The mechanism of formation of 8,8-dimethyl[4.2.1.0 3,7]nonan-6-yl acetate (fortesyl acetate) during acetolysis of nopyl toluene-psulfonate

Attempts to prepare 2-(2-hydroxyethyl)-6,6-dimethylbicyclo[3.1.1]hept-2-ene (nopol; 1) labelled with deuterium at C-10 by a process of oxidation of the primary alcohol group of nopol to the aldehyde, followed by H/D exchange and reduction back to alcohol, were unsuccessful because various oxidation procedures, including reaction with N-chlorosuccinimide at 278 8C, gave instead a carboxylic acid having an oxygen at C-3. Nopol, labelled at C-11 with deuterium, was obtained through a Prins reaction of b-pinene with deuteriated paraformaldehyde. This labelled nopol was converted into its toluene-p-sulfonate ester, and was solvolysed in acetic acid containing acetate ion to give 8,8-dimethyltricyclo[4.2.1.03,7]nonan-6-yl acetate, which is an earlier reported novel fused ring system (fortesyl acetate; 2 acetate). The position of the label in the product showed that the mechanism of this deep-seated carbon skeletal rearrangement proceeds through the intermediate formation of a cyclobutane ring, followed by shift of a methylene bridge to expand the original cyclobutane ring and then subsequent expansion of the new cyclobutane ring. Calculations of heats of formation of possible ions involved in these shifts confirm the proposed mechanism as the most likely pathway.Junta Nacional de Investigação Científica e Tecnológica. Kuwait. Eschenmoser Trust UK

Spatial Particle Condensation for an Exclusion Process on a Ring

We study the stationary state of a simple exclusion process on a ring which was recently introduced by Arndt {\it et al} [J. Phys. A {\bf 31} (1998) L45;cond-mat/9809123]. This model exhibits spatial condensation of particles. It has been argued that the model has a phase transition from a ``mixed phase'' to a ``disordered phase''. However, in this paper exact calculations are presented which, we believe, show that in the framework of a grand canonical ensemble there is no such phase transition. An analysis of the fluctuations in the particle density strongly suggests that the same result also holds for the canonical ensemble.Comment: 20 pages, 4 figure

Islamicization Strategies in Kao Ancient Village, North Halmahera

Situs permukiman Kampung kuno Kao terletak di pedalaman Halmahera Utara, berdiri di atas tanah yang relatif basah diapit oleh sungai Aer Kalak, Ake Ngoali, dan Ake Jodo dan dikelilingi oleh hutan sagu dan rawa. Kondisi permukiman di situs ini membuatnya memiliki keterbatasan ruang hunian, namun orang-orang yang menghuni Kampung kuno Kao bermukim di wilayah ini dalam jangka waktu yang relatif panjang, yaitu antara 100-200 tahun, dan bahkan tercatat dalam rekam sejarah bahwa wilayah Kao dahulu menjadi penyuplai makanan pokok Ternate. Penelitian ini bersifat deduktif, yaitu menyusun sebuah hipotesa yang kemudian diuji di lapangan. Metode pengumpulan data dalam penelitian ini menggunakan metode observasi lapangan dan ekskavasi arkeologi. Ragam data arkeologi baik artefak maupun tradisi lisan yang diperoleh di lapangan kemudian dianalisa dengan merujuk pada sumber referensi yang relevan. Hasil penelitian menunjukkan bahwa Situs Kao merupakan permukiman yang cukup maju  dan memiliki peran cukup penting sebagai wilayah pusat Islamisasi di Halmahera. Orang-orang di Kampung kuno Kao tinggal dalam waktu lama di satu lokasi didukung oleh sumber air dan potensi tanah-tanah pertanian menjadikan wilayah Kao sebagai bagian dari jaringan perdagangan yang ramai. Kao menjadi bagian dari strategi dalam penyebaran Islam ke wilayah-wilayah pedalaman lainnya, juga daerah-daerah pesisir di Halmahera Utara.The Kao Ancient Village settlement site is located in the hinterland of North Halmahera, standing on relatively wet ground flanked by the river Aer Kalak, Ake Ngoali, and Ake Jodo and surrounded by sago and swamp forests. The settlement conditions on the site make it limited for residential space, but a community of Kao people settled in this area for a relatively long period of time between 100-200 years and even recorded in history that Kao region is the main food supplier for Ternate in the past. This research conducted surface surveys and limited excavations, then mapped the areas of artifactual findings, and identified patterns of spatial use by analyzing surface features and artifact scatters. Variety of archeological data both artifacts and oral traditions are then analyzed guided by relevant reference sources. The results show that Kao Site is an advanced settlement and has a significant role as the center of Islamicization in Halmahera. The Kao people settled for a long time in one location supported by water sources and the potential of farming lands making the Kao area a part of bustling trade networks. Kao became part of a strategy in spreading Islam to other inland areas, as well as coastal areas in North Halmahera

A Study of Brain Networks Associated with Swallowing Using Graph-Theoretical Approaches

Functional connectivity between brain regions during swallowing tasks is still not well understood. Understanding these complex interactions is of great interest from both a scientific and a clinical perspective. In this study, functional magnetic resonance imaging (fMRI) was utilized to study brain functional networks during voluntary saliva swallowing in twenty-two adult healthy subjects (all females, 23.1±1.52 years of age). To construct these functional connections, we computed mean partial correlation matrices over ninety brain regions for each participant. Two regions were determined to be functionally connected if their correlation was above a certain threshold. These correlation matrices were then analyzed using graph-theoretical approaches. In particular, we considered several network measures for the whole brain and for swallowing-related brain regions. The results have shown that significant pairwise functional connections were, mostly, either local and intra-hemispheric or symmetrically inter-hemispheric. Furthermore, we showed that all human brain functional network, although varying in some degree, had typical small-world properties as compared to regular networks and random networks. These properties allow information transfer within the network at a relatively high efficiency. Swallowing-related brain regions also had higher values for some of the network measures in comparison to when these measures were calculated for the whole brain. The current results warrant further investigation of graph-theoretical approaches as a potential tool for understanding the neural basis of dysphagia. © 2013 Luan et al

Association of MC1R Variants and host phenotypes with melanoma risk in CDKN2A mutation carriers: a GenoMEL study

<p><b>Background</b> Carrying the cyclin-dependent kinase inhibitor 2A (CDKN2A) germline mutations is associated with a high risk for melanoma. Penetrance of CDKN2A mutations is modified by pigmentation characteristics, nevus phenotypes, and some variants of the melanocortin-1 receptor gene (MC1R), which is known to have a role in the pigmentation process. However, investigation of the associations of both MC1R variants and host phenotypes with melanoma risk has been limited.</p> <p><b>Methods</b> We included 815 CDKN2A mutation carriers (473 affected, and 342 unaffected, with melanoma) from 186 families from 15 centers in Europe, North America, and Australia who participated in the Melanoma Genetics Consortium. In this family-based study, we assessed the associations of the four most frequent MC1R variants (V60L, V92M, R151C, and R160W) and the number of variants (1, ≥2 variants), alone or jointly with the host phenotypes (hair color, propensity to sunburn, and number of nevi), with melanoma risk in CDKN2A mutation carriers. These associations were estimated and tested using generalized estimating equations. All statistical tests were two-sided.</p> <p><b>Results</b> Carrying any one of the four most frequent MC1R variants (V60L, V92M, R151C, R160W) in CDKN2A mutation carriers was associated with a statistically significantly increased risk for melanoma across all continents (1.24 × 10−6 ≤ P ≤ .0007). A consistent pattern of increase in melanoma risk was also associated with increase in number of MC1R variants. The risk of melanoma associated with at least two MC1R variants was 2.6-fold higher than the risk associated with only one variant (odds ratio = 5.83 [95% confidence interval = 3.60 to 9.46] vs 2.25 [95% confidence interval = 1.44 to 3.52]; Ptrend = 1.86 × 10−8). The joint analysis of MC1R variants and host phenotypes showed statistically significant associations of melanoma risk, together with MC1R variants (.0001 ≤ P ≤ .04), hair color (.006 ≤ P ≤ .06), and number of nevi (6.9 × 10−6 ≤ P ≤ .02).</p> <p><b>Conclusion</b> Results show that MC1R variants, hair color, and number of nevi were jointly associated with melanoma risk in CDKN2A mutation carriers. This joint association may have important consequences for risk assessments in familial settings.</p&gt

Substrate protein folds while it is bound to the ATP-independent chaperone Spy

Chaperones assist the folding of many proteins in the cell. While the most well studied chaperones use cycles of ATP binding and hydrolysis to assist protein folding, a number of chaperones have been identified that promote protein folding in the absence of highenergy cofactors. Precisely how ATP-independent chaperones accomplish this feat is unclear. Here we have characterized the kinetic mechanism of substrate folding by the small, ATP-independent chaperone, Spy. Spy rapidly associates with its substrate, Immunity protein 7 (Im7), eliminating its potential for aggregation. Remarkably, Spy then allows Im7 to fully fold into its native state while remaining bound to the surface of the chaperone. These results establish a potentially widespread mechanism whereby ATP-independent chaperones can assist in protein refolding. They also provide compelling evidence that substrate proteins can fold while continuously bound to a chaperone

An overview of the evolution of infrared spectroscopy applied to bacterial typing

The sustained emergence of new declared bacterial species makes typing a continuous challenge for microbiologists. Molecular biology techniques have a very significant role in the context of bacterial typing, but they are often very laborious, time consuming and eventually fail when dealing with very closely related species. Spectroscopic-based techniques appear in some situations as a viable alternative to molecular methods with advantages in terms of analysis time and cost. Infrared and mass spectrometry are among the most exploited techniques in this context: particularly, infrared spectroscopy emerged as a very promising method with multiple reported successful applications. This article presents a systematic review on infrared spectroscopy applications for bacterial typing, highlighting fundamental aspects of infrared spectroscopy, a detailed literature review (covering different taxonomic levels and bacterial species), advantages and limitations of the technique over molecular biology methods and a comparison with other competing spectroscopic techniques such as MALDI-TOF MS, Raman and intrinsic fluorescence. Infrared spectroscopy possesses a high potential for bacterial typing at distinct taxonomic levels and worthy of further developments and systematization. The development of databases appears fundamental towards the establishment of infrared spectroscopy as a viable method for bacterial typing.FCT -Fundação para a Ciência e a Tecnologia(PT2020 UID/QUI/50006/2013)info:eu-repo/semantics/publishedVersio

Applying refinement to the use of mice and rats in rheumatoid arthritis research

Rheumatoid arthritis (RA) is a painful, chronic disorder and there is currently an unmet need for effective therapies that will benefit a wide range of patients. The research and development process for therapies and treatments currently involves in vivo studies, which have the potential to cause discomfort, pain or distress. This Working Group report focuses on identifying causes of suffering within commonly used mouse and rat ‘models’ of RA, describing practical refinements to help reduce suffering and improve welfare without compromising the scientific objectives. The report also discusses other, relevant topics including identifying and minimising sources of variation within in vivo RA studies, the potential to provide pain relief including analgesia, welfare assessment, humane endpoints, reporting standards and the potential to replace animals in RA research

Conserved community structure and simultaneous divergence events in the fig wasps associated with Ficus benjamina in Australia and China

Localised patterns of species diversity can be influenced by many factors, including regional species pools, biogeographic features and interspecific interactions. Despite recognition of these issues, we still know surprisingly little about how invertebrate biodiversity is structured across geographic scales. In particular, there have been few studies of how insect communities vary geographically while using the same plant host. We compared the composition (species, genera) and functional structure (guilds) of the chalcid wasp communities associated with the widespread fig tree, Ficus benjamina, towards the northern (Hainan province, China) and southern (Queensland, Australia) edges of its natural range. Sequence data were generated for nuclear and mtDNA markers and used to delimit species, and Bayesian divergence analyses were used to test patterns of community cohesion through evolutionary time. Both communities host at least 14 fig wasp species, but no species are shared across continents. Community composition is similar at the genus level, with six genera shared although some differ in species diversity between China and Australia; a further three genera occur in only China or Australia. Community functional structure remains very similar in terms of numbers of species in each ecological guild despite community composition differing a little (genera) or a lot (species), depending on taxonomic level. Bayesian clustering analyses favour a single community divergence event across continents over multiple events for different ecological guilds. Molecular dating estimates of lineage splits between nearest inter-continental species pairs are broadly consistent with a scenario of synchronous community divergence from a shared "ancestral community". Fig wasp community structure and genus-level composition are largely conserved in a wide geographic comparison between China and Australia. Moreover, dating analyses suggest that the functional community structure has remained stable for long periods during historic range expansions. This suggests that ecological interactions between species may play a persistent role in shaping these communities, in contrast to findings in some comparable temperate systems

Integrating isotopes and documentary evidence : dietary patterns in a late medieval and early modern mining community, Sweden

We would like to thank the Archaeological Research Laboratory, Stockholm University, Sweden and the Tandem Laboratory (Ångström Laboratory), Uppsala University, Sweden, for undertaking the analyses of stable nitrogen and carbon isotopes in both human and animal collagen samples. Also, thanks to Elin Ahlin Sundman for providing the δ13C and δ15N values for animal references from Västerås. This research (Bäckström’s PhD employment at Lund University, Sweden) was supported by the Berit Wallenberg Foundation (BWS 2010.0176) and Jakob and Johan Söderberg’s foundation. The ‘Sala project’ (excavations and analyses) has been funded by Riksens Clenodium, Jernkontoret, Birgit and Gad Rausing’s Foundation, SAU’s Research Foundation, the Royal Physiographic Society of Lund, Berit Wallenbergs Foundation, Åke Wibergs Foundation, Lars Hiertas Memory, Helge Ax:son Johnson’s Foundation and The Royal Swedish Academy of Sciences.Peer reviewedPublisher PD