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New frontiers in angiogenesis research
No full textAngiogenesis consists in the formation of new blood vessels from preexisting vasculature. It depends on the balance between pro- and antiangiogenic factors. It is essential for growth, embryological development, ovulation, tissue regeneration, and wound healing. Its imbalance leads to pathological conditions, including delayed wound healing, cardiovascular accidents, inflammatory diseases, and growth and metastasis of tumors. Under normal conditions, cancer cells are in a dormant state. The angiogenic switch (escape from dormancy) depends on the disruption of the balance of angiogenic factors. About 50 years ago, Folkman argued that angiogenesis could be a strategic target for anticancer therapy, and several therapeutic protocols have been designed. Not surprisingly, recent research on angiogenesis has been addressed to oncology. This chapter summarizes recent advances in angiogenesis research, with the last concepts that provide new methodological approaches for the investigation of specific patterns of the angiogenic process, including the development of novel therapeutic strategies
Improved residual stress evaluation with Hole-Drilling and DIC through the L-curve tool and super-resolution along depth
No full textFull-field methods such as Electronic Speckle Pattern Interferometry (ESPI) and Digital Image Correlation (DIC) emerge as promising alternatives to strain rosette in the hole-drilling method, each with its own advantages and limitations. In particular, DIC stands out as a method requiring minimal (and cheap) specimen preparation; however, its sensitivity is approximately one order of magnitude lower than that of conventional strain gauge techniques. We address two fundamental questions. First, how can the inverse problem of the hole-drilling method be systematically approached outside the well-established framework of ASTM E837, which provides users with comprehensive guidance, including automated regularization procedures? Second, thanks to full-field measurement techniques, is it possible to retrieve stress distributions at a spatial resolution finer than the drilling step? We revisit the theoretical development of the inverse problem, aiming to directly identify the residual stresses from raw images, without intermediate pre-processing of the displacement fields. We introduce the L-curve method – well established in other scientific domains – as a rational tool for the choice of the regularization parameter. Finally, we show that, in principle, it would be possible to identify the entire stress distribution from a single drilling increment. We perform a deep rolling treatment on an aluminum specimen and compare the residual stresses identified using both a strain gauge rosette and DIC. We demonstrate that the proposed framework yields results comparable to those obtained using strain gauge rosettes, while minimizing user-dependent arbitrariness. Furthermore, we show that depth super-resolution of at least a factor of two is already achievable with current technological capabilities
New evidence on the formation conditions of the Libyan Desert Glass (Western Egypt): Clues from a dendritic zircon inclusion
No full textLibyan Desert Glass (LDG) is an~29 million years old, silica-rich glass found in
Western Egypt. Whether this glass formed in an impact cratering context associated with
the hypervelocity collision of a cometary/asteroidal body or radiative heating during an
airburst is debated. Determination of the formation temperatures and pressures of rare
mineral components in LDG can provide key petrogenetic constraints on its origin. Here,
we report the occurrence of a zircon inclusion, whose textural, chemical, and
crystallographic features point to a rapid formation during solidification of the silica-rich
LDG melt. The study was conducted combining dual beam microscopy, transmission
electron microscopy, energy-dispersive X-ray spectroscopy, and three-dimensional electron
diffraction. The inclusion is a few tens of micrometer in size and consists of dendritic
branches of zircon arranged in a reticulate-cruciform texture. The high-silica glass filling
interstices between dendrites have longer chemical bonds compared to matrix glass, as
indicated by electron pair distribution function analysis, and is enriched in Al2O3. The lack
of incongruent melt products (ZrO2, SiO2) suggests that the inclusion formed during cooling
from supraliquidus conditions, by dynamic crystallization from an (immiscible) undercooled
liquid droplet. Such droplet would derive from shock-induced melting of a precursor zircon
grain, possibly mixed with the SiO2-rich liquid formed by melting of the LDG precursor
material. The formation model proposed for this inclusion does not allow us to discriminate
between the two genetic processes proposed for LDG, but sets a new minimum to the
liquidus temperature of the corresponding chemical system of~2250°C
A fluorescein-tagged pH-low insertion peptide (pHLIP) for glioblastoma imaging: Lipid membrane interaction and cancer cell targeting
No full textGlioblastoma (GB) is the most aggressive and common malignant brain tumor, and despite current therapeutic approaches, prognosis remains poor. Given that surgical resection is frequently the sole potentially curative option, precise intraoperative tumor delineation is crucial for reducing recurrence rates and enhancing patient outcomes. In this study, we developed a novel pH-responsive imaging tool by coupling the pH-low insertion peptide (pHLIP) with fluorescein (FL) to enable targeted fluorescence-guided visualization of tumor margins. We investigated pHLIP–lipid membrane interactions using model systems, including liposomes and supported lipid bilayers (SLB), assessing peptide's pH-dependent insertion mechanism. Complementary in vitro experiments on patient-derived GB cell lines were performed to show the tracer's pH sensitivity, selective membrane targeting, and potential off-target effects. The FL-pHLIP construct showed robust, pH-dependent membrane insertion and selectivity in GB cellular models with minimal interaction under physiological conditions. These findings support FL-pHLIP as a promising candidate for fluorescence-guided surgery in GB and highlight its potential for clinical translation and for the broader development of pH-responsive diagnostic tools
Balancing Mitigation Policies during Pandemics - Economic, Health and Environmental Implications
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Comparison between Xpert ultra and standard M10 for detection of MTBC in clinical samples
No full textThis study compared the STANDARD M10 MDR-TB with GeneXpert® MTB/RIF Ultra test in detecting tuberculosis on 57 samples. Sensitivity and specificity were 92 % and 100 % with a positive predictive value of 100 % with a substantial agreement (0.74) at Kappa agreement test
Mitochondrial epigenetic mechanisms in cancer: an updated overview
No full text: Mitochondria are central organelles in regulating apoptosis, cellular metabolism, metabolite biosynthesis, energy production, and overall cellular homeostasis. Over the past years, abundant evidence has shown that mitochondrial dysfunction and the resulting metabolic reprogramming profoundly influence key hallmarks of tumor development, including initiation, progression, angiogenesis, and metastasis, playing a role also in therapeutic resistance. Consequently, mitochondria have emerged as a promising target for anticancer therapy. Beyond well-known mutational abnormalities in the mitochondrial genome, recent studies indicate that altered mitochondrial epigenetic mechanisms could also contribute to cancer etiology. In the current review, we present a brief, up-to-date overview of the literature on mitochondrial epigenetic regulation in cancer. We will focus on the main characterized mitoepigenetic mechanisms, namely mitochondrial DNA (mtDNA) methylation and activity of mtDNA-encoded non-coding RNAs. We also consider bidirectional epigenetic crosstalk between the nucleus and mitochondria, whereby metabolites and signaling pathways coordinate chromatin states and mitochondrial function. Collectively, available evidence links mitoepigenetic alterations to tumor progression and pharmacoresistance, nominating these pathways as tractable targets for pharmacological intervention
Sport e sfide sociali. I valori della comunità attraverso lo sport: il caso degli oratori.
No full textA state-of-the-art review of R&D for the super critical water-cooled reactor technology. Part I economics, thermalhydraulics, safety and licensing
No full textThis study presents a summary of the most relevant research and development (R&D) carried out to support the development of the only Generation IV water-cooled reactor endorsed by the Generation IV International Forum (GIF). The coolant of the proposed reactor is operated at supercritical water conditions, allowing for an increase in thermodynamic efficiency of the plant and the production of higher-grade process heat. Several collaborations have been established to support the development of this technology under the GIF umbrella, as well as through other international avenues. Therefore, the development is bolstered by a collective effort between numerous R&D institutions across Asia, Europe, and North America. Globally, the R&D programs have been methodologically executed in phases, namely: fundamental R&D, validation and verification of assumptions used in R&D analyses, and pre-conceptualization of supercritical water-cooled reactors (SCWRs). This article summarizes the recent R&D work performed to support the development of the SCWR technology on thermalhydraulics and safety, economics and licensing. Furthermore, R&D highlights, identified knowledge gaps, conclusions, and recommendations are presented