“L’inganno degli occhi”. Borromini’s perspectival niche for the Casa dei Filippini in Rome

The RCIN 905602 sheet of the Royal Collection, Windsor contains an orthogonal projection presentation drawing made by Francesco Borromini in 1627 and showing one of Gianlorenzo Bernini's proposals for the Tomb of Urban VIII. The apsidal frame rendered in perspective can be related to the perspective niche that Borromini himself placed above the fictitious entrance in the center of the facade of the Casa dei Filippini in Rome a few years later. The sheet is studied here in the context of the influence that the diffusion of representation methods and practices has had on the forms of architecture as well as their visual perception. After discussing the reason for the construction of such a perspective device, its representation in the design documents and its reception in the images of the square after its construction, the authors present the results of a geometric analysis and reconstruction after photo-modeling ot the niche itself, aimed at determining the position of the ideal observer on the square considered in designing the device, and they discuss the relationship between this spatial stratagem and the graphic trick atopted in the tomb design

Retinoic Acid Specifically Enhances Embryonic Stem Cell Metastate Marked by Zscan4

Pluripotency confers Embryonic Stem Cells (ESCs) the ability to differentiate in ectoderm, endoderm, and mesoderm derivatives, producing the majority of cell types. Although the majority of ESCs divide without losing pluripotency, it has become evident that ESCs culture consists of multiple cell populations with different degrees of potency that are spontaneously induced in regular ESC culture conditions. Zscan4, a key pluripotency factor, marks ESC subpopulation that is referred to as high-level of pluripotency metastate. Here, we report that in ESC cultures treated with retinoic acid (RA), Zscan4 ESCs metastate is strongly enhanced. In particular, we found that induction of Zscan4 metastate is mediated via RA receptors (RAR-alpha, RAR-beta, and RAR-gamma), and it is dependent on phosphoinositide-3-kinase (PI3K) signaling. Remarkably, Zscan4 metastate induced by RA lacks canonical pluripotency genes Oct3/4 and Nanog but retained both self-renewal and pluripotency capabilities. Finally we demonstrated that the conditional ablation of Zscan4 subpopulation is dispensable for both endoderm and mesoderm but is required for ectoderm lineage. In conclusion, our research provides new insights about the role of RA signaling during ESCs high pluripotency metastate fluctuation

Remote control of a robotic hand using a leap sensor

This paper presents a low-cost gesture-based remote control of a ro-botic hand. The proposed control architecture is based on a commercial leap motion sensor and an Arduino board, which have been chosen due to their low-cost and user-friendly features. A specific Matlab code has been implemented to collect data from the leap motion sensor and to generate proper instructions to control a robotic hand, which has been 3D print at Sheffield Hallam Univer-sity. Experimental tests have been carried out validate the effectiveness of the proposed remote control for performing various grasping tasks

Immunotherapy for recurrent ovarian cancer: a further piece of the puzzle or a striking strategy?

Introduction: Treatment of ovarian cancer has been long standardized with the inclusion of surgery and chemotherapy based on platinum and taxanes, this strategy reaching high remission rates. However, when this treatment fails, further options are available with little benefit. Since ovarian cancer has specific immunologic features, actually immunotherapy is under evalua- 15 tion to overcome treatment failure in patients experiencing recurrence. Areas covered: Immunogenicity of ovarian cancer and its relationship with clinical outcomes is briefly reviewed. The kinds of immunotherapeutic strategies are summarized. The clinical trials investigating immunotherapy in recurrent ovarian cancer patients are reported. 20 Expert opinion: The results of these clinical trials about immunotherapy are interesting, but little clinical benefit has been achieved until now. For this reason, we could conclude that immunotherapy is quite different from other treatment options and it could change the global approach for recurrent ovarian cancer treatment. However, to date only fragmentary findings are 25 available to define the real role of immunotherapy in this setting

hMYH and hMTH1 cooperate for survival in mismatch repair defective T-cell acute lymphoblastic leukemia

hMTH1 is an 8-oxodGTPase that prevents mis-incorporation of free oxidized nucleotides into genomic DNA. Base excision and mismatch repair pathways also restrict the accumulation of oxidized lesions in DNA by removing the mis-inserted 8-oxo-7,8-dihydro-2'-deoxyguanosines (8-oxodGs). In this study, we aimed to investigate the interplay between hMYH DNA glycosylase and hMTH1 for cancer cell survival by using mismatch repair defective T-cell acute lymphoblastic leukemia (T-ALL) cells. To this end, MYH and MTH1 were silenced individually or simultaneously using small hairpin RNAs. Increased sub-G1 population and apoptotic cells were observed upon concurrent depletion of both enzymes. Elevated cell death was consistent with cleaved caspase 3 accumulation in double knockdown cells. Importantly, overexpression of the nuclear isoform of hMYH could remove the G1 arrest and partially rescue the toxicity observed in hMTH1-depleted cells. In addition, expression profiles of human DNA glycosylases were generated using quantitative reverse transcriptase–PCR in MTH1 and/or MYH knockdown cells. NEIL1 DNA glycosylase, involved in repair of oxidized nucleosides, was found to be significantly downregulated as a cellular response to MTH1–MYH co-suppression. Overall, the results suggest that hMYH and hMTH1 functionally cooperate for effective repair and survival in mismatch repair defective T-ALL Jurkat A3 cells

Targeted DNA methylation by homology-directed repair in mammalian cells. Transcription reshapes methylation on the repaired gene.

We report that homology-directed repair of a DNA double-strand break within a single copy Green Fluorescent Protein (GFP) gene in HeLa cells alters the methylation pattern at the site of recombination. DNA methyl transferase (DNMT)1, DNMT3a and two proteins that regulate methylation, Np95 and GADD45A, are recruited to the site of repair and are responsible for selective methylation of the promoter-distal segment of the repaired DNA. The initial methylation pattern of the locus is modified in a transcription-dependent fashion during the 15\u201320 days following repair, at which time no further changes in the methylation pattern occur. The variation in DNA modification generates stable clones with wide ranges of GFP expression. Collectively, our data indicate that somatic DNA methylation follows homologous repair and is subjected to remodeling by local transcription in a discrete time window during and after the damage. We propose that DNA methylation of repaired genes represents a DNA damage code and is source of variation of gene expression

Holographic three-point functions of giant gravitons

Working within the AdS/CFT correspondence we calculate the three-point function of two giant gravitons and one pointlike graviton using methods of semiclassical string theory and considering both the case where the giant gravitons wrap an S^3 in S^5 and the case where the giant gravitons wrap an S^3 in AdS_5. We likewise calculate the correlation function in N=4 SYM using two Schur polynomials and a single trace chiral primary. We find that the gauge and string theory results have structural similarities but do not match perfectly, and interpret this in terms of the Schur polynomials' inability to interpolate between dual giant and pointlike gravitons.Comment: 21 page