Low Velocity Granular Drag in Reduced Gravity

We probe the dependence of the low velocity drag force in granular materials on the effective gravitational acceleration (geff) through studies of spherical granular materials saturated within fluids of varying density. We vary geff by a factor of 20, and we find that the granular drag is proportional to geff, i.e., that the granular drag follows the expected relation Fprobe = {\eta} {\rho}grain geff dprobe hprobe^2 for the drag force, Fprobe on a vertical cylinder with depth of insertion, hprobe, diameter dprobe, moving through grains of density {\rho}grain, and where {\eta} is a dimensionless constant. This dimensionless constant shows no systematic variation over four orders of magnitude in effective grain weight, demonstrating that the relation holds over that entire range to within the precision of our data

The extension problem for partial Boolean structures in Quantum Mechanics

Alternative partial Boolean structures, implicit in the discussion of classical representability of sets of quantum mechanical predictions, are characterized, with definite general conclusions on the equivalence of the approaches going back to Bell and Kochen-Specker. An algebraic approach is presented, allowing for a discussion of partial classical extension, amounting to reduction of the number of contexts, classical representability arising as a special case. As a result, known techniques are generalized and some of the associated computational difficulties overcome. The implications on the discussion of Boole-Bell inequalities are indicated.Comment: A number of misprints have been corrected and some terminology changed in order to avoid possible ambiguitie

Bed-load effects on hydrodynamics of rough-bed open-channel flows

Peer reviewedPublisher PD

Bell inequalities from variable elimination methods

Tight Bell inequalities are facets of Pitowsky's correlation polytope and are usually obtained from its extreme points by solving the hull problem. Here we present an alternative method based on a combination of algebraic results on extensions of measures and variable elimination methods, e.g., the Fourier-Motzkin method. Our method is shown to overcome some of the computational difficulties associated with the hull problem in some non-trivial cases. Moreover, it provides an explanation for the arising of only a finite number of families of Bell inequalities in measurement scenarios where one experimenter can choose between an arbitrary number of different measurements

A system-approach for recoverable spare parts management using the discreteweibull distribution

Optimal spare parts management strategies allow sustaining a system's availability, while ensuring timely and effective maintenance. Following a systemic perspective, this paper starts from the Multi-Echelon Technique for Recoverable Item Control (METRIC) to investigate the potential use of a Weibull distribution for modelling items' demand in case of failure. Adapting the analytic formulation of METRIC through a Discrete Weibull distribution, this study originally proposes a METRIC-based model (DW-METRIC) to be used for modelling the stochastic demand in multi-item systems, in order to ensure process sustainability. The DW-METRIC has been tested in a case study related to an industrial plant constituted by 98 items in a passive redundancy configuration. Comparing the results via a simulation model, the outcomes of the study allow defining applicability criteria for the DW-METRIC, in those settings where the DW-METRIC offers more accurate estimations than the traditional METRIC

Clogging the Ubiquitin-Proteasome Machinery with Marine Natural Products: Last Decade Update.

The ubiquitin-proteasome pathway (UPP) is the central protein degradation system in eukaryotic cells, playing a key role in homeostasis maintenance, through proteolysis of regulatory and misfolded (potentially harmful) proteins. As cancer cells produce proteins inducing cell proliferation and inhibiting cell death pathways, UPP inhibition has been exploited as an anticancer strategy to shift the balance between protein synthesis and degradation towards cell death. Over the last few years, marine invertebrates and microorganisms have shown to be an unexhaustive factory of secondary metabolites targeting the UPP. These chemically intriguing compounds can inspire clinical development of novel antitumor drugs to cope with the incessant outbreak of side effects and resistance mechanisms induced by currently approved proteasome inhibitors (e.g., bortezomib). In this review, we report about (a) the role of the UPP in anticancer therapy, (b) chemical and biological properties of UPP inhibitors from marine sources discovered in the last decade, (c) high-throughput screening techniques for mining natural UPP inhibitors in organic extracts. Moreover, we will tell about the fascinating story of salinosporamide A, the first marine natural product to access clinical trials as a proteasome inhibitor for cancer treatment

Multiportal Combined Transorbital and Transnasal Endoscopic Resection of Fibrous Dysplasia

Introduction Historically, access to the anterior skull base was achieved with open procedures. The paradigms to this approach were challenged with the advent of minimally disruptive endoscopic surgical techniques and supporting technology. The next step in the evolution of minimally disruptive surgery was the combination of multiportal endoscopic surgery. Results The patient was an 18-year-old man who presented with right-sided proptosis. Further diagnostic tests revealed a fibrous dysplasia (FD) occupying the skull base and orbit. The lesion was successfully resected. Conclusions The location of the tumor in this case was challenging, in which surgeons at some centers would have opted to have performed as an open procedure instead of endoscopically. The combined transnasal/transorbital approach is an uncommonly used technique that we have used to remove this tumor successfully. The patient also had a unique disease (FD) in a unique location that was treated without complications. This case report highlights how surgeons may use an expanded armamentarium in dealing with complex pathologies

Direct Expression of Fluorinated Proteins in Human Cells for 19F In-Cell NMR Spectroscopy

: In-cell NMR spectroscopy is a powerful approach to study protein structure and function in the native cellular environment. It provides precious insights into the folding, maturation, interactions, and ligand binding of important pharmacological targets directly in human cells. However, its widespread application is hampered by the fact that soluble globular proteins often interact with large cellular components, causing severe line broadening in conventional heteronuclear NMR experiments. 19F NMR can overcome this issue, as fluorine atoms incorporated in proteins can be detected by simple background-free 1D NMR spectra. Here, we show that fluorinated amino acids can be easily incorporated in proteins expressed in human cells by employing a medium switch strategy. This straightforward approach allows the incorporation of different fluorinated amino acids in the protein of interest, reaching fluorination efficiencies up to 60%, as confirmed by mass spectrometry and X-ray crystallography. The versatility of the approach is shown by performing 19F in-cell NMR on several proteins, including those that would otherwise be invisible by 1H-15N in-cell NMR. We apply the approach to observe the interaction between an intracellular target, carbonic anhydrase 2, and its inhibitors, and to investigate how the formation of a complex between superoxide dismutase 1 and its chaperone CCS modulates the interaction of the chaperone subunit with the cellular environment

Intramammary immunization of pregnant mice with staphylococcal protein a reduces the post-challenge mammary gland bacterial load but not pathology

Protein A, encoded by the spa gene, is one of the major immune evading MSCRAMM of S. aureus, demonstrated to be prevalent in a significant percentage of clinical bovine mastitis isolates in Australia. Given its' reported significance in biofilm formation and the superior performance of S. aureus biofilm versus planktonic vaccine in the mouse mastitis model, it was of interest to determine the immunogenicity and protective potential of Protein A as a potential vaccine candidate against bovine mastitis using the mouse mastitis model. Pregnant Balb/c mice were immunised with Protein A emulsified in an alum-based adjuvant by subcutaneous (s/c) or intramammary (i/mam) routes. While humoral immune response of mice post-immunization were determined using indirect ELISA, cell-mediated immune response was assessed by estimation of interferon-gamma (IFN-γ) produced by protein A-stimulated splenocyte supernatants. Protective potential of Protein A against experimental mastitis was determined by challenge of immunized versus sham-vaccinated mice by i/mam route, based upon manifestation of clinical symptoms, total bacterial load and histopathological damage to mammary glands. Significantly (p<0.05) higher levels of IgG1 isotype were produced in mice immunized by the s/c route. In contrast, significantly higher levels of the antibody isotype IgG2a were produced in mice immunized by the i/mam route (p<0.05). There was significant reduction (p<0.05) in bacterial loads of the mammary glands of mice immunized by Protein A regardless of the route of immunization, with medium level of clinical symptoms observed up to day 3 post-challenge. However, Protein A vaccine failed to protect immunized mice post-challenge with biofilm producing encapsulated S. aureus via i/mam route, regardless of the route of immunization, as measured by the level of mammary tissue damage. It was concluded that, Protein A in its' native state was apparently not a suitable candidate for inclusion in a cell-free vaccine formulation against mastitis

Development of Praziquantel sulphonamide derivatives as antischistosomal drugs

The almost empty armamentarium to treat schistosomiasis, a neglected parasitic disorder caused by trematode flatworms of the genus Schistosoma, except Praziquantel (PZQ), urged to find new alternatives to fight this infection. Carbonic Anhydrase from Schistosoma mansoni (SmCA) is a possible new target against this nematode. Here, we propose new PZQ derivatives bearing a primary sulphonamide group in order to obtain hybrid drugs. All compounds were evaluated for their inhibition profiles on both humans and Schistosoma CAs, X-ray crystal data of SmCA and hCA II in adduct with some inhibitors were obtained allowing the understanding of the main structural factors responsible of activity. The compounds showed in vitro inhibition of immature and adult S. mansoni, but further optimisation is required for improved activity