Competing feedback in an idealized tide-influenced delta network

The morphodynamic evolution of river deltas is intimately tied to flow and sediment partitioning at bifurcations. In this work, the long-term equilibrium configuration of a simple delta network is investigated by means of an analytical model, which accounts for the effect of small tidal oscillations. Differently from individual bifurcations where tidal action is always a stabilizing factor, in the case of a tree-like delta with multiple bifurcations a dual response emerges. Specifically, depending on the values of four reference parameters functions of tidal amplitude, upstream flow conditions, and channels geometry, tides can either promote or discourage an unbalanced discharge distribution. This behavior primarily concerns the apex bifurcation, which is affected by the variations of the relative tidal amplitude at the internal nodes. In turn these variations depend on how flow and sediment are diverted upstream. The stability of steady-state solutions is found to be governed by the sign and magnitude of the slope asymmetry between channels. This work provides a basic modeling framework for the interpretation of the autogenic response of multiple coupled micro-tidal bifurcations, which can potentially be extended to include in a unified scheme erosional and depositional processes typical of fluvio-deltaic systems

In-vitro evaluation of different antimicrobial combinations with and without colistin against carbapenem-resistant acinetobacter baumannii

Carbapenem-resistant Acinetobacter baumannii (CR-Ab) infections are associated with high morbidity and mortality. The aim of the study was to evaluate the in-vitro activity of different antimicrobial combinations (with and without colistin, COL) against clinical isolates of CR-Ab collected from patients with CR-Ab infection, including unconventional combinations such as COL + VANcomycin (VAN) and COL + rifampin (RIF). CR-Ab strains were collected from hospitalized patients at Sapienza University of Rome. Antimicrobial susceptibility patterns were determined throughout MIC50/90s whereas the synergistic activity was evaluated by qualitative (i.e., checkerboard) and quantitative (i.e., killing studies) methods. All the strains were found oxacillinase (OXA) producers and tigecycline (TIG) sensitive whereas 2 strains were resistant to COL. Application of the checkerboard method indicated complete synergism in COL combinations at different extension: 21.4%, 57.1%, 42.8%, 35.7% for COL + meropenem (MEM), COL + RIF, COL + VAN and COL + TIG, respectively, with the non-conventional combinations COL + VAN and COL + RIF exhibiting the highest rate of synergism. Regarding COL-free combination, complete synergism was observed in 35.7% of the strains for MEM + TIG. Killing studies showed that the combinations COL + MEM, COL + TIG and MEM + TIG were bactericidal and synergistic against both colistin-sensitive and low colistin-resistant strains whereas only the combinations COL + VAN and COL + RIF showed an early and durable bactericidal activity against all the tested strains, with absence of growth at 24 h. This study demonstrated that COL-based combinations lead to a high level of synergic and bactericidal activity, especially COL + VAN and COL + RIF, even in the presence of high level of COL resistance

Essential oils and their main chemical components: the past 20 years of preclinical studies in melanoma

The last two decades have seen the development of effective therapies, which have saved the lives of a large number of melanoma patients. However, therapeutic options are still limited for patients without BRAF mutations or in relapse from current treatments, and severe side effects often occur during therapy. Thus, additional insights to improve treatment efficacy with the aim to decrease the likelihood of chemoresistance, as well as reducing side effects of current therapies, are required. Natural products offer great opportunities for the discovery of antineoplastic drugs, and still represent a useful source of novel molecules. Among them, essential oils, representing the volatile fraction of aromatic plants, are always being actively investigated by several research groups and show promising biological activities for their use as complementary or alternative medicine for several diseases, including cancer. In this review, we focused on studies reporting the mechanism through which essential oils exert antitumor action in preclinical wild type or mutant BRAF melanoma models. We also discussed the latest use of essential oils in improving cancer patients’ quality of life. As evidenced by the many studies listed in this review, through their effect on apoptosis and tumor progression-associated properties, essential oils can therefore be considered as potential natural pharmaceutical resources for cancer management

Radon concentration in self-bottled mineral spring waters as a possible public health issue

Since 2013, the Council Directive 2013/51/Euratom has been regulating the content of radioactive substances in water intended for human consumption. However, mineral waters are exempted from this regulation, including self-bottled springs waters, where higher radon concentration are expected. Therefore, a systematic survey has been conducted on all the 33 mineral spring waters of Lazio (a region of Central Italy) in order to assess if such waters, when self-bottled, may be of concern for public health. Waters have been sampled in two different ways to evaluate the impact of bottling on radon concentration. Water sampling was possible for 20 different spring waters, with 6 samples for each one. The results show that 2 (10%) of measured mineral spring waters returned radon concentrations higher than 100 Bq L−1, i.e., the parametric value established by the Council Directive. These results, if confirmed by other surveys involving a higher number of mineral spring waters, would suggest regulating also these waters, especially in countries like Italy for which: (i) mineral water consumption is significant; (ii) mineral concession owners generally allow the consumers to fill bottles and containers, intended for transport and subsequent consumption, directly from public fountains or from fountains within the plant; (iii) the consumers’ habit of drinking self-bottled mineral water is widespread

Study Projectile Motion With Different Initial Conditions Using Digital Image

The aim of this research is building algorithms to study projectile motion in tow dimension  and tracking the object in sequence frames of digital image . Computer program has written in visual basic language (version 6) depend on mathematical models to detect a motion of object in two–dimensions (2-D)with different initial conditions like initial velocity, the height of object from the earth and the angle of motion, to calculate important variables in motion such as distance, displacement, velocity, speed and the energy (kinetic and potential). Color digital images of type (bmp) and (RGB) color model were used in the study for easy handling them, after determining the center of the image on the x-axis, and y-axis and tracking movement on the basis of the center, and the results were expected to conform to the movement of the body. Key words: Projectile, Motion, Digital Image

Experimental data based machine learning classification models with predictive ability to select in vitro active antiviral and non-toxic essential oils

In the last decade essential oils have attracted scientists with a constant increase rate of more than 7% as witnessed by almost 5000 articles. Among the prominent studies essential oils are investigated as antibacterial agents alone or in combination with known drugs. Minor studies involved essential oil inspection as potential anticancer and antiviral natural remedies. In line with the authors previous reports the investigation of an in-house library of extracted essential oils as a potential blocker of HSV-1 infection is reported herein. A subset of essential oils was experimentally tested in an in vitro model of HSV-1 infection and the determined IC50s and CC50s values were used in conjunction with the results obtained by gas-chromatography/mass spectrometry chemical analysis to derive machine learning based classification models trained with the partial least square discriminant analysis algorithm. The internally validated models were thus applied on untested essential oils to assess their effective predictive ability in selecting both active and low toxic samples. Five essential oils were selected among a list of 52 and readily assayed for IC50 and CC50 determination. Interestingly, four out of the five selected samples, compared with the potencies of the training set, returned to be highly active and endowed with low toxicity. In particular, sample CJM1 from Calaminta nepeta was the most potent tested essential oil with the highest selectivity index (IC50 = 0.063 mg/mL, SI > 47.5). In conclusion, it was herein demonstrated how multidisciplinary applications involving machine learning could represent a valuable tool in predicting the bioactivity of complex mixtures and in the near future to enable the design of blended essential oil possibly endowed with higher potency and lower toxicity

RIP1-HAT1-SirT complex identification and targeting in treatment and prevention of cancer

Purpose: Alteration in cell death is a hallmark of cancer. A functional role regulating survival, apoptosis, and necroptosis has been attributed to RIP1/3 complexes.Experimental Design: We have investigated the role of RIP1 and the effects of MC2494 in cell death induction, using different methods as flow cytometry, transcriptome analysis, immunoprecipitation, enzymatic assays, transfections, mutagenesis, and in vivo studies with different mice models.Results: Here, we show that RIP1 is highly expressed in cancer, and we define a novel RIP1/3-SIRT1/2-HAT1/4 complex. Mass spectrometry identified five acetylations in the kinase and death domain of RIP1. The novel characterized pan-SIRT inhibitor, MC2494, increases RIP1 acetylation at two additional sites in the death domain. Mutagenesis of the acetylated lysine decreases RIP1-dependent cell death, suggesting a role for acetylation of the RIP1 complex in cell death modulation. Accordingly, MC2494 displays tumor-selective potential in vitro, in leukemic blasts ex vivo, and in vivo in both xenograft and allograft cancer models. Mechanistically, MC2494 induces bona fide tumor-restricted acetylated RIP1/caspase-8-mediated apoptosis. Excitingly, MC2494 displays tumor-preventive activity by blocking 7,12-dimethylbenz(α)anthracene-induced mammary gland hyperproliferation in vivoConclusions: These preventive features might prove useful in patients who may benefit from a recurrence-preventive approach with low toxicity during follow-up phases and in cases of established cancer predisposition. Thus, targeting the newly identified RIP1 complex may represent an attractive novel paradigm in cancer treatment and prevention

Toward multitasking pharmacological COX-targeting agents: Non-steroidal anti-inflammatory prodrugs with antiproliferative effects

The antitumor activity of certain anti-inflammatory drugs is often attributed to an indirect effect based on the inhibition of COX enzymes. In the case of anti-inflammatory prodrugs, this property could be attributed to the parent molecules with mechanism other than COX inhibition, particularly through formulations capable of slowing down their metabolic conversion. In this work, a pilot docking study aimed at comparing the interaction of two prodrugs, nabumetone (NB) and its tricyclic analog 7-methoxy-2, 3-dihydro-1H-cyclopenta[b]naphthalen-1-one (MC), and their common active metabolite 6-methoxy-2-naphthylacetic acid (MNA) with the COX binding site, was carried out. Cytotoxicity, cytofluorimetry, and protein expression assays on prodrugs were also performed to assess their potential as antiproliferative agents that could help hypothesize an effective use as anticancer therapeutics. Encouraging results suggest that the studied compounds could act not only as precursors of the anti-inflammatory metabolite, but also as direct antiproliferative agents. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Antimicrobial essential oil formulation: chitosan coated nanoemulsions for nose to brain delivery

Brain infections as meningitis and encephalitis are attracting a great interest. Challenges in the treatment of these diseases are mainly represented by the blood brain barrier (BBB) that impairs the efficient delivery of even very potent drugs to reach the brain. The nose to the brain administration route, is a non-invasive alternative for a quick onset of action, and enables the transport of numerous medicinal agents straight to the brain thus workarounding the BBB through the highly vascularized olfactory region. In this report, Thymus vulgaris and Syzygium aromaticum essential oils (EOs) were selected to be included in chitosan coated nanoemulsions (NEs). The EOs were firstly analyzed to determine their chemical composition, then used to prepare NEs, that were deeply characterized in order to evaluate their use in intranasal administration. An in vitro evaluation against a collection of clinical isolated bacterial strains was carried out for both free and nanoemulsioned EOs. Chitosan coated NEs showed to be a potential and effective intranasal formulation against multi-drug resistant Gram-negative bacteria such as methicillin-susceptible Staphylococcus aureus and multi-drug resistant Gram-negative microorganisms including carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae

Pinus mugo essential oil impairs STAT3 activation through oxidative stress and induces apoptosis in prostate cancer cells

Essential oils (EOs) and their components have been reported to possess anticancer properties and to increase the sensitivity of cancer cells to chemotherapy. The aim of this work was to select EOs able to downregulate STAT3 signaling using Western blot and RT-PCR analyses. The molecular mechanism of anti-STAT3 activity was evaluated through spectrophotometric and fluorometric analyses, and the biological effect of STAT3 inhibition was analyzed by flow cytometry and wound healing assay. Herein, Pinus mugo EO (PMEO) is identified as an inhibitor of constitutive STAT3 phosphorylation in human prostate cancer cells, DU145. The down-modulation of the STAT3 signaling cascade decreased the expression of anti-proliferative as well as anti-apoptotic genes and proteins, leading to the inhibition of cell migration and apoptotic cell death. PMEO treatment induced a rapid drop in glutathione (GSH) levels and an increase in reactive oxygen species (ROS) concentration, resulting in mild oxidative stress. Pretreatment of cells with N-acetyl-cysteine (NAC), a cell-permeable ROS scavenger, reverted the inhibitory action of PMEO on STAT3 phosphorylation. Moreover, combination therapy revealed that PMEO treatment displayed synergism with cisplatin in inducing the cytotoxic effect. Overall, our data highlight the importance of STAT3 signaling in PMEO cytotoxic activity, as well as the possibility of developing adjuvant therapy or sensitizing cancer cells to conventional chemotherapy