapeutic formulations; however, the use of modern bio-containment systems is required for the future acceptance of these recLAB by the medical community and patients with IBD.
Ordered Counterfactual Explanation by Mixed-Integer Linear Optimization (2021)

Post-hoc explanation methods for machine learning models have been widely used to support decision-making. One of the popular methods is Counterfactual Explanation (CE), also known as Actionable Recourse, which provides a user with a perturbation vector of features that alters the prediction result. Given a perturbation vector, a user can interpret it as an "action" for obtaining one's desired decision result. In practice, however, showing only a perturbation vector is often insufficient for users to execute the action. The reason is that if there is an asymmetric interaction among features, such as causality, the total cost of the action is expected to depend on the order of changing features. Therefore, practical CE methods are required to provide an appropriate order of changing features in addition to a perturbation vector. For this purpose, we propose a new framework called Ordered Counterfactual Explanation (OrdCE). We introduce a new objective function that evaluates a pair of an action and an order based on feature interaction. To extract an optimal pair, we propose a mixed-integer linear optimization approach with our objective function. Numerical experiments on real datasets demonstrated the effectiveness of our OrdCE in comparison with unordered CE methods.
A Genetically Encoded Fluorescent Probe in Mammalian Cells (2013)

Fluorescent reporters are useful in vitro and in vivo probes of protein structure, function, and localization. Here we report that the fluorescent amino acid, 3-(6-acetylnaphthalen-2-ylamino)-2-aminopropanoic acid (Anap), can be site-specifically incorporated into proteins in mammalian cells in response to the TAG codon with high efficiency using an orthogonal amber suppressor tRNA/aminoacyl-tRNA synthetase (aaRS) pair. We further demonstrate that Anap can be used to image the subcellular localization of proteins in live mammalian cells. The small size of Anap, its environment-sensitive fluorescence, and the ability to introduce Anap at specific sites in the proteome by simple mutagenesis make it a unique and valuable tool in eukaryotic cell biology.
C-C Chemokine Receptor 1 Expression in Human Hematolymphoid Neoplasia (2010)

Chemokine receptor 1 (CCR1) is a G protein-coupled receptor that binds to members of the C-C chemokine family. Recently, CCL3 (MIP-1alpha), a high-affinity CCR1 ligand, was identified as part of a model that independently predicts survival in patients with diffuse large B-cell lymphoma (DLBCL). However, the role of chemokine signaling in the pathogenesis of human lymphomas is unclear. In normal human hematopoietic tissues, we found CCR1 expression in intraepithelial B cells of human tonsil and granulocytic/monocytic cells in the bone marrow. Immunohistochemical analysis of 944 cases of hematolymphoid neoplasia identified CCR1 expression in a subset of B- and T-cell lymphomas, plasma cell myeloma, acute myeloid leukemia, and classical Hodgkin lymphoma. CCR1 expression correlated with the non-germinal center subtype of DLBCL but did not predict overall survival in follicular lymphoma. These data suggest that CCR1 may be useful for lymphoma classification and support a role for chemokine signaling in the pathogenesis of hematolymphoid neoplasia.
IN THE CONTEXT OF MODERNITY AND GLOBALIZATION THE RADICALIZATION ISSUE OF RELIGIOUS GROUPS IN TURKEY (2020)

Modernleşme ve küreselleşme insanoğlunun yaşadığı iki önemli süreçtir. Her iki süreçte toplumsal hayatta çok önemli değişiklikler yaşanmıştır. Bu anlamda modernleşme ve küreselleşmenin etkilediği en önemli sosyal kurumların başında din ve dinin taşıyıcısı dini gruplar gelmektedir. Modernite akla çok büyük önem vermiştir. Bu nedenle toplumsal ilişkilerde ve kurumlarda akılcı esaslar uygulamıştır. Bu yüzden moderniteye “Akıl Çağı” ismi verilmiştir. Modern dönemde, özellikle sekülerleşmeyle birlikte, dinin sahip olduğu güç ve etki kaybolmaya başlamış ve dinin yerini rasyonel bilimin açıklama modelleri almıştır. Bu nedenle modernizmin dini dar bir alana hapsettiğini söylemek mümkündür. Modernitenin dini dar bir alana hapsetmesine rağmen küreselleşmenin başlamasıyla dinin önündeki engeller kalkmaya başlamıştır. Başka bir ifadeyle, insanlar küreselleşme döneminde dinin toplumsal hayattaki canlanmasına ve kutsalın dönüşüne tanıklık etmişlerdir. Türkiye’deki dini gruplar da modernite ve küreselleşme sürecinden etkilenmişler ve çeşitli iddialarla gündeme gelmeye başlamışlardır. Bu iddiaların temelini oluşturan ana unsur dini grupların sekülerleştikleri ve asli görevlerinden uzaklaştıkları söylemidir. İşte bu çalışmanın amacı, Türkiye'deki dini grupların nasıl sekülerleşmeye ve radikalleşmeye başladıklarını tartışmaktır. Bunun için birinci adımda Batı’da modern ve küresel dönemde dine biçilen rol üzerinde durulmaktadır. Daha sonra mevcut durumdan hareketle Türkiye'de sekülerleşen dini grupların radikalleşme tehlikesi ele alınmaktadır. Son olarak da Türkiye'deki dini grupların radikalleşme tehlikesinin önüne geçilebilmesi için çeşitli önerilerde bulunulmaktadır.
FLT3-ITD transduces autonomous growth signals during its biosynthetic trafficking in acute myelogenous leukemia cells. (2021)

Abstract FMS-like tyrosine kinase 3 (FLT3) in hematopoietic cells binds to its ligand at the plasma membrane (PM), then transduces growth signals. FLT3 gene alterations that lead the kinase to assume its permanently active form, such as internal tandem duplication (ITD) and D835Y substitution, are found in 30~40% of acute myelogenous leukemia (AML) patients. Thus, the drugs for molecular targeting of FLT3 mutants have been developed for the treatment of AML. Several groups have reported that compared with wild-type FLT3 (FLT3-wt), FLT3 mutants are retained in organelles, resulting in low levels of PM localization of the receptor. However, the precise subcellular localization of mutant FLT3 remains unclear, and the relationship between oncogenic signaling and the mislocalization is not completely understood. In this study, we show that in cell lines established from AML patients, endogenous FLT3-ITD but not FLT3-wt clearly accumulates in the perinuclear region. Our co-immunofluorescence assays demonstrate that Golgi markers are co-localized with the perinuclear region, indicating that FLT3-ITD mainly localizes to the Golgi region in AML cells. FLT3-ITD biosynthetically traffics to the Golgi apparatus and remains there in a manner dependent on its tyrosine kinase activity. A tyrosine kinase inhibitor midostaurin (PKC412) markedly decreases in FLT3-ITD retention and increases in the PM levels of the mutant. FLT3-ITD activates downstream in the endoplasmic reticulum (ER) and the Golgi apparatus during its biosynthetic trafficking. Results of our trafficking inhibitor treatment assays show that FLT3-ITD in the ER activates STAT5, whereas that in the Golgi can cause the activation of AKT and ERK. We provide evidence that FLT3-ITD signals from the early secretory compartments before reaching the PM in AML cells.
Detection of reaction products induced in plasma focus electrodes (1991)

‘‘Cold Fusion’’ experiment have been performed elsewhere using a dense plasma focus machine. It is the purpose of an oncoming study at the UI to reproduce and extend these experiments using a similar device at the University of Illinois. The Illinois facility is described as well as the technique that will be used. Extensions are suggested.
ChemInform Abstract: General Approach to the Synthesis of Polyquinenes. Part 4. Studies Directed Toward the Preparation of Dicyclopenta(cd,gh)pentalene. (1988)

Abstract The bicyclic bisenol (IV), prepared from glyoxal (I) and the acetonedicarboxylate (II), is hydrolyzed, decarboxylated, and bisallylated to form the isomeric bicyclooctanediones (VI) and (VII).
Introduction to multipath propagation (2012)

Multipath propagation produces different versions of the transmitted signal which combine in the receiver. Multiple paths can be produced by reflection or scattering from the ground or objects such as buildings, inhomogeneity of atmospheric refractivity or multiple ray paths through the ionosphere. Each version of the signal will be affected by the path it has followed, including the effects of polarisation and direction-of-arrival at the receiving antenna. Unless one version dominates all the others, the received signal is a highly modified version of the transmitted signal. This chapter describes the general characteristics of multipath propagation and the type of analysis which is typically performed.
Spectroscopic Ellipsometric Characterization of TiO2/Ag/TiO2 Optical Coatings (1988)

Optical constants (3000-800Å) and layer thicknesses in a three-layer glass/TiO 2 /Ag/TiO 2 structure were determined using variable angle of incidence spectroscopic ellipsometry (VASE). Spectral characteristics due to plasmon effects were observed in n and k spectra for the thin silver layers.
N‐acetyl‐β‐D‐glucopyranosylamine: A potent T‐state inhibitor of glycogen phosphorylase. A comparison with α‐D‐glucose (1995)

Structure-based drug design has led to the discovery of a number of glucose analogue inhibitors of glycogen phosphorylase that have an increased affinity compared to alpha-D-glucose (Ki = 1.7 mM). The best inhibitor in the class of N-acyl derivatives of beta-D-glucopyranosylamine, N-acetyl-beta-D-glucopyranosylamine (1-GlcNAc), has been characterized by kinetic, ultracentrifugation, and crystallographic studies. 1-GlcNAc acts as a competitive inhibitor for both the b (Ki = 32 microM) and the a (Ki = 35 microM) forms of the enzyme with respect to glucose 1-phosphate and in synergism with caffeine, mimicking the binding of glucose. Sedimentation velocity experiments demonstrated that 1-GlcNAc was able to induce dissociation of tetrameric phosphorylase a and stabilization of the dimeric T-state conformation. Co-crystals of the phosphorylase b-1-GlcNAc-IMP complex were grown in space group P4(3)2(1)2, with native-like unit cell dimensions, and the complex structure has been refined to give a crystallographic R factor of 18.1%, for data between 8 and 2.3 A resolution. 1-GlcNAc binds tightly at the catalytic site of T-state phosphorylase b at approximately the same position as that of alpha-D-glucose. The ligand can be accommodated in the catalytic site with very little change in the protein structure and stabilizes the T-state conformation of the 280s loop by making several favorable contacts to Asn 284 of this loop. Structural comparisons show that the T-state phosphorylase b-1-GlcNAc-IMP complex structure is overall similar to the T-state phosphorylase b-alpha-D-glucose complex structure. The structure of the 1-GlcNAc complex provides a rational for the biochemical properties of the inhibitor.
Molecule Generation Experience: An Open Platform of Material Design for Public Users (2021)

Artificial Intelligence (AI)-driven material design has been attracting great attentions as a groundbreaking technology across a wide spectrum of industries. Molecular design is particularly important owing to its broad application domains and boundless creativity attributed to progresses in generative models. The recent maturity of molecular generative models has stimulated expectations for practical use among potential users, who are not necessarily familiar with coding or scripting, such as experimental engineers and students in chemical domains. However, most of the existing molecular generative models are Python libraries on GitHub, that are accessible for only IT-savvy users. To fill this gap, we newly developed a graphical user interface (GUI)-based web application of molecular generative models, Molecule Generation Experience, that is open to the general public. This is the first web application of molecular generative models enabling users to work with built-in datasets to carry out molecular design. In this paper, we describe the background technology extended from our previous work. Our new online evaluation and structural filtering algorithms significantly improved the generation speed by 30 to 1,000 times with a wider structural variety, satisfying chemical stability and synthetic reality. We also describe in detail our Kubernetes-based scalable cloud architecture and user-oriented GUI that are necessary components to achieve a public service. Finally, we present actual use cases in industrial research to design new photoacid generators (PAGs) as well as release cases in educational events.
Nephrotoxicity and Chinese Herbal Medicine (2018)

Chinese herbal medicine has been practiced for the prevention, treatment, and cure of diseases for thousands of years. Herbal medicine involves the use of natural compounds, which have relatively complex active ingredients with varying degrees of side effects. Some of these herbal medicines are known to cause nephrotoxicity, which can be overlooked by physicians and patients due to the belief that herbal medications are innocuous. Some of the nephrotoxic components from herbs are aristolochic acids and other plant alkaloids. In addition, anthraquinones, flavonoids, and glycosides from herbs also are known to cause kidney toxicity. The kidney manifestations of nephrotoxicity associated with herbal medicine include acute kidney injury, CKD, nephrolithiasis, rhabdomyolysis, Fanconi syndrome, and urothelial carcinoma. Several factors contribute to the nephrotoxicity of herbal medicines, including the intrinsic toxicity of herbs, incorrect processing or storage, adulteration, contamination by heavy metals, incorrect dosing, and interactions between herbal medicines and medications. The exact incidence of kidney injury due to nephrotoxic herbal medicine is not known. However, clinicians should consider herbal medicine use in patients with unexplained AKI or progressive CKD. In addition, exposure to herbal medicine containing aristolochic acid may increase risk for future uroepithelial cancers, and patients require appropriate postexposure screening.
NANOWALL ARRAY CHIPS FOR DNA SEPARATION (2011)

A 25 s separation of DNA fragments (48.5 and 1 kbp fragments) was achieved by a nanowall array structure, although the separation of 1 kbp and 100 bp DNA fragments was not. Direct observation of a single DNA molecule indicates that it takes over 20 s for an elongated DNA molecule to relax inside the nanowall array structure. Numerical fitting of DNA molecular dynamics reveals that the balance between times for the transverse of an elongated DNA molecule and the relaxation process of a DNA molecule inside the nanowall array structure governs the separation of DNA.
An NF-κB-microRNA regulatory network tunes macrophage inflammatory responses (2017)

The innate inflammatory response must be tightly regulated to ensure effective immune protection. NF-κB is a key mediator of the inflammatory response, and its dysregulation has been associated with immune-related malignancies. Here, we describe a miRNA-based regulatory network that enables precise NF-κB activity in mouse macrophages. Elevated miR-155 expression potentiates NF-κB activity in miR-146a-deficient mice, leading to both an overactive acute inflammatory response and chronic inflammation. Enforced miR-155 expression overrides miR-146a-mediated repression of NF-κB activation, thus emphasizing the dominant function of miR-155 in promoting inflammation. Moreover, miR-155-deficient macrophages exhibit a suboptimal inflammatory response when exposed to low levels of inflammatory stimuli. Importantly, we demonstrate a temporal asymmetry between miR-155 and miR-146a expression during macrophage activation, which creates a combined positive and negative feedback network controlling NF-κB activity. This miRNA-based regulatory network enables a robust yet time-limited inflammatory response essential for functional immunity.MicroRNAs (miR) are important regulators of gene transcription, with miR-155 and miR-146a both implicated in macrophage activation. Here the authors show that NF-κB signalling, miR-155 and miR-146a form a complex network of cross-regulations to control gene transcription in macrophages for modulating inflammatory responses.
A New Maximum Efficiency Point Tracking Technique for Digital Power Converter with Dual Parameters Control (2018)

This paper proposes a new maximum efficiency point tracking (MEPT) technique that will achieve the highest efficiency for DC-DC converters by automatically tracking converter efficiency while changing the switching frequency and dead-time control parameters. This new technique helps identify optimal values of each parameter at different power levels. In this paper, the developed MEPT technique is theoretically analyzed and practically verified. The experiment is set up based on a 120W Cascaded Buck-Boost converter, controlled by a centralized digital-signal processor (DSP). It will be shown that the expected theoretical and experimental results are in close agreement with each other.
514: “Cool” and “Hot” Receptor MRNA in the Rat and Human Genitourinary Tract (2004)

INTRODUCTION AND OBJECTIVE: The urethra has both proximal smooth muscle and mid urethral striated muscle (MUSM)components with different innervations and neurotransmitters. Which sphincter is more important to guard against stress urinary incontinence (SUI)? We provide data that separate slow tonic and quick phasic components of the urethral continence reflexes.
Spleen tyrosine kinase inhibition is an effective treatment for established vasculitis in a pre-clinical model (2020)

The anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) are a group of life-threatening multi-system diseases characterized by necrotising inflammation of small blood vessels and crescentic glomerulonephritis. ANCA are thought to play a direct pathogenic role. Previous studies have shown that spleen tyrosine kinase (SYK) is phosphorylated during ANCA-induced neutrophil activation in vitro. However, the role of SYK in vivo is unknown. Here, we studied its role in the pathogenesis of experimental autoimmune vasculitis, a pre-clinical model of myeloperoxidase-ANCA-induced pauci-immune systemic vasculitis in the Wistar Kyoto rat. Up-regulation of SYK expression in inflamed renal and pulmonary tissue during early autoimmune vasculitis was confirmed by immunohistochemical and transcript analysis. R406, the active metabolite of fostamatinib, a small molecule kinase inhibitor with high selectivity for SYK, inhibited ANCA-induced pro-inflammatory responses in rat leucocytes in vitro. In an in vivo study, treatment with fostamatinib for 14 days after disease onset resulted in rapid resolution of urinary abnormalities, significantly improved renal and pulmonary pathology, and preserved renal function. Short-term exposure to fostamatinib did not significantly affect circulating myeloperoxidase-ANCA levels, suggesting inhibition of ANCA-induced inflammatory mechanisms in vivo. Finally, SYK expression was demonstrated within inflammatory glomerular lesions in ANCA-associated glomerulonephritis in patients, particularly within CD68<sup>+</sup>ve monocytes/macrophages. Thus, our data indicate that SYK inhibition warrants clinical investigation in the treatment of AAV.
Comparison of the Uptake of Dioxin-Like Compounds by Caged Channel Catfish and Semipermeable Membrane Devices in the Saginaw River, Michigan (1996)

Elevated concentrations of planar, halogenated hydrocarbons have been linked to reproductive problems in a variety of fish-eating birds and mammals in the Great Lakes and in particular Saginaw Bay. Currently, there are no accurate procedures to assess bioavailability of these contaminants. Polychlorinated dibenzo-p-dioxins and dibenzofurans and mono- and non-ortho-chloro-substituted biphenyls in water at the femtogram to picogram per liter range were passively concentrated in semipermeable membrane devices (SPMDs), and these data were compared to the bioconcentration in co-exposed (caged) channel catfish. Sediment-derived water concentration estimates, calculated from a steady-state partitioning model, did not correlate well to those derived from either fish or SPMDs. The use of SPMDs demonstrated the utility of in-situ passive sampling over inference of water concentrations from accumulation in biota or partitioning with sediment. Residues ac cumulated by SPMDs have been shown to be proportional to analyte water concentration, whereas this does not appear to be the case for fish tissues. The greater amounts of 3,3',4,4'-tetrachlorobiphenyl and 2,3,7,8-tetrachlorodibenzofuran accumulated in SPMDs than in exposed channel catfish indicated those non-passive aspects of bioconcentration in organisms, such as biotransformation and elimination, introduced 50−500% error in the assumed degree of exposure.
An acoustic technique to assess particle distribution following transcutaneous needle-free injection (2006)

Needle-free injection is a novel technique enabling pain-free transdermal drug and vaccine delivery. The present work aims at developing a noninvasive, ultrasonic technique to assess distribution of drug particles delivered in this manner beneath an optically opaque layer, such as the skin. Drug particles are modeled as a monodisperse distribution of 50-μm polystyrene spheres that are injected into an agar-based tissue-mimicking material, which they penetrate to a mean depth of 500 μm. A 15-MHz broadband focused immersion transducer, driven in pulse-echo mode, was used to scan the surface of the agar phantom. By assuming that the mean-squared voltage of the received waveform is proportional to the number of particles encountered by the incident pulse, a 3-D map of particle distribution was generated. The resulting acoustic microscopy data were validated by examining phantom slices of thickness similar to the acoustic pulse length under a conventional optical microscope. The acoustic technique was found to provide a good prediction of the mean particle penetration depth and an accurate map of transverse particle distribution in planes normal to the direction of injection. It thus shows great promise as a noninvasive means of assessing the efficacy of needle-free injection, both in vitro and in vivo.