Linear Toric Fibrations

These notes are based on three lectures given at the 2013 CIME/CIRM summer school. The purpose of this series of lectures is to introduce the notion of a toric fibration and to give its geometrical and combinatorial characterizations. Polarized toric varieties which are birationally equivalent to projective toric bundles are associated to a class of polytopes called Cayley polytopes. Their geometry and combinatorics have a fruitful interplay leading to fundamental insight in both directions. These notes will illustrate geometrical phenomena, in algebraic geometry and neighboring fields, which are characterized by a Cayley structure. Examples are projective duality of toric varieties and polyhedral adjunction theory

Response to. comment on optic nerve sheath diameter ultrasound evaluation in intensive care unit: possible role and clinical aspects in neurological critical patients' daily monitoring

Comment on "Optic Nerve Sheath Diameter Ultrasound Evaluation in Intensive Care Unit: Possible Role and Clinical Aspects in Neurological Critical Patients' Daily Monitoring"

Longitudinal sleeve gastrectomy: current perspectives

Emanuele Soricelli, Giovanni Casella, Giorgio Di Rocco, Adriano Redler, Nicola BassoDepartment of Surgical Sciences, Policlinico Umberto I, Sapienza, University of Rome, ItalyAbstract: Since the early 2000s, laparoscopic sleeve gastrectomy has increasingly gained consensus in bariatric surgery, thanks to good to excellent results in terms of weight loss and comorbidity resolution, and to simpler technical aspects than in Roux-en-Y gastric bypass and biliopancreatic diversion. In yearly consensus summits, surgical indications, technical details, and management of complications, together with continuous update of data concerning clinical outcome, have been debated on the basis of increasing collective experience. In experimental studies and clinical trials, the pathophysiological mechanisms of weight loss and remission of cardiometabolic comorbidities subsequent to sleeve gastrectomy have been extensively discussed. The aim of this paper is to offer a review of state of the art laparoscopic sleeve gastrectomy and to focus attention on the currently most debated topics and future prospects of this procedure.Keywords: sleeve gastrectomy, type 2 diabetes mellitus, gastroesophageal reflux disease, revisional, quality of lif

Enhancement of photoacoustic detection of inhomogeneities in polymers

We report a series of experiments on laser pulsed photoacoustic excitationin turbid polymer samples addressed to evaluate the sound speed in the samples and the presence of inhomogeneities in the bulk. We describe a system which allows the direct measurement of the speed of the detected waves by engraving the surface of the piece under study with a fiduciary pattern of black lines. We also describe how this pattern helps to enhance the sensitivity for the detection of an inhomogeneity in the bulk. These two facts are useful for studies in soft matter systems including, perhaps, biological samples. We have performed an experimental analysis on Grilon(R) samples in different situations and we show the limitations of the method.Comment: 8 pages, 7 figure

HISTORICAL EARTHEN WALLS: FROM KNOWLEDGE TO CONSCIOUS CONSERVATION

Abstract. Centuries-old earthen masonry presenting various stages of degradation, earthen walls that have been restored several times: these are the archeological phases of the city walls of Mascarell, on the Spanish Mediterranean coast. Founded in the first half of the 13th century, this town is the only complex in Castellon Province that preserves all its ancient walls, which were built entirely by means of the brick-faced rammed-earth technique (clay with bricks and lime). This article reports the first results of a research project conducted on the multiple information available on these artifacts: bibliographic, archival and iconographic sources and the results of direct material analysis, stratigraphic analysis and archeological analysis. The situation is complex, as these walls have undergone a long sequence of transformations, including interventions carried out since the 18th century and multiple restorations in the period 1942–2015. The research developed and refined architecture archeology tools in order to analyze the rammed-earth techniques adopted during restoration work (similar but not identical to the historical technique), to characterize the materials used in restoration, to evaluate their resistance to degradation over the years, to define a sort of 'critical evolutionary line' of rammed-earth restoration, and to conduct a cross-sectional study of this building technique from the Middle Ages to the present. Finally, we drafted some guidelines for future interventions for conservation and enhancement

Long-term bone outcomes in Italian patients with Gaucher disease type 1 or type 3 treated with imiglucerase: A sub-study from the International Collaborative Gaucher Group (ICGG) Gaucher Registry

Background: Gaucher disease (GD) is a lysosomal storage disorder. We evaluated the “real-world” effectiveness of first-line imiglucerase on long-term bone outcomes in Italian patients in the International Collaborative Gaucher Group (ICGG) Gaucher Registry. Methods: Patients treated with imiglucerase for ≥2 years and with bone assessments at baseline and during follow-up were selected. Data on bone pain, bone crises, marrow infiltration, avascular necrosis, infarction, lytic lesions, Erlenmeyer flask deformity, bone fractures, mineral density, and imiglucerase dosage were evaluated. Results: Data on bone manifestations were available for 73 of 229 patients (31.9 %). Bone crises frequency decreased significantly from baseline to the most recent follow-up (p < 0.001), with some improvement observed in bone pain prevalence. Bone pain and bone crises prevalence decreased significantly from baseline at 2 to <4 and 4 to <6 years (all p < 0.05). A low median (25th, 75th percentile) baseline imiglucerase dosage was identified in patients reporting bone pain or bone crises (15.0 [13.7, 30.0] and 22.8 [17.5, 36.0] U/kg once every 2 weeks, respectively). Conclusion: Our study suggests that the management of GD in Italy, with regards to imiglucerase dosage, is suboptimal and confirms the need for clinicians to monitor and correctly treat bone disease according to best practice guidelines

Hydrogen Peroxide Induces Heme Degradation and Protein Aggregation in Human Neuroglobin: Roles of the Disulfide Bridge and the H-bonding in the Distal Heme Cavity

In this study, human neuroglobin (hNgb) was found to undergo H2O2-induced breakdown of the heme center at a much slower rate than other globins, namely in the timescale of hours against minutes. We studied how the rate of the process is affected by the Cys46/Cys55 disulfide bond and the network of noncovalent interactions in the distal heme side involving Tyr44, Lys67, the His64 heme iron axial ligand and the heme propionate-7. The rate is increased by the Tyr44 to Ala and Phe mutations, however the rate is lowered by Lys67 to Ala swapping. The absence of the disulfide bridge slows down the reaction further. Therefore, the disulfide bond-controlled accessibility of the heme site and the residues at position 44 and 67 affect the activation barrier of the reaction. Wild-type and mutated species form -amyloid aggregates in the presence of H2O2 producing globular structures. Furthermore, the C46A/C55A, Y44A, Y44F and Y44F/C46A/C55A variants yield potentially harmful fibrils. Finally, the nucleation and growth kinetics for the aggregation of the amyloid structures can be successfully described by the Finke-Watzky model

Apoptosis induced by a HIPK2 full-length-specific siRNA is due to off-target effects rather than prevalence of HIPK2-Δe8 isoform.

Small interfering RNAs (siRNAs) are widely used to study gene function and extensively exploited for their potential therapeutic applications. HIPK2 is an evolutionary conserved kinase that binds and phosphorylates several proteins directly or indirectly related to apoptosis. Recently, an alternatively spliced isoform skipping 81 nucleotides of exon 8 (Hipk2-∆e8) has been described. Selective depletion of Hipk2 full-length (Hipk2-FL) with a speci c siRNA that spares the Hipk2-∆e8 isoform has been shown to strongly induce apoptosis, suggesting an unpredicted dominant- negative effect of Hipk2-FL over the ∆e8 isoform. From this observation, we sought to take advantage and assessed the therapeutic potential of generating Hipk2 isoform unbalance in tumor-initiating cells derived from colorectal cancer patients. Strong reduction of cell viability was induced in vitro and in vivo by the originally described exon 8-speci c siRNA, supporting a potential therapeutic application. However, validation analyses performed with additional exon8-speci c siRNAs with different stabilities showed that all exon8-targeting siRNAs can induce comparable Hipk2 isoform unbalance but only the originally reported e8-siRNA promotes cell death. These data show that loss of viability does not depend on the prevalence of Hipk2- ∆e8 isoform but it is rather due to microRNA-like off-target effects

Assessment of resistance mechanisms and clinical implications in patients with kras mutated-metastatic breast cancer and resistance to cdk4/6 inhibitors

Simple SummaryPalbociclib in combination with fulvestrant is used globally to treat metastatic breast cancer, but it was recognized that not all patients benefit from this combination of drugs. However, the predictive factors remain unknown. Here, we show KRAS ctDNA levels as predictive mechanisms of resistance to palbociclib and fulvestrant, and their association with the time to treatment discontinuation of the above treatment. These observations shed light on the potential clinical applications of ctDNA analysis in this setting of patients, in order to provide critical information about tumour dynamics, and to predict who will take advantage from CDK4/6 inhibitors.Despite therapeutic improvements, resistance to palbociclib is a growing clinical challenge which is poorly understood. This study was conducted in order to understand the molecular mechanisms of resistance to palbociclib, and to identify biomarkers to predict who will take advantage from cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). A total of about a thousand blood samples were collected from 106 patients with hormone receptor positive (HR+) human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer who received palbociclib in combination with fulvestrant as the first-line metastatic therapy enrolled in this study. The genotyping of their plasma cell-free DNA was studied, including serial plasma samples. Collectively, our findings identify the appearance of KRAS mutations leading to palbociclib resistance acquisition within 6 months, and provide critical information for the prediction of therapeutic responses in metastatic breast cancer. By monitoring KRAS status through liquid biopsy, we could predict who will take advantage from the combination of palbociclib and fulvestrant, offering highly-individualized treatment plans, thus ensuring the best patient quality of life