Distributed PC Based Routers: Bottleneck Analysis and Architecture Proposal

Recent research in the different functional areas of modern routers have made proposals that can greatly increase the efficiency of these machines. Most of these proposals can be implemented quickly and often efficiently in software. We wish to use personal computers as forwarders in a network to utilize the advances made by researchers. We therefore examine the ability of a personal computer to act as a router. We analyze the performance of a single general purpose computer and show that I/O is the primary bottleneck. We then study the performance of distributed router composed of multiple general purpose computers. We study the performance of a star topology and through experimental results we show that although its performance is good, it lacks flexibility in its design. We compare it with a multistage architecture. We conclude with a proposal for an architecture that provides us with a forwarder that is both flexible and scalable.© IEE

Overcoming resistance to molecularly targeted anticancer therapies: rational drug combinations based on EGFR and MAPK inhibition for solid tumours and haematologic malignancies

Accumulating evidence suggests that cancer can be envisioned as a "signaling disease", in which alterations in the cellular genome affect the expression and/or function of oncogenes and tumour suppressor genes. This ultimately disrupts the physiologic transmission of biochemical signals that normally regulate cell growth, differentiation and programmed cell death (apoptosis). From a clinical standpoint, signal transduction inhibition as a therapeutic strategy for human malignancies has recently achieved remarkable success. However, as additional drugs move forward into the clinical arena, intrinsic and acquired resistance to "targeted" agents becomes an issue for their clinical utility. One way to overcome resistance to targeted agents is to identify genetic and epigenetic aberrations underlying sensitivity/resistance, thus enabling the selection of patients that will most likely benefit from a specific therapy. Since resistance often ensues as a result of the concomitant activation of multiple, often overlapping, signaling pathways, another possibility is to interfere with multiple, cross-talking pathways involved in growth and survival control in a rational, mechanism-based, fashion. These concepts may be usefully applied, among others, to agents that target two major signal transduction pathways: the one initiated by epidermal growth factor receptor (EGFR) signaling and the one converging on mitogen-activated protein kinase (MAPK) activation. Here we review the molecular mechanisms of sensitivity/resistance to EGFR inhibitors, as well as the rationale for combining them with other targeted agents, in an attempt to overcome resistance. In the second part of the paper, we review MAPK-targeted agents, focusing on their therapeutic potential in hematologic malignancies, and examine the prospects for combinations of MAPK inhibitors with cytotoxic agents or other signal transduction-targeted agents to obtain synergistic anti-tumour effects. Originally published Drug Resistance Updates, Vol. 10, No. 3, June 200

Presto-Color: A Photometric Survey Cadence for Explosive Physics and Fast Transients

We identify minimal observing cadence requirements that enable photometric astronomical surveys to detect and recognize fast and explosive transients and fast transient features. Observations in two different filters within a short time window (e.g., g-and-i, or r-and-z, within 1.5 hr) are desirable for this purpose. Such an observing strategy delivers both the color and light curve evolution of transients on the same night. This allows the identification and initial characterization of fast transient—or fast features of longer timescale transients—such as rapidly declining supernovae, kilonovae, and the signatures of SN ejecta interacting with binary companion stars or circumstellar material. Some of these extragalactic transients are intrinsically rare and generally all hard to find, thus upcoming surveys like the Large Synoptic Survey Telescope (LSST) could dramatically improve our understanding of their origin and properties. We colloquially refer to such a strategy implementation for the LSST as the Presto-Color strategy (rapid-color). This cadence's minimal requirements allow for overall optimization of a survey for other science goals

Legal Cannabis sativa L. Dried Inflorescences: Cannabinoids Content and Cytotoxic Activity against Human HepG2 Cell Line

Cannabis sativa L. has health benefits, principally due to the levels and ratios of two impor- tant cannabinoids, ∆9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC:CBD ratio affects their pharmacological interaction for the treatment of different diseases as well as its modulation allows for a custom-made product that utilizes the distinguishing effects of CBD, THC, or both, for a peculiar patient or clinical effect. This study aims to investigate the total content of THC, CBD, and their ratio in 34 dried inflorescence legally sold in physical and online stores, by using a validated liquid chromatography-ultraviolet (HPLC-UV) method, after cannabinoids identification performed through MSn studies. Cannabinol (CBN) content was also monitored to evaluate hemp age or con- servation status. CBN content always resulted lower than limit of quantification, thus confirming well-stored fresh hemp. All investigated samples showed a total THC amount below 0.59% w/w, thus responding to legal requirements.. The total CBD amount ranged from 2.62 to 20.27% w/w and it was not related to THC level. THC:CBD ranged among 1:3 and 1:26, thus ascertaining their suitability for different target pharmacological uses. In vitro studies using human hepatoblastoma cell line HepG2 suggested that hemp extracts with THC:CBD ratios of 1:9 exhibited higher toxicity than pure cannabinoids

Development of 1,2,3-Triazole-Based Sphingosine Kinase Inhibitors and Their Evaluation as Antiproliferative Agents

Two series of N-(aryl)-1-(hydroxyalkyl)pyrrolidine-2-carboxamides (2a-2g and 3a-3g) and 1,4-disubstituted 1,2,3-triazoles (5a-5h and 8a-8h) were synthesized. All the compounds, containing a lipophilic tail and a polar headgroup, were evaluated as sphingosine kinase (SphK) inhibitors by assessing their ability to interfere with the acetylcholine (Ach) induced relaxation of aortic rings pre-contracted with phenylephrine. Moreover, their antiproliferative activity was tested on several cell lines expressing both SphK1 and SphK2. Compounds 5h and 8f, identified as the most efficient antiproliferative agents, showed a different selectivity profile, with 8f being selective for SphK1