gebhart/patrepeval huggingface dataset:
Activity enhancement of a lung cancer–associated human monoclonal antibody HB4C5 by N-deglycosylation (1993)

It has been known that the lung cancer-associated human monoclonal antibody HB4C5 comprises two lambda light chains of 30 and 32 kD and that the 30 kD species is exclusively responsible for the antibody activity. This study demonstrates that the two light chains were both N-glycosylated with glycosyl residues of different sizes, one of which was sensitive to neuraminidase and the other insensitive. Our unpublished data of DNA sequence for the light chain of this monoclonal antibody indicated that the light chain contains only one possible site for N-glycosylation, which located in the CDR-1. N-Deglycosylation of this monoclonal antibody under the denaturing condition resulted in the complete conversion of the two light chains into one identical polypeptide chain of 26 kD. Activity of this monoclonal antibody was found to be significantly enhanced by N-deglycosylation. All the facts described above consistently indicate that the activity of this monoclonal antibody is interfered with by the attachment of bulky glycosyl residues at the antigen binding site on the light chain. The N-deglycosylated antibody was stable under the storage conditions employed, suggesting that the glycosyl residues attached to the light chain do not play any important biological role except for interference with the antibody activity of binding antigen.
Angiogenesis but not collateral growth is associated with ischemia after femoral artery occlusion (1997)

It remains unclear whether capillary sprouting (angiogenesis) and in situ growth of muscular collateral arteries share the same or different molecular mechanisms. To study the role of ischemia in these two forms of vascular proliferation, we measured tissue flows and maximum collateral conductances in hindlimbs of 22 rabbits previously subjected to either acute, 7-day, 21-day, or no femoral artery occlusion. After 1 wk of femoral artery occlusion, corkscrew collaterals were observed radiographically in the thigh. These collaterals showed histochemical evidence for active proliferation of endothelial and smooth muscle cells. Maximum collateral conductance increased sixfold in the 1st wk. Perfusion deficits, however, were only observed in the distal adductor muscles (region of collateral reentry). In the lower leg, which suffered from a profound perfusion deficit, conductance increased in the absence of any visible collateral arteries but with evidence for capillary proliferation. This study therefore demonstrates that upon femoral artery occlusion angiogenesis occurs in regions of profound ischemia, whereas no direct correlation can be drawn between ischemia and collateral artery development.
Optical networking (1998)

Optical networking, as embodied by dense wavelength division multiplexing (DWDM) and optical amplification, has revolutionized long-distance transport and has resulted in capacity expansion, cost reduction, and operations simplification. Extension to more wavelengths, emergence of reconfigurable wavelength add/drop and other optical network elements (NEs), as well as cost reduction of optical amplifiers and laser devices, are pushing the revolution into the local and metropolitan networks. Traffic generated in any format, such as SONET/SDH, asynchronous transfer mode (ATM), and plesiochronous digital hierarchy (PDH), with bit rates ranging from 45 Mb/s to 10 Gb/s, can be economically transported and routed optically without resorting to time division multiplexing (TDM). In this paper, we describe the latest advances in optical NEs and applications in the public and private networks. In addition, we discuss how optical networking creates flexibility in sharing existing fiber inventory between service providers. We present an example of how optical networking is capable of meeting the emerging demand for high-capacity clear-channel end-user services, a demand that TDM systems cannot meet. Finally, we discuss future directions and optical layer restoration as a prime target of network evolution.
Role of neurohormonal mechanisms in determining survival in patients with severe chronic heart failure. (1987)

Support for the concept that neurohormonal mechanisms play an important role in determining the survival of patients with severe chronic heart failure is derived from two lines of evidence: circulating levels of neurohormones are markedly elevated in patients who have a poor long-term prognosis and the survival of high-risk patients may be favorably modified by treatment with specific neurohormonal antagonists. Plasma norepinephrine is a major prognostic factor in patients with severe chronic heart failure, the most markedly elevated levels being observed in patients with the most unfavorable long-term prognosis. Data from uncontrolled studies suggest that low-dose beta-blockade may improve the survival of patients with dilated cardiomyopathy. Similar trends were noted in the Beta-Blocker Heart Attack Trial, in which patients with congestive heart failure before or accompanying their acute myocardial infarction experienced a significant reduction in sudden death when treated with beta-blockers. In contrast, there appeared to be little selective benefit in patients without heart failure, who presumably had low circulating levels of catecholamines. Similarly, serum sodium concentration is a major prognostic factor in patients with severe chronic heart failure, the shortest survival being observed in patients with the most severe hyponatremia. The poor long-term outcome of hyponatremic patients appears to be related to the marked elevation of plasma renin activity in these individuals, since (in retrospective studies) hyponatremic patients appeared to fare significantly better when treated with converting-enzyme inhibitors than when treated with vasodilator drugs that did not interfere with angiotensin II formation. In contrast, there appeared to be no selective benefit of converting-enzyme inhibition on the survival of patients with a normal serum sodium concentration, in whom plasma renin activity was low. These data suggest that neurohormonal systems may exert a deleterious effect on the survival of some patients with severe chronic heart failure, which may be favorably modified by long-term treatment with specific neurohormonal antagonists.
Anion-exchange reactions of layered double hydroxides (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAnion-exchange reactions of layered double hydroxidesMartina Meyn, Klaus Beneke, and Gerhard LagalyCite this: Inorg. Chem. 1990, 29, 26, 5201–5207Publication Date (Print):December 1, 1990Publication History Published online1 May 2002Published inissue 1 December 1990https://pubs.acs.org/doi/10.1021/ic00351a013https://doi.org/10.1021/ic00351a013research-articleACS PublicationsRequest reuse permissionsArticle Views5294Altmetric-Citations666LEARN 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
Detection of homology to the beta bacteriophage integration site in a wide variety of Corynebacterium spp (1986)

In toxigenic conversion of Corynebacterium diphtheriae C7, beta bacteriophage DNA integrates into either of two chromosomal attachment sites, attB1 or attB2. These attB sites share a 96-base-pair sequence with the attP sites of beta-related phages. The distribution of attB-related sites in other species of Corynebacterium was assessed by hybridization with a DNA probe containing both attB sites of the C7 strain and a second DNA probe containing the attP site of a beta-related phage. All but one of the 15 C. diphtheriae strains tested, regardless of origin or colonial type, contained at least two BamHI fragments that hybridized strongly to both of these probes under conditions of high stringency. Strains of C. ulcerans and C. pseudotuberculosis, species in which conversion to toxinogeny has also been demonstrated, also had one or two hybridizing BamHI fragments. The functionality of these sites as integration sites was demonstrated by isolating lysogens of all three species following single infection with one or more beta-related phages. As predicted, following lysogenization one of the DNA fragments that had exhibited homology with the attB1-attB2 probe was replaced by two hybridizing fragments. Other species of Corynebacterium, including pathogens and nonpathogens from animals, plant pathogens, and soil isolates also carried at least one BamHI fragment that hybridized with the attB1-attB2 and attP probes. The data indicate that sequences homologous to the beta phage integration sites in C. diphtheriae have been conserved in members of the genus Corynebacterium.
Inhibition of cancer cell growth by all-trans retinoic acid and its analog N-(4-hydroxyphenyl) retinamide: a possible mechanism of actionvia regulation of retinoid receptors expression (1998)

In order to better understand the mechanisms that underlie the antiproliferative effect of retinoids, we have examined the response of human carcinoma cell lines to all-trans retinoic acid (RA) and N-(4-hydroxyphenyl) retinamide (4HPR) in terms of cell growth, apoptosis and regulation of retinoic acid receptors (RARs) and retinoid X receptors (RXRs) mRNA. GLC82 (lung adenocarcinoma), BGC823 (stomach adenocarcinoma) and EC109 (esophageal squamous carcinoma) cells were treated with 10 microM of RA or 4HPR for various length of time and analyzed. The results show that growth inhibition by RA and 4HPR in GLC82 and BGC823 cells correlates with the induction of RARbeta2 gene, whereas RA resistance in EC109 cells parallels loss of RARbeta2 induction. Exogenous RARbeta2 expression did not restore RA responsiveness in EC109 cells, but potentiated 4HPR-induced growth inhibition, suggesting that 4HPR acts at least in part via the RARbeta receptor. We speculate that the loss of RARbeta2 inducibility in EC109 cells may be due to an unknown repressor.
PEGylation of therapeutic proteins (2010)

Since the first PEGylated product was approved by the Food and Drug Administration in 1990, PEGylation has been widely used as a post-production modification methodology for improving biomedical efficacy and physicochemical properties of therapeutic proteins. Applicability and safety of this technology have been proven by use of various PEGylated pharmaceuticals for many years. It is expected that PEGylation, as the most established technology for extension of drug residence in the body, will play an important role in the next generation therapeutics, such as peptides, protein nanobodies and scaffolds, which due to their diminished molecular size need half-life extension. This review focuses on several factors important in the production of PEGylated biopharmaceuticals enabling efficient preparation of highly purified PEG-protein conjugates that have to meet stringent regulatory criteria for their use in human therapy. Areas addressed are PEG properties, the specificity of PEGylation reactions, separation and large-scale purification, the availability and analysis of PEG reagents, analysis of PEG-protein conjugates, the consistency of products and processes and approaches used for rapid screening of pharmacokinetic properties of PEG-protein conjugates.
Estrogen loss upregulates hematopoiesis in the mouse: a mediating role of IL-6. (1995)

We have previously demonstrated that ovariectomy causes an increase in the number of colony-forming unit granulocyte/macrophage (CFU-GM) and an upregulation of osteoclastogenesis in mice, both of which are mediated by interleukin-6 (IL-6). IL-6 is involved in the development of several hematopoietic progenitors, including the burst-forming unit-erythroid (BFU-E) and multipotent CFUs (CFU-GEMM). Therefore, we performed studies to examine if other hematopoietic progenitors, besides CFU-GM and their progeny, are affected by estrogen loss. We found that ovariectomy caused an increase in the number of CFU-GEMM and BFU-E, as well as an increase of CFU-GM in marrow cells of the femur. Administration of 17 beta-estradiol or a neutralizing antibody against IL-6 prevented the ovariectomy-induced increase in the number of these progenitors in the marrow. Ovariectomy also caused an increase in the number of circulating lymphocytes, neutrophils, and monocytes, which were suppressed by administration of 17 beta-estradiol or the neutralizing antibody against IL-6; however, the number of circulating platelets was unaffected by loss of ovarian function. These data establish that, in addition to upregulation of osteoclastogenesis, loss of estrogens in the mouse causes widespread effects on hematopoiesis, which are apparently mediated by IL-6.
The crystal structure of human CD21: Implications for Epstein–Barr virus and C3d binding (2002)

Human complement receptor type 2 (CD21) is the cellular receptor for Epstein-Barr virus (EBV), a human tumor virus. The N-terminal two short consensus repeats (SCR1-SCR2) of the receptor interact with the EBV glycoprotein gp350/220 and also with the natural CD21 ligand C3d. Here we present the crystal structure of the CD21 SCR1-SCR2 fragment in the absence of ligand and demonstrate that it is able to bind EBV. Based on a functional analysis of wild-type and mutant CD21 and molecular modeling, we identify a likely region for EBV attachment and demonstrate that this region is not involved in the interaction with C3d. A comparison with the previously determined structure of CD21 SCR1-SCR2 in complex with C3d shows that, in both cases, CD21 assumes compact V-shaped conformations. However, our analysis reveals a surprising degree of flexibility at the SCR1-SCR2 interface, suggesting interactions between the two domains are not specific. We present evidence that the V-shaped conformation is induced by deglycosylation of the protein, and that physiologic glycosylation of CD21 would result in a more extended conformation, perhaps with additional epitopes for C3d binding.
1,25-Dihydroxycholecalciferol: Identification of the Proposed Active Form of Vitamin D 3 in the Intestine (1971)

The major polar metabolite of cholecalciferol (vitamin D(3)) present in chick intestinal mucosa has been chemically characterized by mass spectrometric analysis to have a molecular formula of C(27)H(44)0(3) and a structure of 1,25-dihydroxycholecalciferol. This compound, which is produced in the kidney from 25-hydroxycholecalciferol, has been previously shown to be from 4 to 13 times as active as cholecalciferol in stimulating intestinal calcium transport. 1,25-Dihydroxycholecalciferol (previously designated metabolite 4B in this (laboratory) probably represents the biologically active form of cholecalciferol in the intestine.
Differential Expression of Adenosine Receptors in Human Endothelial Cells (2002)

Adenosine has been reported to stimulate or inhibit the release of angiogenic factors depending on the cell type examined. To test the hypothesis that differential expression of adenosine receptor subtypes contributes to endothelial cell heterogeneity, we studied microvascular (HMEC-1) and umbilical vein (HUVEC) human endothelial cells. Based on mRNA level and stimulation of adenylate cyclase, we found that HUVECs preferentially express A2A adenosine receptors and HMEC-1 preferentially express A2B receptors. Neither cells expressed A1 or A3 receptors. The nonselective adenosine agonist 5'-N-ethylcarboxamidoadenosine (NECA) increased expression of interleukin-8 (IL-8), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) in HMEC-1, but had no effect in HUVECs. In contrast, the selective A2A agonist 2-p-(2-carboxyethyl)phenylethylamino-NECA (CGS 21680) had no effect on expression of these angiogenic factors. Cotransfection of each type of adenosine receptors with a luciferase reporter in HMEC-1 showed that A2B receptors, but not A1, A2A, or A3, activated IL-8 and VEGF promoters. These effects were mimicked by constitutively active alphaG(q), alphaG12, and alphaG13, but not alphaG(s) or alphaG(i1-3). Furthermore, stimulation of phospholipase C indicated coupling of A2B receptors to G(q) proteins in HMEC-1. Thus, differential expression of adenosine receptor subtypes contributes to functional heterogeneity of human endothelial cells. A2B receptors, predominantly expressed in human microvascular cells, modulate expression of angiogenic factors via coupling to G(q), and possibly via G12/13.
Fabrication of 200 nm period nanomagnet arrays using interference lithography and a negative resist (1999)

Magnetic information storage density has increased at the rate of 60% per year for the past seven years. There is wide agreement that continuation of this trend beyond the physical limits of the continuous thin-film media currently used will likely require a transition to discrete, lithographically defined magnetic pillars. Interference lithography (IL) appears to be the most cost-effective means of producing two-dimensional arrays of such pillars. IL can rapidly expose large areas with relatively simple equipment, without the need for a mask, and with fine control of the ratio of pillar diameter to period. We show that negative-tone imaging yields three times the contrast of positive-tone imaging for the generation of holes in photoresist, suitable for subsequent deposition or electroplating of magnetic material. We use a negative i-line, chemically-amplified resist (OHKA THMR-iN PS1) to form 200 nm period arrays of magnetic dots in Co and Ni. Such arrays, with a variety of well controlled diameters, are used to study the effect of particle size on magnetic behavior.
Development of dendritic cells in vitro from murine fetal liver–derived lineage phenotype-negative c-kit+hematopoietic progenitor cells (2000)

We describe here that lineage phenotype- negative (Lin)(-)c-kit(+) hematopoietic progenitor cells (HPCs) from day 13 postcoitus (dpc) murine fetal liver (FL) can generate dendritic cell (DC) precursors when cultured in vitro in the presence of PA6 stromal cells plus granulocyte/macrophage colony-stimulating factor (GM-CSF) + stem cell factor (SCF) + Flt3 ligand (Flt3L) for 12 to 14 days, and develop into mature DCs when stimulated with GM-CSF plus mouse tumor necrosis factor alpha (mTNFalpha) for an additional 3 to 5 days. A transwell culture system showed that the generation of DC precursors depended on the support of PA6 cell-secreted soluble factor(s). The mature DCs derived from 13 dpc FL Lin(-)c-kit(+) HPCs showed characteristic morphology and function of DCs and expressed high levels of Ia, CD86, and CD40 molecules, low levels of DEC205, E-cadherin, and F4/80 molecules, but barely detectable CD11c antigen. Once FL-derived HPCs were cultured without GM-CSF, NK1.1(+) cells developed in the presence of PA6 cells + SCF + Flt3L. These NK1.1(+) cells could develop into DC precursors at an earlier stage of differentiation by reculturing with PA6 cells + SCF + Flt3L + GM-CSF, but they would be irreversibly committed to NK cell precursors without GM-CSF after 3 days, suggesting that GM-CSF plays a critical role in controlling the transition of DC and NK cell precursors from 13 dpc FL-derived Lin(-)c-kit(+) HPCs. This study represents the first success in generating mature DCs in vitro from murine FL HPCs. (Blood. 2000;95:138-146)
SIGGRAPH Course 2014 — Skinning: Real-time Shape Deformation Part II: Automatic Skinning via Constrained Energy Optimization (2015)

The traditional character skinning pipeline is labor intensive. We may break the pipeline into three main steps to see where professional riggers and animators spend the most time, and consequently where modern automatic methods will take over or assist. Let us recall the linear blend skinning formula so we may track how each step affects a character’s deformation (see Figure 1). The new position of a point v′ on the shape is computed as the weighted sum of handle transformations applied to its rest position v:
Thioacidolysis of Enzymatic Dehydrogenation Polymers fromp-Hydroxyphenyl, Guaiacyl, and Syringyl Precursors (1997)

Lignin polymer models (DHPs) were obtained from p-coumaryl, coniferyl and/or sinapyl alcohols under conditions simulating the end-wise or the bulk polymerization modes. Their structures were characterized by thioacidolysis followed by Raney nickel desulfuration in order to investigate the correlative variations of DHP structures with polymerization mode and precursor type. Whatever the precursors. addition rates and final concentrations of monolignols in the dehydrogenative medium appeared discriminatory enough to give rise to end-wise and bulk type DHPs. the former mimicking less imperfectly native lignins. The behavior of the p-hydroxyphenyl precursor. less easily oxidized, is influenced by the presence of other types of precursors. Polymerized alone, it gives rise to a very condensed polymer. In contrast, when copolymerized with G and/or S precursors. it is efficiently involved in labile bonds. H units of the copolymers are mainly terminal units with free phenolic groups, in synthetic DHPs as well as in native lignins.
Active compliance in robotic surgery—the use of force control as a dynamic constraint (1997)

Robotic surgery can be carried out automatically by using a robot to move the cutting tool under position control. However, although the surgeon can observe the procedure on a visual display and has the ability to stop the operation in an emergency, he has little direct contact with the task. An alternative approach is to involve the surgeon more directly, by his moving a robot using active force control. The robot is then used to allow motion in preprogrammed regions, by the surgeon back-driving the robot motors, while preventing motion in prohibited areas. This active constraint robot (or ACROBOT) is described in this paper applied to knee surgery, in which the knee bones are accurately machined to allow the fitting of prosthetic knee implants. The ACROBOT is, however, ideally suited to a range of surgical procedure, because it allows the surgeon to feel the forces exerted during cutting and take appropriate action. This ability to be in direct control, while being constrained to cut within a permitted region, enhances safety and makes the system more acceptable to the medical community. The system of programmable constraint also allows the ACROBOT to provide the traditional benefits of robot surgery, namely the ability to machine complex geometrical surfaces very accurately and to make repetitive motions tirelessly. The system also has a potential for minimally invasive procedures. In knee surgery, for example, the robot could operate through a small incision in the skin and excise a volume into which a small, specially designed, unicompartmental prosthesis could fit.
Metabolic Engineering for Production ofβ-Carotene and Lycopene inSaccharomyces cerevisiae (1994)

We have engineered a conventional yeast, Saccharomyces cerevisiae, to confer a novel biosynthetic pathway for the production of beta-carotene and lycopene by introducing the bacterial carotenoid biosynthesis genes, which are individually surrounded by the promoters and terminators derived from S. cerevisiae. beta-Carotene and lycopene accumulated in the cells of this yeast, which was considered to be a result of the carbon flow for the ergosterol biosynthetic pathway being partially directed to the pathway for the carotenoid production.