One-loop spectroscopy of semiclassically quantized strings: bosonic sector

We make a further step in the analytically exact quantization of spinning string states in semiclassical approximation, by evaluating the exact one-loop partition function for a class of two-spin string solutions for which quadratic fluctuations form a non-trivial system of coupled modes. This is the case of a folded string in the SU(2) sector, in the limit described by a quantum Landau–Lifshitz model. The same applies to the full bosonic sector of fluctuations over the folded spinning string in AdS5 with an angular momentum J in S5. Fluctuations are governed by a special class of fourth-order differential operators, with coefficients being meromorphic functions on the torus, which we are able to solve exactly

A self-sustaining endocytic-based loop promotes breast cancer plasticity leading to aggressiveness and pro-metastatic behavior

The subversion of endocytic routes leads to malignant transformation and has been implicated in human cancers. However, there is scarce evidence for genetic alterations of endocytic proteins as causative in high incidence human cancers. Here, we report that Epsin 3 (EPN3) is an oncogene with prognostic and therapeutic relevance in breast cancer. Mechanistically, EPN3 drives breast tumorigenesis by increasing E-cadherin endocytosis, followed by the activation of a \u3b2-catenin/TCF4-dependent partial epithelial-to-mesenchymal transition (EMT), followed by the establishment of a TGF\u3b2-dependent autocrine loop that sustains EMT. EPN3-induced partial EMT is instrumental for the transition from in situ to invasive breast carcinoma, and, accordingly, high EPN3 levels are detected at the invasive front of human breast cancers and independently predict metastatic rather than loco-regional recurrence. Thus, we uncover an endocytic-based mechanism able to generate TGF\u3b2-dependent regulatory loops conferring cellular plasticity and invasive behavior

Mutations in CEP78 Cause Cone-Rod Dystrophy and Hearing Loss Associated with Primary-Cilia Defects.

Cone-rod degeneration (CRD) belongs to the disease spectrum of retinal degenerations, a group of hereditary disorders characterized by an extreme clinical and genetic heterogeneity. It mainly differentiates from other retinal dystrophies, and in particular from the more frequent disease retinitis pigmentosa, because cone photoreceptors degenerate at a higher rate than rod photoreceptors, causing severe deficiency of central vision. After exome analysis of a cohort of individuals with CRD, we identified biallelic mutations in the orphan gene CEP78 in three subjects from two families: one from Greece and another from Sweden. The Greek subject, from the island of Crete, was homozygous for the c.499+1G>T (IVS3+1G>T) mutation in intron 3. The Swedish subjects, two siblings, were compound heterozygotes for the nearby mutation c.499+5G>A (IVS3+5G>A) and for the frameshift-causing variant c.633delC (p.Trp212Glyfs(∗)18). In addition to CRD, these three individuals had hearing loss or hearing deficit. Immunostaining highlighted the presence of CEP78 in the inner segments of retinal photoreceptors, predominantly of cones, and at the base of the primary cilium of fibroblasts. Interaction studies also showed that CEP78 binds to FAM161A, another ciliary protein associated with retinal degeneration. Finally, analysis of skin fibroblasts derived from affected individuals revealed abnormal ciliary morphology, as compared to that of control cells. Altogether, our data strongly suggest that mutations in CEP78 cause a previously undescribed clinical entity of a ciliary nature characterized by blindness and deafness but clearly distinct from Usher syndrome, a condition for which visual impairment is due to retinitis pigmentosa

Insights into the Complex Formed by Matrix Metalloproteinase-2 and Alloxan Inhibitors: Molecular Dynamics Simulations and Free Energy Calculations

Matrix metalloproteinases (MMP) are well-known biological targets implicated in tumour progression, homeostatic regulation, innate immunity, impaired delivery of pro-apoptotic ligands, and the release and cleavage of cell-surface receptors. Hence, the development of potent and selective inhibitors targeting these enzymes continues to be eagerly sought. In this paper, a number of alloxan-based compounds, initially conceived to bias other therapeutically relevant enzymes, were rationally modified and successfully repurposed to inhibit MMP-2 (also named gelatinase A) in the nanomolar range. Importantly, the alloxan core makes its debut as zinc binding group since it ensures a stable tetrahedral coordination of the catalytic zinc ion in concert with the three histidines of the HExxHxxGxxH metzincin signature motif, further stabilized by a hydrogen bond with the glutamate residue belonging to the same motif. The molecular decoration of the alloxan core with a biphenyl privileged structure allowed to sample the deep S1′ specificity pocket of MMP-2 and to relate the high affinity towards this enzyme with the chance of forming a hydrogen bond network with the backbone of Leu116 and Asn147 and the side chains of Tyr144, Thr145 and Arg149 at the bottom of the pocket. The effect of even slight structural changes in determining the interaction at the S1′ subsite of MMP-2 as well as the nature and strength of the binding is elucidated via molecular dynamics simulations and free energy calculations. Among the herein presented compounds, the highest affinity (pIC50 = 7.06) is found for BAM, a compound exhibiting also selectivity (>20) towards MMP-2, as compared to MMP-9, the other member of the gelatinases

Generalized cusp in AdS_4 x CP^3 and more one-loop results from semiclassical strings

We evaluate the exact one-loop partition function for fundamental strings whose world-surface ends on a cusp at the boundary of AdS_4 and has a "jump" in CP^3. This allows us to extract the stringy prediction for the ABJM generalized cusp anomalous dimension Gamma_{cusp}^{ABJM} (phi,theta) up to NLO in sigma-model perturbation theory. With a similar analysis, we present the exact partition functions for folded closed string solutions moving in the AdS_3 parts of AdS_4 x CP^3 and AdS_3 x S^3 x S^3 x S^1 backgrounds. Results are obtained applying to the string solutions relevant for the AdS_4/CFT_3 and AdS_3/CFT_2 correspondence the tools previously developed for their AdS_5 x S^5 counterparts.Comment: 48 pages, 2 figures, version 3, corrected misprints in formulas 2.12, B.86, C.33, added comment on verification of the light-like limi

Special and inclusive education in the Republic of Ireland: reviewing the literature from 2000 to 2009

Provision for pupils with special educational needs in Ireland has undergone considerable change and review in the first decade of the twenty first century. In response to international demands for a more equitable education system which recognises diversity and considers how schools might address the needs of pupils who have been previously marginalised, Irish legislation has focused upon the development of inclusive schooling. Researchers during this period have endeavoured to understand how responses to the demand for greater inclusion have impacted upon the perceived need for change. This paper reviews the research literature for this period and identifies four key themes under which research has been conducted. The literature pertaining to these themes is explored and a possible agenda for future researchers identifie

Remarks on the geometrical properties of semiclassically quantized strings

We discuss some geometrical aspects of the semiclassical quantization of string solutions in type IIB Green–Schwarz action on ADS5xS5 We concentrate on quadratic fluctuations around classical configurations, expressing the relevant differential operators in terms of (intrinsic and extrinsic) invariants of the background geometry. The aim of our exercise is to present some compact expressions encoding the spectral properties of bosonic and fermionic fluctuations. The appearing of non-trivial structures on the relevant bundles and their role in concrete computations are also considered. We corroborate the presentation of general formulas by working out explicitly a couple of relevant examples, namely the spinning string and the latitude BPS Wilson loop

Two-dimensional S-matrices from unitarity cuts

Using unitarity methods, we compute, for several massive two-dimensional models, the cut-constructible part of the one-loop 2 → 2 scattering S-matrices from the tree-level amplitudes. We apply our method to various integrable theories, finding evidence that for supersymmetric models the one-loop S-matrix is cut-constructible, while for models without supersymmetry (but with integrability) the missing rational terms are proportional to the tree-level S-matrix and therefore can be interpreted as a shift in the coupling. Finally, applying our procedure to the world-sheet theory for the light-cone gauge-fixed AdS5 × S 5 superstring we reproduce, at one-loop in the near-BMN expansion, the S-matrix known from integrability techniques

Shape recognition through multi-level fusion of features and classifiers

Shape recognition is a fundamental problem and a special type of image classification, where each shape is considered as a class. Current approaches to shape recognition mainly focus on designing low-level shape descriptors, and classify them using some machine learning approaches. In order to achieve effective learning of shape features, it is essential to ensure that a comprehensive set of high quality features can be extracted from the original shape data. Thus we have been motivated to develop methods of fusion of features and classifiers for advancing the classification performance. In this paper, we propose a multi-level framework for fusion of features and classifiers in the setting of gran-ular computing. The proposed framework involves creation of diversity among classifiers, through adopting feature selection and fusion to create diverse feature sets and to train diverse classifiers using different learn-Xinming Wang algorithms. The experimental results show that the proposed multi-level framework can effectively create diversity among classifiers leading to considerable advances in the classification performance