gebhart/patrepeval huggingface dataset:
Application of Denatured, Electrophoretically Separated, and Immobilized Lysates of Herpes Simplex Virus-Infected Cells for Detection of Monoclonal Antibodies and for Studies of the Properties of Viral Proteins (1983)

We report the use of herpes simplex virus type 1 (HSV-1)- and HSV-2-infected cell polypeptides (ICPs) separated by electrophoresis in polyacrylamide gels and transferred to nitrocellulose to (i) detect monoclonal antibodies to viral polypeptides and to (ii) study the properties of the proteins with the monoclonal antibodies. Our results were as follows. (i) When the antigens were electrophoretically separated in denaturing gels and then immobilized on nitrocellulose strips, we detected a greater diversity of monoclonal antibodies to viral proteins than when we used the technique of immune precipitation of soluble, nondenatured viral antigens. The primary advantage of the technique is in the detection of nonprecipitating antibody and of antibody to poorly soluble antigens not available for reaction in preparations cleared by high-speed centrifugation before immune reaction. (ii) Studies of the viral polypeptides reactive with three monoclonal antibodies indicated that the technique can be used to investigate several properties of the antigens. Specifically, monoclonal antibody to ICP 4 confirmed the accumulation of viral protein in the nucleus and the mapping of the gene in the S component. The results showed, however, that HSV-1 and HSV-2 ICP 4 do have common antigenic determinants. The reaction of a nonprecipitating monoclonal antibody with electrophoretically separated, immobilized polypeptides contained in cytoplasmic and nuclear fractions, those chemically deglycosylated, or those specified by specific HSV-1 x HSV-2 intertypic recombinants identified the antigens reactive with the second monoclonal antibody as various forms of glycoprotein gC. Of particular interest was a set of four antigens, 39,000 to 46,500 in apparent molecular weight, reactive with each of several monoclonal antibodies. These studies showed that two polypeptides partition in the cytoplasm and two in the nucleus and that all comap with the previously mapped ICPs 35 and 37 in the region of the genome defined by the viral thymidine kinase gene on the left and the glycoprotein gA/B gene on the right. Unlike ICP 4 and gC, the four polypeptides are linked by intermolecular bisulfide bonds, inasmuch as the polypeptides were not at the expected locations upon denaturation and electrophoresis in the absence of reducing agents.
A Selective Turn-On Fluorescent Sensor for Imaging Copper in Living Cells (2005)

We present the synthesis, properties, and biological applications of Coppersensor-1 (CS1), a new water-soluble, turn-on fluorescent sensor for intracellular imaging of copper in living biological samples. CS1 utilizes a BODIPY reporter and thioether-rich receptor to provide high selectivity and sensitivity for Cu+ over other biologically relevant metal ions, including Cu2+, in aqueous solution. This BODIPY-based probe is the first Cu+-responsive sensor with visible excitation and emission profiles and gives a 10-fold turn-on response for detecting this ion. Confocal microscopy experiments further establish that CS1 is membrane-permeable and can successfully monitor intracellular Cu+ levels within living cells.
The Taxonomic Position of Phaeodactylum tricornutum (1958)

Summary: A revised taxonomic description of Phaeodactylum tricornutum Bohlin is presented, with special emphasis on the details of the silica valve, a structure hitherto unobserved. The features distinguishing P. tricornutum from Nitzschia closterium (Ehr.) W. Sm., with which it has frequently been confused, are summarized. In view of the unique characters of P. tricornutum, it is proposed to establish within the Bacillariales a new suborder, the Phaeodactylineae, to which Phaeodactylum is assigned as the only known genus.
Antagonising angiogenesis in rheumatoid arthritis (2001)

Rheumatoid arthritis (RA) is a chronic systemic disease characterised by an inflammatory erosive synovitis. Early changes in the synovium are marked by neovascularisation, inflammatory cell infiltration, and associated synoviocyte hyperplasia, which produce a pannus of inflammatory vascular tissue. This pannus covers and erodes articular cartilage, eventually leading to joint destruction.

Angiogenesis is a complex, highly regulated physiological process, which in normal adults is restricted to the female reproductive cycle and wound healing. A coordinated sequence of endothelial cell division, selective degradation of vascular basement membranes and surrounding extracellular matrix (ECM) with migration of endothelial cells1 results in new capillary growth from existing vessels. Pathological angiogenesis is now recognised as a fundamental component of pannus development in RA,2 with evidence of both focal endothelial proliferation and apoptosis in the synovium.3 

The importance of angiogenesis in providing the vascular network to sustain synovial and immune cell proliferation is confirmed by pharmacological inhibition of angiogenesis, resulting in suppression of arthritis in experimental models.4-7 More recently, specific inhibition of vascular endothelial growth factor (VEGF) by soluble receptor, sflt-1,8 and by anti-VEGF antibody9 has been shown to attenuate collagen induced arthritis in mice, supporting the major role of VEGF in promoting angiogenesis.

The initiation of angiogenesis is associated with expression of a number of angiogenic growth factors of which basic fibroblast growth factor-2 (FGF-2) and VEGF are the most potent.10 

In RA, high levels of VEGF,11 FGF-1,12FGF-2,13 transforming growth factor β1(TGFβ1),14 and hepatocyte growth factor15 are present in synovial fluid (SF) or synovial membrane, secreted by synoviocytes or infiltrating leucocytes. The presence of these angiogenic factors confirms earlier studies showing that SF induces capillary-like structures in endothelial cell cultures.16 

We have investigated the control of VEGF production …
Prevention of Autoimmune Diabetes through Immunostimulation with Q Fever Complement‐Fixing Antigen (2003)

The most promising strategies for prevention of type 1 diabetes seem to be in the categories of immunomodulation (e.g., nondepleting anti-CD3, Diapep, linomide) and/or immunostimulation (e.g., QFA, BCG). We are currently undertaking a research program directed toward better understanding of immunostimulants to help maximize the likelihood of success of future human clinical trials for diabetes prevention. This program is focused on the key areas of optimization of vaccine dose and route of administration, development of surrogate immune markers, and elucidation of the mechanism of protection. The mechanism whereby QFA protects against diabetes currently is not known. The elucidation of the mechanism should help identify the optimal way in which to administer QFA to provide diabetes protection. It may also assist the development of even more potent immunostimulatory vaccines.
Reconstitution of apolipoprotein A-I from human high density lipoprotein with bovine brain sphingomyelin. (1983)

Reconstitution of apolipoprotein A-I was found to occur readily with bovine brain sphingomyelin (BBSM), with a maximum rate occurring at a temperature of 28 degrees C, a temperature approximating the phase transition temperature for this naturally occurring phospholipid. At BBSM:A-I weight ratios of 7.5:1 or less, a single recombinant product was observed which contained three A-I molecules per particle, which had a BBSM:A-I molar ratio of 360 to 1 and which appeared in the electron microscope as a discoidal complex with a thickness of 68 A and a diameter of 217 A. By these criteria, as well as by gel filtration, this product appears very similar to that obtained by recombination of A-I with phosphatidylcholine at elevated ratios of phospholipid/protein. No evidence was found for the existence of any BBSM:A-I complexes comparable to the smaller lecithin:A-I complex containing 200-250 mol of phospholipid and two A-I molecules per complex which has been previously reported. At BBSM:A-I ratios of 15:1 (w/w), a new type of complex was observed which was discoidal by electron microscopy but possessed a larger diameter (390 A) and higher phospholipid:protein molar ratio (535:1) than has been observed previously for recombinant complexes. The BBSM:A-I complexes were found to be significantly more resistant to denaturation by guanidine hydrochloride than the dimyristoyl phosphatidylcholine:A-I recombinant complexes. It is concluded that the mechanisms of interaction between apolipoprotein A-I and either bovine brain sphingomyelin or phosphatidylcholines are similar, but that the nature of the protein-lipid interactions with BBSM are such as to produce larger and more stable complexes than are observed with the phosphatidylcholines.
Using geometric corners to build a 2D mosaic from a set of images (2002)

The main problem for building a mosaic is the computation of the warping functions (homographies). In fact two cases are to be distinguished. The first is when the homography is mainly a translation (i.e. The rotation around the optical axis and the zooming factor are small). The second is the general case (when the rotation around the optical axis and zooming are arbitrary). Some efficient methods have been developed to solve the first case. But the second case is more difficult, in particular, when the rotation around the optical axis is very large (90 degrees or more). Often in this case human interaction is needed to provide a first approximation of the transformation that will bring one back to the first case. The authors present a method to solve this problem without human interaction for any rotation around the optical axis and fairly large zooming factors.
A simple and highly sensitive radioenzymatic assay for lysophosphatidic acid quantification (2000)

The objective of the present work was to develop a simple and sensitive radioenzymatic assay to quantify lysophosphatidic acid (LPA). For that, a recombinant rat LPA acid acyltransferase (LPAAT) produced in Escherichia coli was used. In the presence of [(14)C]oleoyl-CoA, LPAAT selectively catalyzes the transformation of LPA and alkyl-LPA into [(14)C]phosphatidic acid. Acylation of LPA was complete and linear from 0 to 200 pmol with a minimal detection of 0.2 pmol. This method was used to quantify LPA in butanol-extracted lipids from bovine sera, as well as from human and mouse plasma. This radioenzymatic assay represents a new, simple, and highly sensitive method to quantify LPA in various biological fluids.
Derivatives of Aminoisoquinolines1 (1942)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDerivatives of Aminoisoquinolines1John J. Craig and W. E. CassCite this: J. Am. Chem. Soc. 1942, 64, 4, 783–784Publication Date (Print):April 1, 1942Publication History Published online1 May 2002Published inissue 1 April 1942https://pubs.acs.org/doi/10.1021/ja01256a012https://doi.org/10.1021/ja01256a012research-articleACS PublicationsRequest reuse permissionsArticle Views258Altmetric-Citations17LEARN 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-Alertsclose Get e-Alerts
Glycoengineered Monoclonal Antibodies with Homogeneous Glycan (M3, G0, G2, and A2) Using a Chemoenzymatic Approach Have Different Affinities for FcγRIIIa and Variable Antibody-Dependent Cellular Cytotoxicity Activities (2015)

Many therapeutic antibodies have been developed, and IgG antibodies have been extensively generated in various cell expression systems. IgG antibodies contain N-glycans at the constant region of the heavy chain (Fc domain), and their N-glycosylation patterns differ during various processes or among cell expression systems. The Fc N-glycan can modulate the effector functions of IgG antibodies, such as antibody-dependent cellular cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC). To control Fc N-glycans, we performed a rearrangement of Fc N-glycans from a heterogeneous N-glycosylation pattern to homogeneous N-glycans using chemoenzymatic approaches with two types of endo-β-N-acetyl glucosaminidases (ENG'ases), one that works as a hydrolase to cleave all heterogeneous N-glycans, another that is used as a glycosynthase to generate homogeneous N-glycans. As starting materials, we used an anti-Her2 antibody produced in transgenic silkworm cocoon, which consists of non-fucosylated pauci-mannose type (Man2-3GlcNAc2), high-mannose type (Man4-9GlcNAc2), and complex type (Man3GlcNAc3-4) N-glycans. As a result of the cleavage of several ENG'ases (endoS, endoM, endoD, endoH, and endoLL), the heterogeneous glycans on antibodies were fully transformed into homogeneous-GlcNAc by a combination of endoS, endoD, and endoLL. Next, the desired N-glycans (M3; Man3GlcNAc1, G0; GlcNAc2Man3GlcNAc1, G2; Gal2GlcNAc2Man3GlcNAc1, A2; NeuAc2Gal2GlcNAc2Man3GlcNAc1) were transferred from the corresponding oxazolines to the GlcNAc residue on the intact anti-Her2 antibody with an ENG'ase mutant (endoS-D233Q), and the glycoengineered anti-Her2 antibody was obtained. The binding assay of anti-Her2 antibody with homogenous N-glycans with FcγRIIIa-V158 showed that the glycoform influenced the affinity for FcγRIIIa-V158. In addition, the ADCC assay for the glycoengineered anti-Her2 antibody (mAb-M3, mAb-G0, mAb-G2, and mAb-A2) was performed using SKBR-3 and BT-474 as target cells, and revealed that the glycoform influenced ADCC activity.
Trigeminal neuralgia: definition and classification (2005)

Based on specific, objective, and reproducible criteria, a classification scheme for trigeminal neuralgia (TN) and related facial pain syndromes is proposed. Such a classification scheme is based on information provided in the patient's history and incorporates seven diagnostic criteria, as follows. 1) and 2) Trigeminal neuralgia Types 1 and 2 (TN1 and TN2) refer to idiopathic, spontaneous facial pain that is either predominantly episodic (as in TN1) or constant (as in TN2) in nature. 3) Trigeminal neuropathic pain results from unintentional injury to the trigeminal nerve from trauma or surgery. 4) Trigeminal deafferentation pain results from intentional injury to the nerve by peripheral nerve ablation, gangliolysis, or rhizotomy in an attempt to treat either TN or other related facial pain. 5) Symptomatic TN results from multiple sclerosis. 6) Postherpetic TN follows a cutaneous herpes zoster outbreak in the trigeminal distribution. 7) The category of atypical facial pain is reserved for facial pain secondary to a somatoform pain disorder and requires psychological testing for diagnostic confirmation. The purpose of a classification scheme like this is to advocate a more rigorous, standardized natural history and outcome studies for TN and related facial pain syndromes.
Degranulation from Human Eosinophils Stimulated with C3a and C5a (1994)

It is unclear what actually induces eosinophil degranulation in vivo. We examined eosinophil cationic protein (ECP) release from normal human eosinophils (Eos) in response to C3a and C5a. C3a and C5a induced remarkable ECP release when Eos were preincubated with cytochalasin B. ECP release induced by C3a or C5a was greater than that induced by PAF at a concentration of 10(-7) M. The ED50 for ECP release was 3 x 10(-8) M and 3 x 10(-9) M for C3a and C5a, respectively. C3a or C5a elicited a rapid and transient rise in [Ca2+]i. These results suggest that C3a and C5a may contribute to hypersensitivity diseases by inducing eosinophil degranulation.
Analysis of T cell receptor Vβ diversity in peripheral CD4+ and CD8+ T lymphocytes in patients with autoimmune thyroid diseases (2008)

Autoimmune thyroid diseases are characterized by intrathyroidal infiltration of CD4(+) and CD8(+) T lymphocytes reactive to self-thyroid antigens. Early studies analysing T cell receptor (TCR) Valpha gene usage have shown oligoclonal expansion of intrathyroidal T lymphocytes but not peripheral blood T cells. However, TCR Vbeta diversity of the isolated CD4(+) and CD8(+) T cell compartments in the peripheral blood has not been characterized fully in these patients. We performed complementarity-determining region 3 (CDR3) spectratyping as well as flow cytometric analysis for the TCR Vbeta repertoire in peripheral CD4(+) and CD8(+) T cells from 13 patients with Graves' disease and 17 patients with Hashimoto's thyroiditis. Polyclonal TCR Vbeta repertoire was demonstrated by flow cytometry in both diseases. In contrast, CDR3 spectratyping showed significantly higher skewing of TCR Vbeta in peripheral CD8(+) T cells but not CD4(+) T cells among patients with Hashimoto's thyroiditis compared with healthy adults. We found trends towards a more skewed CDR3 size distribution in those patients having disease longer than 5 years and requiring thyroid hormone replacement. Patients with Graves' disease exhibited no skewing both in CD4(+) and CD8(+) T cells. These findings indicate that clonal expansion of CD8(+) T cells in Hashimoto's thyroiditis can be detected in peripheral blood and may support the role of CD8(+) T cells in cell-mediated autoimmune attacks on the thyroid gland in Hashimoto's thyroiditis.
Case-based reasoning: A review (1994)

Abstract Case-Based Reasoning (CBR) is a relatively recent problem solving technique that is attracting increasing attention. However, the number of people with first-hand theoretical or practical experience of CBR is still small. The main objective of this review is to provide a comprehensive overview of the subject to people new to CBR. The paper outlines the development of CBR in the US in the 1980s. It describes the fundamental techniques of CBR and contrasts its approach to that of model-based reasoning systems. 1 A critical review of currently available CBR software tools is followed by descriptions of CBR applications both from academic research and, in more detail, three CBR systems that are presently being used commercially. Each of the three commercial case studies highlights features that made CBR particularly suitable for the application. Moreover, the last case study describes a development methodology for implementing CBR systems. The paper concludes with a research agenda for CBR. A detailed categorized bibliography of CBR research is provided in a companion paper (Marir &amp; Watson, 1994).
Non-linear effects in the quenching of fluorescent quantum dots by nitroxyl free radicals (2005)

Quenching of quantum dot luminescence by nitroxides is extremely non-linear and dependent on nanoparticle size, being most effective for the smaller particles; it is proposed to involve an electron exchange mechanism.
Recent Advances in RNA Therapeutics and RNA Delivery Systems Based on Nanoparticles (2018)

Abstract Recently, there have been significant advances in the field of RNA‐based therapeutics harnessing exogenous RNAs including small interfering RNA (siRNA), microRNA (miRNA) mimics, and in vitro transcribed (IVT) mRNAs. RNA‐based therapeutics are one of the most attractive classes of drugs for treating a variety of diseases. In principle, RNA‐based therapeutics offer numerous advantages compared to the conventional small‐molecule‐based therapies. However, there are several drawbacks to overcome in the application of RNA‐based therapeutics, including the instability of RNAs and presence of various biological barriers. In the past decades, there have been various attempts to overcome these key challenges. Here, the authors present an overview of RNA‐based therapeutics and recent advances including their delivery systems and clinical applications. In addition, the current challenges of RNA‐based drugs are discussed, followed by perspectives with regard to the development of these promising drug candidates to elicit successful clinical outcomes.
Clinically isolated syndromes (2007)

Multiple sclerosis (MS) represents a spectrum of demyelination that depends on disease duration and clinical categorization. Most patients present with the relapsing–remitting form of the disease. The earliest clinical presentation of relapsing–remitting MS (RRMS) is the clinically isolated syndrome (CIS). Predicting which CIS patients are at high risk for MS is complicated by the disparity between clinical attacks and the extent of axon pathology. However, recent interferon-beta (IFN-β) trials have demonstrated a delay in time to the second demyelinating event with early treatment, and early treatment could also slow the progression from RRMS to secondary-progressive MS (SPMS). Clinical findings in combination with brain MRI and CSF analysis can be used in CIS patients to evaluate their risk for clinically definite MS (CDMS). Application of the McDonald criteria also allows an earlier MS diagnosis by using new MRI lesions to define dissemination in time. Early immunomodulatory therapy for selected CIS patients may eventually prevent future axon pathology and progression of disability in this lifelong disease.
The Effects of Cryosurgery and Cryoprotectants on Peripheral Nerve Function (1992)

Cryosurgery has many advantages in the treatment of musculoskeletal tumors, but complications can occur, with injuries to the peripheral nerves. Cryoprotectants such as dimethylsulfoxide (DMSO) and glycerol enhance the in vitro survival of cultured Schwann cells, but they have not been studied in vivo. In vitro, 10 percent DMSO provided the maximal survival after freezing to -80 degrees C. The neurologic recovery of a peripheral nerve, following cryoinjury and using liquid nitrogen, was evaluated both with and without pretreatment of the nerve with 10 percent DMSO. There were three experimental groups: 1) one sham operation; 2) with freezing of the sciatic nerve; and 3) with freezing of the sciatic nerve after treatment with DMSO. Gait analyses (sciatic function index, SFI), muscle weights, and histologic evaluations were performed in order to follow the neurologic recovery over a ten-week period. The freezing-only group and the sham-operated control had an excellent functional recovery in terms of the SFI following surgery (-4.2 percent +/- 4.0 percent and -2.4 percent +/- 5.7 percent, respectively), in contrast to the freezing group with DMSO (-34.1 percent +/- 5.5 percent, p less than .01). The average tibialis anterior muscle weight, reported as the ratio of the operated to the unoperated limb (88.2 percent +/- 1.0 percent) in the freezing-only group, was greater than the average for the freezing-with-DMSO-treated group (70.6 percent +/- 3.9 percent, p less than .01). Cryoprotectants are routinely used to optimize the survival of cells in tissue culture. However, DMSO not only failed to protect peripheral nerves from cryoinjury, but it also inhibited functional recovery.
Heparin sequencing brings structure to the function of complex oligosaccharides (2000)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.