Topology by Design in Magnetic nano-Materials: Artificial Spin Ice

Artificial Spin Ices are two dimensional arrays of magnetic, interacting nano-structures whose geometry can be chosen at will, and whose elementary degrees of freedom can be characterized directly. They were introduced at first to study frustration in a controllable setting, to mimic the behavior of spin ice rare earth pyrochlores, but at more useful temperature and field ranges and with direct characterization, and to provide practical implementation to celebrated, exactly solvable models of statistical mechanics previously devised to gain an understanding of degenerate ensembles with residual entropy. With the evolution of nano--fabrication and of experimental protocols it is now possible to characterize the material in real-time, real-space, and to realize virtually any geometry, for direct control over the collective dynamics. This has recently opened a path toward the deliberate design of novel, exotic states, not found in natural materials, and often characterized by topological properties. Without any pretense of exhaustiveness, we will provide an introduction to the material, the early works, and then, by reporting on more recent results, we will proceed to describe the new direction, which includes the design of desired topological states and their implications to kinetics.Comment: 29 pages, 13 figures, 116 references, Book Chapte

Systematic discovery of unannotated genes in 11 yeast species using a database of orthologous genomic segments

<p>Abstract</p> <p>Background</p> <p>In standard BLAST searches, no information other than the sequences of the query and the database entries is considered. However, in situations where two genes from different species have only borderline similarity in a BLAST search, the discovery that the genes are located within a region of conserved gene order (synteny) can provide additional evidence that they are orthologs. Thus, for interpreting borderline search results, it would be useful to know whether the syntenic context of a database hit is similar to that of the query. This principle has often been used in investigations of particular genes or genomic regions, but to our knowledge it has never been implemented systematically.</p> <p>Results</p> <p>We made use of the synteny information contained in the Yeast Gene Order Browser database for 11 yeast species to carry out a systematic search for protein-coding genes that were overlooked in the original annotations of one or more yeast genomes but which are syntenic with their orthologs. Such genes tend to have been overlooked because they are short, highly divergent, or contain introns. The key features of our software - called SearchDOGS - are that the database entries are classified into sets of genomic segments that are already known to be orthologous, and that very weak BLAST hits are retained for further analysis if their genomic location is similar to that of the query. Using SearchDOGS we identified 595 additional protein-coding genes among the 11 yeast species, including two new genes in <it>Saccharomyces cerevisiae</it>. We found additional genes for the mating pheromone a-factor in six species including <it>Kluyveromyces lactis</it>.</p> <p>Conclusions</p> <p>SearchDOGS has proven highly successful for identifying overlooked genes in the yeast genomes. We anticipate that our approach can be adapted for study of further groups of species, such as bacterial genomes. More generally, the concept of doing sequence similarity searches against databases to which external information has been added may prove useful in other settings.</p

Implementing GDPR in the Charity Sector: A Case Study

Due to their organisational characteristics, many charities are poorly prepared for the General Data Protection Regulation (GDPR). We present an exemplar process for implementing GDPR and the DPIA Data Wheel, a DPIA framework devised as part of the case study, that accounts for these characteristics. We validate this process and framework by conducting a GDPR implementation with a charity that works with vulnerable adults. This charity processes both special category (sensitive) and personally identifiable data. This GDPR implementation was conducted and devised for the charity sector, but can be equally applied in any organisation that needs to implement GDPR or conduct DPIAs

Chemoprevention of Colonic Polyps with Balsalazide: An Exploratory, Double-Blind, Placebo-Controlled Study

A number of agents, including aspirin, nonsteroidal antiinflammatory drugs, cyclooxygenase-2 inhibitors, folic acid, calcium, and vitamins, have been evaluated for their potential in chemoprevention of sporadic colorectal adenomas or cancer. Preclinical data suggest that 5-aminosalicylates also may have a chemopreventive effect. To investigate chemoprevention of colonic polyps with balsalazide, a 5-aminosalicylate prodrug. In this randomized, double-blind, placebo-controlled study, adults diagnosed with small polyps in the rectosigmoid colon were treated with either balsalazide 3 g/d or placebo for 6 months. Follow-up lower endoscopy was performed, and all polyps were measured and analyzed histologically. The primary endpoint was reduction in mean size of the largest polyp per subject. Among 241 participants screened, 86 were randomized to treatment, with 75 subjects evaluable. Balsalazide 3 g/d (n = 38) did not significantly reduce the mean size of the largest colonic polyp or the number of polyps compared with placebo (n = 37). Although not significant, post-hoc analysis revealed that total adenoma burden per subject, calculated as the sum of the volumes of all adenomas in mm3, increased by 55% in the balsalazide group compared with 95% in the placebo group. Although balsalazide did not have significant chemopreventive effects on established colonic polyps, these results can aid in designing future prospective studies

Cyclophosphamide-Induced Cystitis Increases Bladder CXCR4 Expression and CXCR4-Macrophage Migration Inhibitory Factor Association

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine involved in cystitis and a non-cognate ligand of the chemokine receptor CXCR4 in vitro. We studied whether CXCR4-MIF associations occur in rat bladder and the effect of experimental cystitis. METHODS AND FINDINGS: Twenty male rats received saline or cyclophosphamide (40 mg/kg; i.p.; every 3(rd) day) to induce persistent cystitis. After eight days, urine was collected and bladders excised under anesthesia. Bladder CXCR4 and CXCR4-MIF co-localization were examined with immunhistochemistry. ELISA determined MIF and stromal derived factor-1 (SDF-1; cognate ligand for CXCR4) levels. Bladder CXCR4 expression (real-time RTC-PCR) and protein levels (Western blotting) were examined. Co-immunoprecipitations studied MIF-CXCR4 associations.Urothelial basal and intermediate (but not superficial) cells in saline-treated rats contained CXCR4, co-localized with MIF. Cyclophosphamide treatment caused: 1) significant redistribution of CXCR4 immunostaining to all urothelial layers (especially apical surface of superficial cells) and increased bladder CXCR4 expression; 2) increased urine MIF with decreased bladder MIF; 3) increased bladder SDF-1; 4) increased CXCR4-MIF associations. CONCLUSIONS: These data demonstrate CXCR4-MIF associations occur in vivo in rat bladder and increase in experimental cystitis. Thus, CXCR4 represents an alternative pathway for MIF-mediated signal transduction during bladder inflammation. In the bladder, MIF may compete with SDF-1 (cognate ligand) to activate signal transduction mediated by CXCR4

FUTURE PERSPECTIVES IN MELANOMA RESEARCH. Meeting report from the “Melanoma Research: a bridge from Naples to the World. Napoli, December 5th–6 th2011”

After more than 30 years, landmark progress has been made in the treatment of cancer, and melanoma in particular, with the success of new molecules such as ipilimumab, vemurafenib and active specific immunization

Digital reconstruction of the inner ear of Leptictidium auderiense (Leptictida, Mammalia) and North American leptictids reveals new insight into leptictidan locomotor agility

Leptictida are basal Paleocene to Oligocene eutherians from Europe and North America comprising species with highly specialized postcranial features including elongated hind limbs. Among them, the European Leptictidium was probably a bipedal runner or jumper. Because the semicircular canals of the inner ear are involved in detecting angular acceleration of the head, their morphometry can be used as a proxy to elucidate the agility in fossil mammals. Here we provide the first insight into inner ear anatomy and morphometry of Leptictida based on high-resolution computed tomography of a new specimen of Leptictidium auderiense from the middle Eocene Messel Pit (Germany) and specimens of the North American Leptictis and Palaeictops. The general morphology of the bony labyrinth reveals several plesiomorphic mammalian features, such as a secondary crus commune. Leptictidium is derived from the leptictidan groundplan in lacking the secondary bony lamina and having proportionally larger semicircular canals than the leptictids under study. Our estimations reveal that Leptictidium was a very agile animal with agility score values (4.6 and 5.5, respectively) comparable to Macroscelidea and extant bipedal saltatory placentals. Leptictis and Palaeictops have lower agility scores (3.4 to 4.1), which correspond to the more generalized types of locomotion (e.g., terrestrial, cursorial) of most extant mammals. In contrast, the angular velocity magnitude predicted from semicircular canal angles supports a conflicting pattern of agility among leptictidans, but the significance of these differences might be challenged when more is known about intraspecific variation and the pattern of semicircular canal angles in non-primate mammals

Charcot-Marie-Tooth–Linked Mutant GARS Is Toxic to Peripheral Neurons Independent of Wild-Type GARS Levels

Charcot-Marie-Tooth disease type 2D (CMT2D) is a dominantly inherited peripheral neuropathy caused by missense mutations in the glycyl-tRNA synthetase gene (GARS). In addition to GARS, mutations in three other tRNA synthetase genes cause similar neuropathies, although the underlying mechanisms are not fully understood. To address this, we generated transgenic mice that ubiquitously over-express wild-type GARS and crossed them to two dominant mouse models of CMT2D to distinguish loss-of-function and gain-of-function mechanisms. Over-expression of wild-type GARS does not improve the neuropathy phenotype in heterozygous Gars mutant mice, as determined by histological, functional, and behavioral tests. Transgenic GARS is able to rescue a pathological point mutation as a homozygote or in complementation tests with a Gars null allele, demonstrating the functionality of the transgene and revealing a recessive loss-of-function component of the point mutation. Missense mutations as transgene-rescued homozygotes or compound heterozygotes have a more severe neuropathy than heterozygotes, indicating that increased dosage of the disease-causing alleles results in a more severe neurological phenotype, even in the presence of a wild-type transgene. We conclude that, although missense mutations of Gars may cause some loss of function, the dominant neuropathy phenotype observed in mice is caused by a dose-dependent gain of function that is not mitigated by over-expression of functional wild-type protein