gebhart/patrepeval huggingface dataset:
Thioredoxin Peroxidase Secreted by <i>Fasciola hepatica</i> Induces the Alternative Activation of Macrophages (2004)

Alternatively activated macrophages (AAMphi) are primarily associated with the chronic stages of parasitic infections and the development of a polarized Th2 response. We have shown that Fasciola hepatica infection of BALB/c mice induces a polarized Th2 response during both the latent and chronic stage of disease. The activation status of macrophages was analyzed in this model of helminth infection by evaluating the expression of genetic markers of alternative activation, namely, Fizz1, Ym1, and Arg1. AAMphi were recruited to the peritoneum of mice within 24 h of F. hepatica infection and after intraperitoneal injection of parasite excretory-secretory (ES) products. Administration of a recombinant antioxidant thioredoxin peroxidase (TPx), which is contained within the ES products, also induced the recruitment of AAMphi to the peritoneum. In vitro studies showed that this recombinant TPx directly converts RAW 264.7 macrophages to an alternatively activated phenotype characterized by the production of high levels of interleukin-10 (IL-10), prostaglandin E(2), corresponding with low levels of IL-12. Our data suggest that the Th2 responses induced by the helminth F. hepatica are mediated through the secretion of molecules, one of which is TPx, that induce the recruitment and alternative activation of macrophages.
Dinaciclib, a cyclin-dependent kinase inhibitor, suppresses cholangiocarcinoma growth by targeting CDK2/5/9 (2020)

Cholangiocarcinoma (CCA) is a highly invasive cancer, diagnosed at an advanced stage, and refractory to surgical intervention and chemotherapy. Cyclin-dependent kinases (CDKs) regulate cell cycle progression and transcriptional processes, and are considered potential therapeutic targets for cancer. Dinaciclib is a small molecule multi-CDK inhibitor targeting CDK 2/5/9. In this study, the therapeutic efficacy of dinaciclib was assessed using patient-derived xenograft cells (PDXC) and CCA cell lines. Treatment with dinaciclib significantly suppressed cell proliferation, induced caspase 3/7 levels and apoptotic activity in PDXC and CCA cell lines. Dinaciclib suppressed expression of its molecular targets CDK2/5/9, and anti-apoptotic BCL-XL and BCL2 proteins. Despite the presence of cyclin D1 amplification in the PDXC line, palbociclib treatment had no effect on cell proliferation, cell cycle or apoptosis in the PDXC as well as other CCA cell lines. Importantly, dinaciclib, in combination with gemcitabine, produced a robust and sustained inhibition of tumor progression in vivo in a PDX mouse model, greater than either of the treatments alone. Expression levels of two proliferative markers, phospho-histone H3 and Ki-67, were substantially suppressed in samples treated with the combination regimen. Our results identify dinaciclib as a novel and potent therapeutic agent alone or in combination with gemcitabine for the treatment of CCA.
Effect of stimulation frequency on tremor suppression in essential tremor (2004)

We sought to determine the effect of deep brain stimulation (DBS) frequency on tremor suppression in essential tremor (ET) patients with deep brain stimulators implanted in the ventral intermediate nucleus (VIM) of the thalamus. A uniaxial accelerometer was used to measure tremor in the right upper extremity of subjects with a diagnosis of ET who had DBS electrodes implanted in the left VIM. The root-mean-square acceleration was used as the index of tremor magnitude and normalized to the OFF DBS condition. There was a highly significant inverse sigmoidal relationship between stimulation frequency and normalized tremor acceleration (X(2)/DoF = 0.42, r(2) = 0.997). Tremor acceleration had a nearly linear response to stimulation frequencies between 45 and 100 Hz with little additional benefit above 100 Hz. These findings have two important implications. Clinically, frequency of thalamic stimulation is an important variable for optimal tremor control with maximal benefit achieved with 100 to 130 Hz in most patients. Second, thalamic DBS provides tremor benefit in a graded manner and is not an all-or-nothing phenomenon.
Hydrophthalmia or Congenital Glaucoma. Its Causes, Treatment and Outlook. (1940)

This monograph is one of the publications sponsored by the<i>British Journal of Ophthalmology</i>. It is a handsome volume, profusely and beautifully illustrated. The subject of hydrophthalmia is exhaustively treated under the chapter headings of general etiology, differential diagnosis, the structure and development of the involved tissue, their embryology and comparative anatomy, the pathology of congenital glaucoma, pathogenesis, treatment, prognosis and general reflections. The terms congenital glaucoma and hydrophthalmia are preferred by the author. He suggests that the use of all other terms be abandoned. The author states that "the condition to be described is that of an eye which has become enlarged under the influence of increased tension." Subsequently, he says that "the ocular condition that we are to consider is that which is due to a rise in tension occurring at so early an age that the coats of the globe distend." The latter definition seems to be
A rapid procedure for the isolation of plasmid DNA from environmental bacteria. (1999)

The INSTA-MINI-PREP method, a rapid protocol for plasmid DNA extraction, was originally developed to prepare plasmid DNA from 1 to 3 ml miniprep Escherichia coli cultures. Direct extraction of plasmid DNA is achieved by a two-phase solution which is separated by centrifugation in the presence of the INSTA-PREP gel barrier material. This method has been successfully tested on various environmental Salmonella strains, although it was not suitable for Pseudomonas aeruginosa and enterococci strains. The INSTA-MINI-PREP method is a new alternative procedure to screen plasmid contents of Salmonella and E. coli strains rapidly and easily.
Synthesis of Nanostructured Mesoporous Manganese Oxides with Three-Dimensional Frameworks and Their Application in Supercapacitors (2011)

Nanostructured mesoporous manganese oxides were easily prepared by mixing KMnO4 with ascorbic acid in an aqueous solution under ambient conditions. The obtained manganese oxides were identified as having an α-MnO2 tunnel structure composed of an edge-shared network of [MnO6] octahedra. TEM observations revealed that the obtained MnO2 materials had three-dimensional frameworks which consisted of homogeneous nanoparticles with sizes of ca. 5 nm. Nitrogen sorption analyses showed that these MnO2 nanoparticles exhibited a type IV isotherm, indicating a mesoporous character. Large surface areas up to 284 m2 g−1 were recorded. The electrochemical performances of the synthesized α-MnO2 nanoparticles as supercapacitor electrode materials were studied using cyclic voltammetry and galvanostatic charge−discharge cycling in a three-electrode system at a potential range from 0 to 1.0 V vs a saturated calomel electrode in 0.5 M sodium sulfate solution. The result showed that mesoporous MnO2 with three-dimensional frameworks exhibit a high capacitance up to ∼200 F g−1. Furthermore, a hybrid supercapacitor was assembled by using MnO2 mixed with a small amount of activated carbon as the positive electrode and activated carbon as the negative electrode in a 0.5 M Na2SO4 electrolyte. By balancing the mass of MnO2 and activated carbon, a practical cell voltage of 1.8 V could be obtained in aqueous medium with a capacitance of 23.1 F g−1. After 1200 cycles, the maximum energy density is 10.4 Wh kg−1 and power density is 14.7 kW kg−1. Thus, the obtained α-MnO2 nanoparticles are suitable for use as supercapacitor electrode materials.
Cyclic AMP Receptor Protein-Dependent Activation of the <i>Escherichia coli acs</i> P2 Promoter by a Synergistic Class III Mechanism (2003)

The cyclic AMP receptor protein (CRP) activates transcription of the Escherichia coli acs gene, which encodes an acetate-scavenging enzyme required for fitness during periods of carbon starvation. Two promoters direct transcription of acs, the distal acsP1 and the proximal acsP2. In this study, we demonstrated that acsP2 can function as the major promoter and showed by in vitro studies that CRP facilitates transcription by "focusing" RNA polymerase to acsP2. We proposed that CRP activates transcription from acsP2 by a synergistic class III mechanism. Consistent with this proposal, we showed that CRP binds two sites, CRP I and CRP II. Induction of acs expression absolutely required CRP I, while optimal expression required both CRP I and CRP II. The locations of these DNA sites for CRP (centered at positions -69.5 and -122.5, respectively) suggest that CRP interacts with RNA polymerase through class I interactions. In support of this hypothesis, we demonstrated that acs transcription requires the surfaces of CRP and the C-terminal domain of the alpha subunit of RNA polymerase holoenzyme (alpha-CTD), which is known to participate in class I interactions: activating region 1 of CRP and the 287, 265, and 261 determinants of the alpha-CTD. Other surface-exposed residues in the alpha-CTD contributed to acs transcription, suggesting that the alpha-CTD may interact with at least one protein other than CRP.
Measurement of the adhesive strength of hair-hairspray junctions (2015)

A method for measuring the adhesive strength of hairspray bonds joining individual hair fibers has been developed. The method involves application of 0.7 Ixl of hairspray to the overlapping portion of a hair loop and breaking the resulting junction on a tensile tester. Junction strength depends on polymer concentra-tion, polymer type, and formulation variables such as the type of neutralizer used or the presence of plasticizers. Relative humidity may also have a significant effect on junction strength, depending on the polymer system used. Optical microscopy shows that failure of hair-hairspray junctions is usually adhesive failure rather than cohesive failure of the resin itself. Often a replica of the hair cuticle scale is left in the hairspray resin after bond breaking. However, some resins shatter when the bond breaks, still leaving cuticle imprints in pieces of resin, indicating that both cohesive and adhesive failure may have occurred.
NGF-like trophic support from peripheral nerve for grafted rhesus adrenal chromaffin cells (1990)

Autopsy results on patients and corresponding studies in nonhuman primates have revealed that autografts of adrenal medulla into the striatum, used as a treatment for Parkinson's disease, do not survive well. Because adrenal chromaffin cell viability may be limited by the low levels of available nerve growth factor (NGF) in the striatum, the present study was conducted to determine if transected peripheral nerve segments could provide sufficient levels of NGF to enhance chromaffin cell survival in vitro and in vivo. Aged female rhesus monkeys, rendered hemiparkinsonian by the drug MPTP (n-methyl-4-phenyl-1,2,3,6 tetrahydropyridine), received autografts into the striatum using a stereotactic approach, of either sural nerve or adrenal medulla, or cografts of adrenal medulla and sural nerve (three animals in each group). Cell cultures were established from tissue not used in the grafts. Adrenal chromaffin cells either cocultured with sural nerve segments or exposed to exogenous NGF differentiated into a neuronal phenotype. Chromaffin cell survival, when cografted with sural nerve into the striatum, was enhanced four- to eightfold from between 8000 and 18,000 surviving cells in grafts of adrenal tissue only up to 67,000 surviving chromaffin cells in cografts. In grafts of adrenal tissue only, the implant site consisted of an inflammatory focus. Surviving chromaffin cells, which could be identified by both chromogranin A and tyrosine hydroxylase staining, retained their endocrine phenotype. Cografted chromaffin cells exhibited multipolar neuritic processes and numerous chromaffin granules, and were also immunoreactive for tyrosine hydroxylase and chromogranin A. Blood vessels within the graft were fenestrated, indicating that the blood-brain barrier was not intact. Additionally, cografted chromaffin cells were observed in a postsynaptic relationship with axon terminals from an undetermined but presumably a host origin.
Monoclonal antibodies to three phospholipase C isozymes from bovine brain. (1988)

Murine hybridoma cell lines secreting antibodies against the three bovine isozymes of phosphoinositide-specific phospholipase C (PLC) were established: 6, 23, and 12 lines were obtained for PLC-I (150 kDa), PLC-II (145 kDa), and PLC-III (85 kDa), respectively. The antibodies were purified from ascites fluid, and their properties were studied in detail. All the antibodies cross-reacted with their corresponding PLC enzymes, but not with the other two isozymes, suggesting that the three enzymes contain very different antigenic determinants. The six antibodies elicited by bovine PLC-I also cross-reacted with human and rat enzyme, whereas three each from anti-PLC-II antibodies and anti-PLC-III antibodies did not react with the enzymes from different species. Each antibody exerts different effects on the phosphatidylinositol-hydrolyzing activity of PLC. The most inhibitory antibody for either isozyme PLC-I or PLC-II exhibits 80% inhibition, whereas no more than 20% inhibition was observed for the anti-PLC-III antibodies. Purified PLC-I frequently contains catalytically active 140- and 100-kDa forms and an inactive 41-kDa protein in addition to the intact 150-kDa form, probably due to its high sensitivity to an unidentified endogenous protease. The five anti-PLC-I antibodies which bind to the denatured 150-kDa polypeptide also recognized the 140-kDa form, whereas only three cross-reacted with the 100-kDa form, and the remaining two bound to the 41-kDa protein. Competitive binding studies with intact PLC enzymes and Western blot experiments with proteolytic digests revealed that the 6 anti-PLC-I, 23 anti-PLC-II, and 12 anti-PLC-III antibodies bind at least five, six, and seven different epitopes on PLC-I, PLC-II, and PLC-III, respectively. The fact that these monoclonal antibodies bind to different epitopes on the same enzyme allowed one to develop a highly specific and sensitive tandem radioimmunoassay for quantitating PLC-I, PLC-II, and PLC-III. The principle of the assay is that binding of an 125I-labeled antibody to the antigen immobilized by another antibody at a distinctive binding site is proportional to the amount of antigen present. By using this method, PLC-I, PLC-II, and PLC-III could be measured quantitatively in the presence of other proteins, detergents, lipids, polyanions, and metal ions, all of which greatly affect the activity of PLC enzymes.
Uptake of CO<sub>2</sub>by Roots of Xanthium Plants (1962)

1. The magnitude of CO2 uptake and fixation by Xanthium plant roots was reinvestigated in an attempt to explain unexpectedly low C14/C12 ratios of tree leaves with regard to fixation of radiocarbon of nuclear-test origin. 2. It was found that plants derive relatively insignificant amounts of carbon from CO2 via the roots, and the minute amounts that are incorporated are approximately one hundred times less than the amount lost by root respiration. 3. The results permit the conclusion that the previously noted C14/C12 ratios of the tree leaves were most likely obtained by incorporation of carbon from sources stored in the tree.
Oral immunosuppressive medication for growing pigs in transplantation studies (2012)

Immunosuppressive (IS) medication is needed to avoid graft rejection in porcine transplantation models. An ideal IS therapy should have no side-effects, but increased susceptibility to infections, disturbed intestinal microflora and toxic effects on organs and tissues are commonly reported. The aim of the present study was to design an IS protocol with tacrolimus and mycophenolic acid to be used for maintenance therapy in the post-transplant period. An eligible whole blood trough value for tacrolimus was 5-15 μg/L. Conventional specific pathogen-free pigs were fitted with an indwelling catheter under general anaesthesia, and after the acclimatization period three groups were formed: group A (n= 4) received 0.15 mg/kg body weight (BW) twice daily tacrolimus and 500 mg twice daily mycophenolic acid; group B (n= 4) received 0.3 mg/kg BW twice daily tacrolimus and 500 mg twice daily mycophenolic acid; group C (n= 2) did not receive any medication. Daily clinical examinations and analyses of blood concentrations of tacrolimus and glucose were performed. Total and differential white blood cell counts, enzyme activities, bilirubin and electrolyte concentrations were measured every fourth day. At the end of the experiment, the pigs were killed with an overdose of pentobarbital intravenously and a necropsy was performed immediately. All animals seemed to tolerate the IS treatment well. No alterations in their clinical state of health were observed throughout the study and daily weight gain was similar for the three groups. The necropsy did not reveal any pathological findings related to medication. The study showed that 0.25 mg/kg BW twice daily tacrolimus and 500 mg twice daily mycophenolic acid would be an appropriate maintenance dosage for conventional pigs.
Incomplete global myocardial ischemia during cardiac arrest and resuscitation (1988)

During cardiac arrest (no flow) and CPR (low flow), the onset of myocardial ischemia is followed by myocardial respiratory acidosis. Myocardial contractility is more decreased by respiratory than by metabolic acidosis. We demonstrated in a porcine model of cardiac arrest and in human patients increases in mixed venous PCO2 during CPR, whereas PaCO2 was decreased. Consequently, there was a striking increase in the venoarterial gradients for both [H+] and CO2. Both cardiac output (pulmonary blood flow) and the concentration of expired CO2 were simultaneously decreased. In great cardiac vein blood, even more profound respiratory acidosis with only minor decreases in bicarbonate and only moderate increases in lactate were observed. Intramyocardial pH was profoundly decreased. The severity of respiratory acidosis as a determinant of resuscitability and survival should be further investigated.
Photodamage Generates 7‐keto‐ and 7‐hydroxycholesterol in the Rat Retina <i>via</i> a Free Radical‐mediated Mechanism (2009)

Abstract Albino Sprague–Dawley rats are known to undergo photoreceptor degeneration after exposure to constant light, but the molecular mechanism(s) by which the photoreceptors degenerate is not fully understood. We hypothesized that cytotoxic oxysterols are generated in situ in the retina under such conditions and may be involved in the degenerative mechanism. Thus, photodamaged and control rat retinas were analyzed for oxysterols by liquid chromatography mass spectroscopy. Elevated levels of two known cytotoxic oxysterols, 7‐ketocholesterol (7KCh) and 7αβ‐hydroxycholesterol (7HCh), were found in the photodamaged retinas, at levels six‐fold and 50‐fold greater, respectively, than those found in non photodamaged controls. Notably, two key intermediates, 5,6α,β‐epoxycholesterol (5,6‐epoxyCh) and 7αβ‐hydroperoxy‐cholesterol, were also identified, indicating that the formation of 7KCh and 7HCh is mediated by a free radical mechanism. By immunohistochemistry, 7KCh was localized to the ganglion cell layer, photoreceptor inner segments and retinal pigment epithelium (RPE), which coincides with the localization of ferritin in the retina. Exposure of a mixture of ferritin and low‐density lipoprotein to intense white light in vitro produced similar oxysterol species as seen in vivo . We propose that the increased levels of 7KCh and 7HCh, especially in photoreceptor inner segments and RPE, may arise due to ferritin‐catalyzed reactions and may be important contributors to the photoreceptor degeneration observed in photodamaged rats.
Local stability identification and the role of a key aromatic amino acid residue in staphylococcal nuclease refolding (2005)

Staphylococcal nuclease (SNase) is a model protein that contains one domain and no disulfide bonds. Its stability in the native state may be maintained mainly by key amino acids. In this study, two point-mutated proteins each with a single base substitution [alanine for tryptophan (W140A) and alanine for lysine (K133A)] and two truncated fragment proteins (positions 1-139 [SNase(1-139) or W140O] and positions 1-141 [SNase(1-141) or E142O]) were generated. Differential scanning microcalorimetry in thermal denaturation experiments showed that K133A and E142O have nearly unchanged DeltaH(cal) relative to the wild-type, whereas W140A and W140O display zero enthalpy change (DeltaH(cal) approximately 0). Far-UV CD measurements indicate secondary structure in W140A but not W140O, and near-UV CD measurements indicate no tertiary structure in either W140 mutant. These observations indicate an unusually large contribution of W140 to the stability and structural integrity of SNase.
Cerebral ischemia-reperfusion injury and adhesion (1997)

Prompt reperfusion of ischemic tissue is critical for restoring normal function, but it can precipitate a progressive destruction of reversibly damaged cells, leading to paradoxical tissue dysfunction and necrosis. This reperfusion injury has a multifactorial etiology but it is associated with a fulminating infiltration of leukocytes, with subsequent release of cytotoxic mediators, into the previously ischemic tissue.1,2 An early event in the reperfusion process is the adhesion and accumulation of neutrophils. Although this is expected as part of the healing process, it can be fulminating due to a vascular endothelium that has been activated by inflammatory mediators such as platelet activating factor (PAF) and reactive oxygen metabolites. Accumulation of neutrophils, together with red blood cells and platelets, can lead to capillary plugging3 and a reduction in microvascular blood flow, resulting in focal areas of stasis. Once infiltrated into tissues, neutrophils are capable of releasing various proteases, lipid-derived mediators, and reactive oxygen species that can injure potentially salvageable cells.

The adhesion and migration of neutrophils are orchestrated by several classes of cell surface glycoproteins. These include the leukocyte integrins(CD11/CD18), the immunoglobulin supergene family [intercellular adhesion molecule-1 (ICAM-1); vascular cell adhesion molecule-1 (VCAM-1)], and the selectins (L-, P-, and E-selectin).4 Studies employing monoclonal antibodies (MAbs) directed at specific members of these various pathways have been instrumental in demonstrating the importance of neutrophils in ischemia-reperfusion injury. In the heart, studies by Simpson et al.5 (anti-CD11b) and Seewaldt-Becker et al.6 (anti-CD11a, anti-CD18, anti-ICAM-1) were among the first to demonstrate that MAbs directed against either leukocyte or endothelial cell adhesion glycoproteins were effective in limiting the myocardial necrosis that developed in response to an ischemia-reperfusion protocol. Efficacy has also been demonstrated for MAbs administered just before reperfusion directed against the following molecules: L- …