The Sub-Commission\u27s Initiative on Human Rights and Intellectual Property

In 2000 the United Nations Sub-Commission on the Promotion and Protection of Human Rights adopted a resolution raising concerns about the consistency of international intellectual property protections and human rights norms. This article summarises human rights norms relevant to intellectual property and the pertinent aspects of the Agreement on Trade-Related Aspects of Intellectual Property Rights, which overlap or potentially conflict. The article provides several examples of potential conflict and how they might be resolved. The article demonstrates that the Sub-Commission resolution helped to initiate a major international discussion and some action on the relationship between human rights and intellectual property

Insights into the behaviour of systems biology models from dynamic sensitivity and identifiability analysis: a case study of an NF-kB signaling pathway

Mathematical modelling offers a variety of useful techniques to help in understanding the intrinsic behaviour of complex signal transduction networks. From the system engineering point of view, the dynamics of metabolic and signal transduction models can always be described by nonlinear ordinary differential equations (ODEs) following mass balance principles. Based on the state-space formulation, many methods from the area of automatic control can conveniently be applied to the modelling, analysis and design of cell networks. In the present study, dynamic sensitivity analysis is performed on a model of the IB-NF-B signal pathway system. Univariate analysis of the Euclidean-form overall sensitivities shows that only 8 out of the 64 parameters in the model have major influence on the nuclear NF-B oscillations. The sensitivity matrix is then used to address correlation analysis, identifiability assessment and measurement set selection within the framework of least squares estimation and multivariate analysis. It is shown that certain pairs of parameters are exactly or highly correlated to each other in terms of their effects on the measured variables. The experimental design strategy provides guidance on which proteins should best be considered for measurement such that the unknown parameters can be estimated with the best statistical precision. The whole analysis scheme we describe provides efficient parameter estimation techniques for complex cell networks

Rapid and quantitative detection of the microbial spoilage of meat by Fourier Transform Infrared Spectroscopy and machine learning

Fourier transform infrared (FT-IR) spectroscopy is a rapid, noninvasive technique with considerable potential for application in the food and related industries. We show here that this technique can be used directly on the surface of food to produce biochemically interpretable “fingerprints.” Spoilage in meat is the result of decomposition and the formation of metabolites caused by the growth and enzymatic activity of microorganisms. FT-IR was exploited to measure biochemical changes within the meat substrate, enhancing and accelerating the detection of microbial spoilage. Chicken breasts were purchased from a national retailer, comminuted for 10 s, and left to spoil at room temperature for 24 h. Every hour, FT-IR measurements were taken directly from the meat surface using attenuated total reflectance, and the total viable counts were obtained by classical plating methods. Quantitative interpretation of FT-IR spectra was possible using partial least-squares regression and allowed accurate estimates of bacterial loads to be calculated directly from the meat surface in 60 s. Genetic programming was used to derive rules showing that at levels of 10(7) bacteria·g(−1) the main biochemical indicator of spoilage was the onset of proteolysis. Thus, using FT-IR we were able to acquire a metabolic snapshot and quantify, noninvasively, the microbial loads of food samples accurately and rapidly in 60 s, directly from the sample surface. We believe this approach will aid in the Hazard Analysis Critical Control Point process for the assessment of the microbiological safety of food at the production, processing, manufacturing, packaging, and storage levels

Functional genomics via metabolic footprinting: monitoring metabolite secretion by Escherichia coli tryptophan metabolism mutants using FT-IR and direct injection electrospray mass spectrometry

We sought to test the hypothesis that mutant bacterial strains could be discriminated from each other on the basis of the metabolites they secrete into the medium (their ‘metabolic footprint’), using two methods of ‘global’ metabolite analysis (FT–IR and direct injection electrospray mass spectrometry). The biological system used was based on a published study of Escherichia coli tryptophan mutants that had been analysed and discriminated by Yanofsky and colleagues using transcriptome analysis. Wild-type strains supplemented with tryptophan or analogues could be discriminated from controls using FT–IR of 24 h broths, as could each of the mutant strains in both minimal and supplemented media. Direct injection electrospray mass spectrometry with unit mass resolution could also be used to discriminate the strains from each other, and had the advantage that the discrimination required the use of just two or three masses in each case. These were determined via a genetic algorithm. Both methods are rapid, reagentless, reproducible and cheap, and might beneficially be extended to the analysis of gene knockout libraries

Reactivity of Phenylacetylene toward Unsymmetrical Disilenes: Regiodivergent [2+2] Cycloaddition vs. CH Addition

We report the regiodivergent reaction of phenylacetylene with a selection of disilenes Tip2Si=SiTipR as well as bridged tetrasiladienes Tip2Si=SiTip−LU−SiTip=SiTip2 (Tip=2,4,6-iPr3C6H2, R=aryl groups; LU=arylene linkers). The regioselectivity of the [2+2] cycloaddition as determined by NMR spectroscopy and X-ray crystallography is shown to strongly depend on the nature of the substituent R. The small size of the substituents compared to the Tip groups in both cases suggests a change in mechanism between the substrates with only hydrogen in the ortho-positions of R and LU and those with either ortho-methyl groups or condensed aromatic rings. In contrast, the presence of catalytic quantities of base completely suppresses cycloaddtion in favor of the formal CH addition of phenylacetylene. Quenching reactions with either MeI or MeOH after the stoichiometric application of deprotonated phenylacetylene as well as NMR studies at low temperature prove the intermediacy of an alkynyl-substituted disilanyl lithium and thus suggest a carbolithiation pathway for the net CH addition

Preparation, characterization, and safety evaluation of poly(lactide-co-glycolide) nanoparticles for protein delivery into macrophages.

International audienceFollowing infection, HIV establishes reservoirs within tissues that are inaccessible to optimal levels of antiviral drugs or within cells where HIV lies latent, thus escaping the action of anti-HIV drugs. Macrophages are a persistent reservoir for HIV and may contribute to the rebound viremia observed after antiretroviral treatment is stopped. In this study, we further investigate the potential of poly(lactic-co-glycolic) acid (PLGA)-based nanocarriers as a new strategy to enhance penetration of therapeutic molecules into macrophages. We have prepared stable PLGA nanoparticles (NPs) and evaluated their capacity to transport an active molecule into the human monocyte/macrophage cell line THP-1 using bovine serum albumin (BSA) as a proof-of-concept compound. Intracellular localization of fluorescent BSA molecules encapsulated into PLGA NPs was monitored in live cells using confocal microscopy, and cellular uptake was quantified by flow cytometry. In vitro and in vivo toxicological studies were performed to further determine the safety profile of PLGA NPs including inflammatory effects. The size of the PLGA NPs carrying BSA (PLGA-BSA) in culture medium containing 10% serum was ~126 nm in diameter, and they were negatively charged at their surface (zeta potential =-5.6 mV). Our confocal microscopy studies and flow cytometry data showed that these PLGA-BSA NPs are rapidly and efficiently taken up by THP-1 monocyte-derived macrophages (MDMs) at low doses. We found that PLGA-BSA NPs increased cellular uptake and internalization of the protein in vitro. PLGA NPs were not cytotoxic for THP-1 MDM cells, did not modulate neutrophil apoptosis in vitro, and did not show inflammatory effect in vivo in the murine air pouch model of acute inflammation. In contrast to BSA alone, BSA encapsulated into PLGA NPs increased leukocyte infiltration in vivo, suggesting the in vivo enhanced delivery and protection of the protein by the polymer nanocarrier. We demonstrated that PLGA-based nanopolymer carriers are good candidates to efficiently and safely enhance the transport of active molecules into human MDMs. In addition, we further investigated their inflammatory profile and showed that PLGA NPs have low inflammatory effects in vitro and in vivo. Thus, PLGA nanocarriers are promising as a drug delivery strategy in macrophages for prevention and eradication of intracellular pathogens such as HIV and Mycobacterium tuberculosis

Ultrasonic study of the gelation of gelatin: phase diagram, hysteresis and kinetics

We map the ultrasonic (8 MHz) speed and attenuation of edible-grade gelatin in water, exploring the key dependencies on temperature, concentration and time. The ultrasonic signatures of the sol-gel transition, confirmed by rheological measurements, and incomplete gel formation at low concentrations, enable a phase diagram of the system to be constructed. Sensitivity is also demonstrated to the kinetics of gel formation and melting, and associated hysteresis effects upon cyclic temperature sweeps. Furthermore, simple acoustic models of the sol and gel state enable estimation of the speed of sound and compressibility of gelatin. Our results demonstrate the potential of ultrasonic measurements to characterise the structure and visco-elasticity of gelatin hydrogels.Comment: 15 pages, 8 figure

An Analysis of x86-64 Inline Assembly in C Programs

C codebases frequently embed nonportable and unstandardized elements such as inline assembly code. Such elements are not well understood, which poses a problem to tool developers who aspire to support C code. This paper investigates the use of x86-64 inline assembly in 1264 C projects from GitHub and combines qualitative and quantitative analyses to answer questions that tool authors may have. We found that 28.1% of the most popular projects contain inline assembly code, although the majority contain only a few fragments with just one or two instructions. The most popular instructions constitute a small subset concerned largely with multicore semantics, performance optimization, and hardware control. Our findings are intended to help developers of C-focused tools, those testing compilers, and language designers seeking to reduce the reliance on inline assembly. They may also aid the design of tools focused on inline assembly itself

Information-theoretic sensitivity analysis: a general method for credit assignment in complex networks

Most systems can be represented as networks that couple a series of nodes to each other via one or more edges, with typically unknown equations governing their quantitative behaviour. A major question then pertains to the importance of each of the elements that act as system inputs in determining the output(s). We show that any such system can be treated as a ‘communication channel’ for which the associations between inputs and outputs can be quantified via a decomposition of their mutual information into different components characterizing the main effect of individual inputs and their interactions. Unlike variance-based approaches, our novel methodology can easily accommodate correlated inputs