gebhart/patrepeval huggingface dataset:
Effect of formulation on the stability and aerosol performance of a nebulized antibody (2014)

Most monoclonal antibodies (mAbs) are administered to patients intravenously to ensure high bioavailability as rapidly as possible. The airways, however, are an attractive delivery route for mAbs for the treatment of lung diseases, making it possible to increase their concentration in the target organ while limiting their systemic passage. Several challenges must be overcome for translation into clinical practice. For example, the drug and device must be paired for the efficient and reliable deposition of a pharmacologically active and safe mAb in the lung region of interest. Mesh nebulizers appear to be the most effective aerosol-producing devices for delivering large amounts of biopharmaceutical while limiting protein instability during nebulization. We used metrological and analytic methods to analyze the effect of both antibody concentration and surfactant addition on aerosol performance and antibody integrity. These two factors had a limited effect on aerosol performance, but affected antibody aggregation. The addition of surfactants to antibody formulations at concentrations appropriate for lung administration markedly reduced the formation of medium or large aggregates, as shown by dynamic light scattering and fluorescence microscopy. Aggregation was also dependent on the type of mesh nebulizer, highlighting the need to optimize drug and device together.
Macrosialin, a mouse macrophage-restricted glycoprotein, is a member of the lamp/lgp family (1993)

Macrosialin is a heavily glycosylated transmembrane protein of 87-115 kDa, highly and specifically expressed by mouse tissue macrophages, and to a lesser extent by dendritic cells. We have isolated cDNA clones encoding macrosialin from a thioglycollate-elicited peritoneal macrophage cDNA library by transient expression in COS cells and panning with the anti-macrosialin monoclonal antibody FA/11. A single 1.3-kilobase macrosialin transcript was detected in both untreated and phorbol 12-myristate 13-acetate-stimulated RAW cells. The cDNA sequence predicts a type I integral membrane protein of 326 residues with a heavily glycosylated extracellular domain of 306 residues containing nine potential N-linked glycosylation sites and numerous potential O-linked glycosylation sites. The extracellular domain consists of two distinct regions, separated by an extended 12 residue proline-rich hinge; a membrane-distal mucin-like domain of 89 residues containing short peptide repeats and consisting of 44% serine and threonine residues; and a membrane proximal domain of 170 residues, which has significant sequence homology to a family of lysosomal associated glycoproteins known as the lamp-1 group. Macrosialin is the murine homologue of the human macrophage glycoprotein CD68 (72% identity, 80% similarity). Both proteins are preferentially expressed by macrophages and share the same bipartite structure having a mucin-like domain and a domain common to the lamp family. Macrosialin and CD68 are the first examples of a lamp family protein with a restricted cell-type-specific expression. They may have evolved from the lamps to carry out specialized functions in dedicated phagocytic cells.
Long PCR and its application to hepatitis viruses: amplification of hepatitis A, hepatitis B, and hepatitis C virus genomes (1996)

In this study we amplified virtually the entire genomes of hepatitis A virus (a member of the Picornaviridae family), hepatitis B virus (a member of the Hepadnaviridae family), and hepatitis C virus (a member of the Flaviviridae family) by using the recently described technique of long PCR. In order to do this, we first demonstrated, using the lambda phage, that long PCR can be made highly sensitive and the sensitivity can be further enhanced by nested long PCR. We also showed, using tobacco mosaic virus as a model, that a reverse transcriptase reaction can be linked to a long PCR, enabling the nearly full-length amplification of the genomes of RNA viruses. We then applied these techniques to serial dilutions of titrated stocks of well-characterized strains of hepatitis A, B, and C viruses. We amplified the nearly full-length sequence of each of these viruses from a small number of viral genomes, demonstrating the sensitivity of the process.
Glucose sensing by the hepatoportal sensor is GLUT2-dependent: in vivo analysis in GLUT2-null mice. (2000)

In the preceding article, we demonstrated that activation of the hepatoportal glucose sensor led to a paradoxical development of hypoglycemia that was associated with increased glucose utilization by a subset of tissues. In this study, we tested whether GLUT2 plays a role in the portal glucose-sensing system that is similar to its involvement in pancreatic beta-cells. Awake RIPGLUT1 x GLUT2-/- and control mice were infused with glucose through the portal (Po-) or the femoral (Fe-) vein for 3 h at a rate equivalent to the endogenous glucose production rate. Blood glucose and plasma insulin concentrations were continuously monitored. Glucose turnover, glycolysis, and glycogen synthesis rates were determined by the 3H-glucose infusion technique. We showed that portal glucose infusion in RIPGLUT1 x GLUT24-/- mice did not induce the hypoglycemia observed in control mice but, in contrast, led to a transient hyperglycemic state followed by a return to normoglycemia; this glycemic pattern was similar to that observed in control Fe-mice and RIPGLUT1 x GLUT2-/- Fe-mice. Plasma insulin profiles during the infusion period were similar in control and RIPGLUT1 x GLUT2-/- Po- and Fe-mice. The lack of hypoglycemia development in RIPGLUT1 x GLUT2-/- mice was not due to the absence of GLUT2 in the liver. Indeed, reexpression by transgenesis of this transporter in hepatocytes did not restore the development of hypoglycemia after initiating portal vein glucose infusion. In the absence of GLUT2, glucose turnover increased in Po-mice to the same extent as that in RIPGLUT1 x GLUT2-/- or control Fe-mice. Finally, co-infusion of somatostatin with glucose prevented development of hypoglycemia in control Po-mice, but it did not affect the glycemia or insulinemia of RIPGLUT1 x GLUT2-/- Po-mice. Together, our data demonstrate that GLUT2 is required for the function of the hepatoportal glucose sensor and that somatostatin could inhibit the glucose signal by interfering with GLUT2-expressing sensing units.
Structure of hepatitis B virus core and e-antigen. A single precore amino acid prevents nucleocapsid assembly. (1993)

The hepatitis B virus core gene codes for two polypeptides: the core protein, which assembles to form particles (HBcAg), and the secreted precore protein (HBeAg). Expression vectors directing the synthesis in Escherichia coli of a recombinant HBeAg corresponding in sequence to serum-derived HBeAg encompassing the 10 precore amino acids remaining after cleavage of the precursor and residues 1-149 of HBcAg (PC-HBeAg) were constructed. Recombinant PC-HBeAg, HBcAg, and C-terminally truncated HBcAg were isolated from E. coli and analyzed by sucrose velocity sedimentation, electron microscopy, anti-HBc/e specific monoclonal antibody analysis, and for immunogenicity. HBcAg and truncated HBcAg formed 27-nm particles and displayed HBc antigenicity. In contrast, PC-HBeAg was nonparticulate and did not band in sucrose gradients. PC-HBeAg was recognized efficiently by HBeAg-specific antibodies and displayed little HBc antigenicity. Immunogenicity studies including T and B cell recognition confirmed that PC-HBeAg demonstrates HBe antigenicity. The presence of the 10 precore amino acids therefore prevented particle formation. To analyze which precore amino acids might be responsible for the prevention of particle formation a cysteine to glutamine substitution at amino acid position -7 was introduced into PC-HBeAg (-7C-->Q)PC-HBeAg. This single amino acid change at position -7 restored particle formation and HBc antigenicity. The evolutionarily conserved cysteine at position -7 thus appears responsible for the prevention of particle assembly in the HBeAg biosynthesis pathway.
All-optical digital-to-analog conversion using pulse pattern recognition based on optical correlation processing (2005)

We propose and demonstrate a novel all-optical digital-to-analog (D/A) conversion using pulse pattern recognition based on optical correlation processing. It is composed of pulse pattern recognition based on correlation processing and intensity adjustment using an optical attenuator. We obtain a single pulse as a result of pulse pattern recognition by using correlation processing between a target digital signal and a prepared correlation filter function. The obtained single pulse can be promptly fed to an output port as a corresponding analog signal through adequate intensity adjustment. Experimental results show that four-bit digital signals with 1.65ps interval can be successfully converted to analog signals corresponding to input digital signals.
Intragenerational Income Mobility in Latin America (2007)

1. Daly and Duncan (1997). 2. The thrust of the discussion here applies if y denotes income rather than earnings, assuming that other sources of income (such as capital, public and private transfers, and so on) are also structurally related to individual characteristics and their market returns. However, this is no longer in the human capital (life cycle) framework.
Degradative Action of Reactive Oxygen Species on Hyaluronan (2006)

Many human diseases are associated with harmful action of reactive oxygen species (ROS). These species are involved in the degradation of essential tissue or related components. One of such components is synovial fluid that contains a high-molecular-weight polymer--hyaluronan (HA). Uninhibited and/or inhibited hyaluronan degradation by the action of various ROS has been studied in many in vitro models. In these studies, the change of the molecular weight of HA or a related parameter, such as HA solution viscosity, has been used as a marker of inflicted damage. The aim of the presented review is to briefly summarize the available data. Their correct interpretation could contribute to the implementation of modern methods of evaluation of the antioxidative capacity of natural and synthetic substances and prospective drugs--potential inflammatory disease modifying agents. Another focus of this review is to evaluate briefly the impact of different available analytical techniques currently used to investigate the structure of native high-molecular-weight hyaluronan and/or of its fragments.
Evidence for a role of ganglioside GM1 in antigen presentation: binding enhances presentation of Escherichia coli enterotoxin B subunit (EtxB) to CD4+ T cells (2001)

Successful antigen presentation by antigen-presenting cells is governed by a number of factors including the efficiency of antigen capture by cell-surface receptors, targeting to compartments of antigen processing, surface expression of MHC II-peptide complexes and presence of co-stimulatory signals. Ganglioside GM1 is an important component of membrane glycosphingolipids, and has been implicated in cell differentiation, apoptosis and signal transduction pathways. Using the B subunit of Escherichia coli enterotoxin (EtxB), a potent immunogen that binds GM1 with high affinity, and a non-binding mutant of EtxB, EtxB(G33D), we demonstrate that GM1 is intimately involved in several aspects of antigen presentation. Thus, GM1-mediated presentation of EtxB by B cells and CD11c(+) dendritic cells (DC) significantly enhanced the proliferation and cytokine expression of EtxB-specific CD4(+) T cells. Investigation regarding potential mechanisms revealed that EtxB binding directly augments the expression of MHC class II on B cells, and fractionation of B cells demonstrated that EtxB binding to GM1 results in rapid internalization and targeting to class II-rich compartments. GM1-mediated uptake of antigens and access to class II compartments in B cells can be exploited to significantly enhance the presentation of ovalbumin-conjugated to EtxB. These results demonstrate that GM1 can play an important role in antigen presentation via the MHC II pathway.
RESPIRATORY VIRUS IMMUNIZATION (1969)

Journal Article RESPIRATORY VIRUS IMMUNIZATION: A FIELD TRIAL OF TWO INACTIVATED RESPIRATORY VIRUS VACCINES; AN AQUEOUS TRIVALENT PARATNFLUENZA VIRUS VACCINE AND AN ALUM-PRECIPITATED RESPIRATORY SYNCYTIAL VIRUS VACCINE Get access V. A. FULGINITI, V. A. FULGINITI 2Department of Pediatrics, University of Colorado Medical Center. Currently, Department of Pediatrics, University of Arizons College of MedicineTucson, Arizona 85721 Search for other works by this author on: Oxford Academic PubMed Google Scholar J. J. ELLER, J. J. ELLER 3Department of Pediatrics, University of Colorado Medical Center. Currently, Virology Section, U. S. Army Medical Research and Nutrition Laboratory, Fitzsimons General HospitalDenver, Colorado Search for other works by this author on: Oxford Academic PubMed Google Scholar O. F. SIEBER, O. F. SIEBER 4Pediatric Service, Fitzsimons General Hospital Search for other works by this author on: Oxford Academic PubMed Google Scholar J. W. JOYNER, J. W. JOYNER 5Department of Pediatrics, University of Colorado Medical Center Search for other works by this author on: Oxford Academic PubMed Google Scholar M. MINAMITANI, M. MINAMITANI 6Department of Pediatrics, University of Colorado Medical Center. Currently, University of TokyoTokyo, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar G. MEIKLEJOHN G. MEIKLEJOHN 7Department of Medicine, University of Colorado Medical Center Search for other works by this author on: Oxford Academic PubMed Google Scholar American Journal of Epidemiology, Volume 89, Issue 4, April 1969, Pages 435–448, https://doi.org/10.1093/oxfordjournals.aje.a120956 Published: 01 April 1969 Article history Received: 23 August 1968 Published: 01 April 1969
BLOOD MANAGEMENT: Large‐dose intravenous ferric carboxymaltose injection for iron deficiency anemia in heavy uterine bleeding: a randomized, controlled trial (2009)

In patients with iron deficiency anemia due to heavy uterine bleeding, rapid IV administration of large doses of a new iron agent, ferric carboxymaltose, is more effective than oral iron therapy in correcting anemia, replenishing iron stores, and improving quality of life.
Photo-induced Friedel-Crafts Reactions. IV. Indoleacetic Acids (1972)

The photoreaction of indole with methyl chloroacetate afforded a mixture of seven isomeric methyl indoleacetates, mainly the 4-isomer, whose separation into each component was carried out by repeated column chromatographies. The structues of all of them confirmed by their spectral data and by the unequivocal sysntheses. The unusual reactivity of the 4-position on the indole nucleus was explained on the basis of the calculation data by SCF-CI-MO method.
Gain-of-function polymorphism in mouse and human Ltk: implications for the pathogenesis of systemic lupus erythematosus (2003)

Systemic lupus erythematosus (SLE), a complex multigenic disease, is a typical antibody-mediated autoimmune disease characterized by production of autoantibodies against a variety of autoantigens and immune complex-type tissue inflammation, most prominently in the kidney. Evidence suggests that genetic factors predisposing to aberrant proliferation/maturation of self-reactive B cells initiate and propagate the disease. In SLE-prone New Zealand Black (NZB) mice and their F1 cross with New Zealand White (NZW) mice, B cell abnormalities can be ascribed mainly to self-reactive CD5+ B1 cells. Our genome-wide scans to search for susceptibility genes for aberrant activation of B1 cells in these mice showed evidence that the gene, Ltk, encoding leukocyte tyrosine kinase (LTK), is a possible candidate. LTK is a receptor-type protein tyrosine kinase, belonging to the insulin receptor superfamily, and is mainly expressed in B lymphocyte precursors and neuronal tissues. Sequence and functional analyses of the gene revealed that NZB has a gain-of-function polymorphism in the LTK kinase domain near YXXM, a binding motif of the p85 subunit of phosphatidylinositol 3-kinase (PI3K). SLE patients also had this type of Ltk polymorphism with a significantly higher frequency compared with the healthy controls. Our findings suggest that these polymorphic LTKs cause up-regulation of the PI3K pathway and possibly form one genetic component of susceptibility to abnormal proliferation of self-reactive B cells in SLE.
Use of New Synthetic Substrates for Assays of Cathepsin L and Cathepsin B1 (1983)

Efficient methods were developed for synthesizing synthetic substrates for assays of cathepsin B and cathepsin L. Several 2-naphthylamide compounds with a blocked NH2-terminus, Suc-Tyr-Met-NA, beta-Ala-Tyr-Met-NA, and D-Leu-Tyr-Met-NA, were specific and sensitive substrates for cathepsin L and cathepsin B; they were not specific for cathepsin L only, because all of them were also hydrolyzed by cathepsin B. Some kinetic constants for the hydrolyses of these three synthetic substrates by cathepsin B and cathepsin L are given.
Design and expression of soluble CTLA‐4 variable domain as a scaffold for the display of functional polypeptides (1999)

We have designed and engineered the human cytotoxic T-lymphocyte associated protein-4 (CTLA-4) variable (V-like) domain to produce a human-based protein scaffold for peptide display. First, to test whether the CTLA-4 CDR-like loops were permissive to loop replacement/insertion we substituted either the CDR1 or CDR3 loop with somatostatin, a 14-residue intra-disulfide-linked neuropeptide. Upon expression as periplasmic-targeted proteins in Escherichia coli, molecules with superior solubility characteristics to the wild-type V-domain were produced. These mutations in CTLA-4 ablated binding to its natural ligands CD80 and CD86, whereas binding to a conformation-dependent anti-CTLA-4 monoclonal antibody showed that the V-domain framework remained correctly folded. Secondly, to develop a system for library selection, we displayed both wild-type and mutated CTLA-4 proteins on the surface of fd-bacteriophage as fusions with the geneIII protein. CTLA-4 displayed on phage bound specifically to immobilized CD80-Ig and CD86-Ig and in one-step panning enriched 5,000 to 2,600-fold respectively over wild-type phage. Bacteriophage displaying CTLA-4 with somatostatin in CDR3 (CTLA-4R-Som3) specifically bound somatostatin receptors on transfected CHO-K1 cells pre-incubated with 1μg/ml tunicamycin to remove receptor glycosylation. Binding was specific, as 1 μM somatostatin successfully competed with CTLA-4R-Som3. CTLA-4R-Som3 also activated as well as binding preferentially to non-glycosylated receptor subtype Sst4. The ability to substitute CDR-like loops within CTLA-4 will enable design and construction of more complex libraries of single V-like domain binding molecules. Proteins 1999;36:217–227. © 1999 Wiley-Liss, Inc.
Smad3 as a mediator of the fibrotic response (2004)

Transforming growth factor-beta (TGF-beta) plays a central role in fibrosis, contributing to the influx and activation of inflammatory cells, the epithelial to mesenchymal transdifferentiation (EMT) of cells and the influx of fibroblasts and their subsequent elaboration of extracellular matrix. TGF-beta signals through transmembrane receptor serine/threonine kinases to activate novel signalling intermediates called Smad proteins, which modulate the transcription of target genes. The use of mice with a targeted deletion of Smad3, one of the two homologous proteins which signals from TGF-beta/activin, shows that most of the pro-fibrotic activities of TGF-beta are mediated by Smad3. Smad3 null inflammatory cells and fibroblasts do not respond to the chemotactic effects of TGF-beta and do not autoinduce TGF-beta. The loss of Smad3 also interferes with TGF-beta-mediated induction of EMT and genes for collagens, plasminogen activator inhibitor-1 and the tissue inhibitor of metalloprotease-1. Smad3 null mice are resistant to radiation-induced cutaneous fibrosis, bleomycin-induced pulmonary fibrosis, carbon tetrachloride-induced hepatic fibrosis as well as glomerular fibrosis induced by induction of type 1 diabetes with streptozotocin. In fibrotic conditions that are induced by EMT, such as proliferative vitreoretinopathy, ocular capsule injury and glomerulosclerosis resulting from unilateral ureteral obstruction, Smad3 null mice also show an abrogated fibrotic response. Animal models of scleroderma, cystic fibrosis and cirrhosis implicate involvement of Smad3 in the observed fibrosis. Additionally, inhibition of Smad3 by overexpression of the inhibitory Smad7 protein or by treatment with the small molecule, halofuginone, dramatically reduces responses in animal models of kidney, lung, liver and radiation-induced fibrosis. Small moleucule inhibitors of Smad3 may have tremendous clinical potential in the treatment of pathological fibrotic diseases.
Gel-Like Lyomesophases Formed in Organic Solvents by Self-Assembled Guanine Ribbons (2002)

Lipophilic guanosine derivatives are self-assembled into ribbonlike aggregates, both in the crystal state and in solution. The structure of the ribbons has been characterised by single-crystal X-ray diffraction and, in solution, by NMR spectroscopy and ESI-MS. Two different ribbons with different patterns of hydrogen bonds are present in the solid state and in chloroform solutions. The gel-like phases obtained in hexadecane, toluene and chloroform have been investigated by optical microscopy and small-angle X-ray diffraction: the type of phase observed is related to the molecular structure of the compounds and depends dramatically on the solvent. The structures of the phases are discussed, with the presence of the two different ribbons being taken into account.
Historical Perspective on Scan Compression (2008)

Since gaining popularity in the late 1990s, the term "scan compression" has maintained a solid hold within the IC test lexicon. In recent years, however, this technology has taken the test industry by storm. As the cost of test increased to previously unseen heights, some companies complained that the cost to test a single transistor was nearly equal to the cost of manufacturing it. Scan compression technology, however, proved to be a powerful antidote to this problem, as it catalyzed reductions in test data volume and test application time of up to 100x. As a result, the cost of test may well be contained for many years to come. This article sketches a brief history of test technology research that has led to the stunning success of scan compression. This article is not intended to attribute inventors for innovations on a fine-grained timeline. The important concepts of technologies are presented at the high level on a coarse timeline.
How far 3D shapes can be understood from 2D silhouettes (1995)

Each 2D silhouette of a 3D unknown object O constrains O inside the volume obtained by back-projecting the silhouette from the corresponding viewpoint. A set of silhouettes specifies a boundary volume R obtained by intersecting the volumes due to each silhouette. R more or less closely approximates O, depending on the viewpoints and the object itself. This approach to the reconstruction of 3D objects is usually referred to as volume intersection. This correspondence addresses the problem of inferring the shape of the unknown object O from the reconstructed object R. For doing this, the author divides the points of the surface of R into hard points, which belong to the surface of any possible object originating R, and soft points, which may or may not belong to O. The author considers two cases: In the first case R is the closest approximation of O which can be obtained from its silhouettes, i.e., its visual hull; in the second case, R is a generic reconstructed object. In both cases the author supplies necessary and sufficient conditions for a point to be hard and gives rules for computing the hard surfaces.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>