gebhart/patrepeval huggingface dataset:
Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase– and cathepsin-dependent emphysema (2000)

Cigarette smoke exposure is the major cause of chronic obstructive pulmonary disease (COPD). However, only a minority of smokers develop significant COPD, and patients with asthma or asthma-like airway hyperresponsiveness or eosinophilia experience accelerated loss of lung function after cigarette smoke exposure. Pulmonary inflammation is a characteristic feature of lungs from patients with COPD. Surprisingly, the mediators of this inflammation and their contributions to the pathogenesis and varied natural history of COPD are not well defined. Here we show that IL-13, a critical cytokine in asthma, causes emphysema with enhanced lung volumes and compliance, mucus metaplasia, and inflammation, when inducibly overexpressed in the adult murine lung. MMP-2, -9, -12, -13, and -14 and cathepsins B, S, L, H, and K were induced by IL-13 in this setting. In addition, treatment with MMP or cysteine proteinase antagonists significantly decreased the emphysema and inflammation, but not the mucus in these animals. These studies demonstrate that IL-13 is a potent stimulator of MMP and cathepsin-based proteolytic pathways in the lung. They also demonstrate that IL-13 causes emphysema via a MMP- and cathepsin-dependent mechanism(s) and highlight common mechanisms that may underlie COPD and asthma.
Peptide-mediated modulation of T-cell allorecognition. (1988)

Antigen-specific helper T cells recognize a complex of peptide antigen and class II major histocompatibility complex (MHC) gene products. Whether T cells recognize MHC class II alloantigen by a similar mechanism or the native conformation of MHC molecules themselves has yet to be determined. The demonstration that peptide antigens bind directly and specifically to class II molecules has allowed us to examine the influence of foreign peptide binding on T-cell recognition of allogeneic MHC molecules. We report here that an immunodominant, HLA-DR1-restricted peptide of influenza virus hemagglutinin (HA residues 306-320) is able to modulate the recognition of alloantigen by human DR1-specific T-cell clones. For some T-cell clones, but not all, the HA peptide inhibited allorecognition in a dose-dependent manner. However, in one instance, the proliferative response to alloantigen was enhanced in the presence of HA peptide. These results suggest that the specificities of T-cell responses to allogeneic MHC molecules are heterogeneous, which may be influenced by different peptides occupying the class II MHC combining site and by the diversity of antigen-specific receptors of T lymphocytes recognizing the same MHC/peptide complex.
High-Flux SAPO-34 Membrane for CO2/N2 Separation (2010)

SAPO-34 membranes, synthesized by using multiple templates and reduced crystallization time, showed high CO2 permeability for separating CO2/N2 mixtures up to 230 °C. At a trans-membrane pressure drop of 138 kPa and an atmospheric pressure in the permeate side, one such membrane had a CO2 permeance of 1.2 × 10−6 mol/m2·s·Pa (= 3500 GPU) with a CO2/N2 separation selectivity of 32 for a 50/50 feed at 22 °C. At a feed pressure of 2.3 MPa (23 bar), the CO2 flux was as high as 75 kg/m2 h. The CO2/N2 separations were also investigated in part by using vacuum permeate pumping, where the membrane showed a CO2 permeance of 7.7 × 10−7 mol/m2·s·Pa and a CO2 permeate concentration of 93% for an equimolar feed at 22 °C. At 105 °C, adding 8% water vapor to the feed had almost no effect on the CO2/N2 separation selectivity. The CO2 permeance decreased by 37%, but it was recovered by calcination.
Probabilistic manipulation of entangled photons (2001)

We propose probabilistic controlled-NOT and controlled-phase gates for qubits stored in the polarization of photons. The gates are composed of linear optics and photon detectors, and consume polarization entangled photon pairs. The fraction of the successful operation is only limited by the efficiency of the Bell-state measurement. The gates work correctly under the use of imperfect detectors and lossy transmission of photons. Combined with single-qubit gates, they can be used for producing arbitrary polarization states and for designing various quantum measurements.
Cell cycle co-ordination in embryo cloning by nuclear transfer (1996)

Exciting new opportunities in embryo cloning have been made possible by recent studies on the interaction of the donor nucleus with the recipient cytoplasm after embryo reconstruction. This article reviews information regarding the co-ordination of nuclear and cytoplasmic events during embryo reconstruction, in particular the direct and indirect effects of maturation/ meiosis/mitosis-promoting factor (MPF), upon the transferred nucleus. This will be discussed in relation to DNA replication, the maintenance of correct ploidy, the occurrence of chromosomal abnormalities and development of reconstructed embryos. Although this review is primarily concerned with the reconstruction of mammalian embryos, specific examples from amphibians will also be cited.
Mitochondrial/Cell-Surface Protein p32/gC1qR as a Molecular Target in Tumor Cells and Tumor Stroma (2008)

A tumor homing peptide, LyP-1, selectively binds to tumor-associated lymphatic vessels and tumor cells in certain tumors and exhibits an antitumor effect. Here, we show that the protein known as p32 or gC1q receptor is the receptor for LyP-1. Various human tumor cell lines were positive for p32 expression in culture, and the expression was increased in xenograft tumors grown from the positive cell lines. Fluorescence-activated cell sorting analyses with anti-p32 antibodies showed that p32-positive cell lines expressed p32 at the cell surface. These cells bound and internalized LyP-1 peptide in proportion to the cell-surface expression level, which correlated with malignancy rather than total p32 expression in the cells. Like the LyP-1 peptide, p32 antibodies highlighted hypoxic areas in tumors, where they bound to both tumor cells and cells that expressed macrophage/myeloid cell markers and often seemed to be incorporated into the walls of tumor lymphatics. Significant p32 expression was common in human cancers and the p32 levels were often greatly elevated compared with the corresponding normal tissue. These results establish p32, particularly its cell-surface-expressed form, as a new marker of tumor cells and tumor-associated macrophages/myeloid cells in hypoxic/metabolically deprived areas of tumors. Its unique localization in tumors and its relative tumor specificity may make p32 a useful target in tumor diagnosis and therapy.
Ionic mechanisms of anoxic injury in mammalian CNS white matter: role of Na+ channels and Na(+)-Ca2+ exchanger (1992)

White matter of the mammalian CNS suffers irreversible injury when subjected to anoxia/ischemia. However, the mechanisms of anoxic injury in central myelinated tracts are not well understood. Although white matter injury depends on the presence of extracellular Ca2+, the mode of entry of Ca2+ into cells has not been fully characterized. We studied the mechanisms of anoxic injury using the in vitro rat optic nerve, a representative central white matter tract. Functional integrity of the nerves was monitored electrophysiologically by quantitatively measuring the area under the compound action potential, which recovered to 33.5 +/- 9.3% of control after a standard 60 min anoxic insult. Reducing Na+ influx through voltage-gated Na+ channels during anoxia by applying Na+ channel blockers (TTX, saxitoxin) substantially improved recovery; TTX was protective even at concentrations that had little effect on the control compound action potential. Conversely, increasing Na+ channel permeability during anoxia with veratridine resulted in greater injury. Manipulating the transmembrane Na+ gradient at various times before or during anoxia greatly affected the degree of resulting injury; applying zero-Na+ solution (choline or Li+ substituted) before anoxia significantly improved recovery; paradoxically, the same solution applied after the start of anoxia resulted in more injury than control. Thus, ionic conditions that favored reversal of the normal transmembrane Na+ gradient during anoxia promoted injury, suggesting that Ca2+ loading might occur via reverse operation of the Na+)-Ca2+ exchanger. Na(+)-Ca2+ exchanger blockers (bepridil, benzamil, dichlorobenzamil) significantly protected the optic nerve from anoxic injury. Together, these results suggest the following sequence of events leading to anoxic injury in the rat optic nerve: anoxia causes rapid depletion of ATP and membrane depolarization leading to Na+ influx through incompletely inactivated Na+ channels. The resulting rise in the intracellular [Na+], coupled with membrane depolarization, causes damaging levels of Ca2+ to be admitted into the intracellular compartment through reverse operation of the Na(+)-Ca2+ exchanger. These observations emphasize that differences in the pathophysiology of gray and white matter anoxic injury are likely to necessitate multiple strategies for optimal CNS protection.
Autocrine transformation by chimeric signal peptide-basic fibroblast growth factor: reversal by suramin. (1990)

NIH 3T3 cells transfected with basic fibroblast growth factor (bFGF) fused to an immunoglobulin signal peptide sequence are transformed in vitro and tumorigenic in vivo. The transformed phenotype of chimeric signal peptide-bFGF (spbFGF) cells is characterized by an enhanced proliferation rate compared to parental NIH 3T3 cells, density- and anchorage-independent growth, a transformed morphology, and lack of cell adhesion. The rate of spbFGF cell proliferation is not diminished by anti-bFGF neutralizing antibodies. 125I-labeled bFGF receptor cross-linking and binding studies suggest that surface FGF receptors in spbFGF cells are unavailable and down-regulated. The FGF receptors are also down-regulated in K-fgf-transformed cells but not in parental 3T3, native bFGF-transfected, and ras-transformed NIH 3T3 cells. The addition of suramin to spbFGF and K-fgf cells rapidly promotes the up-regulation of FGF receptors. Suramin also induces lowering of the proliferation rate to that of parental cells, anchorage-dependent growth, assembly of cytoskeletal filaments, cellular adhesion, and spreading. These results suggest that spbFGF cells undergo autocrine transformation, possibly by an internal autocrine loop, in which there is constitutive activation of the FGF receptor. Suramin inhibits autocrine transformation, leading to a normal untransformed phenotype.
Murine epidermal antigen-presenting cells in primary and secondary T-cell proliferative responses to herpes simplex virus in vitro. (1991)

The role of epidermal Langerhans' cells in infection with herpes simplex virus (HSV) was investigated using a culture system that supports antigen-specific primary and secondary T-cell proliferative responses. Epidermal cell suspensions were capable of restimulating the response of in vivo primed T cells to UV-inactivated HSV. This capability was also present in cell suspensions enriched for Langerhans' cells, but was abrogated by the depletion of I-A-bearing cells. The magnitude, kinetics and phenotype of the responding cells were similar to those elicited when HSV was presented to primed T cells by antigen-presenting cells from the spleen. In marked contrast, whereas splenic antigen-presenting cells induced strong antigen-specific proliferation of unprimed T cells (primarily of the helper phenotype), Langerhans' cells failed to invoke any detectable reaction of such cells.
Varicella-zoster virus Fc receptor gE glycoprotein: serine/threonine and tyrosine phosphorylation of monomeric and dimeric forms (1997)

Varicella-zoster virus (VZV) glycoprotein gE is the predominant viral cell surface molecule; it behaves as an Fc receptor for immunoglobulin G, but its central function may be more closely related to viral egress and cell-to-cell spread. To further analyze the receptor properties of VZV gE, the gE gene (also called open reading frame 68) was expressed by a baculovirus vector in insect cells. The recombinant baculovirus gE product had a molecular mass of 64 kDa, smaller than the previously documented 98 kDa of mature gE expressed in mammalian cells. The major reason for the lowered molecular mass was diminished glycosylation. In addition to the 64-kDa form, a larger (130-kDa) form was observed in insect cells and represented dimerized 64-kDa molecules. Both the monomeric and dimeric gE forms were highly phosphorylated in insect cells. Protein kinase assays conducted in vitro with [gamma-32P]ATP and [gamma-32P]GTP indicated that endogenous casein kinase II was phosphorylating monomeric gE, while the dimeric gE form was phosphorylated by another kinase which did not utilize [gamma-32P]GTP. When immobilized recombinant gE molecules were probed with a monoclonal antibody which specifically recognizes a phosphotyrosine linkage, the gE dimer was found to be tyrosine phosphorylated whereas the monomer was not similarly modified. When recombinant gE produced in HeLa cells was probed with the same antiphosphotyrosine antibody, a dimeric gE form at 130 kDa was detected on the cell surface. These results suggested that VZV gE closely resembled other cell surface receptors, being modified on its various forms by both serine/threonine and tyrosine protein kinases. In this case, tyrosine phosphorylation occurred on a previously unrecognized and underglycosylated VZV gE dimeric product.
Integrative analysis of shared genetic pathogenesis by obsessive‑compulsive and eating disorders (2018)

A number of common pathological features have been observed in obsessive‑compulsive disorder (OCD) and eating disorders (EDs). The present study examined the association between OCD and EDs at the genetic level in order to gain an improved understanding of the shared genetic basis of the diseases and identify novel potential risk genes for the two diseases. An integrated analysis using large‑scale disease‑gene association data and gene expression data was conducted. Disease‑gene association data were acquired from the Pathway Studio Mammalian database. Gene expression data were acquired from samples of 133 subjects, including 15 ED cases, 16 OCD cases and 102 normal controls. Genes associated with OCD and ED presented significant overlap (21 genes, P=6.70x10‑34), serving roles within multiple common genetic pathways (top 10 pathway enrichment P<4.30x10‑7) that were implicated in the two diseases. A genetic network of 17 genes was constructed, through which OCD and ED were observed to influence each other. Expression analysis revealed four novel common significant genes for OCD and ED (oxytocin receptor, glutamate decarboxylase 2, neuropeptide Y and glutamate ionotropic receptor kainate type subunit 3). These genes demonstrated a strong functional association with the two diseases. The results of the present study supported the presence of complex genetic associations between OCD and ED. Genes associated with one disease are worthy of further investigation as potential risk factors for the other. The findings of the present study may provide novel insights into the understanding of the pathogenesis of OCD and ED.
Use of site-directed mutagenesis to define the limits of sequence variation tolerated for processing of the M13 procoat protein by the Escherichia coli leader peptidase (1991)

Leader peptidase cleaves the leader sequence from the amino terminus of newly made membrane and secreted proteins after they have translocated across the membrane. Analysis of a large number of leader sequences has shown that there is a characteristic pattern of small apolar residues at -1 and -3 (with respect to the cleavage site) and a helix-breaking residue adjacent to the central apolar core in the region -4 to -6. The conserved sequence pattern of small amino acids at -1 and -3 around the cleavage site most likely represents the substrate specificity of leader peptidase. We have tested this by generating 60 different mutations in the +1 to -6 domain of the M13 procoat protein. These mutants were analyzed for in vivo and in vitro processing, as well as for protein insertion into the cytoplasmic membrane. We find that in vivo leader peptidase was able to process procoat with an alanine, a serine, a glycine, or a proline residue at -1 and with a serine, a glycine, a threonine, a valine, or a leucine residue at -3. All other alterations at these sites were not processed, in accordance with predictions based on the conserved features of leader peptides. Except for proline and threonine at +1, all other residues at this position were processed by leader peptidase. None of the mutations at -2, -4, or -5 of procoat (apart from proline at -4) completely abolished leader peptidase cleavage in vivo although there were large effects on the kinetics of processing.(ABSTRACT TRUNCATED AT 250 WORDS)
Are Cost Benefits of Anticoagulation for Stroke Prevention in Atrial Fibrillation Underestimated? (2005)

Existing economic models underestimate the cost benefits of anticoagulation for stroke prevention because they do not adjust for poorer outcomes associated with cardioembolic strokes.
CMOS/SOS/LSI switching regulator control device (1978)

This paper will describe the simultaneous processing of enhancement and depletion-mode CMOS/SOS transistors, providing five flipflops, three opamps and two voltage comparators, supplying all of the A/D control functions necessary for pulsewidth modulated switching regulators.
Expression and crystallization of a soluble and functional form of an Fc receptor related to class I histocompatibility molecules. (1992)

Maternal transport of immunoglobulin to the newborn mammal is important for immune defense during the first weeks of independent life. Receptors for the Fc portion of IgG mediate the transfer of immunoglobulin from milk to the bloodstream of newborn mice and rats, by passage through intestinal epithelial cells. Neonatal Fc receptors (FcRn) isolated from intestinal epithelial cells of suckling rats bear a striking resemblance to class I histocompatibility molecules. The heavy chain of FcRn has sequence similarity in three extracellular domains to the corresponding domains of class I molecules, and the light chain of both types of molecules is beta 2-microglobulin. To facilitate biochemical characterization and crystallization of FcRn, we have expressed a secreted form, as well as two different lipid-linked forms solubilizable by phospholipase treatment. The lipid-linked forms are heterodimers consisting of beta 2-microglobulin and the extracellular portion of the heavy chain and are anchored to the membrane by a phosphatidylinositol linkage attached to either the heavy chain or beta 2-microglobulin. Cells expressing either lipid-linked form bind rat Fc, reproducing the known physiological pH dependence of binding. Secreted FcRn has been purified in yields up to 40 mg/liter from cell supernatants. Circular dichroism spectra of soluble FcRn appear similar to spectra of class I MHC molecules, suggesting that the similarities in primary sequence extend also to a similarity in secondary structure. Soluble FcRn crystallizes in a form amenable to a structure determination by x-ray diffraction methods, which will ultimately allow a detailed comparison of the two types of molecules.
Insulin Detemir Is Associated With More Predictable Glycemic Control and Reduced Risk of Hypoglycemia Than NPH Insulin in Patients With Type 1 Diabetes on a Basal-Bolus Regimen With Premeal Insulin Aspart (2003)

Treatment with insulin detemir resulted in more predictable glycemic control, with smoother plasma glucose profiles than NPH insulin and a significant reduction in the risk of hypoglycemia. The reduction in body weight with insulin detemir is a potential additional advantage. Regimens optimized for insulin detemir may be able to improve glycemic control beyond that possible with NPH insulin.
Effects of noradrenaline on membrane currents and action potential shape in smooth muscle cells from guinea‐pig ureter. (1994)

1. The effects of noradrenaline (NA) on action potential shape and underlying membrane currents were examined in single smooth muscle cells freshly isolated from the ureter of the guinea-pig. 2. The voltage-dependent Ca2+ current (ICa) elicited upon depolarization from -50 to 0 mV was reduced by 27% upon application of 10 microM NA. This reduction was inhibited or converted to potentiation by internal application of low molecular weight heparin or 5 mM EGTA, indicating that it may be mediated by Ca(2+)-dependent Ca2+ channel inactivation via inositol 1,4,5-trisphosphate production and subsequent Ca2+ release from intracellular Ca2+ storage sites. 3. In contrast, Ba2+ current (IBa) through Ca2+ channels was potentiated by 36% in the presence of 10 microM NA. Internal application of GTP gamma S made it difficult to remove potentiation of IBa by wash-out; internal application of GDP beta S abolished potentiation. 4. NA caused a greater reduction in the transient Ca(2+)-dependent K+ current (IK(Ca)) upon depolarization than it did in ICa. This reduction was inhibited by internally applied heparin, suggesting that the amount of releasable Ca2+ in the storage sites was markedly reduced in the presence of NA. The sustained component of IK(Ca) which gradually increased during depolarization was also reduced by NA. 5. Action potential duration, which was recorded in a standard solution containing Ca2+, was prolonged by the application of NA. 6. It can be concluded that Ca2+ channel activity in ureter smooth muscle cells is regulated by a dual mechanism: Ca(2+)-dependent inhibition and GTP-binding protein-mediated potentiation. Under physiological conditions, both ICa and IK(Ca) were reduced by NA but the reduction of IK(Ca) was much larger than that of ICa; this results in an increase in net inward current during the action potential plateau and prolongs the action potential.
Avidity and Subclasses of IgG after Immunization of Infants with an 11‐Valent Pneumococcal Conjugate Vaccine with or without Aluminum Adjuvant (2001)

Finnish and Israeli infants received an 11-valent mixed-carrier pneumococcal conjugate vaccine with or without aluminum adjuvant at 2, 4, 6, and 12 months of age. The relative avidity of serotype 1-, 5-, 6B-, 14-, 19F-, and 23F-specific IgG antibodies in serum obtained at 7, 12, and 13 months of age was measured by EIA, using thiocyanate as a chaotropic agent. For all serotypes, except 14, avidity increased between the ages of 7 and 12 months. After boosting at 12 months, avidity further increased for all serotypes. The adjuvant improved antibody avidity against serotype 5. The IgG antibodies produced were mainly IgG1 subclass, although some infants also produced IgG2 after boosting. In conclusion, the immunization of infants with this 11-valent pneumococcal conjugate vaccine increased avidity of IgG, suggesting successful immunologic priming.
Use of Atomic Force Microscopy for Making Addresses in DNA Coatings (2002)

Nanoscale DNA surfaces are manipulated by coating ultraflat gold with short thiolated single-stranded (ss) and double-stranded (ds) DNA. Hybridization and 6-mercapto-1-hexanol (MCH) are used to modulate the thickness of the layers, all the changes being monitored using atomic force microscopy (AFM) in situ. Short thiolated ssDNA forms irregular 3.5 nm thick coatings, which are converted into more uniform 6.0 nm thick layers upon hybridization with complementary DNA. Holes formed in a monolayer of short thiolated dsDNA can be partially filled with a longer length thiolated ssDNA, which then protrudes from the surface after hybridization with a complementary strand. MCH is used to modulate the depth of a ssDNA layer and improve hybridization to it.