Bifurcation analysis and phase diagram of a spin-string model with buckled states

We analyze a one-dimensional spin-string model, in which string oscillators are linearly coupled to their two nearest neighbors and to Ising spins representing internal degrees of freedom. String-spin coupling induces a long-range ferromagnetic interaction among spins that competes with a spin-spin antiferromagnetic coupling. As a consequence, the complex phase diagram of the system exhibits different flat rippled and buckled states, with first or second order transition lines between states. The two-dimensional version of the model has a similar phase diagram, which has been recently used to explain the rippled to buckled transition observed in scanning tunnelling microscopy experiments with suspended graphene sheets. Here we describe in detail the phase diagram of the simpler one-dimensional model and phase stability using bifurcation theory. This gives additional insight into the physical mechanisms underlying the different phases and the behavior observed in experiments.Comment: 15 pages, 7 figure

Cooperative activation of the ATR checkpoint kinase by TopBP1 and damaged DNA

TopBP1, acting in concert with DNA containing bulky base lesions, stimulates ATR kinase activity under physiologically relevant reaction conditions. Here, we analyze the roles of the three components in ATR activation: DNA, base damage and TopBP1. We show that base adducts caused by a potent carcinogen, benzo[a]pyrene diol epoxide (BPDE), constitute a strong signal for TopBP1-dependent ATR kinase activity on Chk1 and p53. We find that the C-terminus of TopBP1 binds preferentially to damaged DNA and is sufficient to mediate damaged DNA-dependent ATR activation in a manner similar to full-length TopBP1. Significantly, we find that stimulation of ATR by BPDE-damaged DNA exhibits strong dependence on the length of DNA, with essentially no stimulation with fragments of 0.2 kb and reaching maximum stimulation with 2 kb fragments. Moreover, TopBP1 shows preferential binding to longer DNA fragments and, in contrast to previous biochemical studies, TopBP1 binding is completely independent of DNA ends. We find that TopBP1 binds to circular and linear DNAs with comparable affinities and that these DNA forms elicit the same level of TopBP1-dependent ATR activation. Taken together, these findings suggest a cooperative activation mechanism for the ATR checkpoint kinase by TopBP1 and damaged DNA

Coro Trasito (Tella-Sin, Huesca): una cueva redil del Neolítico Antiguo en la alta montaña

En este trabajo se presentan los resultados preliminares de las intervenciones arqueológicas llevadas a cabo en la Cueva de Coro Trasito, situada en el Pirineo central aragonés, dentro del municipio de Tella-Sin, Huesca. Estas intervenciones corresponden tanto a los sondeos llevados a cabo durante el 2011 y el 2013, como la excavación en extensión de la parte central de la cueva, aproximadamente de unos 70m2, durante las campañas de 2014 y 2015. Estos trabajos han permitido documentar una secuencia de ocupaciones neolíticas de la cueva datadas entre 5300 y 4600 cal ANE, sucedidas por una última fase prehistórica de mediados del II Milenio cal ANE. De esta forma, repasaremos los principales hallazgos que se han documentado en las diferentes campañas arqueológicas, materiales líticos, cerámicos, así como los diferentes estudios realizados sobre la fauna y la carpología provenientes del sondeo nº 3 (2013). Así mismo, presentaremos algunas de las características más relevantes de la excavación en extensión de la cueva, así como las diferentes estructuras documentadas asociadas al Neolítico Medio. Estas evidencias, junto con los estudios que se han llevado a cabo hasta este momento, nos hacen intuir que la ocupación de la cueva durante este periodo fue recurrente y con una economía plenamente neolítica.Peer Reviewe

Research training needs in Peruvian national TB/HIV programs

<p>Abstract</p> <p>Background</p> <p>There are few published reports of <it>research training </it>needs assessments and research training programs. In an effort to expand this nascent field of study and to bridge the gap between research and practice, we sought to systematically assess the research training needs of health care professionals working at Peruvian governmental institutions leading HIV and tuberculosis (TB) control and among senior stakeholders in the field.</p> <p>Methods</p> <p>Six institutional workshops were conducted with the participation of 161 mid-level health professionals from agencies involved in national HIV and TB control. At each workshop informants completed a structured questionnaire and participated in small and large group discussions. Additional data and institutional commitment was obtained through in-depth interviews from 32 senior managers and researchers from the Ministry of Health, academia and NGOs.</p> <p>Results</p> <p>Participants exhibited an overwhelming receptivity for additional research training, observing a gap between current levels of research training and their perceived importance. Specialized skills in obtaining funding, developing research protocols, particularly in operational, behavioral and prevention research were considered in greatest need. Beyond research training, participants identified broader social, economic and political factors as influential in infectious disease control.</p> <p>Conclusions</p> <p>The needs assessment suggests that future training should focus on operational research techniques, rather than on clinical skill building or program implementation only. Strengthening health systems not only requires additional research training, but also adequate financial resources to implement research findings.</p

Metal-based nanoparticles as antimicrobial agents: an overview

Metal-based nanoparticles have been extensively investigated for a set of biomedical applications. According to the World Health Organization, in addition to their reduced size and selectivity for bacteria, metal-based nanoparticles have also proved to be effective against pathogens listed as a priority. Metal-based nanoparticles are known to have non-specific bacterial toxicity mechanisms (they do not bind to a specific receptor in the bacterial cell) which not only makes the development of resistance by bacteria difficult, but also broadens the spectrum of antibacterial activity. As a result, a large majority of metal-based nanoparticles efficacy studies performed so far have shown promising results in both Gram-positive and Gram-negative bacteria. The aim of this review has been a comprehensive discussion of the state of the art on the use of the most relevant types of metal nanoparticles employed as antimicrobial agents. A special emphasis to silver nanoparticles is given, while others (e.g., gold, zinc oxide, copper, and copper oxide nanoparticles) commonly used in antibiotherapy are also reviewed. The novelty of this review relies on the comparative discussion of the different types of metal nanoparticles, their production methods, physicochemical characterization, and pharmacokinetics together with the toxicological risk encountered with the use of different types of nanoparticles as antimicrobial agents. Their added-value in the development of alternative, more effective antibiotics against multi-resistant Gram-negative bacteria has been highlighted.M.L.G., M.E. (Miren Ettcheto), A.C., and E.S.L. belong to 2017SGR-1477. E.S.-L., A.C., M.E. (Marta Espina), and M.L.G. acknowledge the support of Institute of Nanoscience and Nanotechnology (ART2018 project). E.B.S. wants to acknowledge the Portuguese Science and Technology Foundation (FCT/MCT) and European Funds (PRODER/COMPETE) for the projects M-ERA-NET-0004/2015-PAIRED and UIDB/04469/2020, co-funded by FEDER, under the partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

Limb-girdle muscular dystrophy 1F is caused by a microdeletion in the transportin 3 gene

In 2001, we reported linkage of an autosomal dominant form of limb-girdle muscular dystrophy, limb-girdle muscular dystrophy 1F, to chromosome 7q32.1-32.2, but the identity of the mutant gene was elusive. Here, using a whole genome sequencing strategy, we identified the causative mutation of limb-girdle muscular dystrophy 1F, a heterozygous single nucleotide deletion (c.2771del) in the termination codon of transportin 3 (TNPO3). This gene is situated within the chromosomal region linked to the disease and encodes a nuclear membrane protein belonging to the importin beta family. TNPO3 transports serine/arginine-rich proteins into the nucleus, and has been identified as a key factor in the HIV-import process into the nucleus. The mutation is predicted to generate a 15-amino acid extension of the C-terminus of the protein, segregates with the clinical phenotype, and is absent in genomic sequence databases and a set of >200 control alleles. In skeletal muscle of affected individuals, expression of the mutant messenger RNA and histological abnormalities of nuclei and TNPO3 indicate altered TNPO3 function. Our results demonstrate that the TNPO3 mutation is the cause of limb-girdle muscular dystrophy 1F, expand our knowledge of the molecular basis of muscular dystrophies and bolster the importance of defects of nuclear envelope proteins as causes of inherited myopathies

VAMOS: a Pathfinder for the HAWC Gamma-Ray Observatory

VAMOS was a prototype detector built in 2011 at an altitude of 4100m a.s.l. in the state of Puebla, Mexico. The aim of VAMOS was to finalize the design, construction techniques and data acquisition system of the HAWC observatory. HAWC is an air-shower array currently under construction at the same site of VAMOS with the purpose to study the TeV sky. The VAMOS setup included six water Cherenkov detectors and two different data acquisition systems. It was in operation between October 2011 and May 2012 with an average live time of 30%. Besides the scientific verification purposes, the eight months of data were used to obtain the results presented in this paper: the detector response to the Forbush decrease of March 2012, and the analysis of possible emission, at energies above 30 GeV, for long gamma-ray bursts GRB111016B and GRB120328B.Comment: Accepted for pubblication in Astroparticle Physics Journal (20 pages, 10 figures). Corresponding authors: A.Marinelli and D.Zaboro