gebhart/patrepeval huggingface dataset:
Polyisoprenylation of Ras in vitro by a farnesyl-protein transferase. (1990)

Farnesylation of Ras occurs in vivo on a Cys residue in the C-terminal sequence -Cys-Val-Leu-Ser (termed a CAAX box). This modification is required for Ras membrane localization and cell transforming activity. Using [3H]farnesyl-PPi as precursor and Escherichia coli-expressed Ras, forms of Ras having the CAAX sequence were radiolabeled upon incubation with the cytosolic fraction of bovine brain. Forms of Ras having a deletion of the CAAX sequence or a Cys to Ser substitution in this sequence were not substrates. Radioactivity incorporated into Ras by bovine brain cytosol was released by treatment with iodomethane but not with methanolic KOH indicating a thioether linkage. High pressure liquid chromatography analysis of the cleavage products on a C-18 column showed a major peak of radioactivity that co-eluted with a farnesol standard. The enzyme responsible for Ras farnesylation in bovine brain was approximately 190 kDa as estimated by gel filtration and required a divalent cation for activity. Nonradioactive farnesyl-PPi, geranylgeranyl-PPi, and Ras peptides having the C-terminal sequence -Cys-Val-Leu-Ser competed in the assay with IC50 values of 0.7, 1.4, and 1-3 microM, respectively. Farnesol and Ras peptides having the sequence -Ser-Val-Leu-Ser were not inhibitory. These results identify a farnesyl-protein transferase activity that may be responsible for the polyisoprenylation of Ras in intact cells.
Molecular Analysis of 11q13 Breakpoints in Multiple Myeloma (1999)

The t(11;14)(q13;q32) chromosomal translocation, which is the hallmark of mantle cell lymphoma (MCL), is found in approximately 30% of multiple myeloma (MM) tumors with a 14q32 translocation. Although the overexpression of cyclin D1 has been found to be correlated with MM cell lines carrying the t(11;14), rearrangements of theBCL-1/cyclin D1 regions frequently involved in MCL rarely occur in MM cell lines or primary tumors. To test whether specific 11q13 breakpoint clusters may occur in MM, we investigated a representative panel of primary tumors by means of Southern blot analysis using probes derived from MM-associated 11q13 breakpoints. To this end, we first cloned the breakpoints and respective germ-line regions from a primary tumor and the U266 cell line, as well as the germ-line region from the KMS-12 cell line. DNA from 50 primary tumors was tested using a large panel of probes, but a rearrangement was detected in only one case using the KMS-12 breakpoint probe. Our results confirm previous findings that the 11q13 breakpoints in MM are scattered throughout the 11q13 region encompassing the cyclinD1 gene, thus suggesting the absence of 11q13 breakpoint clusters in MM.
Neuronal accumulation of α- and β-synucleins in the brain of a GM2 gangliosidosis mouse model (2003)

Sandhoff disease (SD) is a heritable lysosomal storage disease resulting from impaired degradation of GM2 ganglioside. The hallmark pathology of the SD model mouse brain is GM2 ganglioside accumulation in neurons. In the present study, we immunohistochemically investigated the neuronal pathology in SD mouse brains, and demonstrated neuronal accumulation of alpha- and beta-synucleins in addition to GM2 ganglioside. Synuclein-positive neurons were extensively observed throughout SD mouse brains, although the distribution of beta-synuclein was less extensive than that of alpha-synuclein. Synuclein-positive neurons were negative to ubiquitin and PHF-tau. These findings suggest that neuronal synucleins may accumulate secondarily to GM2 ganglioside in SD mouse brains, and that neuronal accumulation of synucleins may be more critical than that of GM2 ganglioside for SD mice.
Electron microscopy of the leucocytes of the typhlosole in ammocoetes, with special attention to the antibody‐ producing cells (1982)

In an attempt to determine the role in the immune responses of the typhlosole, a hematopoietic tissue along the ventral wall of the larval lamprey Lampetra reissneri, scanning and transmission electron microscopic observations were made on ammocoetes hyperimmunized with sheep red blood cells. Besides including the cells of the erythrocyte series, this tissue also contained the following leucocytes forming an amorphous parenchyma: the cells of the granulocyte series, the most predominant cell type, possessing a markedly lobed nucleus and membrane-bounded granules of various sizes; the macrophages possessing primary and secondary lysosomes and long lamellipodia on the cell surface; the lymphocytes of a large nucleocytoplasmic ratio with a number of long, spiky microvilli, constituting a major type of rosette-forming (antigen-binding) cells; and the plasma cells possessing highly extended cisternae of rough endoplasmic reticula that are characteristic of the higher vertebrates. The immunoperoxidase technique, which employs rabbit antibodies against lamprey immunoglobulin, proved that these plasma cells do contain immunoglobulin. These results strongly indicate that the typhlosole of the larval lamprey, besides functioning as a hematopoietic tissue, is actively involved in the antibody responses. It is also stressed that the plasma cell occurs in the most primitive vertebrates as an immunologically competent cell.
Self-cleaning coatings (2004)

This review summarises the key topics in the field of self-cleaning coatings, concentrating on the materials that have been used in commercial applications and recent research that aims to improve these materials. Hydrophobic and hydrophilic coatings are discussed, and the various mechanisms of self-cleaning are described and related to the material properties of the coatings. Although several multinational companies have released products incorporating self-cleaning coatings, there remains much potential in this field.
Towards standardization of RNA quality assessment using user-independent classifiers of microcapillary electrophoresis traces (2005)

While it is universally accepted that intact RNA constitutes the best representation of the steady-state of transcription, there is no gold standard to define RNA quality prior to gene expression analysis. In this report, we evaluated the reliability of conventional methods for RNA quality assessment including UV spectroscopy and 28S:18S area ratios, and demonstrated their inconsistency. We then used two new freely available classifiers, the Degradometer and RIN systems, to produce user-independent RNA quality metrics, based on analysis of microcapillary electrophoresis traces. Both provided highly informative and valuable data and the results were found highly correlated, while the RIN system gave more reliable data. The relevance of the RNA quality metrics for assessment of gene expression differences was tested by Q-PCR, revealing a significant decline of the relative expression of genes in RNA samples of disparate quality, while samples of similar, even poor integrity were found highly comparable. We discuss the consequences of these observations to minimize artifactual detection of false positive and negative differential expression due to RNA integrity differences, and propose a scheme for the development of a standard operational procedure, with optional registration of RNA integrity metrics in public repositories of gene expression data.
Cannabinol-mediated inhibition of nuclear factor-kappaB, cAMP response element-binding protein, and interleukin-2 secretion by activated thymocytes. (1999)

Cannabinol (CBN), an immunosuppressive cannabinoid and ligand for the peripheral cannabinoid receptor CB2, inhibits the cAMP signaling cascade in forskolin-stimulated thymocytes. The objective of the present studies was to further characterize the mechanism of CBN immune modulation by investigating its effects on interleukin-2 (IL-2) secretion, cAMP response element (CRE), and kappaB DNA binding activity in phorbol ester (phorbol-12-myristate-13-acetate, PMA) plus calcium ionophore (PMA/Io)-activated thymocytes. PMA/Io treatment induced CRE and kappaB DNA binding activity that was attenuated in the presence of CBN. A concomitant and concentration-related inhibition of IL-2 also was produced by CBN in PMA/Io-activated thymocytes. PMA/Io induced two CRE DNA binding complexes, a major complex consisting of a cAMP response element-binding protein (CREB)-1 homodimer, and a minor CREB-1/activating transcription factor (ATF)-2 complex. Both CRE complexes were inhibited by CBN. Conversely, two kappaB DNA binding complexes were observed, but only one was PMA/Io-inducible. However, the DNA binding activity of both complexes was diminished in the presence of CBN. The PMA/Io-inducible kappaB complex was a p65/c-Rel heterodimer. Analysis of up-stream regulation revealed a decrease in phosphorylated CREB/ATF nuclear proteins in PMA/Io-activated thymocytes after CBN treatment. Similarly, CBN prevented the phosphorylation-dependent degradation of the nuclear factor-kappaB inhibitory protein IkappaB-alpha. These results provide a potential link between the CBN-mediated inhibition of thymocyte function, including IL-2 production, and the inhibition of two critical transcription factor families, CREB/ATF and NF-kappaB/Rel.
Life after medicine (2000)

Ron Elisha graduated in medicine in 1975, and has spent most of his career in full-time general practice. He has written stage plays, radio plays, teleplays, screenplays, children's stories, short stories and feature articles. Many of these have been published or produced, both in Australia and overseas (including the USA. the UK, Canada, New Zealand, Israel, France, Belgium and Poland). He has won four Australian Writers' Guild Awards (AWGIES) for best scripts for works for stage and television, including the Major Award in 1982 for the play Einstein. Other highlights of his writing career have been a US tour of Einstein, a trip to London to work on a screenplay with Istvan Szabo and a trip to Paris as a guest of the Comédie Française.
BIODIESEL PRODUCTION VIAACID CATALYSIS (1999)

Vegetable oils and animal fats can be transesterified to biodiesel for use as an alternative diesel fuel.Conversion of low cost feedstocks such as used frying oils is complicated if the oils contain large amounts of free fattyacids that will form soaps with alkaline catalysts. The soaps can prevent separation of the biodiesel from the glycerinfraction. Alternative processes are available that use an acid catalyst. The objective of this study was to investigate theeffect of process variables on acid-catalyzed transesterification. The molar ratio of alcohol, reaction temperature, catalystamount, reaction time, water content, and free fatty acids were investigated to determine the best strategy for producingbiodiesel. Food grade soybean oil was used to prepare esters using excess methanol and sulfuric acid as a catalyst. Tocompare the effect of different alcohol types on ester formation, methanol, ethanol, 2-propanol, and n-butanol werecompared. The American Oil Chemists Society Method Ca 14-56 was used to measure the biodiesels total glycerinamount as an indicator of the completeness of the reaction. It was found that acid catalysis can provide high conversionrates but much longer times are required than for alkaline catalysts. The acid catalyst also requires the concentration ofwater to be less than 0.5%, which is about the same as is required for alkaline catalysts. Water formed by theesterification of free fatty acids limited their presence in the oil to 5%.
Inhibition of the Neutral Magnesium-dependent Sphingomyelinase by Glutathione (1997)

Sphingomyelin hydrolysis through the activation of sphingomyelinases has become a potentially important signaling pathway with the product ceramide implicated in the regulation of cell growth, differentiation, apoptosis, and inflammatory responses. However, little is known about the regulation of sphingomyelinases. In this study, we show that the magnesium-dependent, neutral pH-optimum and membrane-associated sphingomyelinase (N-SMase) is inhibited, in a dose-dependent manner, by glutathione (GSH) at physiological concentrations with a greater than 95% inhibition observed at 5 mM GSH. The inhibitory effect of GSH was reproduced by gamma-glutamyl-cysteine, but not the cysteinyl-glycine fragment of GSH. The S-modified GSH analogs were as effective as GSH in inhibiting the N-SMase. On the other hand, neither dithiothreitol nor beta-mercaptoethanol had any effect on the N-SMase, suggesting that the sulfhydryl in GSH is not required for inhibition of N-SMase. GSH had no effect on the acid pH-optimum SMase, whereas dithiothreitol inhibited the acid SMase. These results suggest that in cells the N-SMase is inactive in the presence of physiological concentrations of GSH (1-20 mM). Finally, treatment of cultured Molt-4 cells with the GSH synthesis inhibitor, L-buthionine-(SR)-sulfoximine, resulted in a time-dependent depletion of GSH, accompanied by an increased hydrolysis of sphingomyelin and production of ceramide. Since GSH depletion is observed in a variety of cells in the process of cellular injury and apoptosis, these studies suggest that depletion of GSH may be an important mechanism in activation of N-SMase. This mechanism may therefore bring together the fields of oxidative stress and signaling through products of sphingomyelin hydrolysis.
Conjugated Dendrimers for Light-Emitting Diodes: Effect of Generation (1999)

Conjugated dendrimers are a promising new class of material for organic LEDs. The authors report here an investigation into a new family of conjugated light-emitting dendrimers based on the phenylenevinylene structure, and the effect of generation number (level of branching) on both the electroluminescence and photophysical properties of the materials. High fluorescence was found for all three of the first, second, and third generation dendrimers, while concentration quenching effects are substantially avoided by the dendritic molecular architecture.
Absorption and metabolism of nicotine from cigarettes. (1975)

Eight men volunteers each smoked a single cirgarette containing 14C-nicotine and gave arterial blood samples during and for 50 minutes after smoking. The maximum concentration of nicotine in the arterial blood ranged from 31 to 41 mug/l in four regular cigarette smokers who inhaled. Two non-smokers achieved maximum levels of 2 and 4 mug/l. On a separate occasion two of the inhalers received 1 mg. 14C-nicotine in 10 divided doses injected intravenously. In both cases the peak arterial nicotine concentrations bore a similar relationship to the intravenous dose, as did the peak nicotine concentrations to the retained doses during smoking.
The chromophore of pholasin: A highly luminescent protein (1990)

Pholasin is the photoprotein extracted from the marine bivalve Pholas dactylus. It undergoes an oxidative chemiluminescent reaction to oxypholasin with superoxide anion, hypochlorite, peroxidases and other oxidants. Since the observed absorbance and chemiluminescent emission spectra of pholasin solutions cannot be brought about solely by the amino acids composing the protein, there has to be a chemiluminescent chromophore. However, little is known about the chemical nature of this molecule. This work seeks to identify the chemical structure of the luminescent prosthetic group of pholasin. Pholasin could not be reactivated using chromophores from the hydroid Obelia geniculata (coelenterazine) and from the ostracod shrimp Vargula (formerly Cypridina) hilgendorfi. Furthermore, the reaction product of the Vargula chromophore could not be detected in solutions containing oxypholasin. Fluorescence analysis of such a solution revealed a compound with an emission spectrum (lambda max 480 nm; excitation at 320 nm), resembling the emission spectrum of the chemiluminescent reaction. This fluorescent substance was separated by gel filtration. It exhibited an apparent molecular mass of less than 2000. Fluorescence measurements of extracts of partially purified pholasin suggested that a flavin moiety may be involved in pholasin luminescence.
Role of the phosphatidylinositol 3'-kinase/PTEN/Akt kinase pathway in tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in non-small cell lung cancer cells. (2002)

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)/APO-2L is a member of the TNF superfamily and has been shown to have selective antitumor activity. We here show that TRAIL does not induce apoptosis in some non-small cell lung cancer (NSCLC) cells. These cells are resistant to TRAIL because of the phosphatidylinositol 3'-kinase (PI3-K)-dependent activation of Akt/protein kinase B. The expression of phospho-Akt varies at the functional level but not at the mRNA level in NSCLC cells. Akt induces cell survival in NSCLC cells by blocking the Bid cleavage, upstream of cytochrome c release in the mitochondrial-dependent apoptotic pathway. The use of PI3-K inhibitors, Wortmannin or LY-294002, down-regulates the active Akt and reverses cellular resistance to TRAIL. In addition, genetically altering Akt expression by transfecting dominant negative Akt, sensitizes NSCLC cells to TRAIL. Conversely, transfection of constitutively active Akt into cells that express low, constitutively active Akt, increases TRAIL resistance. Alternate to this approach, transfection with PTEN, a lipid phosphatase, promotes sensitivity to TRAIL, whereas a PTEN mutant (PTEN-G129E) at the catalytic site is inactive in dephosphorylating active Akt. Furthermore, the loss of PTEN activity or overexpression of PI3-K-dependent Akt/protein kinase B activity promotes the survival of NSCLC cells. Modulation of Akt activity by combining pharmacological drugs or genetic alterations of the Akt expression induces cellular responsiveness to TRAIL. Thus, TRAIL can be used to treat NSCLC-resistant cells when combined with agents that down-regulate Akt activity.
[Low dose vasopressin is effective for catecholamine-resistant hypotension after resection of pheochromocytoma]. (2013)

The perioperative management of pheochromocytoma is challenging for anesthesiologists and persistent hypotension secondary to cathecholamine depletion after tumor resection can be refractory to treatment. A 64-year-old man underwent right adrenalectomy for treatment of massive pheochromocytoma. Doxazosin administration was started and increased gradually to 12 mg daily. He was premedicated with doxazosin on the day of the surgery. Induction was uneventful but there was a sudden increase of blood pressure with tachycardia on handling of tumor which was controlled by intravenous remifentanil, landiolol, diltiazem, and magnesium sulfate. With dissection of the tumor, the blood pressure dropped to 65/40 mmHg, which was resistant to fluid and cathecholamine treatment. After commencement of low dose vasopressin administration (two boluses of 0.08 U followed by 1.6 U x hr(-1)), blood pressure gradually recovered to normal ranges. Low dose vasopressin can be safely used to treat postadrenalectomy hypotension and also can reduce the cathecholamine dose.
Cytotoxic T lymphocyte antigen-4 and immune checkpoint blockade (2015)

The relationship between cancer and the immune system is complex and provides unique therapeutic opportunities. Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a regulatory molecule that suppresses T cell effector function following initial activation by costimulatory signals. Fully human monoclonal antibodies targeting CTLA-4 have been shown to increase T cell function and antitumor responses in patients with advanced metastatic melanoma. Responses observed with such immune checkpoint therapy can follow a different pattern from that seen with cytotoxic chemotherapy or targeted therapy and may continue after therapy is discontinued. In addition, the toxicities that are associated with anti-CTLA-4 therapy may differ from those of conventional therapies and consist of inflammatory events in parts of the body that do not contain cancerous cells. Early recognition of these inflammatory events and intervention is important, and the identification of predictive biomarkers continues to be an unfulfilled need in the field of immunotherapy. Combinatorial approaches with targeted therapies, radiation therapy, chemotherapy, or other immune checkpoint agonists/antagonists have the potential to increase the efficacy of CTLA-4 blockade.
Synthesizing realistic spine motion using traditional rig controllers (2004)

This thesis presents a specific method for simulating realistic spine motion through the use of traditional rig control objects. The spine's motion and flexibility is based on a curve as opposed to the more traditional three bone spine. This allows for a more fluid animation more closely resembling that of a spinal column. However, this setup keeps the traditional three control rig setup in order to mimic the control system of a traditional three bone spine. Currently, three bone systems are well understood by animators and the motion is easy to control. The problem with this setup is that although easy to control, these rigs lack the fluid curving motion of a true spine. The proposed method creates a solution to this problem by creating a curve that's length, shape, and twist is based on that of the three traditional bones. This solution allows traditional animators to quickly and effectively begin animating without having to alter the traditional control setup. This thesis describes how this animation pipeline can be set up using commercial software primarily focusing on Softimage XSI. Finally, a program was created using visual basic script that will allow other users to easily integrate the spine into future characters. The program is also based on the idea that the user is accustomed to the three bone spine set-up, and allows the user to create an advanced curve based spine rig by simply drawing the traditional three bone spine.
Relationship Between Insulin Resistance and Endothelium-Dependent Vascular Relaxation in Patients With Essential Hypertension (1997)

The infusion of L-arginine induces the production of nitric oxide and stimulates the immediate secretion of insulin. To examine the relationship between insulin resistance and endothelium-dependent vascular relaxation in patients with essential hypertension, we evaluated the renal and insulin responses to L-arginine, 500 mg/kg infused intravenously over 30 minutes, in 23 patients with mild essential hypertension who were neither obese nor diabetic and in 20 normotensive control subjects. We found no difference between the two groups in blood glucose or insulin in the fasting condition. The renovascular relaxation induced by L-arginine was significantly less in patients with essential hypertension than in normotensive control subjects. The increase in plasma cyclic GMP in response to L-arginine was lower in hypertensive patients than in normotensive subjects. Although the serum concentrations of glucose in response to L-arginine were similar in the two groups, the serum insulin response of the essential hypertensives was significantly higher than that of the normotensive subjects. In all subjects, the peak cyclic GMP response to L-arginine was significantly correlated with the peak delta glucose/ delta insulin ratio response to L-arginine (r = .69, P < .001). Findings suggested that an impairment of endothelium-dependent renal vascular relaxation and a reduced sensitivity to insulin are present in patients with essential hypertension. A link may be present between the abnormality of the L-arginine/nitric oxide/cyclic GMP pathway and insulin resistance in patients with essential hypertension.