gebhart/patrepeval huggingface dataset:
Molecular clustering identifies complement and endothelin induction as early events in a mouse model of glaucoma (2011)

Glaucoma is one of the most common neurodegenerative diseases. Despite this, the earliest stages of this complex disease are still unclear. This study was specifically designed to identify early stages of glaucoma in DBA/2J mice. To do this, we used genome-wide expression profiling of optic nerve head and retina and a series of computational methods. Eyes with no detectable glaucoma by conventional assays were grouped into molecularly defined stages of disease using unbiased hierarchical clustering. These stages represent a temporally ordered sequence of glaucoma states. We then determined networks and biological processes that were altered at these early stages. Early-stage expression changes included upregulation of both the complement cascade and the endothelin system, and so we tested the therapeutic value of separately inhibiting them. Mice with a mutation in complement component 1a (C1qa) were protected from glaucoma. Similarly, inhibition of the endothelin system with bosentan, an endothelin receptor antagonist, was strongly protective against glaucomatous damage. Since endothelin 2 is potently vasoconstrictive and was produced by microglia/macrophages, our data provide what we believe to be a novel link between these cell types and vascular dysfunction in glaucoma. Targeting early molecular events, such as complement and endothelin induction, may provide effective new treatments for human glaucoma.
The Web of Augmented Physical Objects (2005)

This article investigates the growing complexity and connectivity between two former separated interaction spaces - the real and the virtual world. It is our attempt to augment the physical world to a world of digitally augmented objects. Moreover we are looking at real products tagged with digital communication units like embedded systems or the RFID technology. To understand these impacts we need to identify the different levels of connectivity between real and virtual worlds and therefore the relationship of a product with its digital counterpart. As a point of departure we define the terms medium and agent to get a theoretical view on the associations in the real and virtual world. We identify the digital identification of virtually enhanced products as a main part for the creation of a new networked physical world where real products are heavily connected to and with their digital counterparts.
CYP2W1 (cytochrome P450, family 2, subfamily W, polypeptide 1) (2011)

Review on CYP2W1 (cytochrome P450, family 2, subfamily W, polypeptide 1), with data on DNA, on the protein encoded, and where the gene is implicated.
Synthesis of a C-Glycoside Analogue of -D-Galactosyl Hydroxynorvaline and Its Use in Immunological Studies (2000)

A C-linked isostere of β-D-galactosylated hydroxynorvaline has been prepared in eight steps from per-O-benzylated galactopyranolactone. Addition of a homoallylic Grignard reagent to the lactone, reduction of the resulting hemiacetal with triethylsilane, and a Wittig reaction with Garner's aldehyde were key steps in this synthesis. The C-linked building block was then incorporated at position 264 into the fragment CII(256–270) from type II collagen by solid-phase synthesis using a combination of the tert-butoxycarbonyl (Boc) and 9-fluorenylmethoxycarbonyl (Fmoc) protective group strategies. Deprotection of the benzylated C-linked galactosyl moiety was achieved simultaneously with cleavage of the glycopeptide from the solid phase by using triethylsilyl trifluoromethanesulfonate in TFA. Helper T-cell hybridomas obtained in a mouse model for rheumatoid arthritis responded to the C-linked glycopeptide when presented by class II MHC molecules. However, 10- to 20-fold higher concentrations were required as compared to when O-linked β-D-galactosylated hydroxynorvaline or hydroxylysine (Hyl) were present at position 264 of CII(256–270). Thus, replacement of a single oxygen atom by a methylene group in the carbohydrate moiety of a glycopeptide antigen had a substantial influence on the T-cell response. This reveals that T cells are able to recognize the carbohydrate moiety of glycopeptide antigens with high specificity. Finally, the results suggest that structural modifications of β-D-Gal-Hyl264 in CII(256–270) may give altered peptide ligands that can be used for induction of tolerance in autoimmune rheumatoid arthritis.
Critical Evaluation of Use of the Procedure of Superpave Volumetric Mixture Design for Modified Binders (2005)

This study examined the possible interference of modified binders with the standard procedure of Superpave® volumetric mixture design. Sensitivity of volumetric properties and moisture damage performance were evaluated with four binders modified with and without polymeric additives. The study focused on effects of compaction temperatures and vertical pressure on densification of mixtures and on effects of compaction temperatures on moisture damage. The zero shear viscosity concept was used to estimate acceptable mixing and compaction temperatures. The compaction energy index was used to study changes in compaction effort, and cohesion and adhesion of binders were measured to study moisture damage potential. Results indicated that temperature effects were somewhat marginal and that unless temperatures were reduced to below 80°C, effects on volumetric properties were rather small. It was also found that using a target zero shear viscosity of 1.5 Pa·s for mixing and 3.0 Pa·s for compaction could provide reasonable compaction temperatures for binders used in this study. Varying vertical stress used in the gyratory compactor showed significant effects on volumetric properties. Changing pressure from 600 kPa to 300 kPa resulted in 3.0% to 4.0% increase in air voids, more significant than changing viscosity by more than 10 times. It is postulated that the focus on keeping temperature high during compaction in the lab and in the field might be unfounded. Moisture damage does not appear to be affected significantly by the variation in binder viscosity profiles for the binders and aggregates used in this study. Because of the limited sample size, more work is needed in this area to study the effect of mixing and compaction temperatures on moisture damage.
DAGsim: Simulation of DAG-based distributed ledger protocols. (2018)

Scalability of distributed ledgers is a key adoption factor. As an alternative to blockchain-based protocols, directed acyclic graph (DAG) protocols are proposed with the intention to allow a higher volume of transactions to be processed. However, there is still limited understanding of the behaviour and security considerations of DAG-based systems. We present an asynchronous, continuous time, and multi-agent simulation framework for DAG-based cryptocurrencies. We model honest and semi-honest actors in the system to analyse the behaviour of one specific cryptocurrency, IOTA. Our simulations show that the agents that have low latency and a high connection degree have a higher probability of having their transactions accepted in the network with honest and semi-honest strategies. Last, the simulator is built with extensibility in mind. We are in the process of implementing SPECTRE as well as including malicious agents.
Association between mutations in gyrA and parC genes of Acinetobacter baumannii clinical isolates and ciprofloxacin resistance. (2015)

Simultaneous mutations in gyrA and parC genes are expected to play a major role in high-level fluoroquinolone resistance in A. baumannii; albeit a single mutation in DNA topoisomerase IV could occasionally be associated with intermediate-resistance to these antimicrobials.
Processing and characterization of halloysite nanotubes filled polypropylene nanocomposites based on a masterbatch route: effect of halloysites treatment on structural and mechanical properties (2011)

Halloysites/polypropylene nanocomposites with different nanotubes contents were prepared by diluting a masterbatch containing 30 wt.% halloysites with polypropylene (PP). Unmodified (HNTs) and quaternary ammonium salt treated (QM-HNTs) halloysite nanotubes were used. Both degree of crystallinity and crystallization temperature increase upon addition of halloysites into PP, thus indicating a potential nucleation effect induced by the nanotubes. An homogeneous distribution and dispersion of nanotubes was observed throughout the PP matrix, with a slightly better dispersion in the case of modified QM-HNTs compared to unmodified HNTs. Mechanical tests in tension, bending and notched impact demonstrated that strength and modulus of the nanocomposites significantly increase with addition of halloysites without significant loss of ductility. An halloysite content of 6 wt.% appears as an optimum. Modified halloysites (QM-HNTs) lead to globally better performances due to strong interfacial interaction between the polymer matrix and the nanotubes.
Inflammatory agents regulate <i>in vivo</i> expression of fractalkine in endothelial cells of the rat heart (1999)

Fractalkine is distinguished structurally from other chemokines in that it contains a mucin-like stalk that tethers a CX3C chemokine module to a transmembrane-spanning region; its expression in cultured endothelial cells has been shown to be up-regulated by tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1). The purpose of this study was to determine whether fractalkine is expressed, in a proinflammatory agent-regulated manner, by cardiac endothelial cells in vivo. Steady state levels of fractalkine mRNA were increased in rat cardiac tissues after in vivo treatment with lipopolysaccharide (LPS), IL-1, or TNF-alpha. In situ hybridization and immunohistochemical analysis revealed that endothelial cells of the coronary vasculature and endocardium were the principal source of proinflammatory agent-inducible fractalkine, although some fractalkine immunoreactivity was also found on the myocytes. These data are the first demonstration of in vivo cardiac endothelial cell fractalkine expression and regulation by proinflammatory agents such as LPS, IL-1, or TNF-alpha. Cardiac endothelial cell-expressed fractalkine may contribute to the influx of leukocytes into the heart during inflammation.
Novel digital integrator and differentiator (1993)

A novel digital integrator and a novel digital differentiator are presented. Both the integrator and the differentiator are of first order and thus eminently suitable for real-time applications. Both have an almost linear phase. The integrator is obtained by interpolationg two popular digital integration techniques, the rectangular and the trapezoidal rules. The resulting integrator outperforms both the rectangular and the trapezoidal integrators in range and accuracy. The new differentiator is obtained by taking the inverse of the transfer function of the integrator. The effective range of the differentiator is about 0.8 of the Nyquist frequency.
Learned Image Compression with Discretized Gaussian Mixture Likelihoods and Attention Modules (2020)

Image compression is a fundamental research field and many well-known compression standards have been developed for many decades. Recently, learned compression methods exhibit a fast development trend with promising results. However, there is still a performance gap between learned compression algorithms and reigning compression standards, especially in terms of widely used PSNR metric. In this paper, we explore the remaining redundancy of recent learned compression algorithms. We have found accurate entropy models for rate estimation largely affect the optimization of network parameters and thus affect the rate-distortion performance. Therefore, in this paper, we propose to use discretized Gaussian Mixture Likelihoods to parameterize the distributions of latent codes, which can achieve a more accurate and flexible entropy model. Besides, we take advantage of recent attention modules and incorporate them into network architecture to enhance the performance. Experimental results demonstrate our proposed method achieves a state-of-the-art performance compared to existing learned compression methods on both Kodak and high-resolution datasets. To our knowledge our approach is the first work to achieve comparable performance with latest compression standard Versatile Video Coding (VVC) regarding PSNR. More importantly, our approach generates more visually pleasant results when optimized by MS-SSIM. This project page is at this https URL https://github.com/ZhengxueCheng/Learned-Image-Compression-with-GMM-and-Attention
Intramolecular competition between histidine and methionine side chains in reactions of dipeptides with [Pt(en)(H2O)2]2+ (en = H2NCH2CH2NH2) (1997)

The pH- and time-dependent reactions of [Pt(en)(H2O)2]2+ (en = H2NCH2CH2NH2) with the histidylmethionine dipeptides cyclo(-his-met-), his-Hmet and met-Hhis at 313 K have been studied by ion-pairing reversed-phase HPLC and 1H and 195Pt NMR spectroscopy. Quantitative formation of the unusually large 12-membered chelate ring in the remarkably inert complex [Pt(en){cyclo(-his-met-)}]2+ is complete within a few minutes. A base-catalysed configuration inversion for one of the diketopiperazine α-C atoms at pH > 9 leads to the observation of two well separated HPLC fractions for both the prevailing κ2N′met,S co-ordinated species and the peptide itself. An analogous likewise kinetically stable macrochelate is present after 14 d as a major species in the [Pt(en)(H2O)2]2+–his-Hmet reaction mixture over the whole range 3.2 < pH < 11.2. Time-dependent HPLC indicated that a kinetically favoured κ2O,S chelate is rapidly formed at pH 4.55 only slowly to convert into competitive S-bound complexes with κ2N1,S and κ2N′met,S co-ordination. After reaching a quasi-stationary state (50 h), amide N′met anchoring in the latter species facilitates co-ordination of the adjacent amino nitrogen to afford the thermodynamically preferred κ2N (amino),N′met chelate. At a 2∶1 molar ratio, slow reaction of the macrochelate with a second (en)PtII fragment led to formation of [{Pt(en)}2(hisH–1-Hmet-1κ2N,N3∶2κ2N1,S)]3+. In met-Hhis, κ2N (amino),S chelation is kinetically and thermodynamically preferred in acid solution. At pH 9.6, however, sulfur binding is thermodynamically unfavourable, and the initially formed κ2N (amino),S complex slowly converts into a κ2N (amino),N′his species, which subsequently affords [Pt(en-κN){met-his-κ3N (amino),N′his,N3}]+ on cleavage of the Pt–N (en) bond trans to the amino N atom.
An Automatic Hybrid Method for Retinal Blood Vessel Extraction (2008)

An Automatic Hybrid Method for Retinal Blood Vessel Extraction The extraction of blood vessels from retinal images is an important and challenging task in medical analysis and diagnosis. This paper presents a novel hybrid automatic approach for the extraction of retinal image vessels. The method consists in the application of mathematical morphology and a fuzzy clustering algorithm followed by a purification procedure. In mathematical morphology, the retinal image is smoothed and strengthened so that the blood vessels are enhanced and the background information is suppressed. The fuzzy clustering algorithm is then employed to the previous enhanced image for segmentation. After the fuzzy segmentation, a purification procedure is used to reduce the weak edges and noise, and the final results of the blood vessels are consequently achieved. The performance of the proposed method is compared with some existing segmentation methods and hand-labeled segmentations. The approach has been tested on a series of retinal images, and experimental results show that our technique is promising and effective.
Kinetics of myeloid progenitor cells in human micro long-term bone marrow cultures. (1988)

Hemopoiesis was analyzed in a miniaturized long-term culture of human bone marrow cells by quantifying the production of granulocyte-macrophage progenitor cells. As in the conventional long-term culture system, hemopoiesis was dependent on the presence of a marrow-derived adherent layer. Adipocytes proved to be essential for long-term proliferation. Optimal growth conditions were maintained by incubation in McCoy's medium supplemented with hydrocortisone, fetal calf serum, and horse serum. When calculated back to the volume of conventional cultures, the numbers and kinetics of nucleated cells and granulocyte-macrophage colony-forming cells were comparable in both culture systems. The microsystem is therefore suitable for performing multiple analyses on small samples of cells.
Oxathiaphospholane Approach to the Synthesis of P-Chiral, Isotopomeric Deoxy(ribonucleoside phosphorothioate)s and Phosphates Labeled with an Oxygen Isotope (2001)

Diastereomerically pure and isotopically labeled 5'-O-DMT-nucleoside-3'-O-(2-thio- and -oxo-4,4-"spiro"-pentamethylene-1,3,2-[<sup>18</sup> O]oxathiaphospholane)s were used for stereocontrolled synthesis of P-chiral, isotopically labeled oligonucleotide phosphorothioates and phosphates, as well as "chimeric" PS<sup>18</sup> O/P<sup>18</sup> O oligomers without loss of isotope enrichment. DBU=1,8-diazabicyclo[5.4.0]undec-7-ene, DMT=4,4'-dimethoxytrityl, ROH=3'-O-acetylthymidine, Bz=benzoyl.
Constructing de Novo Biosynthetic Pathways for Chemical Synthesis inside Living Cells (2011)

Living organisms have evolved a vast array of catalytic functions that make them ideally suited for the production of medicinally and industrially relevant small-molecule targets. Indeed, native metabolic pathways in microbial hosts have long been exploited and optimized for the scalable production of both fine and commodity chemicals. Our increasing capacity for DNA sequencing and synthesis has revealed the molecular basis for the biosynthesis of a variety of complex and useful metabolites and allows the de novo construction of novel metabolic pathways for the production of new and exotic molecular targets in genetically tractable microbes. However, the development of commercially viable processes for these engineered pathways is currently limited by our ability to quickly identify or engineer enzymes with the correct reaction and substrate selectivity as well as the speed by which metabolic bottlenecks can be determined and corrected. Efforts to understand the relationship among sequence, structure, and function in the basic biochemical sciences can advance these goals for synthetic biology applications while also serving as an experimental platform for elucidating the in vivo specificity and function of enzymes and reconstituting complex biochemical traits for study in a living model organism. Furthermore, the continuing discovery of natural mechanisms for the regulation of metabolic pathways has revealed new principles for the design of high-flux pathways with minimized metabolic burden and has inspired the development of new tools and approaches to engineering synthetic pathways in microbial hosts for chemical production.
Antitumor effects of hyaluronic acid inhibitor 4-methylumbelliferone in an orthotopic hepatocellular carcinoma model in mice (2011)

Liver cirrhosis is characterized by an excessive accumulation of extracellular matrix components, including hyaluronan (HA). In addition, cirrhosis is considered a pre-neoplastic disease for hepatocellular carcinoma (HCC). Altered HA biosynthesis is associated with cancer progression but its role in HCC is unknown. 4-Methylumbelliferone (4-MU), an orally available agent, is an HA synthesis inhibitor with anticancer properties. In this work, we used an orthotopic Hepa129 HCC model established in fibrotic livers induced by thioacetamide. We evaluated 4-MU effects on HCC cells and hepatic stellate cells (HSCs) in vitro by proliferation, apoptosis and cytotoxicity assays; tumor growth and fibrogenesis were also analyzed in vivo. Our results showed that treatment of HCC cells with 4-MU significantly reduced tumor cell proliferation and induced apoptosis, while primary cultured hepatocytes remained unaffected. 4-MU therapy reduced hepatic and systemic levels of HA. Tumors systemically treated with 4-MU showed the extensive areas of necrosis, inflammatory infiltrate and 2-3-fold reduced number of tumor satellites. No signs of toxicity were observed after 4-MU therapy. Animals treated with 4-MU developed a reduced fibrosis degree compared with controls (F1-2 vs F2-3, respectively). Importantly, 4-MU induced the apoptosis of HSCs in vitro and decreased the amount of activated HSCs in vivo. In conclusion, our results suggest a role for 4-MU as an anticancer agent for HCC associated with advanced fibrosis.
Enantioselective Organocatalytic α-Fluorination of Cyclic Ketones (2011)

The first highly enantioselective α-fluorination of ketones using organocatalysis has been accomplished. The long-standing problem of enantioselective ketone α-fluorination via enamine activation has been overcome via high-throughput evaluation of a new library of amine catalysts. The optimal system, a primary amine functionalized Cinchona alkaloid, allows the direct and asymmetric α-fluorination of a variety of carbo- and heterocyclic substrates. Furthermore, this protocol also provides diastereo-, regio-, and chemoselective catalyst control in fluorinations involving complex carbonyl systems.
Intracellular localization of human monocyte associated interleukin 1 (IL 1) activity and release of biologically active IL 1 from monocytes by trypsin and plasmin. (1986)

The production of interleukin (IL 1) by normal human peripheral blood monocytes purified by Ficoll-Hypaque density sedimentation, Percoll-gradient sedimentation, and plastic adherence can be detected as early as 30 min intracellularly, and extracellularly within 1 hr after stimulation with lipopolysaccharide (LPS). Production of mRNA coding for the isoelectric point 7.0 species of IL 1 was also detected as early as 1 hr after LPS stimulation and reached a maximum level at 6 hr. Cell-associated IL 1 activity could be extracted with CHAPS detergent from every cell fraction (i.e., membranes, cytosol, and particulates), but was present mainly (greater than 95%) in the cytosol of LPS-activated monocytes and the myelomonocytic cell line, THP-1. The apparent m.w. of IL 1 activity on high pressure liquid chromatography gel filtration in every cell fraction was approximately 23,000 daltons, with a minor peak at 31,000 daltons, whereas the IL 1 activity in the culture supernatants was 17,000 daltons. Western blotting analysis of LPS-stimulated monocyte extracts showed two forms of IL 1 corresponding to 31,000 daltons and 25,000 daltons. Exposure of viable cells to trypsin and plasmin released biologically active 23,000 dalton IL 1 only from IL 1-producing cells such as activated monocytes and IL 1-producing Ebstein-Barr virus B lymphocyte cell lines. Consequently, biologically active IL 1 is presumably exposed on the outer surface of cell membranes. Furthermore, IL 1 release by human monocytes in plasminogen-depleted fetal calf serum was considerably decreased. Conversely, supplementation of plasminogen-depleted serum with purified plasminogen restored the IL 1 production, suggesting that plasmin or plasmin-like factors may be involved in the regulation of the release of IL 1 from IL 1-producing cells. In conclusion, the results suggest that IL 1 is rapidly produced, is pooled in the cytosol, and in part is processed by enzymes, is transferred to the plasma membranes, and is then released from the cells. Tissue plasminogen activator and serum enzymes such as plasmin may therefore be involved in the release of IL 1 from IL 1-producing cells.