gebhart/patrepeval huggingface dataset:
Systemic suppression of delayed-type hypersensitivity by supernatants from UV-irradiated keratinocytes. An essential role for keratinocyte-derived IL-10 (1992)

Exposing murine keratinocyte cultures to UV radiation causes the release of a suppressive cytokine that mimics the immunosuppressive effects of total-body UV exposure. Injecting supernatants from UV-irradiated keratinocyte cultures into mice inhibits their ability to generate a delayed-type hypersensitivity reaction against allogeneic histocompatibility Ag, and spleen cells from mice injected with supernatant do not respond to alloantigen in the in vitro MLR. A unique feature of the immunosuppression induced by either total-body UV-exposure or injecting the suppressive cytokine from UV-irradiated keratinocytes is the selectivity of suppression. Although cellular immune reactions such as delayed-type hypersensitivity are suppressed antibody production is unaffected. Because the selective nature to the UV-induced immunosuppression is similar to the biologic activity of IL-10, we examined the hypothesis that UV exposure of keratinocytes causes the release of IL-10. Keratinocyte monolayers were exposed to UV radiation and at specific times after exposure mRNA was isolated or the culture supernatant from the cells was collected. IL-10 mRNA expression was enhanced in UV-irradiated keratinocytes. The secretion of IL-10 by the irradiated keratinocytes was determined by Western blot analysis. A band reactive with anti-IL-10 mAb was found in supernatants from the UV-irradiated but not the mock-irradiated cells. IL-10 biologic activity was determined by the ability of the supernatants from the UV-irradiated keratinocytes to suppress IFN-gamma production by Ag-activated Th 1 cell clones. Anti-IL-10 mAb neutralized the ability of supernatants from UV-irradiated keratinocytes to suppress the induction of delayed-type hypersensitivity in vivo. Furthermore, injecting UV-irradiated mice with antibodies against IL-10 partially inhibited in vivo immunosuppression. These data indicate that activated keratinocytes are capable of secreting IL-10 and suggest that the release of IL-10 by UV-irradiated keratinocytes plays an essential role in the induction of systemic immunosuppression after total-body UV exposure.
Antimitotic natural products combretastatin A-4 and combretastatin A-2: studies on the mechanism of their inhibition of the binding of colchicine to tubulin (1989)

Combretastatin A-4 (CS-A4), 3,4,5-trimethoxy-3'-hydroxy-4'-methoxy-(Z)-stilbene, and combretastatin A-2 (CS-A2), 3,4-(methylenedioxy)-5-methoxy-3'-hydroxy-4'-methoxy-(Z)-stilbene, are structurally simple natural products isolated from the South African tree Combretum caffrum. They inhibit mitosis and microtubule assembly and are competitive inhibitors of the binding of colchicine to tubulin [Lin et al. (1988) Mol. Pharmacol. 34, 200-208]. In contrast to colchicine, drug effects on tubulin were not enhanced by preincubating CS-A4 or CS-A2 with the protein. The mechanism of their binding to tubulin was examined indirectly by evaluating their effects on the binding of radiolabeled colchicine to the protein. These studies demonstrated rapid binding of both compounds to tubulin even at 0 degrees C (binding was complete at the earliest times examined), in contrast to the relatively slow and temperature-dependent binding of colchicine. Although the binding of the C. caffrum compounds to tubulin was quite tight, permitting ready isolation of near-stoichiometric amounts of drug-tubulin complex even in the absence of free drug, both CS-A4 and CS-A2 dissociated rapidly from tubulin in the presence of high concentrations of radiolabeled colchicine. Apparent rate constants for drug dissociation from tubulin at 37 degrees C were 3.2 x 10(-3) s-1 for CS-A4, 4.8 x 10(-3) s-1 for CS-A2, and 2.9 x 10(-5) s-1 for colchicine (half-lives of 3.6, 2.4, and 405 min, respectively). Thus, the effectiveness of the C. caffrum compounds as antimitotic agents appears to derive primarily from the rapidity of their binding to tubulin.(ABSTRACT TRUNCATED AT 250 WORDS)
Platinum-based nanocages with subnanometer-thick walls and well-defined, controllable facets (2015)

A cost-effective catalyst should have a high dispersion of the active atoms, together with a controllable surface structure for the optimization of activity, selectivity, or both. We fabricated nanocages by depositing a few atomic layers of platinum (Pt) as conformal shells on palladium (Pd) nanocrystals with well-defined facets and then etching away the Pd templates. Density functional theory calculations suggest that the etching is initiated via a mechanism that involves the formation of vacancies through the removal of Pd atoms incorporated into the outermost layer during the deposition of Pt. With the use of Pd nanoscale cubes and octahedra as templates, we obtained Pt cubic and octahedral nanocages enclosed by {100} and {111} facets, respectively, which exhibited distinctive catalytic activities toward oxygen reduction.
Structure and functions of the Bordetella tracheal cytotoxin. (1988)

Of the various toxins and virulence-related factors produced by Bordetella pertussis, only one has been demonstrated to reproduce the specific respiratory epithelial cytopathology characteristic of the pertussis syndrome. That molecule is tracheal cytotoxin (TCT), which is released by B. pertussis during log phase growth. An HPLC-based method has allowed us to purify TCT from culture supernatants, resulting in a preparation with undetectable levels of endotoxin and which is homogeneous by all analytical criteria, including fast atom bombardment-mass spectrometry (FAB-MS). Exposure to purified TCT specifically damages ciliated epithelial cells, causing ciliostasis and extrusion of these cells. Other species of Bordetella, which generate remarkably similar respiratory tract infections and ciliated cell-specific pathology, produce a chemically identical TCT. Compositional analysis and FAB-MS have unambiguously defined the structure of TCT as N-acetylglucosaminyl-1, 6-anhydro-N-acetylmuramylalanyl-gamma-glutamyl-diaminopimelylalanine+ ++. This particular disaccharide-tetrapeptide composition and arrangement reveals that TCT is apparently formed by cleavage of peptidoglycan. Unlike other gram-negative bacteria, however, B. pertussis seems to be very selective in its release of cell wall fragments: greater than 95% of soluble peptidoglycan in culture supernatants is TCT. The structure of TCT places it in the "muramyl peptide" family, a group of structurally related molecules that are responsible for a diverse array of biological activities. Neisseria gonorrhoeae also releases muramyl peptides (one of which is identical to TCT) that can cause ciliated cell-specific damage like that seen during gonococcal infection of fallopian tube mucosa. In addition, TCT is absolutely identical in structure to FSu, a potent sleep-promoting factor isolated from humans.(ABSTRACT TRUNCATED AT 250 WORDS)
Pharmacokinetics of cyclophosphamide and its metabolites in bone marrow transplantation patients* (1998)

The AUC of 4-hydroxycyclophosphamide increased from day 1 to day 2 as a result of increased formation and decreased elimination clearances of 4-hydroxycyclophosphamide. Aldehyde dehydrogenase-1 activity appears to decline as a consequence of cyclophosphamide administration.
AN IMPROVED SYNTHESIS OF 9-DEAZAGUANINE (2002)

A new, improved synthesis of 9-deazaguanine is described. The method involves use of the benzyloxymethyl group to protect the N 3-position of 2-[(dimethylaminomethylene)- amino]-6-methyl-5-nitro-4(3H)-pyrimidinone, followed by treatment with DMF-dimethylacetal, reductive cyclization, treatment with ethanolic ammonia and removal of the protecting group by catalytic hydrogenation.
Immunogenetic Factors Associated with Severe Respiratory Illness Caused by Zoonotic H1N1 and H5N1 Influenza Viruses (2011)

Following the 2009 H1N1 pandemic and ongoing sporadic avian-to-human transmission of H5N1 viruses, an emphasis has been placed on better understanding the determinants and pathogenesis of severe influenza infections. Much of the current literature has focused on viral genetics and its impact on host immunity as well as novel risk factors for severe infection (particularly within the H1N1 pandemic). An understanding of the host genetic determinants of susceptibility and severe respiratory illness, however, is currently lacking. By better defining the role of genetic variability in influenza infection and identifying key polymorphisms that impair the host immune response or correlate with protection, we will be able to better identify at-risk populations and new targets for therapeutic interventions and vaccines. This paper will summarize known immunogenetic factors associated with susceptibility or severity of both pH1N1 and H5N1 infections and will also identify genetic pathways and polymorphisms of high relevance for future study.
Smooth optimal control with Floquet theory (2013)

This paper describes an approach to construct temporally shaped control pulses that drive a quantum system toward desired properties. A parametrization in terms of periodic functions with predefined frequencies permits us to realize a smooth, typically simple shape of the pulses; their optimization can be performed based on a variational analysis with Floquet theory. As we show with selected specific examples, this approach permits us to control the dynamics of interacting spins, such that gate operations and entanglement dynamics can be implemented with very high accuracy.
The Enzyme Ribonucleotide Reductase: Target for Antitumor and Anti-HIV Therapy (1997)

Ribonucleotide reductase is the rate-limiting enzyme of DNA synthesis, and it has been shown to be linked with malignant transformation and tumor cell proliferation. It was therefore considered as an excellent target for cancer chemotherapy. This article reviews the in vitro and in vivo effects of hydroxyurea the first inhibitor of the enzyme, which is currently used in general clinical practice. In addition, we summarize the results obtained with other inhibitors of the enzyme; for instance, polyhydroxy-substituted benzohydroxamic acid derivatives, a promising group of inhibitors of ribonucleotide reductase that was synthesized by Bart van'T Riet and investigated by our group. In vitro as well as animal data and pharmacokinetic results are reviewed and possible implications for an improvement in the management of various patient groups are outlined.
Multivalent sialyl-LeX: potent inhibitors of E-selectin-mediated cell adhesion; reagent for staining activated endothelial cells (1994)

Free, monovalent, SLeX (Neu5Ac alpha 2-3Gal beta 1-4(Fuc alpha 1-3)-GlcNAc), SLn (Neu5Ac alpha 2-3Gal beta 1-4GlcNAc) and corresponding BSA-conjugated forms--displaying different ratios of SLeX and SLn to protein--were tested for their ability to inhibit binding of HL-60 cells to immobilized E-selectin. Free SLeX and conjugated SLeX-BSA inhibited cell binding in a dose-dependent manner. SLn and SLn-BSA did not inhibit binding. SLeX16BSA (16 mol tetrasaccharide/mol BSA) and monovalent SLeX inhibited cell binding with measured inhibitory concentrations (IC50S) of 1 microM and 1 mM, respectively, demonstrating a three-order-of-magnitude enhancement of inhibitory activity with the multivalent form of SLeX. A SLex7BSA conjugate was 10-fold less potent than those with 11 or 16 mol SLeX/mol BSA. An assay which measured neutrophil rolling on interleukin (IL)-1 beta-activated human umbilical vein endothelial cells (HUVECs) showed 50% reduction in the number of rolling neutrophils in the presence of 1 microM SLeX16BSA, whereas the level of free, monovalent SLeX oligosaccharide required to produce the same effect was approximately 0.3 mM. SLeX-BSA was found to be an excellent reagent for staining endothelial cells expressing E-selectin. Biotinylated SLeX-BSA in conjunction with Texas red avidin-stained lipopolysaccharide (LPS)-activated HUVECs, and co-incubation of activated cells with anti-E-selectin, specifically blocked staining. The distribution of E-selectin, as determined by binding of SLeX-BSA, was virtually identical with that obtained by binding of anti-E-selectin antibody.(ABSTRACT TRUNCATED AT 250 WORDS)
Insulating Properties of Self-Assembled Monolayers Monitored by Impedance Spectroscopy (2000)

The ionic insulating properties of n-alkylthiol self-assembled monolayers (SAMs) and a related fluorinated SAM are characterized by electrochemical ac impedance spectroscopy. CH3(CH2)nS/Au (n = 7−15) SAMs prepared via prolonged incubation in a thiol solution obey the Helmholtz ideal capacitor model and thus are virtually defect-free. The electrochemical properties of SAM-coated electrodes are compared with those of a bare gold electrode. The phase angle at an ion-diffusion-related frequency (1 Hz) is ≥ 88° and is independent of the electrolyte concentration. The thiol chains act as a dielectric material whose impedance (modulus) is 105 Ω cm2 at 1 Hz. Both the phase angle and the complex dielectric constant in the low-frequency region are good indicators of the film's ability to act as an ionic insulator.
ChemInform Abstract: COMPETITION BETWEEN THE DIPOLAROPHILIC AND NUCLEOPHILIC REACTIVITIES OF 2‐PYRAZOLINES IN THE PRESENCE OF BENZONITRILE OXIDE. SYNTHESIS, IDENTIFICATION, AND THE CHEMICAL BEHAVIOR OF TETRAHYDROPYRAZOLO(4,5‐B)‐1,2,4‐OXADIAZOLES (1979)

Abstract Die Reaktion der 2‐Pyrazoline (I) mit Benzonitriloxid (II) liefert Addukte (III) und (IV).
Adjuvant surgical decompression gastrostomy: audit of a procedure coming of age. (2004)

Adjuvant Stamm-Kader gastrostomy is a safe procedure. The incidence of pneumonia was comparatively low and a pertinent prophylactic effectivity appears plausible but remains unproven due to study design. Postoperative ileus exceeding 3 days affects 35%, exceeding 5 days 19% and exceeding 8 days only 7% of pertinent patients, and ileus duration cannot be predicted at the time of surgery. Thus, a substantial number of patients may be overtreated by prophylactic adjuvant surgical gastrostomy. The procedure improves patient's comfort and avoids complications of nasogastric suction. Prophylactic surgical gastrostomy remains a timely adjunct to general surgery but the indication should be individualized.
A inter-relação trabalho-saúde mental: um estudo de caso (1992)

A autora, após sintetizar algumas das vertentes de estudo e conceitos atuais na temática da inter-relação trabalho-saúde mental, apresenta um estudo de caso individual. Trata-se do caso de um mecânico industrial do setor siderúrgico que desenvolveu um quadro psicopatol6gico. A evolução de manifestações de fadiga crônica e desencadeamento de uma crise mental aguda são examinadas em suas correlações ao hist6rico de vida e trabalho e a dinâmicas referidas às condições e à organização do trabalho no emprego atual.
Brassinosteroid-Insensitive-1 Is a Ubiquitously Expressed Leucine-Rich Repeat Receptor Serine/Threonine Kinase (2000)

Brassinosteroid (BR) mutants of Arabidopsis have pleiotropic phenotypes and provide evidence that BRs function throughout the life of the plant from seedling development to senescence. Screens for BR signaling mutants identified one locus, BRI1, which encodes a protein with homology to leucine-rich repeat receptor serine (Ser)/threonine (Thr) kinases. Twenty-seven alleles of this putative BR receptor have been isolated to date, and we present here the identification of the molecular lesions of 14 recessive alleles that represent five new mutations. BR-insensitive-1 (BRI1) is expressed at high levels in the meristem, root, shoot, and hypocotyl of seedlings and at lower levels later in development. Confocal microscopy analysis of full-length BRI1 fused to green fluorescent protein indicates that BRI1 is localized in the plasma membrane, and an in vitro kinase assay indicates that BRI1 is a functional Ser/Thr kinase. Among the bri1 mutants identified are mutants in the kinase domain, and we demonstrate that one of these mutations severely impairs BRI1 kinase activity. Therefore, we conclude that BRI1 is a ubiquitously expressed leucine-rich repeat receptor that plays a role in BR signaling through Ser/Thr phosphorylation.
Determination of bovine lymphocyte responses to extracted proteins of Brucella abortus by using protein immunoblotting (1988)

Isolation and identification of Brucella antigenic determinants important to cellular responses have been difficult. In this study, bovine peripheral blood mononuclear (PBM) cells from cattle vaccinated with Brucella abortus 19 proliferated to extracted bacterial proteins blotted onto nitrocellulose. Proteins were extracted from gamma-irradiated B. abortus 19 with a sodium dodecyl sulfate extraction buffer. The extracted proteins were separated electrophoretically by sodium dodecyl sulfate-polyacrylamide gel electrophoresis prior to electroblotting onto nitrocellulose. Nitrocellulose sections corresponding to individual lanes of the gel (containing all separated proteins) were then cultured with the PBM cells. Primary and secondary stimulation responses of the PBM cells with the whole protein blots were similar kinetically to the responses of the PBM cells stimulated with whole irradiated B. abortus 19 or with whole irradiated B. abortus 19 blotted onto nitrocellulose. Although lipopolysaccharide was determined to be associated with the extracted proteins and transferred onto the blots, the lipopolysaccharide did not stimulate cellular proliferation, as indicated by the antigen-specific secondary responses. Stimulating PBM cells with portions of the blot containing high (greater than 45,000)-, medium (25,000 to 45,000)- or low (25,000)-molecular-weight proteins demonstrated that the responding cells were specific only to the proteins of corresponding molecular weights. These results indicate that cellular responses to individual proteins can be studied without cloning the bacterial genes or purifying the individual proteins.
Induced plant responses to pathogen attack (1991)

In soybean (Glycine max L.), pathogen attack induces the formation of glyceollin-type phytoalexins. The biosynthetic key enzyme is a reductase which synthesizes 4,2', 4'-trihydroxychalcone in co-action with chalcone synthase. Screening of a soybean cDNA library from elicitor-induced RNA in lambda gt11 yielded two classes of reductase-specific clones. The deduced proteins match to 100% and 95%, respectively, with 229 amino acids sequenced in the purified plant protein. Four clones of class A were expressed in Escherichia coli, and the proteins were tested for enzyme activity in extracts supplemented with chalcone synthase. All were active in 4,2',4'-trihydroxychalcone formation, and the quantification showed that shorter lengths of the cDNAs at the 5' end correlated with progressively decreasing enzyme activities. Genomic blots with DNA from plants capable of 4,2',4'-trihydroxychalcone synthesis revealed related sequences in bean (Phaseolus vulgaris L.) and peanut (Arachis hypogaea L.), but not in pea (Pisum sativum L.). No hybridization was observed with parsley (Petroselinum crispum) and carrot (Daucus carota) which synthesize other phytoalexins. The reductase protein contains a leucine-zipper motif and reveals a marked similarity with other oxidoreductases most of which are involved in carbohydrate metabolism.
Cross entropy guided ant-like agents finding dependable primary/backup path patterns in networks (2003)

Telecommunication network owners and operators have for half a century been well aware of the potential loss of revenue if a major trunk is damaged, thus dependability at high cost has been implemented. A simple, effective and common dependability scheme is 1:1 protection with 100% capacity redundancy in the network. A growing number of applications in need of dependable connections with specific requirements to bandwidth and delay have started using the internet (which only provides best effort transport) as their base communication service. In this paper we adopt the 1:1 protection scheme and incorporate it as part of a routing system applicable for internet infrastructures. 100% capacity redundancy is no longer required. A distributed stochastic path finding (routing) algorithm based on Rubinstein's Cross Entropy method for combinatorial optimisation is presented. Early results from Monte Carlo simulations indeed indicate that the algorithm is capable of finding pairs of independent primary and backup paths satisfying specific bandwidth constraints.
Emergency Medicine Top Stories of 2009 (2009)

Dear Readers,The editors of Journal Watch Emergency Medicine are pleased to provide our second annual top stories lists. As was the case last year, we
Ginseng improves strategic learning by normal and brain-damaged rats (1998)

Adult rats were prepared with either sham or medial prefrontal cortex lesions and administered, beginning on the third post-operative day, either, 0, 40, or 80 mg kg-1 crude ginseng extract suspended in saline daily for the next 30 days. Later, kinetic functions were evaluated on an elevated rotating rod. No long-term influences of the treatments were observed on this task. Significant positive influences of ginseng were observed in the position reversal task. The learning deficits observed in the saline control brain-damaged rats were significantly attenuated in the ginseng-treated animals. An analysis of trial 2 response accuracy across reversals revealed enhanced cognitive abilities (i.e. acquisition of a win-stay, lose-shift strategy) in both the brain damaged and sham control rats administered ginseng. Generally, administration of the higher dose resulted in better performance in the learning paradigm. The exact mechanism responsible for these promising results remains to be discovered. Several possible mechanisms are discussed.
A live attenuated recombinant dengue-4 virus vaccine candidate with restricted capacity for dissemination in mosquitoes and lack of transmission from vaccinees to mosquitoes. (2001)

2Adelta30 is a live dengue-4 virus vaccine candidate with a 30-nucleotide deletion in its 3'-untranslated region. To assess the transmissibility of 2Adelta30 by mosquitoes, we compared its in vivo replication in mosquitoes with that of its wild type DEN-4 parent. Both the vaccine candidate and wild type virus were equally able to infect the mosquito Toxorhynchites splendens after intrathoracic inoculation. Relative to its wild type parent, 2Adelta30 was slightly restricted in its ability to infect the midgut of Aedes aegypti mosquitoes fed on an artificial blood meal and was even more restricted in its ability to disseminate from the midgut to the salivary glands. Thus, the 30-nucleotide deletion rendered the vaccine candidate more sensitive than its wild type parent to the mosquito midgut escape barrier. Most significantly, 2Adelta30 was not transmitted to 352 Ae. albopictus mosquitoes fed on 10 vaccinees, all of whom were infected with the vaccine candidate.
Regulation of immune responses by I-J gene products. III. GT-specific suppressor factor is composed of separate I-J and idiotype-bearing chains. (1983)

Injection of poly(Glu50Tyr50)(GT) into B10.BR (H-2k) mice induces GT-specific suppressor T cells and a T cell-derived suppressor factor (TsF1), which in turn induces a second-order suppressor T cell (TS2). In the present study, we show that B10.BR GT-TSF1 is composed of separate I-Jk and idiotype-bearing chains linked by disulfide bond(s). Functional suppressive activity requires both chains to be in association. Neither chain alone can induce TS2, indicating that both chains must be seen in association and suggesting a single cellular target for the two chains. Experiments designed to interchange I-J-bearing chains of GT-TSF1 derived from different H-2 haplotypes indicate that only the homologous I-J and idiotype-bearing chains can reassociate into a suppressive moiety. These experiments may imply heterogeneity of I-J region gene products.