Superprocesses as models for information dissemination in the Future Internet

Future Internet will be composed by a tremendous number of potentially interconnected people and devices, offering a variety of services, applications and communication opportunities. In particular, short-range wireless communications, which are available on almost all portable devices, will enable the formation of the largest cloud of interconnected, smart computing devices mankind has ever dreamed about: the Proximate Internet. In this paper, we consider superprocesses, more specifically super Brownian motion, as a suitable mathematical model to analyse a basic problem of information dissemination arising in the context of Proximate Internet. The proposed model provides a promising analytical framework to both study theoretical properties related to the information dissemination process and to devise efficient and reliable simulation schemes for very large systems

The Science of Sungrazers, Sunskirters, and Other Near-Sun Comets

This review addresses our current understanding of comets that venture close to the Sun, and are hence exposed to much more extreme conditions than comets that are typically studied from Earth. The extreme solar heating and plasma environments that these objects encounter change many aspects of their behaviour, thus yielding valuable information on both the comets themselves that complements other data we have on primitive solar system bodies, as well as on the near-solar environment which they traverse. We propose clear definitions for these comets: We use the term near-Sun comets to encompass all objects that pass sunward of the perihelion distance of planet Mercury (0.307 AU). Sunskirters are defined as objects that pass within 33 solar radii of the Sun’s centre, equal to half of Mercury’s perihelion distance, and the commonly-used phrase sungrazers to be objects that reach perihelion within 3.45 solar radii, i.e. the fluid Roche limit. Finally, comets with orbits that intersect the solar photosphere are termed sundivers. We summarize past studies of these objects, as well as the instruments and facilities used to study them, including space-based platforms that have led to a recent revolution in the quantity and quality of relevant observations. Relevant comet populations are described, including the Kreutz, Marsden, Kracht, and Meyer groups, near-Sun asteroids, and a brief discussion of their origins. The importance of light curves and the clues they provide on cometary composition are emphasized, together with what information has been gleaned about nucleus parameters, including the sizes and masses of objects and their families, and their tensile strengths. The physical processes occurring at these objects are considered in some detail, including the disruption of nuclei, sublimation, and ionisation, and we consider the mass, momentum, and energy loss of comets in the corona and those that venture to lower altitudes. The different components of comae and tails are described, including dust, neutral and ionised gases, their chemical reactions, and their contributions to the near-Sun environment. Comet-solar wind interactions are discussed, including the use of comets as probes of solar wind and coronal conditions in their vicinities. We address the relevance of work on comets near the Sun to similar objects orbiting other stars, and conclude with a discussion of future directions for the field and the planned ground- and space-based facilities that will allow us to address those science topics

Twenty-six years of HIV science: an overview of anti-HIV drugs metabolism

From the identification of HIV as the agent causing AIDS, to the development of effective antiretroviral drugs, the scientific achievements in HIV research over the past twenty-six years have been formidable. Currently, there are twenty-five anti-HIV compounds which have been formally approved for clinical use in the treatment of AIDS. These compounds fall into six categories: nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), cell entry inhibitors or fusion inhibitors (FIs), co-receptor inhibitors (CRIs), and integrase inhibitors (INIs). Metabolism by the host organism is one of the most important determinants of the pharmacokinetic profile of a drug. Formation of active or toxic metabolites will also have an impact on the pharmacological and toxicological outcomes. Therefore, it is widely recognized that metabolism studies of a new chemical entity need to be addressed early in the drug discovery process. This paper describes an overview of the metabolism of currently available anti-HIV drugs.Da identificação do HIV como o agente causador da AIDS, ao desenvolvimento de fármacos antirretrovirais eficazes, os avanços científicos na pesquisa sobre o HIV nos últimos vinte e seis anos foram marcantes. Atualmente, existem vinte e cinco fármacos anti-HIV formalmente aprovados pelo FDA para utilização clínica no tratamento da AIDS. Estes compostos são divididos em seis classes: inibidores nucleosídeos de transcriptase reversa (INTR), inibidores nucleotídeos de transcriptase reversa (INtTR), inibidores não-nucleosídeos de transcriptase reversa (INNTR), inibidores de protease (IP), inibidores da entrada celular ou inibidores de fusão (IF), inibidores de co-receptores (ICR) e inibidores de integrase (INI). O metabolismo consiste em um dos maiores determinantes do perfil farmacocinético de um fármaco. A formação de metabólitos ativos ou tóxicos terá impacto nas respostas farmacológicas ou toxicológicas do fármaco. Portanto, é amplamente reconhecido que estudos do metabolismo de uma nova entidade química devem ser realizados durante as fases iniciais do processo de desenvolvimento de fármacos. Este artigo descreve uma abordagem do metabolismo dos fármacos anti-HIV atualmente disponíveis na terapêutica

Bio-analytical Assay Methods used in Therapeutic Drug Monitoring of Antiretroviral Drugs-A Review

Background: Several clinical trials, as well as observational statistics, have exhibited that the advantages of antiretroviral [ARV] treatment for humans with Human Immunodeficiency Virus / Acquired Immune Deficiency Syndrome HIV/AIDS exceed their risks. Therapeutic drug monitoring [TDM] plays a key role in optimization of ARV therapy. Determination of ARV's in plasma, blood cells, and other biological matrices frequently requires separation techniques capable of high effectiveness, specific selectivity and high sensitivity. High-performance liquid chromatography [HPLC] coupled with ultraviolet [UV], Photodiode array detectors [PDA], Mass spectrophotometer [MS] detectors etc. are the important quantitative techniques used for the estimation of pharmaceuticals in biological samples. Objective: This review article is aimed to give an extensive outline of different bio-analytical techniques which have been reported for direct quantitation of ARV's. This article aimed to establish an efficient role played by the TDM in the optimum therapeutic outcome of the ARV treatment. It also focused on establishing the prominent role played by the separation techniques like HPLC and UPLC along with the detectors like UV and Mass in TDM. Methods: TDM is based on the principle that for certain drugs, a close relationship exists between the plasma level of the drug and its clinical effect. TDM is of no value if the relationship does not exist. The analytical methodology employed in TDM should: 1) distinguish similar compounds; 2) be sensitive and precise and 3) is easy to use Results: This review highlights the advancement of the chromatographic techniques beginning from the HPLC-UV to the more advanced technique like UPLC-MS/MS. TDM is essential to ensure adherence, observe viral resistance and to personalize ARV dose regimens. It is observed that the analytical methods like immunoassays and liquid chromatography with detectors like UV, PDA, Florescent, MS, MS/MS and Ultra performance liquid chromatography (UPLC)-MS/MS have immensely contributed to the clinical outcome of the ARV therapy. Assay methods are not only helping physicians in limiting the side effects and drug interactions but also assisting in monitoring patient's compliance. Conclusion: The present review revealed that HPLC has been the most widely used system irrespective of the availability of more sensitive chromatographic technique like UPLC.VRAID (ex DIPUC

Tissue engineering of cartilage using poly-ɛ-caprolactone nanofiber scaffolds seeded in vivo with periosteal cells

SummaryObjectiveTo determine the potential of periosteal cells to infiltrate poly-ɛ-caprolactone (PCL) nanofiber scaffolds in vivo and subsequently produce cartilage in vitro.DesignPCL nanofiber scaffolds, with or without chitosan-coating were implanted under periosteum in 6-month-old rabbits. Transforming growth factor-β1 (TGF-β1) or vehicle was injected into each implant site. After 1, 3, 5 or 7 days, scaffolds were removed, separated from the periosteum, and the scaffolds and periosteum were cultured separately for 6 weeks under chondrogenic conditions. Sulfated glycosaminoglycan (GAG), type II collagen, DNA content, cartilage yield, and calcium deposition were then analyzed.ResultsCell infiltration was observed in all scaffolds. Cartilage formation in the uncoated scaffolds increased with duration of implantation (maximum at 7 days). Cells in the uncoated scaffolds implanted for 7 days produced significantly higher levels of both GAG [560 (95% confidence interval (CI), 107–1013) vs 228 (95% CI, 177–278)μgGAG/μgDNA] and cartilage yield [9% (95% CI, 3–14%) vs 0.02% (95% CI, 0–0.22%)] compared to chitosan-coated scaffolds (P=0.006 or less). There was no significant difference in GAG content or cartilage yield between the TGF-β1-injected and vehicle-injected scaffolds. However, significantly more mineral deposition was detected in TGF-β1-injected scaffolds compared to vehicle-injected scaffolds (P<0.0001). Cartilage yield from the periosteum, moreover, was significantly increased by subperiosteal TGF-β1 injections (P<0.001). However, this response was reduced when chitosan-coated scaffolds were implanted.ConclusionsThis study demonstrates that it is possible to seed PCL nanofiber scaffolds with periosteal cells in vivo and subsequently produce engineered cartilage in vitro

Pretreatment of periosteum with TGF-β1 in situ enhances the quality of osteochondral tissue regenerated from transplanted periosteal grafts in adult rabbits

SummaryObjectiveTo compare the efficacy of in situ transforming growth factor-beta1 (TGF-β1)-pretreated periosteum to untreated periosteum for regeneration of osteochondral tissue in rabbits.MethodsIn the pretreatment group, 12 month-old New Zealand white rabbits received subperiosteal injections of 200ng of TGF-β1 percutaneously in the medial side of the proximal tibia, 7 days prior to surgery. Control rabbits received no treatment prior surgery. Osteochondral transverse defects measuring 5mm proximal to distal and spanning the entire width of the patellar groove were created and repaired with untreated or TGF-β1-pretreated periosteal grafts. Post-operatively the rabbits resumed normal cage activity for 6 weeks.ResultsComplete filling of the defects with regenerated tissue was observed in both the TGF-β1-pretreated and control groups with reformation of the original contours of the patellar groove. The total histological score (modified O’Driscoll) in the TGF-β1-pretreated group, 20 (95% Confidence Interval (CI), 19–21), was significantly higher (P=0.0001) than the control group, 18 (16–19). The most notable improvements were in structural integrity and subchondral bone regeneration. No significant differences in glycosaminoglycan or type II collagen content, or equilibrium modulus were found between the surgical groups. The cambium of the periosteum regenerated at the graft harvest site was significantly thicker (P=0.0065) in the TGF-β1-pretreated rabbits, 121μm (94–149), compared to controls, 74μm (52–96), after 6 weeks.ConclusionsThis study demonstrates that in situ pretreatment of periosteum with TGF-β1 improves osteochondral tissue regeneration at 6-weeks post-op compared to untreated periosteum in 12 month-old rabbits