Long term discharge simulation through a geomorphological model

Flow duration curve estimation must be performed on the basis of continuous rainfall-runoff simulations. In ungauged basins, a under-parameterised model is needed to reduce the uncertainty of the results. In this paper a geomorphological model based on a width function (WFIUH) was used to simulate low flows in a mean-sized basin in Central Italy. The WFIUH model [9]introduces a new approachto the curvenumber method and was used to evaluate the stream-flow for hourly event representation. The aim of this work is to evaluate the behaviour of the WFIUH model for long term simulation and then to compare the standard curve number approach to the curve number method implemented in the WFIUH model. To predict the behaviour of catchments for a long term, to know the response of catchments in different seasons or in different years, it is necessary to improve the model and to identify a new method for calculating base-flow. To obtain these results, it is necessary to separate base-flow and stream-flow, simulate the two contributions and build a unique series of values that reproduces the answer of the basin to different rainfalls during the year to estimate the low flow during a dry period. The model can also be used in ungauged basins because a unique parameter is used. © 2013 AIP Publishing LLC

Soil Conservation Service curve number: how to take into account spatial and temporal variability

The most commonly used method to evaluate rainfall excess, is the Soil Conservation Service (SCS) runoff curve number model. This method is based on the determination of the CN valuethat is linked with a hydrological soil group, cover type, treatment, hydrologic condition and antecedent runoff condition. To calculate the antecedent runoff condition the standard procedure needs to calculate the rainfall over the entire basin during the five days previous to the beginning of the event in order to simulate and then to use that volume of rainfall to calculate the antecedent moisture condition (AMC). This is necessary in order to obtain the correct curve number value. The value of the modified parameter is then kept constant throughout the whole event. The aim of this work is to evaluate the possibility of improving the curve number method. The various assumptions are focused on modifying those related to rainfall and the determination of an AMC condition and their role in the determination of the value of the curve number parameter. In order to consider the spatial variability we assumed that the rainfall which influences the AMC and the CN value does not account for the rainfall over the entire basin, but for the rainfall within a single cell where the basin domain is discretized. Furthermore, in order to consider the temporal variability of rainfall we assumed that the value of the CN of the single cell is not maintained constant during the whole event, but instead varies throughout it according to the time interval used to define the AMC conditions

Breast Cancer Chemotherapeutic Options: A General Overview on the Preclinical Validation of a Multi-Target Ruthenium(III) Complex Lodged in Nucleolipid Nanosystems

In this review we have showcased the preclinical development of original amphiphilic nanomaterials designed for ruthenium-based anticancer treatments, to be placed within the current metallodrugs approach leading over the past decade to advanced multitarget agents endowed with limited toxicity and resistance. This strategy could allow for new options for breast cancer (BC) interventions, including the triple-negative subtype (TNBC) with poor therapeutic alternatives. BC is currently the second most widespread cancer and the primary cause of cancer death in women. Hence, the availability of novel chemotherapeutic weapons is a basic requirement to fight BC subtypes. Anticancer drugs based on ruthenium are among the most explored and advanced next-generation metallotherapeutics, with NAMI-A and KP1019 as two iconic ruthenium complexes having undergone clinical trials. In addition, many nanomaterial Ru complexes have been recently conceived and developed into anticancer drugs demonstrating attractive properties. In this field, we focused on the evaluation of a Ru(III) complex-named AziRu-incorporated into a suite of both zwitterionic and cationic nucleolipid nanosystems, which proved to be very effective for the in vivo targeting of breast cancer cells (BBC). Mechanisms of action have been widely explored in the context of preclinical evaluations in vitro, highlighting a multitarget action on cell death pathways which are typically deregulated in neoplasms onset and progression. Moreover, being AziRu inspired by the well-known NAMI-A complex, information on non-nanostructured Ru-based anticancer agents have been included in a precise manner

Charge-transfer interactions stabilize g-quadruplex-forming thrombin binding aptamers and can improve their anticoagulant activity

In the search for optimized thrombin binding aptamers (TBAs), we herein describe the synthesis of a library of TBA analogues obtained by end-functionalization with the electron-rich 1,5-dialkoxy naphthalene (DAN) and the electron-deficient 1,8,4,5-naphthalenetetra-carboxylic diimide (NDI) moieties. Indeed, when these G-rich oligonucleotides were folded into the peculiar TBA G-quadruplex (G4) structure, effective donor–acceptor charge transfer interactions between the DAN and NDI residues attached to the extremities of the sequence were induced, providing pseudo-cyclic structures. Alternatively, insertion of NDI groups at both extremities produced TBA analogues stabilized by π–π stacking interactions. All the doubly-modified TBAs were characterized by different biophysical techniques and compared with the analogues carrying only the DAN or NDI residue and unmodified TBA. These modified TBAs exhibited higher nuclease resistance, and their G4 structures were markedly stabilized, as evidenced by increased Tm values compared to TBA. These favorable properties were also associated with improved anticoagulant activity for one DAN/NDI-modified TBA, and for one NDI/NDI-modified TBA. Our results indicated that TBA pseudo-cyclic structuring by ad hoc designed end-functionalization represents an efficient approach to improve the aptamer features, while pre-organizing and stabilizing the G4 structure but allowing sufficient flexibility to the aptamer folding, which is necessary for optimal thrombin recognition

Safety and efficacy evaluation in vivo of a cationic nucleolipid nanosystem for the nanodelivery of a ruthenium(Iii) complex with superior anticancer bioactivity

Selectivity and efficacy towards target cancer cells, as well as biocompatibility, are current challenges of advanced chemotherapy powering the discovery of unconventional metal‐based drugs and the search for novel therapeutic approaches. Among second‐generation metal‐based chemotherapeutics, ruthenium complexes have demonstrated promising anticancer activity cou-pled to minimal toxicity profiles and peculiar biochemical features. In this context, our research group has recently focused on a bioactive Ru(III) complex—named AziRu—incorporated into a suite of ad hoc designed nucleolipid nanosystems to ensure its chemical stability and delivery. In-deed, we proved that the structure and properties of decorated nucleolipids can have a major impact on the anticancer activity of the ruthenium core. Moving in this direction, here we describe a preclinical study performed by a mouse xenograft model of human breast cancer to establish safety and efficacy in vivo of a cationic Ru(III)‐based nucleolipid formulation, named HoThyRu/DOTAP, endowed with superior antiproliferative activity. The results show a remarkable reduction in tu-mour with no evidence of animal suffering. Blood diagnostics, as well as biochemical analysis in both acute and chronic treated animal groups, demonstrate a good tolerability profile at the therapeutic regimen, with 100% of mice survival and no indication of toxicity. In addition, ruthenium plasma concentration analysis and tissue bioaccumulation were determined via appropriate sam-pling and ICP‐MS analysis. Overall, this study supports both the efficacy of our Ru‐containing nanosystem versus a human breast cancer model and its safety in vivo through well‐tolerated animal biological responses, envisaging a possible forthcoming use in clinical trials

Interfacing aptamers, nanoparticles and graphene in a hierarchical structure for highly selective detection of biomolecules in OECT devices

In several biomedical applications, the detection of biomarkers demands high sensitivity, selectivity and easy-to-use devices. Organic electrochemical transistors (OECTs) represent a promising class of devices combining a minimal invasiveness and good signal transduction. However, OECTs lack of intrinsic selectivity that should be implemented by specific approaches to make them well suitable for biomedical applications. Here, we report on a biosensor in which selectivity and a high sensitivity are achieved by interfacing, in an OECT architecture, a novel gate electrode based on aptamers, Au nanoparticles and graphene hierarchically organized to optimize the final response. The fabricated biosensor performs state of the art limit of detection monitoring biomolecules, such as thrombin-with a limit of detection in the picomolar range (≤ 5 pM) and a very good selectivity even in presence of supraphysiological concentrations of Bovine Serum Albumin (BSA-1mM). These accomplishments are the final result of the gate hierarchic structure that reduces sterich indrance that could contrast the recognition events and minimizes false positive, because of the low affinity of graphene towards the physiological environment. Since our approach can be easily applied to a large variety of different biomarkers, we envisage a relevant potential for a large series of different biomedical applications

The Society for Immunotherapy of Cancer perspective on regulation of interleukin-6 signaling in COVID-19-related systemic inflammatory response

The pandemic caused by the novel coronavirus SARS-CoV-2 has placed an unprecedented burden on healthcare systems around the world. In patients who experience severe disease, acute respiratory distress is often accompanied by a pathological immune reaction, sometimes referred to as ‘cytokine storm’. One hallmark feature of the profound inflammatory state seen in patients with COVID-19 who succumb to pneumonia and hypoxia is marked elevation of serum cytokines, especially interferon gamma, tumor necrosis factor alpha, interleukin 17 (IL-17), interleukin 8 (IL-8) and interleukin 6 (IL-6). Initial experience from the outbreaks in Italy, China and the USA has anecdotally demonstrated improved outcomes for critically ill patients with COVID-19 with the administration of cytokine-modulatory therapies, especially anti-IL-6 agents. Although ongoing trials are investigating anti-IL-6 therapies, access to these therapies is a concern, especially as the numbers of cases worldwide continue to climb. An immunology-informed approach may help identify alternative agents to modulate the pathological inflammation seen in patients with COVID-19. Drawing on extensive experience administering these and other immune-modulating therapies, the Society for Immunotherapy of Cancer offers this perspective on potential alternatives to anti-IL-6 that may also warrant consideration for management of the systemic inflammatory response and pulmonary compromise that can be seen in patients with severe COVID-19

Sorafenib plus long-acting octreotide in advanced hepatocellular carcinoma. Preliminary results of a multicenter ongoing study

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