SL(2,R)-geometric phase space and (2+2)-dimensions

We propose an alternative geometric mathematical structure for arbitrary phase space. The main guide in our approach is the hidden SL(2,R)-symmetry which acts on the phase space changing coordinates by momenta and vice versa. We show that the SL(2,R)-symmetry is implicit in any symplectic structure. We also prove that in any sensible physical theory based on the SL(2,R)-symmetry the signature of the flat target "spacetime" must be associated with either one-time and one-space or at least two-time and two-space coordinates. We discuss the consequences as well as possible applications of our approach on different physical scenarios.Comment: 17 pages, no figure

El hogar inteligente

La sociedad actual ha acogido la tecnología con los brazos abiertos : pocos subsistirían un día sin móvil y hay quien tiene un televisor mayor que su salón. Muchos vivimos en hogares tecnológicos, pero ¿vivimos ya en hogares inteligentes

The relevance of grated inlets within surface drainage systems in the field of urban flood resilience. A review of several experimental and numerical simulation approaches

Urban drainage networks should be designed and operated preferably under open channel flow conditions without flux return, backwater, or overflows. In the case of extreme storm events, urban pluvial flooding is generated by the excess of surface runoff that could not be conveyed by pressurized sewer pipes, due to its limited capacity or, many times, due to the poor efficiency of surface drainage systems to collect uncontrolled overland flow. Generally, the hydraulic design of sewer systems is addressed more for underground networks, neglecting the surface drainage system, although inadequate inlet spacings and locations can cause dangerous flooding with rele-vant socio-economic impacts and the interruption of critical services and urban activities. Several experimental and numerical studies carried out at the Technical University of Catalonia (UPC) and other research institutions demonstrated that the hydraulic efficiency of inlets can be very low under critical conditions (e.g., high circulating overland flow on steep areas). In these cases, the hydraulic efficiency of conventional grated inlets and continuous transverse elements can be around 10–20%. Their hydraulic capacity, expressed in terms of discharge coefficients, shows the same criticism with values quite far from those that are usually used in several project practice phases. The grate clogging phenomenon and more intense storm events produced by climate change could further reduce the inlets’ performance. In this context, in order to improve the flood urban resilience of our cities, the relevance of the hydraulic behavior of surface drainage systems is clear

Time for change: a new training programme for morpho-molecular pathologists?

The evolution of cellular pathology as a specialty has always been driven by technological developments and the clinical relevance of incorporating novel investigations into diagnostic practice. In recent years, the molecular characterisation of cancer has become of crucial relevance in patient treatment both for predictive testing and subclassification of certain tumours. Much of this has become possible due to the availability of next-generation sequencing technologies and the whole-genome sequencing of tumours is now being rolled out into clinical practice in England via the 100 000 Genome Project. The effective integration of cellular pathology reporting and genomic characterisation is crucial to ensure the morphological and genomic data are interpreted in the relevant context, though despite this, in many UK centres molecular testing is entirely detached from cellular pathology departments. The CM-Path initiative recognises there is a genomics knowledge and skills gap within cellular pathology that needs to be bridged through an upskilling of the current workforce and a redesign of pathology training. Bridging this gap will allow the development of an integrated 'morphomolecular pathology' specialty, which can maintain the relevance of cellular pathology at the centre of cancer patient management and allow the pathology community to continue to be a major influence in cancer discovery as well as playing a driving role in the delivery of precision medicine approaches. Here, several alternative models of pathology training, designed to address this challenge, are presented and appraised

Anti-proliferative but not anti-angiogenic tyrosine kinase inhibitors enrich for cancer stem cells in soft tissue sarcoma.

BackgroundIncreasing studies implicate cancer stem cells (CSCs) as the source of resistance and relapse following conventional cytotoxic therapies. Few studies have examined the response of CSCs to targeted therapies, such as tyrosine kinase inhibitors (TKIs). We hypothesized that TKIs would have differential effects on CSC populations depending on their mechanism of action (anti-proliferative vs. anti-angiogenic).MethodsWe exposed human sarcoma cell lines to sorafenib, regorafenib, and pazopanib and assessed cell viability and expression of CSC markers (ALDH, CD24, CD44, and CD133). We evaluated survival and CSC phenotype in mice harboring sarcoma metastases after TKI therapy. We exposed dissociated primary sarcoma tumors to sorafenib, regorafenib, and pazopanib, and we used tissue microarray (TMA) and primary sarcoma samples to evaluate the frequency and intensity of CSC markers after neoadjuvant therapy with sorafenib and pazopanib. Parametric and non-parametric statistical analyses were performed as appropriate.ResultsAfter functionally validating the CSC phenotype of ALDHbright sarcoma cells, we observed that sorafenib and regorafenib were cytotoxic to sarcoma cell lines (P < 0.05), with a corresponding 1.4 - 2.8 fold increase in ALDHbright cells from baseline (P < 0.05). In contrast, we observed negligible effects on viability and CSC sub-populations with pazopanib. At low doses, there was progressive CSC enrichment in vitro after longer term exposure to sorafenib although the anti-proliferative effects were attenuated. In vivo, sorafenib improved median survival by 11 days (P < 0.05), but enriched ALDHbright cells 2.5 - 2.8 fold (P < 0.05). Analysis of primary human sarcoma samples revealed direct cytotoxicity following exposure to sorafenib and regorafenib with a corresponding increase in ALDHbright cells (P < 0.05). Again, negligible effects from pazopanib were observed. TMA analysis of archived specimens from sarcoma patients treated with sorafenib demonstrated significant enrichment for ALDHbright cells in the post-treatment resection specimen (P < 0.05), whereas clinical specimens obtained longitudinally from a patient treated with pazopanib showed no enrichment for ALDHbright cells (P > 0.05).ConclusionsAnti-proliferative TKIs appear to enrich for sarcoma CSCs while anti-angiogenic TKIs do not. The rational selection of targeted therapies for sarcoma patients may benefit from an awareness of the differential impact of TKIs on CSC populations

Numerical and experimental approaches to estimate discharge coefficients and energy loss coefficients in pressurized grated inlets

Numerical models concerning inlet systems are run to assess the hydraulic performance of existing or new systems and estimate the flow interchanges between the surface overland and sewer flows. In most programs, these interactions are modelled using the orifice equation, with estimated discharge coefficients around 0.6. In this paper, discharge values and energy loss coefficients for several pressurized grated inlets were obtained by experimental and numerical approaches and compared. To achieve these goals, a numerical model replicating several experimental tests carried out at the hydraulic laboratory of Universitat Politècnica de Catalunya (UPC) was produced using a CFD model (Flow 3D). This numerical model was found to be highly sensitive to the mesh size used; however, it was able to accurately simulate the experimental processes. The comparison considered different combinations of pressurized flow though the grate, between 10 to 50 l/s, and different longitudinal gradients. The experimental discharge coefficient was found to increase with surcharging flowrate (ranging from 0.14 and 0.41), whereas the longitudinal gradient was found to have no effect. The discharge coefficients obtained in this study show that the standard 0.6 value commonly used by practitioners should be revised to a range between 0.14 to 0.41, depending on circulating flow and inlet type. In addition, the loss coefficient values range from 0.25 to 3.41. © 2021 by the authors. Licensee MDPI, Basel, Switzerland