Are Forest Fires Predictable?

Dynamic mean field theory is applied to the problem of forest fires. The starting point is the Monte Carlo simulation in a lattice of million cells. The statistics of the clusters is obtained by means of the Hoshen--Kopelman algorithm. We get the map $p_n\to p_{n+1}$, where $p_n$ is the probability of finding a tree in a cell, and $n$ is the discrete time. We demonstrate that the time evolution of $p$ is chaotic. The arguments are provided by the calculation of the bifurcation diagram and the Lyapunov exponent. The bifurcation diagram reveals several windows of stability, including periodic orbits of length three, five and seven. For smaller lattices, the results of the iteration are in qualitative agreement with the statistics of the forest fires in Canada in years 1970--2000.Comment: 13 pages, 13 figure

Chipped and ground stone implements from the Middle Neolithic site of Polgár 31 (North-East Hungary)

The site of Polgár 31 (Ferenci-hát) is situated on the left bank of the Upper Tisza, within the so-called “Polgár Island”. The site consists of single features dated at the Alföld Linear Pottery Culture (ALP) I-III, while the majority of features belong to the youngest phase (ALP IV) attached to the Bükk Culture. Our analysis focuses on both the chipped stone and the ground stone implements. The most important raw material used for the chipped stone industry of ALP IV phase was obsidian, followed by limno-hydroquartzites. Extra local raw materials played a minor role. Both in the case of obsidian as well as limnohydroquartzites on-site production was limited, while most artefacts were produced off-site. The structure of retouched tools shows that end-scrapers dominate slightly over marginally retouched blades. The most commonly exploited raw material in the ground stone industry were various types of rhyolites deriving from the areas 40 to 50 km north of the site. Among tools predominate implements related to food preparation such as a variety of grinding stones, pestles, grinders etc. As part of rituals these tools were destroyed. Sometimes the fragments were used for crushing mineral dyes. Both: fragments of ground stone as well as chipped stone tools occur also in the graves

Mesolithic occupations and environments on the island of Ikaria, Aegean, Greece

The most important Mesolithic site on the Island of Ikaria, Kerame 1, extends 80 m along the sloping edge of the cliff and is up to 40 m wide. The site is a sum of repeated sojourns of Mesolithic groups that had left behind concentrations of lithic artefacts, which were subsequently displaced by post-depositional agents, fi rst of all by erosion. As a result, the site reveals now a large concentration of fi nds in Trenches E, C, and G. Moreover, post-depositional agents caused the destruction of permanent features such as the hearths associated with the various khsemenitsas, or - possibly - stone rings surrounding the dwelling structures. Only in trenches D, B and E the remains of a circular stone rings, probably around hearths, were registered. The lithic industry of Kerame 1 displays considerable similarity to the site of Maroulas on Kythnos; the techno-morphological differences are, probably, the effect of differing raw materials structure at Kerame 1 and at Maroulas. At Kerame 1, the distant interregional contacts and the infl ux of extralocal raw materials (documented by the fl ow of obsidian nodules from Melos and Yali) caused that production in a full cycle was carried out on-site. Thus, there was no specialization of lithic production, and unworked nodules of raw material were exploited in the particular social clusters in a full cycle, whose outcome were tools to be used by a given unit. Regretfully, because organic materials (also bones) have not been preserved we have no data to determine seasonality at Kerame 1. Nevertheless, we can say with all certainty that Mesolithic groups visiting Kerame 1 were mobile, which is evidenced by the network of interregional contacts. The most noticeable similarity between Kerame 1 and Maroulas can be accounted for by the chronological closeness of the two sites. The AMS determinations from Maroulas concentrate in the fi rst half of the 9th millenium cal. BC (Facorellis et al. 2010). Similarly, the dates from obsidian dehydration from Kerame 1 (if their broad standard deviation is overlooked) correspond to the fi rst half of the 9th millenium cal. BC

Substituierte Pyridine für die Entwicklung neuer antifungischer und antidiabetischer Wirkstoffe

In dieser Arbeit, die der Entdeckung neuer antifungischer und antidiabetischer Wirkstoffe gewidmet ist, wurde der Fokus auf Pyridinderivative gelegt. Die substituiertenPyridine und Pyrazolopyridine wurden als ein viel versprechendes „Scaffold“ in der Suche nach neuartiger Therapeutik gewählt. In demKapitel Pyridines as scaffolds for antifungals and antidiabetics wurde eine Übersicht über Pyridin-basierenden antifungischen Wirkstoffe und Antidiabetika erstellt. Um die Zielverbindungen darzustellen wurden kombinatorische Methoden der Lösungs- und Festphasensynthese verwendet. Effiziente Protokolle, unter Verwendung von Polymer immobilizierten 2-Oxo-4-aryl-but-3-ensäuren und 4-Oxo-4-aryl-but-2-ensäuren, wurden für die Synthese von Pyridine und Pyrazolopyridine evaluiert. Die weitere Umsetzung von harzgebundenen Intermediaten wurde untersucht und eine Vielzahl von substituierten Pyrimidinen und Dihydropyrimidinen wurde erstellt (Kapitel 4. 1. 1). Die Reaktionsbedingungen für die Festephasensynthese wurden auf die Darstellung von Pyridinen in Lösung übertragen und optimiert. Die Pyridine wurden weiter modifiziert um eine breite Variation von Derivativen zu erhalten. Es wurde die Reaktionsfähigkeit von 2-Aryl-pyridinen und 4-Aryl-pyridinen untersucht. Abhängig von der Position wurde eine Deaktivierung oder Aktivierung des Substituenten festgestellt (Kapitel 4. 1. 2). Basierend auf der Literatur für das Enzym DPP-4 wurde eine Reihe von potenziellen DPP-4-Inhibitoren (Aminomethyl-pyridine: 5-Aminomethyl-6-methyl-4-aryl-pyridine-2- carbonsäureamide, 6-aminomethyl-2-methyl-4-aryl-nicotinamide und 3-Aminomethyl-2-methyl-6-aryl-isonicotinamide) designed und synthetisiert. Mehrere Synthesewege unter Verwendung von 2-Aryl-pyridinen und 4-Aryl-pyridinen als Edukte wurden bewertet um Analoga zu erhalten. Alle Verbindungen wurden isoliert und durch HPLC-ESI-MS analysiert und vereinzelt ebenfalls durch NMR, IR Spektroskopie und FT-ICR-MS charakterisiert. Zur Bestätigung wurden zusätzlich 2D NMR-Experimente (COSY und HMBC NMR) verwendet. Die synthetisierte Wirkstoff-Kollektion wurde auf ihre antifungischen Eigenschaften in einem in Vitro-Test bewertet. Infolgedessen wurden zwei Hit-Strukturen, 6-(2,4-Dichloro-phenyl)-3-methyl-1h-pyrazolo[3,4-b]pyridin-4-carbonsäure (Candida albicans) und 4-(5-Chloro-thiophen-2-yl)-1,3-dimethyl-1h-pyrazolo[3,4-b]pyridin-6-carbonsäure (Candida glabrata), identifiziert. Die 6-(2,4-Dichloro-phenyl)-3-methyl-1H-pyrazolo[3,4-b]pyridine-4-carbonsäure wurde als eine Leitstruktur wegen ihren toxischen Wirkung auf die Wirtszelle zurückgestellt. Die Inhibitorwirkung von 4-(5-Chloro-thiophen-2-yl)-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-carbonsäure auf Candida glabrata Zellen war allerdings zu schwach, um sie als eine Leitstruktur zu erwägen (Kapitel 4.1.3). Die Kollektion von Aminomethyl-pyridinen wurde auf ihre anti-DPP-4 Aktivität in einem In Vitro-Assay untersucht. Die Leitstruktur, 5-Aminomethyl-6-methyl-4-aryl-pyridin-2- carbonsäureamid wurde so gefunden, und Struktur-Aktivität-Relations (SAR) Studien führten zu einer aktiven Reihe von neuartigen DPP-4-Inhibitoren. In Vitro-Experimente bewiesen außerdem die ausgezeichnete Selektivität. Zum Beispiel wurde DPP-4 um das 6600-fache besser von 5-Aminomethyl-4-(2,4-dichloro-phenyl)-6-methyl-pyridin-2-carbonsäure cyanomethyl-amid gehemmt als DPP-8 (Kapitel 4. 2. 3). Diese Ergebnisse wurden beschrieben und patentiert. Diese Studie bestätigt das Potenzial der untersuchten „Scaffolds“. Da die biologische Aktivität von Pyridinen stark von der Ringsubstitution abhängt, sollten die in dieser Arbeit beschriebene Wirkstoffe weiter auf biologische Aktivitäten untersucht werden. Die Vortests der neuartigen DPP-4-Inhibitoren sind vielversprechend, jedoch sind zusätzliche biologische Experimente erforderlich um das pharmakologische Profil zu definieren und die Struktur weiter zu optimieren. Neben dem vom Glucosemetabolismus sind mehrere verschiedene biologische Funktionen von DPP-4 kürzlich bekannt. Die Entdeckungen ziehen eine große Aufmerksamkeit auf die DPP-4-Inhibitoren, weil solche Wirkstoffe für die Behandlung anderer Krankheiten nützlich sein könnten. Ist es deshalb wichtig weitere Studie der beschriebenen Verbindungen durch zu führen, um das therapeutisches Potenzial des DPP-4 Enzyms in Gänze zu erforschen.In this work dedicated to the discovery of novel biologically active compounds, antifungals and antidiabetics, the focus was placed on the pyridine motif. The substituted pyridines and pyrazolopyridines were chosen as a promising scaffold in a search for novel therapeutics. The overview of the pyridine-based antifungals and antidiabetics was reported in the part Pyridines as scaffolds for antifungals and antidiabetics. Solution and solid phase combinatorial chemistry methods were used to approach target compounds. Efficient protocols were evaluated for the synthesis of pyridines and pyrazolopyridines applying solid supported 2-oxo-4-aryl-but-3-enoic acids and 4-oxo-4-aryl-but-2-enoic acids. In addition, the synthetic possibilities of the resin-bound intermediates were investigated and resulted in a collection of easily accessible pyrimidines and dihydropyrimidines (Chapter 4. 1. 1). The solid phase protocol was adapted to the solution phase. A series of pyridines was synthesized in gram scale as starting materials for the generation of sub-sets of compounds varying only on the pyridine ring substitution. Differences in the reactivity of 2-aryl pyridines and 4-aryl pyridines were observed and investigated. Depending on the ring substitution pattern, deactivation or activation of certain positions resulted in reactivity limitations, but on the other hand, gave a possibility of additional structural variations (Chapter 4. 1. 2). Based on the data available for the enzyme DPP-4 in the literature, a series of potential DPP-4 inhibitors (aminomethyl-pyridines: 5-aminomethyl-6-methyl-4-aryl-pyridine-2-carboxylic acid amides, 6-aminomethyl-2-methyl-4-aryl-nicotinamides and 3-aminomethyl-2-methyl-6-aryl-isonicotinamides) were designed and synthesized. Several synthetic pathways using 2-aryl pyridines and 4-aryl pyridines as starting materials were evaluated in order to obtain analogs. All compounds were isolated and analyzed by HPLC-ESI-MS. Representative products were characterized using NMR and IR spectroscopy and FT-ICR-MS. For structure confirmation additional 2-D NMR experiments were used (COSY and HMBC NMR). The synthesized compound collection was evaluated for its antifungal properties in an in vitro screening. As a result, two hit structures 6-(2,4-dichloro-phenyl)-3-methyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (Candida albicans) and 4-(5-chloro-thiophen-2-yl)-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine-6-carboxylic acid (Candida glabrata) were identified. The compound 6-(2,4-dichloro-phenyl)-3-methyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid was disqualified as a lead structure due to its toxic effect on the host cells. Inhibitory effect of 4-(5-chloro-thiophen-2-yl)-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine-6-carboxylic acid on Candida glabrata cells was too weak to consider the compound as a lead structure (Chapter 4.1.3). The collection of aminomethyl-pyridines was investigated for its DPP-4 inhibitory activity in an in vitro assay. The lead structure of 5-aminomethyl-6-methyl-4-aryl-pyridine-2-carboxylic acid amides was found and structure activity relationship led to a potent series of the novel DPP-4 inhibitors. Furthermore, in vitro experiments proved excellent selectivity (up to 6600 fold for 5-aminomethyl-4-(2,4-dichloro-phenyl)-6-methyl-pyridine-2-carboxylic acid cyanomethyl-amide) of the inhibitors over closely related DPP-8 (Chapter 4. 2. 3). The results were described and patented. This study clearly confirms the potential of the investigated scaffolds. As the biological activity of substituted pyridines highly depends on its substitution pattern, the synthesized and described herein compounds should be extensively investigated for other pharmaceutical targets. Although preliminary biological data of the novel DPP-4 inhibitors are doubtlessly promising, the crucial point for their further development is the pharmacological profile of 5-aminomethyl-6-methyl-4-aryl-pyridine-2-carboxylic acid amides. Therefore additional biological experiments are required to further optimize the structure and to identify a clinical candidate. Apart from the glucose metabolism, a number of different biological functions of DPP-4 have been recognized recently. The discoveries attract a great attention to the DPP-4 inhibitors, as such compounds could be useful for the treatment of other metabolic, but also autoimmune and inflammatory diseases.74b It is therefore important to further study of the described series in order to fully explore therapeutic potential of the DPP-4 enzyme

Czy w wychowaniu w rodzinie ważna jest znajomość praw dziecka?

"Prawa dziecka, będące pewnym uszczegółowieniem praw człowieka, są rozważane na ogół albo w związku z niepokojącymi zjawiskami społeczno-politycznymi zagrażającymi prawidłowemu funkcjonowaniu rodziny, albo też w kontekście rosnącej liczby rodzin niewydolnych wychowawczo, zaniedbujących lub krzywdzących własne dzieci."(...

A bullet core specimen form NE Bulgaria

The paper discusses the first find of a bullet core from the territory of Bulgaria. This core fills in a gap in the occurrence of this technology in between the Marmara Sea basin and the northwestern part of the Pontic region. Because the core from the vicinity of Varna is a surface find it is difficult to determine its chronological position

GABAB receptor allosteric modulators exhibit pathway-dependent and species-selective activity.

Positive modulation of the GABAB receptor (GABABR) represents a potentially useful therapeutic approach for the treatment of nicotine addiction. The positive allosteric modulators (PAMs) of GABABR GS39783 and BHF177 enhance GABA-stimulated [35S]GTP γS-binding, and have shown efficacy in a rodent nicotine self-administration procedure reflecting aspects of nicotine dependence. Interestingly, the structural related analog, NVP998, had no effect on nicotine self-administration in rats despite demonstrating similar pharmacokinetic properties. Extensive in vitro characterization of GS39783, BHF177, and NVP998 activity on GABABR-regulated signaling events, including modulation of cAMP, intracellular calcium levels, and ERK activation, revealed that these structurally related molecules display distinct pathway-specific signaling activities that correlate with the dissimilarities observed in rodent models and may be predictive of in vivo efficacy. Furthermore, these GABABR allosteric modulators exhibit species-dependent activity. Collectively, these data will be useful in guiding the development of GABABR allosteric modulators that display optimal in vivo efficacy in a preclinical model of nicotine dependence, and will identify those that have the potential to lead to novel antismoking therapies

Early/Middle Neolithic Western (LBK) vs Eastern (ALPC) Linear Pottery Cultures : ceramics and lithic raw materials circulation

In this paper we focused on the relations between the north-eastern range of the Linear Bandkeramik (LBK) in the Upper Vistula basin and the area of Eastern (Alföld) Linear Pottery Culture (ALPC) in eastern Slovakia, separated by the main ridge of the Western Carpathians. Contacts between these two Early/Middle Neolithic cultural zones were manifested by the exchange of lithic raw materials (Carpathian obsidian from south-eastern Slovakia and north eastern Hungary vs Jurassic flint from Kraków-Częstochowa) and pottery. Ceramic exchange was studied by comparing the mineralogical-petrographic composition of the local LBK pottery from sites in the Upper Vistula basin and sherds from the same LBK sites showing ALPC stylistic features, and pottery samples from ALPC sites in eastern Slovakia. Observation under polarized light microscope and SEM-EDS analyses resulted in identification of a group of pottery samples with ALPC stylistic features which could be imports to LBK sites in southern Poland from Slovakia, and a group of vessels with ALPC decorations but produced in the Upper Vistula basin from local ceramic fabric, which were imitations by the local LBK population. The second group of pottery appears mostly in the pre-Notenkopf and Notenkopf phases of the LBK, correlated with Tiszadob-Kapušany Groups of ALPC, in contrast to the pottery imports attributed mostly to the Želiezovce group/ phase, synchronous with the Bükk Culture/Group

Before the neolithization: Causes of mesolithic diversity in the Southern Balkans

The Balkans, particularly southern and central, were sparsely populated in the Mesolithic and the occupation networks in that period were discontinous and highly diversified, contrasting with the density and homogeneity of the Early Neolithic. The aim of this paper is to describe the environmental conditions of the Mesolithic sites in relation to Early Holocene climatic fluctuations and to discuss the causes of specificity and diversity of culture and behaviour at this period. Some general trends are observable in the adaptation to Early Holocene environments (trends in faunal exploitation; for ex. shift from high ranked large game to low ranked small animals) but also particular adaptations to local conditions (technological changes due to difficulties in access to better quality lithic raw materials, adaptations to coastal or to terrestrial resources reflecting the unique features of site use, etc). The diversity of the Mesolithic is also reflected in cultural taxonomy: in some sequences continuity of the Balkan Epigravettian techno-morphological tradition can be seen as opposed, in other sequences, to highly isolated groups with technology and tool morphology adapted to local raw materials and specific activities. The Balkan Mesolithic was not completely cut-off from the Western Mediterranean techno-morphological influences (particularly in Southern Greece) and from the Anatolian lithic traditions (seen only in the Northern Aegean). A more intensive network of marine contacts is confirmed by obsidian circulation in the Aegean Basin