gebhart/patrepeval huggingface dataset:
[Treatment of multiple sclerosis. The present and the future. Study Group on Diagnosis and Therapy of Multiple Sclerosis]. (1999)

The last years have produced a plethora of new information including extensive studies, retrospective analysis and new perspectives on data interpretation on multiple sclerosis (MS) treatment. Considering how difficult it is to study a disease such MS with its variability, unpredictability and duration, it seems hard to resemble definite results from this experience. However, corticosteroids have been the mainstay of treatment for the management of acute relapses, showing the capacity to shorten the duration of relapses, accelerate the recovery. At present, interferon beta is generally considered to be the treatment of choice for patients with relapsing remitting disease. Glatiramer acetate is still not available in many parts of Europe, but its results demonstrate a reduction of relapses in 30% of cases. Most European experts only consider as alternative treatment the immunosuppressive drugs, chosen if patients demonstrate unacceptable side effects of interferon or clearly do not respond. Very different and even more confusing data still come from experimental trial in secondary progressive MS, where the target of treatment is to slow the progression of disability. Different drugs (methotrexate, mitoxantrone, linomide, steroids and even interferons) are employed, but the results are still debated. Future therapies are being derived from constantly changing and evolving concept of MS immunopathogenesis: therefore many experimental and clinical trials use anti-integrin antibodies or insulin growth factors, metallo-proteinase inhibitors or T-cell vaccination. Some of the above treatment may have a chance of producing the gaining control of the disease without much inner toxicity.
Angiopoietin-1 preconditioning enhances survival and functional recovery of mesenchymal stem cell transplantation (2012)

Ang1 preconditioning enhances MSC survival, contributing to further improvement of heart function.
Ultrafast optical ranging using microresonator soliton frequency combs (2018)

Light detection and ranging is widely used in science and industry. Over the past decade, optical frequency combs were shown to offer advantages in optical ranging, enabling fast distance acquisition with high accuracy. Driven by emerging high-volume applications such as industrial sensing, drone navigation, or autonomous driving, there is now a growing demand for compact ranging systems. Here, we show that soliton Kerr comb generation in integrated silicon nitride microresonators provides a route to high-performance chip-scale ranging systems. We demonstrate dual-comb distance measurements with Allan deviations down to 12 nanometers at averaging times of 13 microseconds along with ultrafast ranging at acquisition rates of 100 megahertz, allowing for in-flight sampling of gun projectiles moving at 150 meters per second. Combining integrated soliton-comb ranging systems with chip-scale nanophotonic phased arrays could enable compact ultrafast ranging systems for emerging mass applications.
Molecular Control of Cell Fate in the Neural Crest: The Sympathoadrenal Lineage (1993)

Over the past five years, new insights have been gained into the biology of the SA lineage. These advances have been powered by the development of immunologic methods to isolate embryonic SA progenitors from fetal adrenal glands and sympathetic ganglia. Analysis of these embryonic progenitors has confirmed many of the ideas derived from earlier studies of postnatal cells, but has necessitated several revisions in our thinking, as well. First, embryonic SA progenitors appear to be distinct from mature SIF cells, a cell type initially postulated to be the central intermediate in the SA lineage. Second, FGF, not NGF, appears to be an important early influence on neuronal fate; NGF responsiveness appears relatively late in differentiation. Third, the development of both sympathetic neurons and adrenal chromaffin cells is not a one-step process, but rather involves a series of events, in which the cells change their responsiveness to growth factors and glucocorticoids. Fourth, emerging circumstantial evidence suggests that SA progenitors may have additional developmental potentials. Finally, new insights have been gained into the molecular mechanisms that underlie both the differentiation of SA progenitors and their determination from earlier multipotent neural crest cells. These advances have made the SA progenitor a well-defined system for studying the molecular control of cell fate in a vertebrate neurogenic precursor cell. The analysis of the SA lineage at the cell biological level has raised several interesting molecular questions for future investigation. In the neuronal branch of the SA lineage, how is the acquisition of NGF-responsiveness and NGF-dependence controlled, and what is the relationship of these events to the expression of p140trk and p75? In the chromaffin branch of the pathway, which molecules control the timing of PNMT expression? In the uncommitted SA progenitor, what is the molecular basis of the antagonism between the competing neuronal and chromaffin pathways of differentiation, and how does commitment to neuronal differentiation occur? Can SA progenitors differentiate to enteric neurons in vitro, and which differentiation and survival factors control this phenotype, as well as the other classical neurotransmitter and neuropeptide phenotypes expressed by SA derivatives? What are the roles of MASH1 and other regulatory genes in controlling early stages in neural crest cell determination, and how is the expression of these molecules in turn controlled? How much of the genetic regulatory network controlling neuronal differentiation in Drosophila has been conserved in vertebrates?(ABSTRACT TRUNCATED AT 400 WORDS)
Product and mechanistic studies of the anodic oxidation of methoxylated naphthalenes. The EECrCp mechanism (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProduct and mechanistic studies of the anodic oxidation of methoxylated naphthalenes. The EECrCp mechanismMark G. Dolson and John S. SwentonCite this: J. Am. Chem. Soc. 1981, 103, 9, 2361–2371Publication Date (Print):May 1, 1981Publication History Published online1 May 2002Published inissue 1 May 1981https://pubs.acs.org/doi/10.1021/ja00399a037https://doi.org/10.1021/ja00399a037research-articleACS PublicationsRequest reuse permissionsArticle Views772Altmetric-Citations55LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
The Basis of Natural and Artificial Postzygotic Hybridization Barriers in Arabidopsis Species (2003)

The success or failure of interspecific crosses is vital to evolution and to agriculture, but much remains to be learned about the nature of hybridization barriers. Several mechanisms have been proposed to explain postzygotic barriers, including negative interactions between diverged sequences, global genome rearrangements, and widespread epigenetic reprogramming. Another explanation is imbalance of paternally and maternally imprinted genes in the endosperm. Interspecific crosses between diploid Arabidopsis thaliana as the seed parent and tetraploid Arabidopsis arenosa as the pollen parent produced seeds that aborted with the same paternal excess endosperm phenotype seen in crosses between diploid and hexaploid A. thaliana. Doubling maternal ploidy restored seed viability and normal endosperm morphology. However, substituting a hypomethylated tetraploid A. thaliana seed parent reestablished the hybridization barrier by causing seed abortion and a lethal paternal excess phenotype. We conclude from these findings that the dominant cause of seed abortion in the diploid A. thaliana x tetraploid A. arenosa cross is parental genomic imbalance. Our results also demonstrate that manipulation of DNA methylation can be sufficient to erect hybridization barriers, offering a potential mechanism for speciation and a means of controlling gene flow between species.
Magnetic‐Field‐Induced Growth of Single‐Crystalline Fe3O4 Nanowires (2004)

Single‐crystalline nanowires of Fe 3 O 4 hydrothermally synthesized under a magnetic field are reported. The square and hexagonal crystals formed in zero applied field are shown to give way to nanowires as the magnetic field is increased. The Figure shows the situation for a 0.25 T field. The structure and magnetic properties are characterized by transmission electron microscopy, X‐ray and electron diffraction, and magnetometry.
Is Oxidative Stress the Pathogenic Mechanism Underlying Insulin Resistance, Diabetes, and Cardiovascular Disease? The Common Soil Hypothesis Revisited (2004)

Type 2 diabetes is a worldwide increasing disease resulting from the interaction between a subject's genetic makeup and lifestyle. In genetically predisposed subjects, the combination of excess caloric intake and reduced physical activity induces a state of insulin resistance. When beta cells are no longer able to compensate for insulin resistance by adequately increasing insulin production, impaired glucose tolerance appears, characterized by excessive postprandial hyperglycemia. Impaired glucose tolerance may evolve into overt diabetes. These 3 conditions, ie, insulin resistance, impaired glucose tolerance, and overt diabetes, are associated with an increased risk of cardiovascular disease. Because all these conditions are also accompanied by the presence of an oxidative stress, this article proposes oxidative stress as the pathogenic mechanism linking insulin resistance with dysfunction of both beta cells and endothelium, eventually leading to overt diabetes and cardiovascular disease. This hypothesis, moreover, may also contribute to explaining why treating cardiovascular risk with drugs, such as calcium channel blockers, ACE inhibitors, AT-1 receptor antagonists, and statins, all compounds showing intracellular preventive antioxidant activity, results in the onset of new cases of diabetes possibly being reduced.
53.2: Distinguished Paper : Novel Laser Transfer Technology for Manufacturing Large‐Sized OLED Displays (2007)

Abstract A novel laser transfer technology has been developed for manufacturing large‐Sized organic light emitting diode (OLED) displays. OLED materials are transferred from glass donors to a substrate by laser‐induced pattern‐wise sublimation (LIPS). RGB pixels are precisely patterned by LIPS. The LIPS OLED device performance has been examined in comparison with conventional evaporated device. Using this technology, we have fabricated a 27.3‐inch active matrix OLED display.
INTERLEUKIN-6: From Basic Science to Medicine—40 Years in Immunology (2004)

This essay summarizes my 40 years of research in immunology. As a young physician, I encountered a patient with Waldenström's macroglobulinemia, and this inspired me to study the structure of IgM. I began to ask how antibody responses are regulated. In the late 1960s, the essential role of T cells in antibody production had been reported. In search of molecules mediating T cell helper function, I discovered activities in the culture supernatant of T cells that induced proliferation and differentiation of B cells. This led to my life's work: studying one of those factors, interleukin-6 (IL-6). To my surprise, IL-6 turned out to play additional roles, including myeloma growth factor and hepatocyte-stimulating factor activities. More importantly, it was involved in a number of diseases, such as rheumatoid arthritis and Castleman's disease. I feel exceptionally fortunate that my work not only revealed the framework of cytokine signaling, including identification of the IL-6 receptor, gp130, NF-IL6, STAT3, and SOCS-1, but also led to the development of a new therapy for chronic inflammatory diseases.
Biochemical and Cellular Profile of NIK Inhibitors with Long Residence Times (2020)

Two different signaling pathways lead to the activation of the transcription factor NF-κB, initiating distinct biological responses: The canonical NF-κB pathway activation has been implicated in host immunity and inflammatory responses, whereas the noncanonical pathway activation has been involved in lymphoid organ development and B-cell maturation, as well as in the development of chronic inflammatory diseases and some hematologic cancers. The NF-κB-inducing kinase (NIK) is a cytoplasmic Ser/Thr kinase and is a key regulator of the noncanonical pathway. NIK activation results in the processing of the p100 subunit to p52, leading to the formation of the RelB/p52 complex and noncanonical pathway activation. Because of its role in the development of lymphoid malignancies, this kinase has always been considered as an attractive target for the treatment of certain types of cancers and immune diseases. We at Takeda have pursued a drug discovery program to identify small-molecule inhibitors against NIK. This report provides an overview of the data generated from our screening campaign using a small fragment library. Most importantly, we also provide a kinetic analysis of published compounds and chemical series developed at Takeda that are associated with a slow tight-binding mechanism and excellent cellular potency.
Structural heterogeneity of the noncollagenous domain of basement membrane collagen. (1988)

The noncollagenous domain of collagen from three different basement membranes of bovine origin (glomerular, lens capsule, and placental) was excised with bacterial collagenase, purified under nondenaturing conditions, and characterized. In each case the domain existed as a hexamer comprised of four distinct subunits (alpha 1 (IV) NC1, alpha 2 (IV) NC1, M2*, and M3). Each subunit exists in both monomeric and dimeric (disulfide-cross-linked) forms. Certain dimers also exist which contain nonreducible cross-links. The hexamers from the three membranes differ with respect to stoichiometry of subunits and subunit isoforms and to the degree of cross-linking of monomers into dimers. The minor subunits, M2* and M3, vary in quantity over a 20-fold range relative to the major ones among the three hexamers. The results indicate that: 1) at least two populations of triple-helical collagen molecules, differing in chain composition, exist in each membrane and that their relative proportions are tissue-specific; and 2) the chemical nature of the noncollagenous domain of these populations is tissue-specific with regard to subunit isoforms and relative proportion of reducible and nonreducible cross-links in dimers. A novel structural feature of the noncollagenous domain of basement membrane collagen was also evinced from these studies. Namely, that each of the four monomeric subunits exists in charge isoforms.
Rage: A Novel Cellular Receptor for Advanced Glycation End Products (1996)

Exposure of proteins to reducing sugars results in nonenzymatic glycation with the ultimate formation of advanced glycation end products (AGEs). One means through which AGEs modulate cellular functions is through binding to specific cell surface acceptor molecules. The receptor for AGEs (RAGE) is such a receptor and is a newly identified member of the immunoglobulin superfamily expressed on endothelial cells (ECs), mononuclear phagocytes (MPs), and vascular smooth muscle cells (SMCs) in both vivo and in vitro. Binding of AGEs to RAGE results in induction of cellular oxidant stress, as exemplified by the generation of thiobarbituric acid-reactive substances, expression of heme oxygenase type I, and activation of the transcription factor NF-kB, with consequences for a range of cellular functions. AGEs on the surface of diabetic red cells enhance binding to endothelial RAGE and result in enhanced oxidant stress in the vessel wall. By using reagents to selectively block access to RAGE, the role of this receptor in AGE-mediated perturbation of cellular properties can be dissected in detail.
Design And Performance Of High-Speed Optically-Addressed Spatial Light Modulators (1988)

Optically-addressed spatial light modulators (OASLMs) utilizing a hydrogenated amorphous silicon photodiode as the photosensor and a ferroelectric liquid crystal as the modulator show great promise in high-speed, high-contrast spatial light modulation. We present the initial design, modelling, and performance of such devices. The devices are driven by a square-wave voltage, such that write and read operations take place under reverse bias, and an erase operation occurs under forward bias. Under continuous write-beam illumination the optical modulation is determined by the photoconductivity of the photosensor under forward bias. During chopped write-beam illumination the modulation is produced by the photocurrent produced under reverse bias. We find an increase in the contrast with reduced bias voltage, which is explained in terms of a series capacitance effect. Several polarization-based logic gates are described which utilize a single OASLM devices.
Epitope Mapping of Atlantic Salmon Major Allergen by Peptide Microarray Immunoassay (2011)

We have identified three antigenic regions in Sal s 1 beta 1 using a peptide microarray immunoassay. These three sequential epitopes formed a unique antigenic determinant in the three-dimensional model of the protein. In addition, we proved that isoforms from the same protein might have a different allergenic behavior.
A novel 87,000-Mr protein associated with acetylcholine receptors in Torpedo electric organ and vertebrate skeletal muscle. (1989)

To identify proteins associated with nicotinic postsynaptic membranes, mAbs have been prepared to proteins extracted by alkaline pH or lithium diiodosalicylate from acetylcholine receptor-rich (AChR) membranes of Torpedo electric organ. Antibodies were obtained that recognized two novel proteins of 87,000 Mr and a 210,000:220,000 doublet as well as previously described proteins of 43,000 Mr, 58,000 (51,000 in our gel system), 270,000, and 37,000 (calelectrin). The 87-kD protein copurified with acetylcholine receptors and with 43- and 51-kD proteins during equilibrium centrifugation on continuous sucrose gradients, whereas a large fraction of the 210/220-kD protein was separated from AChRs. The 87-kD protein remained associated with receptors and 43-kD protein during velocity sedimentation through shallow sucrose gradients, a procedure that separated a significant amount of 51-kD protein from AChRs. The 87- and 270-kD proteins were cleaved by Ca++-activated proteases present in crude preparations and also in highly purified postsynaptic membranes. With the exception of anti-37-kD antibodies, some of the monoclonals raised against Torpedo proteins also recognized determinants in frozen sections of chick and/or rat skeletal muscle fibers and in permeabilized chick myotubes grown in vitro. Anti-87-kD sites were concentrated at chick and rat endplates, but the antibodies also recognized determinants present at lower site density in the extrasynaptic membrane. Anti-210:220-kD labeled chick endplates, but studies of neuron-myotube cocultures showed that this antigen was located on neurites rather than the postsynaptic membrane. As reported in other species, 43-kD determinants were restricted to chick endplates and anti-51-kD and anti-270-kD labeled extrasynaptic as well as synaptic membranes. None of the cross reacting antibodies recognized determinants on intact (unpermeabilized) myotubes, so the antigens must be located on the cytoplasmic aspect of the surface membrane. The role that each intracellular determinant plays in AChR immobilization at developing and mature endplates remains to be investigated.
Purification and Characterization of an Erythrocyte Membrane Protein Complex Carrying Duffy Blood Group Antigenicity (1989)

A murine monoclonal antibody, named anti-Fy6, which agglutinates all human red cells except those of Fy(a-b) phenotype was used for purification and characterization of Duffy antigens. Duffy antigens are multimeric red cell membrane proteins composed of different subunits of which only one, designated pD protein, reacts in immunoblots with the murine monoclonal antibody anti-Fy6. Affinity-purified detergent-soluble antigen-antibody complex obtained from red cells, surface-labeled with 125I yielded a complex pattern of bands when separated by polyacrylamide gel electrophoresis. Proteins that react with anti-Fy6 in immunoblots are: pA and pB (greater than 100 kDa) and pD (36-46 kDa). Electroeluted pD protein aggregates and generates bands of similar molecular mass to pA and pB proteins. Electroeluted pA and pB proteins disaggregate yielding pD protein. Oligomers and monomers of pD protein are present in red cells carrying Duffy antigens and absent in Fy(a-b-) cells. Six other proteins of molecular weight ranging from 68 to 21 kDa either associate or co-purify with pD protein. These proteins are only present in Duffy antigen positive cells. The pD protein is different in Fy(a+b-) and Fy(a-b+) cells by fingerprint analysis. Human antisera identify the same proteins in red cell carrying Duffy antigens as the murine monoclonal antibody anti-Fy6.
Receptor-mediated Transport of Therapeutics across the Blood-Brain Barrier (1994)

THE DELIVERY OF nonlipophilic compounds to the brain is severely hindered by the blood-brain barrier (BBB). However, brain capillary endothelial cells, which form the BBB, do possess specific receptor-mediated transport mechanisms that potentially can be exploited as a means to transport therapeutic molecules to the brain. We have found that antibodies that bind to the transferrin receptor selectively target BBB endothelium, are transported into the brain, and can function as carriers for the delivery of compounds, including proteins, to the central nervous system. This drug delivery system has been used to transport nerve growth factor across the BBB in a biologically active form and at levels sufficient to prevent the degeneration of nerve growth factor-dependent neurons.
Coadministration of Epithelial Junction Opener JO-1 Improves the Efficacy and Safety of Chemotherapeutic Drugs (2012)

Our preliminary data suggest that JO-1 cotherapy has the potential to improve the therapeutic outcome of cancer chemotherapy.
Chitosan: A New Topical Hemostatic Agent for Diffuse Capillary Bleeding in Brain Tissue (1984)

The effectiveness of chitosan as an intraoperative topical hemostatic agent for brain tissue was tested. Cerebral cortical lesions were made in 10 cats. Chitosan was used to obtain hemostasis. The elapsed time from the application of the hemostatic agent to hemostasis was determined. The animals were killed and the lesions were examined grossly and microscopically to evaluate the biocompatibility of chitosan. Chitosan was easy to apply and required minimal subsequent manipulation. Histopathological examination revealed that chitosan is biocompatible with cerebral cortex.
Reduction of Sympathetic Hyperactivity by Enalapril in Patients with Chronic Renal Failure (1999)

Increased sympathetic activity contributes to hypertension in patients with chronic renal disease. ACE inhibition controls hypertension and decreases sympathetic hyperactivity.