Marcadores del discurso derivados de los verbos de percepción: un análisis comparativo entre el español y el italiano

Despite the growing interest in discourse markers over the past two decades, few studies are dedicated to the interlinguistic comparison of discourse markers. By means of a corpus-based approach the present study proposes a comparison between the discourse markers derived from verbs of perception in Italian (guarda/guardi, senti/senta) and Spanish (mira/mire, oye/oiga). The results of a comparable corpus study reveals that the discourse markers sharing the original perception modality display a similar formal behaviour (mira/mire ~ guarda/guardi, oye/oiga ~ senti/senta). From the parallel corpus on the other hand it results that the most frequent equivalent of mira/mire is senti/senta, which can be linked to the original semantics of both verbs. These two main observations confirm the relevance of a parallel corpus as a complementary source to a comparable corpus when comparing phenomena in two (or more) languages. This combined corpus approach brings about not only interlinguistic insights but provides at the same time knowledge about the relation and uses of the discourse markers within the languages

Epidemic syphilis exhibits diverse manifestations

Copyright to Australian Family Physician. Reproduced with permission. Permission to reproduce must be sought from the publisher, The Royal Australian College of General Practitioners.There are recent reports of a sustained increase in the incidence of syphilis around the world, including in the Australian cities of Sydney and Melbourne. In Queensland, there has been both an increase in the number of notifications and also a change in the epidemiology of the disease. While syphilis was previously predominantly seen in indigenous men and women, it now mostly occurs in nonindigenous men who have sex with other men - although per capita, indigenous Queenslanders remain overrepresented. Efforts to improve screening and treatment have shortened the time from diagnosis to treatment and appear to have been successful in reducing the rates of disease in remote indigenous populations. These efforts have included the establishment of a state wide syphilis register and active encouragement to remote practitioners to offer testing to patients aged 15–39 years as a part of the annual adult health check. Adoption of single dose azithromycin for syndromic treatment of urethritis and cervicitis and their contacts, albeit at a dose of only 1 g, may be having an impact as well.Andrew M Redmond; Craig M Dancer; Andrew R Doolan; Diane F Rowling; Marion L Wood

Characterisation of the androgen regulation of glycine N-methyltransferase in prostate cancer cells

The development and growth of prostate cancer is dependent on androgens; thus, the identification of androgen-regulated genes in prostate cancer cells is vital for defining the mechanisms of prostate cancer development and progression and developing new markers and targets for prostate cancer treatment. GlycineN-methyltransferase (GNMT) is aS-adenosylmethionine-dependent methyltransferase that has been recently identified as a novel androgen-regulated gene in prostate cancer cells. Although the importance of this protein in prostate cancer progression has been extensively addressed, little is known about the mechanism of its androgen regulation. Here, we show that GNMT expression is stimulated by androgen in androgen receptor (AR) expressing cells and that the stimulation occurs at the mRNA and protein levels. We have identified an androgen response element within the first exon of theGNMTgene and demonstrated that AR binds to this elementin vitroandin vivo. Together, these studies identify GNMT as a direct transcriptional target of the AR. As this is an evolutionarily conserved regulatory element, this highlights androgen regulation as an important feature of GNMT regulation.</jats:p

Dissecting and reprogramming the folding and assembly of tandem-repeat proteins.

Studying protein folding and protein design in globular proteins presents significant challenges because of the two related features, topological complexity and co-operativity. In contrast, tandem-repeat proteins have regular and modular structures composed of linearly arrayed motifs. This means that the biophysics of even giant repeat proteins is highly amenable to dissection and to rational design. Here we discuss what has been learnt about the folding mechanisms of tandem-repeat proteins. The defining features that have emerged are: (i) accessibility of multiple distinct routes between denatured and native states, both at equilibrium and under kinetic conditions; (ii) different routes are favoured for folding compared with unfolding; (iii) unfolding energy barriers are broad, reflecting stepwise unravelling of an array repeat by repeat; (iv) highly co-operative unfolding at equilibrium and the potential for exceptionally high thermodynamic stabilities by introducing consensus residues; (v) under force, helical-repeat structures are very weak with non-co-operative unfolding leading to elasticity and buffering effects. This level of understanding should enable us to create repeat proteins with made-to-measure folding mechanisms, in which one can dial into the sequence the order of repeat folding, number of pathways taken, step size (co-operativity) and fine-structure of the kinetic energy barriers.We acknowledge funding from the Medical Research Council of the UK (grant G1002329) and the Leverhulme Trust. AP is funded by a BBSRC Doctoral Training Program studentship. LSI acknowledges support of a Fellowship from the Medical Research Foundation.This is the accepted manuscript. The final version is available at http://www.biochemsoctrans.org/content/43/5/881

Cave Aragonites of New South Wales

Abstract Aragonite is a minor secondary mineral in many limestone caves throughout the world. It has been claimed that it is the second-most common cave mineral after calcite (Hill & Forti 1997). Aragonite occurs as a secondary mineral in the vadose zone of some caves in New South Wales. Aragonite is unstable in fresh water and usually reverts to calcite, but it is actively depositing in some NSW caves. A review of current literature on the cave aragonite problem showed that chemical inhibitors to calcite deposition assist in the precipitation of calcium carbonate as aragonite instead of calcite. Chemical inhibitors work by physically blocking the positions on the calcite crystal lattice which would have otherwise allowed calcite to develop into a larger crystal. Often an inhibitor for calcite has no effect on the aragonite crystal lattice, thus aragonite may deposit where calcite deposition is inhibited. Another association with aragonite in some NSW caves appears to be high evaporation rates allowing calcite, aragonite and vaterite to deposit. Vaterite is another unstable polymorph of calcium carbonate, which reverts to aragonite and calcite over time. Vaterite, aragonite and calcite were found together in cave sediments in areas with low humidity in Wollondilly Cave, Wombeyan. Several factors were found to be associated with the deposition of aragonite instead of calcite speleothems in NSW caves. They included the presence of ferroan dolomite, calcite-inhibitors (in particular ions of magnesium, manganese, phosphate, sulfate and heavy metals), and both air movement and humidity. Aragonite deposits in several NSW caves were examined to determine whether the material is or is not aragonite. Substrates to the aragonite were examined, as was the nature of the bedrock. The work concentrated on Contact Cave and Wiburds Lake Cave at Jenolan, Sigma Cave, Wollondilly Cave and Cow Pit at Wombeyan and Piano Cave and Deep Hole (Cave) at Walli. Comparisons are made with other caves. The study sites are all located in Palaeozoic rocks within the Lachlan Fold Belt tectonic region. Two of the sites, Jenolan and Wombeyan, are close to the western edge of the Sydney Basin. The third site, Walli, is close to a warm spring. The physical, climatic, chemical and mineralogical influences on calcium carbonate deposition in the caves were investigated. Where cave maps were unavailable, they were prepared on site as part of the study. %At Jenolan Caves, Contact Cave and Wiburds Lake Cave were examined in detail, %and other sites were compared with these. Contact Cave is located near the eastern boundary of the Late Silurian Jenolan Caves Limestone, in an area of steeply bedded and partially dolomitised limestone very close to its eastern boundary with the Jenolan volcanics. Aragonite in Contact Cave is precipitated on the ceiling as anthodites, helictites and coatings. The substrate for the aragonite is porous, altered, dolomitised limestone which is wedged apart by aragonite crystals. Aragonite deposition in Contact Cave is associated with a concentration of calcite-inhibiting ions, mainly minerals containing ions of magnesium, manganese and to a lesser extent, phosphates. Aragonite, dolomite and rhodochrosite are being actively deposited where these minerals are present. Calcite is being deposited where minerals containing magnesium ions are not present. The inhibitors appear to be mobilised by fresh water entering the cave as seepage along the steep bedding and jointing. During winter, cold dry air pooling in the lower part of the cave may concentrate minerals by evaporation and is most likely associated with the ``popcorn line'' seen in the cave. Wiburds Lake Cave is located near the western boundary of the Jenolan Caves Limestone, very close to its faulted western boundary with Ordovician cherts. Aragonite at Wiburds Lake Cave is associated with weathered pyritic dolomitised limestone, an altered, dolomitised mafic dyke in a fault shear zone, and also with bat guano minerals. Aragonite speleothems include a spathite, cavity fills, vughs, surface coatings and anthodites. Calcite occurs in small quantities at the aragonite sites. Calcite-inhibitors associated with aragonite include ions of magnesium, manganese and sulfate. Phosphate is significant in some areas. Low humidity is significant in two areas. Other sites briefly examined at Jenolan include Glass Cave, Mammoth Cave, Spider Cave and the show caves. Aragonite in Glass Cave may be associated with both weathering of dolomitised limestone (resulting in anthodites) and with bat guano (resulting in small cryptic forms). Aragonite in the show caves, and possibly in Mammoth and Spider Cave is associated with weathering of pyritic dolomitised limestone. Wombeyan Caves are developed in saccharoidal marble, metamorphosed Silurian Wombeyan Caves Limestone. Three sites were examined in detail at Wombeyan Caves: Sigma Cave, Wollondilly Cave and Cow Pit (a steep sided doline with a dark zone). Sigma Cave is close to the south east boundary of the Wombeyan marble, close to its unconformable boundary with effusive hypersthene porphyry and intrusive gabbro, and contains some unmarmorised limestone. Aragonite occurs mainly in a canyon at the southern extremity of the cave and in some other sites. In Sigma Cave, aragonite deposition is mainly associated with minerals containing calcite-inhibitors, as well as some air movement in the cave. Calcite-inhibitors at Sigma Cave include ions of magnesium, manganese, sulfate and phosphate (possibly bat origin), partly from bedrock veins and partly from breakdown of minerals in sediments sourced from mafic igneous rocks. Substrates to aragonite speleothems include corroded speleothem, bedrock, ochres, mud and clastics. There is air movement at times in the canyon, it has higher levels of CO2 than other parts of the cave and humidity is high. Air movement may assist in the rapid exchange of CO2 at speleothem surfaces. Wollondilly Cave is located in the eastern part of the Wombeyan marble. At Wollondilly Cave, anthodites and helictites were seen in an inaccessible area of the cave. Paramorphs of calcite after aragonite were found at Jacobs Ladder and the Pantheon. Aragonite at Star Chamber is associated with huntite and hydromagnesite. In The Loft, speleothem corrosion is characteristic of bat guano deposits. Aragonite, vaterite and calcite were detected in surface coatings in this area. Air movement between the two entrances of this cave has a drying effect which may serve to concentrate minerals by evaporation in some parts of the cave. The presence of vaterite and aragonite in fluffy coatings infers that vaterite may be inverting to aragonite. Calcite-inhibitors in the sediments include ions of phosphate, sulphate, magnesium and manganese. Cave sediment includes material sourced from detrital mafic rocks. Cow Pit is located near Wollondilly Cave, and cave W43 is located near the northern boundary of the Wombeyan marble. At Cow Pit, paramorphs of calcite after aragonite occur in the walls as spheroids with minor huntite. Aragonite is a minor mineral in white wall coatings and red phosphatic sediments with minor hydromagnesite and huntite. At cave W43, aragonite was detected in the base of a coralloid speleothem. Paramorphs of calcite after aragonite were observed in the same speleothem. Dolomite in the bedrock may be a source of magnesium-rich minerals at cave W43. Walli Caves are developed in the massive Belubula Limestone of the Ordovician Cliefden Caves Limestone Subgroup (Barrajin Group). At the caves, the limestone is steeply bedded and contains chert nodules with dolomite inclusions. Gypsum and barite occur in veins in the limestone. At Walli Caves, Piano Cave and Deep Hole (Deep Cave) were examined for aragonite. Gypsum occurs both as a surface coating and as fine selenite needles on chert nodules in areas with low humidity in the caves. Aragonite at Walli caves was associated with vein minerals and coatings containing calcite-inhibitors and, in some areas, low humidity. Calcite-inhibitors include sulfate (mostly as gypsum), magnesium, manganese and barium. Other caves which contain aragonite are mentioned. Although these were not major study sites, sufficient information is available on them to make a preliminary assessment as to why they may contain aragonite. These other caves include Flying Fortress Cave and the B4-5 Extension at Bungonia near Goulburn, and Wyanbene Cave south of Braidwood. Aragonite deposition at Bungonia has some similarities with that at Jenolan in that dolomitisation of the bedrock has occurred, and the bedding or jointing is steep allowing seepage of water into the cave, with possible oxidation of pyrite. Aragonite is also associated with a mafic dyke. Wyanbene cave features some bedrock dolomitisation, and also features low grade ore bodies which include several known calcite-inhibitors. Aragonite appears to be associated with both features. Finally, brief notes are made of aragonite-like speleothems at Colong Caves (between Jenolan and Wombeyan), a cave at Jaunter (west of Jenolan) and Wellington (240\,km NW of Sydney)

Franklin Roosevelt\u27s advisory system: The institutionalization of the Executive office of the President

Since its inception in 1787, the Office of the President of the United States has had to deal with many governmental problems, burdening the President with extraordinary decisions. As the country has grown in population, in geography, and in world influence the number of problems and decisions has escalated, placing immense pressure upon the decision making procress. Today, decisions made by the President of the United States can affect the future of the entire world. Consequently, the advice and administrative assistance a president receives when he is making these decisions is crucial. Furnishing the President with this advice and assistance is one of the most influential elements in the Executive Branch of the Federal Government, the Presidential Advisory System

Nutritional and hormonal modulation of glycine N-methyltransferase: implications for aberrant methyl group metabolism

Glycine N-methyltransferase (GNMT) regulates S-adenosylmethionine (SAM) levels and the SAM/S-adenosylhomocysteine (SAH) ratio. Therefore, up-regulation of GNMT may lead to wastage of methyl groups required for transmethylation reactions. Previously, we demonstrated 13-cis-retinoic acid (CRA) reduced hepatic SAM concentrations and the SAM/SAH ratio in rats. In Study 1 the ability of CRA, as well as all-trans-retinoic acid (ATRA), to regulate hepatic GNMT were examined as a potential basis for our observations. Rats were fed either a control or a methionine-supplemented (MS) diet and given either ATRA, CRA (30 mumol/kg BW), or vehicle daily for 7 d. In control rats, both CRA and ATRA elevated hepatic GNMT activity (49 and 34%, respectively), compared to the control group. Similar results were observed in MS rats. Moreover, enzymatic activity was reflected in GNMT protein abunDance; The second study determined that vitamin A had a similar ability to up-regulate GNMT. Additionally, GNMT induction down-regulated the transmethylation pathway. Rats were given retinyl palmitate (RP), CRA, ATRA, or vehicle daily for 10 d. RP, CRA, and ATRA elevated hepatic GNMT activity 32, 74, and 124% respectively, compared to the control group. Moreover, the retinoid-mediated changes in GNMT activity were reflected in GNMT abundance (38, 89, and 107% increase for RP-, CRA-, and ATRA-treated rats, respectively). In addition, hepatic DNA was hypomethylated (~100%) following ATRA treatment compared to the control group, whereas the transsulfuration product glutathione was unaffected. Because retinoids stimulate gluconeogenesis, the third study was undertaken to determine the relationship between ATRA and gluconeogenic hormones on these metabolic pathways. Adrenal function was not required for ATRA to induce and activate hepatic GNMT; however, treatment of rats with dexamethasone (1 mg/kg BW, daily for 5 d) induced hepatic GNMT (~2-fold). Increased plasma total homocysteine levels observed in adrenalectomized rats were normalized by either ATRA or DEX, indicating that homocysteine catabolism was enhanced. Moreover, co-administration of ATRA and DEX resulted in an additive effect on hepatic GNMT induction in both rats and rat hepatoma cells. Collectively, these results demonstrate that both ATRA and DEX alter methyl group metabolism, thereby having implications for an interaction between retinoid administration and diabetes

Top tagging: an analytical perspective

In this paper we study aspects of top tagging from first principles of QCD. We find that the method known as the CMS top tagger becomes collinear unsafe at high pt and propose variants thereof which are IRC safe, and hence suitable for analytical studies, while giving a comparable performance to the CMS tagger. We also develop new techniques to identify three-pronged jet substructure, based on adaptations of the Y-splitter method and its combination with grooming. A novel feature of our studies, relative to previous calculations of two-pronged substructure, is our use of triple-collinear splitting functions combined with all-order resummation, which owes to the presence of two mass scales of the same order, mt and mW , in the signal jet. We carry out leading logarithmic resummed calculations for the various top-taggers, for both background and signal jets, and compare the results to those from parton showers. We also identify and comment on the main features driving tagger performance at high pt and discuss the role of non-perturbative effects