Geo-hydrological hazard underlined by toponymy of Italian Military Geographycal Institute maps at 1:25,000 scale. Contributions to the knowledge of floodplain and hillslope dinamycs

Toponymy is a linguistic discipline, which has already been used as a tool for geographical studies in Italy and particularly in Liguria. Geographical studies have already classified the toponyms in several categories: physical geography, human geography and socio-economic geography. By selecting the place names connected to physical geography, we study those suggesting the presence of landslides or floods. We focussed on the Italian Military Geographic Institute maps at 1: 25.000 scale, edited between 1936-1939 and related to a territory approximately located between Genoa and Chiavari, in Ligurian coastal area, and Tortona and Piacenza in Po valley. On the Ligurian slopes we have examined the maps relating to the Polcevera, Bisagno and Entella streams catchments. For the Po side we dealt with maps of the Scrivia and Trebbia rivers catchments: From the Ligurian-Po watershed, these rivers flow into the Adriatic Sea. The place names have been compared with landslide and flood hazard maps of Basin Master Plans for geo-hydrological risk reduction. The toponyms feature a linguistic layer linked to different historical periods. In particular in the study area several layers have been recognized: the ancient Ligurian pre-Roman, Latin, ancient Lombard, vulgar Gaulish-Italic of local languages and Italian terms related to the twentieth century. The first three layers and the last one match in the entire area of study. The vulgar Gaulish-Italic is structured into two Ligurian and Emilian groups: the latter is further splitted into the Oltrepo variants of Tortona and Piacenza. The identified names were distinguished in related-landslides or floods. In addition, the toponyms have been further divided into three linguistic influence areas: Ligurian, from Ligurian Sea up to Novi Ligure and Bobbio, the language of Tortona, downstream of Novi Ligure and Piacenza from Bobbio to Po river. Overall, place names linked to physical geography features represent nearly 25% of toponyms with a density of about 0.5 per km2. Almost half of these are toponyms related to landslides, floods or predisposing factors such as erosion, steepness or water. The names of places linked to landsliding prevail in Liguria, while those related to the waters or floods in the Po areas are located in plain areas or in very gentle slopes. The most common names related to landslides or erosion are \u201cmoggia\u201d, \u201cliggia\u201d or \u201ccrosi\u201d and similar, which respectively mean swampy deposits, landslides or gullies. Names related to floods are \u201criva\u201d, \u201cpiana\u201d \u201cponte\u201d or \u201cisola\u201d which mean respectively edge of fluvial scarp, floodplain, bridge or isle. The comparison with the Basin Master Plan gave satisfying results: we found a good correspondence between names and geo-hydrological hazard. The use of toponyms allowed a geographycal interpretation of the slope and floodplain dynamics. It suggests a possible use of toponymys in land planning activities

Cystic Fibrosis: A New Target for 4-Imidazo[2,1-b]thiazole-1,4-dihydropyridines

The pharmacology of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel has attracted significant interest in recent years with the aim to search for rational new therapies for diseases caused by CFTR malfunction. Mutations that abolish the function of CFTR cause the life-threatening genetic disease cystic fibrosis (CF). The most common cause of CF is the deletion of phenylalanine 508 (ΔF508) in the CFTR chloride channel. Felodipine, nifedipine, and other antihypertensive 1,4-dihydropyridines (1,4-DHPs) that block L-type Ca(2+) channels are also effective potentiators of CFTR gating, able to correct the defective activity of ΔF508 and other CFTR mutants ( Mol. Pharmacol. 2005 , 68 , 1736 ). For this purpose, we evaluated the ability of the previously and newly synthesized 4-imidazo[2,1-b]thiazoles-1,4-dihydropyridines without vascular activity and inotropic and/or chronotropic cardiac effects ( J. Med. Chem. 2008 , 51 , 1592 ) to enhance the activity of ΔF508-CFTR. Our studies indicate compounds 17, 18, 20, 21, 38, and 39 as 1,4-DHPs with an interesting profile of activity

Evidence for a merger of binary white dwarfs: the case of GD 362

GD 362 is a massive white dwarf with a spectrum suggesting a H-rich atmosphere which also shows very high abundances of Ca, Mg, Fe and other metals. However, for pure H-atmospheres the diffusion timescales are so short that very extreme assumptions have to be made to account for the observed abundances of metals. The most favored hypothesis is that the metals are accreted from either a dusty disk or from an asteroid belt. Here we propose that the envelope of GD 362 is dominated by He, which at these effective temperatures is almost completely invisible in the spectrum. This assumption strongly alleviates the problem, since the diffusion timescales are much larger for He-dominated atmospheres. We also propose that the He-dominated atmosphere of GD 362 is likely to be the result of the merger of a binary white dwarf.Comment: 4 pages, 3 figures. Accepted for publication in Astrophysical Journal Letter

Proteostasis Regulators in Cystic Fibrosis: Current Development and Future Perspectives

In cystic fibrosis (CF), the deletion of phenylalanine 508 (F508del) in the CF transmembrane conductance regulator (CFTR) leads to misfolding and premature degradation of the mutant protein. These defects can be targeted with pharmacological agents named potentiators and correctors. During the past years, several efforts have been devoted to develop and approve new effective molecules. However, their clinical use remains limited, as they fail to fully restore F508del-CFTR biological function. Indeed, the search for CFTR correctors with different and additive mechanisms has recently increased. Among them, drugs that modulate the CFTR proteostasis environment are particularly attractive to enhance therapy effectiveness further. This Perspective focuses on reviewing the recent progress in discovering CFTR proteostasis regulators, mainly describing the design, chemical structure, and structure-activity relationships. The opportunities, challenges, and future directions in this emerging and promising field of research are discussed, as well

A New Taxonomy of Sudden Stops: Which Sudden Stops Should Countries Be Most Concerned About?

This paper proposes a new taxonomy of Sudden Stops comprised of seven categories with definitions depending on the behavior of gross and net capital flows. The incidence of different types of Sudden Stops is tracked over time and the type of Sudden Stop related to economic performance. Sudden Stops in Net Flows associated with reductions in Gross Inflows are more disruptive than those where surges in (only) Gross Outflows dominate. The paper further discusses the mechanisms that might result in Sudden Stops in Gross Flows that are not Sudden Stops in Net Flows, such that shifts in financial assets or liabilities do not require a sharp current account adjustment. Still, it is found that Sudden Stops in Gross Inflows that do not provoke a sharp contraction in Net Flows may also be disruptive, including Sudden Stops that are driven by 'other flows' -which include banking flows. The results suggest new avenues for research and future policy analysis

‘Warrant’ revisited: Integrating mathematics teachers’ pedagogical and epistemological considerations into Toulmin’s model for argumentation

In this paper, we propose an approach to analysing teacher arguments that takes into account field dependence—namely, in Toulmin’s sense, the dependence of warrants deployed in an argument on the field of activity to which the argument relates. Freeman, to circumvent issues that emerge when we attempt to determine the field(s) that an argument relates to, proposed a classification of warrants (a priori, empirical, institutional and evaluative). Our approach to analysing teacher arguments proposes an adaptation of Freeman’s classification that distinguishes between: epistemological and pedagogical a priori warrants, professional and personal empirical warrants, epistemological and curricular institutional warrants, and evaluative warrants. Our proposition emerged from analyses conducted in the course of a written response and interview study that engages secondary mathematics teachers with classroom scenarios from the mathematical areas of analysis and algebra. The scenarios are hypothetical, grounded on seminal learning and teaching issues, and likely to occur in actual practice. To illustrate our proposed approach to analysing teacher arguments here, we draw on the data we collected through the use of one such scenario, the Tangent Task. We demonstrate how teacher arguments, not analysed for their mathematical accuracy only, can be reconsidered, arguably more productively, in the light of other teacher considerations and priorities: pedagogical, curricular, professional and personal

Management of oromandibular dystonia with botulinum A toxin: a series of cases.

Oromandibular dystonia is a disorder of movement that is often misdiagnosed. We present our experience of six patients treated with botulinum A toxin, for whom we recorded the symptoms, the group of muscles targeted, and the quantity of botulinum toxin used. We used the Glasgow Benefit Inventory (GBI) questionnaire to record and analyse outcomes after treatment. Five of the six patients had a good outcome as recorded by the GBI, the mean (SD) score of which was +40 (28), which reflected that the patients were well satisfied. The overall improvement in the categories of general health, social health, and physical health were 82%, 37%, and 31%, respectively. Botulinum type A toxin is an effective treatment of oromandibular dystonia. It is important for clinicians to recognise the condition, as treatment is well-tolerated and can improve quality of life

VERIFICATION OF LIMITED-AREA MODELS PRECIPITATION FORECASTS DURING THE MAP-SOP

This contribution presents an extensive study about the performances and forecast skills for rain precipitations of several limited area models operating during the Special Observing Period of the Mesoscale Alpine Programme (MAP-SOP, Autumn 1999). Verification is carried out using the updated version of the MAP dataset. Observed data are submitted to a further validation procedure aimed at pointing out defective gauges. As a result, more than 500 stations over a domain surrounding the Alps have been selected. Several statistical indexes widely used in literature are computed using the ECMWF global model as reference. The performances of the limited area models are discussed in detail, paying particular attention to their behavior as a function of rain threshold

Virtual Drug Repositioning as a Tool to Identify Natural Small Molecules That Synergize with Lumacaftor in F508del-CFTR Binding and Rescuing

Cystic fibrosis is a hereditary disease mainly caused by the deletion of the Phe 508 (F508del) of the cystic fibrosis transmembrane conductance regulator (CFTR) protein that is thus withheld in the endoplasmic reticulum and rapidly degraded by the ubiquitin/proteasome system. Cystic fibrosis remains a potentially fatal disease, but it has become treatable as a chronic condition due to some CFTR-rescuing drugs that, when used in combination, increase in their therapeutic effect due to a synergic action. Also, dietary supplementation of natural compounds in combination with approved drugs could represent a promising strategy to further alleviate cystic fibrosis symptoms. On these bases, we screened by in silico drug repositioning 846 small synthetic or natural compounds from the AIFA database to evaluate their capacity to interact with the highly druggable lumacaftor binding site of F508del-CFTR. Among the identified hits, nicotinamide (NAM) was predicted to accommodate into the lumacaftor binding region of F508del-CFTR without competing against the drug but rather stabilizing its binding. The effective capacity of NAM to bind F508del-CFTR in a lumacaftor-uncompetitive manner was then validated experimentally by surface plasmon resonance analysis. Finally, the capacity of NAM to synergize with lumacaftor increasing its CFTR-rescuing activity was demonstrated in cell-based assays. This study suggests the possible identification of natural small molecules devoid of side effects and endowed with the capacity to synergize with drugs currently employed for the treatment of cystic fibrosis, which hopefully will increase the therapeutic efficacy with lower doses

Анализ распространения трещин гидравлического разрыва пласта (ГРП) после проведения повторного многостадийного ГРП на горизонтальных скважинах на примере нефтяного месторождения Нюрольской впадины

Объектом исследования является пласт Ю11 верхневасюганской подсвиты месторождения N, в который пробурены вертикальные и горизонтальные скважины, в которых был произведен гидравлический разрыв пласта. Целью работы является определение направления распространения трещин повторного гидравлического разрыва пласта (ГРП) в зависимости от времени работы скважины и дальнейший дизайн оптимальной операции. В процессе работы произведен анализ существующей литературы по исследуемой теме, выявлены не разрешенные вопросы на настоящий момент. Методика расчета изменения поля напряжений в результате отбора флюда была предложена и обоснована. Произведено моделирование поля напряжений для различных типов скважин, а также гидродинамическое моделирование.The objects of the study is U11 horizon of Verhne-Vasyoganian formation, which is penetrated by vertical and horizontal wells which were hydraulically fractured. The aim of the study is to determine the direction of fracture propagation which was induced during refracturing treatment depending on well flowing time and to design following optimal treatment. The analysis of exist literature about the theme was made and the exist problems were determined during the study. The method of stress field changing estimation due to the was proposed and approved. Stress field modelling around various types of wells and following simulation study in order to select the most effective treatment were performed