gebhart/patrepeval huggingface dataset:
Endobronchial Infection in Cystic Fibrosis (1989)

In symptomatic patients with cystic fibrosis, the recovery of bacteria in an inflammatory exudate from the lower respiratory tract is strong evidence of endobronchitis. It is not known when this chronic infection begins, the etiologic agents during infancy or the mechanism of evolution from Haemophilus influenzae and Staphylococcus aureus to Pseudomonas aeruginosa. Antibiotic administration to "suppress" the infection in relatively well patients is an unproven benefit. During an exacerbation of bronchitis, administration of appropriate antibiotics decreases sputum bacterial density and is accompanied by decreased amounts of indicators of inflammation in sputum: pulmonary function improves, particularly that reflecting medium to small airway status. In the future aggressive diagnostic procedures will be followed by therapeutic and prophylactic antibiotic administration conducted in a manner to minimize emergence of antibiotic-resistant bacteria. Adjunctive therapy, to minimize those aspects of the host response which inflict lung damage, will become standard.
Intermolecular crosslinking of fatty acyl chains in phospholipids: use of photoactivable carbene precursors. (1979)

Phospholipids containing photolysable carbene precursors (beta-trifluoro-alpha-diazopropionoxy and m-diazirinophenoxy groups) in omega-positions of sn-2 fatty acyl chains were prepared. Photolysis of their vesicles produced crosslinked products in 40-60% yields. Crosslinking was mostly intermolecular and occurred by carbene insertion into the C-H bonds of a second fatty acyl chain. Crosslinking products were characterized by (i) their gel permeation behavior, (ii) analysis of products formed by base-catalyzed transesterification, (iii) degradation with phospholipases A2 and C, (iv) gas chromatography/mass spectrometry, and (v) use of mixtures of phospholipids carrying the carbene precursors and a phospholipid containing radioactively labeled fatty acyl groups. Nitrenes generated from the aliphatic or aromatic azido groups in phospholipids were unsatisfactory for forming crosslinks by insertion in C-H bonds.
Cellular and Cytokine-Mediated Mechanisms of Inflammation and its Modulation in Immune-Mediated Liver Injury (2007)

The immune response to foreign or self antigens mediates liver damage during viral or autoimmune hepatitis. However, it now appears that also specific antigen-independent liver diseases, where liver damage has been attributed to occur from oxygen radical formation, seem to be mediated by cells of the innate and adaptive immune response. These liver disorders include alcoholic liver disease, non-alcoholic fatty liver disease or non-alcoholic steatohepatitis, and ischemia/reperfusion injury that impairs the function of liver grafts. Here it seems that breakdown of the gastrointestinal barrier might increase the concentration of bacterial toxins in the portal blood, which then activate cells of the innate immune system, e. g., Kupffer cells, but, depending on the nature of the toxin, probably also conventional T cells. Invariant NKT cells which specifically recognize glycolipid antigens were supposed to become activated during metabolic disorders related to obesity. However, both steatohepatitis as well as ischemia/reperfusion injury are associated with a Th1 cytokine response characterized by IFNgamma and TNFalpha elevation, that might reflect an NKT cell response on the one hand, but also conventional T lymphocytes, in particular CD4 (+) T cells, are critical for the pathophysiology of these disorders. In 1992 we described a model of T cell-dependent liver injury inducible by the T cell-mitogenic lectin concanavalin A. This model of immune-mediated liver injury was intensively used to study pathophysiological immune effector mechanisms as well as cytokine signaling important for hepatocellular apoptosis, inhibition of apoptosis and regeneration. Recently it became evident that the inflammatory response in this model is regulated by specific cytokine signals as well as by immune regulator cells. The immune-regulatory functions of the liver are of particular interest with respect to the scavenger function of this organ, being continuously exposed to foreign antigenic material from the gut which should be eliminated without causing chronic disease.
Emergence of Idiotype Variants during Treatment of B-Cell Lymphoma with Anti-Idiotype Antibodies (1985)

We studied two patients with malignant B-cell lymphoma that manifested resistance to the therapeutic effects of anti-idiotype antibody because of the emergence of subclones with changes in their immunoglobulin idiotypes. In both patients, tumor-cell populations arose that were unreactive with anti-idiotype antibody but that retained surface immunoglobulin. One of the patients had an additional subpopulation of tumor cells that had switched from mu to gamma heavy-chain expression. Study of the immunoglobulin genes in the tumors confirmed that the subpopulations were derived from the same original clone of neoplastic B cells in each patient. The available data suggest that the idiotypic variation observed was the result of somatic mutation in the variable region of the active immunoglobulin genes. The fact that such mutations became evident over a short time and in the context of a partial tumor response suggests that the antibody therapy exerted a strong selective force against tumor cells that expressed the idiotype determinant. Multiple anti-idiotype antibodies may therefore be needed to identify all cells of a malignant clone, and some patients may require treatment with more than one monoclonal antibody.
Identification and purification of a hemoglobin-binding outer membrane protein from Neisseria gonorrhoeae (1996)

The majority of in vitro-grown Neisseria gonorrhoeae strains were unable to use hemoglobin as the sole source of iron for growth (Hgb-), but a minor population was able to do so (Hgb+). The ability of Hgb+ gonococci to utilize hemoglobin as the iron source was associated with the expression of an iron-repressible 89-kDa hemoglobin-binding protein in the outer membrane. The N-terminal amino acid sequence of this protein revealed amino acids, from positions 2 to 16, identical to those of HpuB, an 85 kDa iron-regulated hemoglobin-haptoglobin utilization outer membrane protein of Neisseria meningitidis. Isogenic mutants constructed by allelic replacement with a meningococcal hpu::mini-Tn3erm construct no longer expressed the 89-kDa protein. Mutants could not utilize hemoglobin to support growth but still grew on heme. Thus, the gonococcal HpuB homolog is a functional hemoglobin receptor and is essential for growth with hemoglobin.
Evidence for the ventral origin of oligodendrocyte precursors in the rat spinal cord (1991)

The neuroepithelial cells of the mammalian neural tube are thought to give rise to all classes of differentiated neurons and macroglial cells in the adult CNS. In most cases, the regulation and timing of commitment of neuroepithelial cells to specific differentiative pathways are unknown. It has been proposed that in developing spinal cord, the macroglial cells--astrocytes and oligodendrocytes--arise either by the direct transformation of radial glial cells in the developing cord or, alternatively, by the differentiation of distinct precursor cells which migrate to presumptive white matter from the region of the central canal during development. In this study, the timing of oligodendrocyte differentiation in different levels of the spinal cord and the capacity of specific regions of the spinal cord to give rise to oligodendrocytes at various ages was tested in vitro. At embryonic day 14, all complete segments, as well as all ventral regions along the rostral-caudal axis of the spinal cord, have the capacity for oligodendrogenesis. By contrast, dorsal regions of the thoracic and lumbar spinal cord do not develop the capacity for oligodendrogenesis until later in development. The capacity of dorsal rat spinal cord to give rise to oligodendrocytes appears to be associated with the ventral-to-dorsal migration of oligodendrocyte precursors. These observations suggest that commitment to an oligodendrocyte differentiative pathway appears to occur in a distinct population of ventrally located glial precursors in the embryonic rat spinal cord.
DNA gyrase, topoisomerase IV, and the 4-quinolones (1997)

For many years, DNA gyrase was thought to be responsible both for unlinking replicated daughter chromosomes and for controlling negative superhelical tension in bacterial DNA. However, in 1990 a homolog of gyrase, topoisomerase IV, that had a potent decatenating activity was discovered. It is now clear that topoisomerase IV, rather than gyrase, is responsible for decatenation of interlinked chromosomes. Moreover, topoisomerase IV is a target of the 4-quinolones, antibacterial agents that had previously been thought to target only gyrase. The key event in quinolone action is reversible trapping of gyrase-DNA and topoisomerase IV-DNA complexes. Complex formation with gyrase is followed by a rapid, reversible inhibition of DNA synthesis, cessation of growth, and induction of the SOS response. At higher drug concentrations, cell death occurs as double-strand DNA breaks are released from trapped gyrase and/or topoisomerase IV complexes. Repair of quinolone-induced DNA damage occurs largely via recombination pathways. In many gram-negative bacteria, resistance to moderate levels of quinolone arises from mutation of the gyrase A protein and resistance to high levels of quinolone arises from mutation of a second gyrase and/or topoisomerase IV site. For some gram-positive bacteria, the situation is reversed: primary resistance occurs through changes in topoisomerase IV while gyrase changes give additional resistance. Gyrase is also trapped on DNA by lethal gene products of certain large, low-copy-number plasmids. Thus, quinolone-topoisomerase biology is providing a model for understanding aspects of host-parasite interactions and providing ways to investigate manipulation of the bacterial chromosome by topoisomerases.
TERMITE (ISOPTERA) SUPPRESSION WITH TOXIC BAITS (1975)

Abstract A field trial with toxic-bait blocks for suppression of subterranean termite activity was initiated in Toronto. Decayed, mirex-impregnated red pine wood blocks 2.5 × 3.8 × 0.5 cm were placed individually in soil at 1.5-m intervals. Attack on bait blocks effectively suppressed termite activity for 3 years in the eight plots. The method offers a cheaper, environmentally sound, effective alternative to conventional soil-poisoning methods.
Ethyl 9-adeninylacetate at 122 K (1994)

The structure of the title compound, C 9 H 11 N 5 O 2 , at 122 K has been established by X-ray diffraction methods. The ethyl acetate moiety is virtually planar and almost perpendicular to the adenine ring system. Hydrogen bonds between the amino groups and two adenine N atoms connect the molecules in chains parallel to the c axis
In vivo enhanced antitumor activity of carmustine [N,N'-bis(2-chloroethyl)-N-nitrosourea] by simvastatin. (1995)

The effects of a combination of simvastatin, a cholesterol-lowering agent, and carmustine (BCNU; N,N'-bis(2-chloroethyl)-N-nitrosourea) on experimental C6 glioma were studied in vitro and in vivo. In vitro simvastatin and BCNU alone inhibited cell proliferation in a dose-dependent fashion. A subliminal concentration of simvastatin (0.1 microM) markedly and synergistically increased the BCNU toxicity to C6 glioma cells. The cytofluorimetric analysis of DNA from simvastatin-treated C6 glioma cells showed, besides the already described arrest in G1, an arrest/retardation in G2-M. Mitotic index from C6 cells incubated with simvastatin (10 microM) decreased by about 90%, indicating a specific C6 arrest/retardation in G2. The drug effects could be completely reversed by simvastatin withdrawal or mevalonate addition to the cultured cells. The combination of simvastatin and BCNU resulted predominantly from the profound retardation of cells in the G2-M compartment of the cell cycle. In vivo simvastatin (administered daily mixed with food) and BCNU (single i.p. injection), when given separately, caused a dose-dependent inhibition of labeling index in C6 glioma homografts (ID50, 61 mg/kg/day and 8.7 mg/kg, respectively). The combination of the lowest doses tested (simvastatin, 25 mg/kg/day and BCNU 0.3 mg/kg) resulted in a significant growth delay (compared to either drug alone) in C6 glioma (P < 0.05). There was no significant increase in toxicity as assessed by myelosuppression (WBC counts and bone marrow labeling index) and body weight. The results provide in vivo support for the combined use of simvastatin, a cholesterol-lowering agent, and BCNU in brain tumor treatment.
Recombinant IL-12 administration induces tumor regression in association with IFN- gamma production. (1994)

Recent evidence supports the critical and proximate role of IL-12 in regulating both T and NK cell function during inflammation. In these studies, we evaluated the in vivo antitumor activity of murine IL-12 in murine adenocarcinoma and sarcoma models using both systemic and peritumoral administration. Antitumor effects were consistently demonstrated both in models of microdisease, in which IL-12 treatment was initiated soon after tumor inoculation (1 to 5 days), and in animals bearing large established tumors (7 to 14 days). Treatment with IL-12 markedly prolonged survival and, in most cases, caused complete tumor regression. Significant reduction in pulmonary metastases after systemic treatment was observed when treatment was delayed for 10 days after tumor inoculation. Increases in serum IFN-gamma, TNF-alpha, and nitrogen oxides were demonstrated, exceeding those observed with IL-2 treatment. Systemic administration of anti-IFN-gamma Abs before IL-12 treatment nearly completely abrogated the antitumor effect in experiments using subcutaneous tumors or pulmonary metastases. Depletion of the individual T cell subsets CD4 and CD8 by systemic administration of mAbs diminished the effectiveness of IL-12 when administered in combination. An infiltrate composed primarily of CD8+ + cells was demonstrated by using immunohistochemical analysis of tumors after IL-12 treatment. Minimal apparent toxicity was demonstrated at effective doses (0.1 to 1.0 microgram/day) of IL-12. These results indicate that IL-12 is an effective and minimally toxic antitumor agent in murine tumor models and leads to an immune-mediated rejection involving, at least in part, IFN-gamma, CD4+, and CD8+ cells. Human clinical trials of IL-12 for the treatment of malignancy are supported by these studies.
Interaction of Yersinia enterocolitica with macrophages leads to macrophage cell death through apoptosis (1997)

Suppression of the host defense is one of the hallmarks of Yersinia enterocolitica infection. This enteric pathogen resists phagocytosis and interferes with macrophage functions from an extracellular localization (oxidative-burst generation and tumor necrosis factor alpha production). In this study, we investigated the fate of the Y. enterocolitica-infected macrophage. We found that murine J774A.1 macrophages and macrophages derived from human monocytes were killed by infection with Y. enterocolitica. Analysis of cellular morphology and DNA fragmentation revealed that macrophage cell death occurs through the induction of apoptosis. A total of 92% +/- 5% (mean +/- standard deviation) of murine J774A.1 macrophages and 74% +/- 6% of human monocyte-derived macrophages underwent apoptosis upon Yersinia infection after 4 and 20 h, respectively. The broad-spectrum caspase inhibitor Z-Val-Ala-DL-Asp-fluoromethylketone blocked completion of the Yersinia-induced apoptotic program but not the surface exposure of phosphatidylserine as an early-stage apoptotic event. Analysis of different Yersinia mutants showed that macrophage apoptosis depends on a functional Y. enterocolitica type III protein secretion system. Apoptotic cell death of macrophages was not related to the YopE-mediated cytotoxic effect of Yersinia, since disruption of actin microfilaments by a Y. enterocolitica strain expressing a restricted repertoire of yop genes, including YopE, did not result in macrophage apoptosis. Furthermore, Yersinia-induced cytotoxic alterations in epithelial HeLa cells, which are conferred by YopE, did not lead to apoptosis. Our data demonstrate for the first time that Y. enterocolitica promotes the apoptosis of macrophages, an effect which is clearly distinct from the morphological alterations mediated by Yersinia on epithelial HeLa cells.
Adiabatic elimination for open quantum systems with effective Lindblad master equations (2016)

We consider an open quantum system described by a Lindblad-type master equation with two time scales. The fast time scale is strongly dissipative and drives the system towards a low-dimensional decoherence-free space. To perform the adiabatic elimination of this fast relaxation, we propose a geometric asymptotic expansion based on the small positive parameter describing the time scale separation. This expansion exploits geometric singular perturbation theory and center-manifold techniques. We conjecture that, at any order, it provides an effective slow Lindblad master equation and a completely positive parameterization of the slow invariant sub-manifold associated to the low-dimensional decoherence-free space. By preserving complete positivity and trace, two important structural properties attached to open quantum dynamics, we obtain a reduced-order model that directly conveys a physical interpretation since it relies on effective Lindbladian descriptions of the slow evolution. At the first order, we derive simple formulae for the effective Lindblad master equation. For a specific type of fast dissipation, we show how any Hamiltonian perturbation yields Lindbladian second-order corrections to the first-order slow evolution governed by the Zeno-Hamiltonian. These results are illustrated on a composite system made of a strongly dissipative harmonic oscillator, the ancilla, weakly coupled to another quantum system.
Selective Acylation of 1-Acylglycerophosphorylinositol by Rat Brain Microsomes (1973)

Rat brain microsomes were shown to acylate 1-acylglycerophosphorylinositol (1-acylGPI) when incubated with radioactive fatty acids, ATP, CoA and MgCl2, or with chemically synthesized acyl esters of CoA. Both acylation systems showed a concentration dependence on added lysolipid acceptor and free fatty acids, cofactors, or CoA esters. With free fatty acids, relative acylation rates varied with concentration of lysolipid; at low levels arachidonate, linoleate, and oleate were superior to palmitate and stearate, but at higher levels the differential was greatly reduced. With CoA esters, acylation of 1-acylGPI was determined either spectrophotometrically or by measuring radioactivity incorporated from 14C- or 3H-labeled acyl-CoA. The radioassay showed that a large proportion of acyl groups was incorporated into polyphosphoinositides, principally phosphatidylinositol phosphate, as well as phosphatidylinositol, possibly as a result of the concerted action of acyltransferase and membrane-bound phosphatidylinositol kinase. Acylation rates were much higher with acyl-CoA esters than with free fatty acids and cofactors. The most striking feature was that rates with arachidonoyl-CoA were 2 to 5 times higher than with linoleoyl-, linolenoyl-, or eicosatrienoyl-CoA and 5 to 10 times higher compared with oleoyl- and docosahexaenoyl-CoA. Positional analysis of the labeled products with snake venom phospholipase A2 showed that unsaturated acyl groups were incorporated almost exclusively into the 2-position of inositol lipid but 25 to 30% of radioactivity from palmitoyl- and stearoyl-CoA appeared in the 1-position, indicating that some isomerization of the lysolipid acceptor had occurred. Maximal acylation of 1-acylglycerophosphorylcholine (1-acylGPC) occurred under conditions similar to that for the inositol lipid, but a somewhat different selectivity was shown. Acylation rates with 1-acylGPC were the same or higher than for the inositol lipid except with arachidonoyl-CoA, where the rate with 1-acylGPI was 2 to 3 times higher than with 1-acylGPC. It is suggested that the acylation of 1-acylGPI constitutes an important and highly selective mechanism for achieving the strict species specificity exhibited by inositides in rat brain. The marked difference in acylation rates between arachidonoyl-CoA (20:4, n-6) and eicosatrienoyl-CoA (20:3, n-6) indicates that the double bond between carbons 5 and 6 may be critical in directing enzyme selectivity for arachidonoyl-CoA.
Novel Members of the Two-Component Signal Transduction Genes in Escherichia coli1 (1993)

A variety of adaptive response systems in prokaryotes often involve two families (two components) of signal transduction proteins, namely, sensory kinases and response-regulators. To extend the list of such sensor/regulator genes for Escherichia coli, we adopted a random screening method in this study. In particular, we isolated a series of recombinant plasmids that are able phenotypically to suppress mutational lesions of both the envZ and phoR/creC genes, each of which encodes a well-characterized sensory-kinase. Among the recombinant plasmids thus isolated, two clones (named pSN11 and pSN25) were subjected to characterization in detail. These analyses allowed us to identify the genetic loci specifying novel members of the sensor/regulator families. One (pSN11) is located around 45 min on the E. coli genetic map, that contains two adjacent coding-sequences (baeS and baeR). The other (pSN25) is located around 93 min of the genetic map, that also comprises two adjacent coding-sequences (basS and basR). These two pairs of gene-products, thus newly identified, were revealed to belong to typical members of the sensor/regulator families. Furthermore, they were demonstrated to exhibit the in vitro phosphotransfer reaction in the presence of ATP, that is also a characteristic of the sensory-kinase and response-regulator proteins.
High Electrical Conductivity in Ni3(2,3,6,7,10,11-hexaiminotriphenylene)2, a Semiconducting Metal–Organic Graphene Analogue (2014)

Reaction of 2,3,6,7,10,11-hexaaminotriphenylene with Ni(2+) in aqueous NH3 solution under aerobic conditions produces Ni3(HITP)2 (HITP = 2,3,6,7,10,11-hexaiminotriphenylene), a new two-dimensional metal-organic framework (MOF). The new material can be isolated as a highly conductive black powder or dark blue-violet films. Two-probe and van der Pauw electrical measurements reveal bulk (pellet) and surface (film) conductivity values of 2 and 40 S·cm(-1), respectively, both records for MOFs and among the best for any coordination polymer.
Identification and Enzymatic Characterization of the Maltose-Inducible α-Glucosidase MalL (Sucrase-Isomaltase-Maltase) of Bacillus subtilis (1998)

A gene coding for a putative alpha-glucosidase has been identified in the open reading frame yvdL (now termed malL), which was sequenced as part of the Bacillus subtilis genome project. The enzyme was overproduced in Escherichia coli and purified. Further analyses indicate that MalL is a specific oligo-1,4-1,6-alpha-glucosidase (sucrase-maltase-isomaltase). MalL expression in B. subtilis requires maltose induction and is subject to carbon catabolite repression by glucose and fructose. Insertional mutagenesis of malL resulted in a complete inactivation of the maltose-inducible alpha-glucosidase activity in crude protein extracts and a Mal- phenotype.