999 resultados para preliminary discovery
Resumo:
The enforcement of Intellectual Property rights poses one of the greatest current threats to the privacy of individuals online. Recent trends have shown that the balance between privacy and intellectual property enforcement has been shifted in favour of intellectual property owners. This article discusses the ways in which the scope of preliminary discovery and Anton Piller orders have been overly expanded in actions where large amounts of electronic information is available, especially against online intermediaries (service providers and content hosts). The victim in these cases is usually the end user whose privacy has been infringed without a right of reply and sometimes without notice. This article proposes some ways in which the delicate balance can be restored, and considers some safeguards for user privacy. These safeguards include restructuring the threshold tests for discovery, limiting the scope of information disclosed, distinguishing identity discovery from information discovery, and distinguishing information preservation from preliminary discovery.
Resumo:
This chapter provides an overview of a recent shift in regulatory strategies to address copyright infringement toward enlisting the assistance of general purpose Internet Service Providers. In Australia, the High Court held in 2012 that iiNet, a general purpose ISP, had no legal duty to police what its subscribers did with their internet connections. We provide an overview of three recent developments in Australian copyright law since that decision that demonstrate an emerging shift in the way that obligations are imposed on ISPs to govern the actions of their users without relying on secondary liability. The first is a new privately negotiated industry code that introduces a 'graduated response' system that requires ISPs to pass on warnings to subscribers who receive allegations of infringement. The second involves a recent series of Federal Court cases where rightsholders made a partially successful application to require ISPs to hand over the identifying details of subscribers whose households are alleged to have infringed copyright. The third is a new legislative scheme that will require ISPs to block access to foreign websites that 'facilitate' infringement. We argue that these shifts represent a greater sophistication in approaches to enrolling general purpose intermediaries in the regulatory project. We also suggest that these shifts represent a potentially disturbing trend towards enforcement of copyright law in a way that does not provide strong safeguards for the legitimate constitutional due process interests of users. We conclude with a call for greater attention and research to better understand how intermediaries make decisions when governing the conduct of users, how those decisions may be influenced by both state and non-state actors, and how the rights of individuals to due process can be adequately protected.
Resumo:
In this paper, the isolation of dillapiole (1) from Piper aduncum was reported as well as the semi-synthesis of two phenylpropanoid derivatives [di-hydrodillapiole (2), isodillapiole (3)], via reduction and isomerization reactions. Also, the compounds' molecular properties (structural, electronic, hydrophobic, and steric) were calculated and investigated to establish some preliminary structureactivity relationships (SAR). Compounds were evaluated for in vitro antileishmanial activity and cytotoxic effects on fibroblast cells. Compound 1 presented inhibitory activity against Leishmania amazonensis (IC50?=?69.3 mu M) and Leishmania brasiliensis (IC50?=?59.4 mu M) and induced cytotoxic effects on fibroblast cells mainly in high concentrations. Compounds 2 (IC50?=?99.9 mu M for L. amazonensis and IC50?=?90.5 mu M for L. braziliensis) and 3 (IC50?=?122.9 mu M for L. amazonensis and IC50?=?109.8 mu M for L. brasiliensis) were less active than dillapiole (1). Regarding the molecular properties, the conformational arrangement of the side chain, electronic features, and the hydrophilic/hydrophobic balance seem to be relevant for explaining the antileishmanial activity of dillapiole and its analogues.
Resumo:
Intelligent software agents are promising in improving the effectiveness of e-marketplaces for e-commerce. Although a large amount of research has been conducted to develop negotiation protocols and mechanisms for e-marketplaces, existing negotiation mechanisms are weak in dealing with complex and dynamic negotiation spaces often found in e-commerce. This paper illustrates a novel knowledge discovery method and a probabilistic negotiation decision making mechanism to improve the performance of negotiation agents. Our preliminary experiments show that the probabilistic negotiation agents empowered by knowledge discovery mechanisms are more effective and efficient than the Pareto optimal negotiation agents in simulated e-marketplaces.
Resumo:
The caudate is a subcortical brain structure implicated in many common neurological and psychiatric disorders. To identify specific genes associated with variations in caudate volume, structural magnetic resonance imaging and genome-wide genotypes were acquired from two large cohorts, the Alzheimer's Disease NeuroImaging Initiative (ADNI; N=734) and the Brisbane Adolescent/Young Adult Longitudinal Twin Study (BLTS; N=464). In a preliminary analysis of heritability, around 90% of the variation in caudate volume was due to genetic factors. We then conducted genome-wide association to find common variants that contribute to this relatively high heritability. Replicated genetic association was found for the right caudate volume at single-nucleotide polymorphism rs163030 in the ADNI discovery sample (P=2.36 × 10 -6) and in the BLTS replication sample (P=0.012). This genetic variation accounted for 2.79 and 1.61% of the trait variance, respectively. The peak of association was found in and around two genes, WDR41 and PDE8B, involved in dopamine signaling and development. In addition, a previously identified mutation in PDE8B causes a rare autosomal-dominant type of striatal degeneration. Searching across both samples offers a rigorous way to screen for genes consistently influencing brain structure at different stages of life. Variants identified here may be relevant to common disorders affecting the caudate.
Resumo:
An understanding of application I/O access patterns is useful in several situations. First, gaining insight into what applications are doing with their data at a semantic level helps in designing efficient storage systems. Second, it helps create benchmarks that mimic realistic application behavior closely. Third, it enables autonomic systems as the information obtained can be used to adapt the system in a closed loop.All these use cases require the ability to extract the application-level semantics of I/O operations. Methods such as modifying application code to associate I/O operations with semantic tags are intrusive. It is well known that network file system traces are an important source of information that can be obtained non-intrusively and analyzed either online or offline. These traces are a sequence of primitive file system operations and their parameters. Simple counting, statistical analysis or deterministic search techniques are inadequate for discovering application-level semantics in the general case, because of the inherent variation and noise in realistic traces.In this paper, we describe a trace analysis methodology based on Profile Hidden Markov Models. We show that the methodology has powerful discriminatory capabilities that enable it to recognize applications based on the patterns in the traces, and to mark out regions in a long trace that encapsulate sets of primitive operations that represent higher-level application actions. It is robust enough that it can work around discrepancies between training and target traces such as in length and interleaving with other operations. We demonstrate the feasibility of recognizing patterns based on a small sampling of the trace, enabling faster trace analysis. Preliminary experiments show that the method is capable of learning accurate profile models on live traces in an online setting. We present a detailed evaluation of this methodology in a UNIX environment using NFS traces of selected commonly used applications such as compilations as well as on industrial strength benchmarks such as TPC-C and Postmark, and discuss its capabilities and limitations in the context of the use cases mentioned above.
Resumo:
The tachykinins hylambatin and (Thr)11-hylambatin have been isolated from the defensive skin secretion of the African hyperoliid frog, Kassina maculata,. Hylambatin (DPPDPNRFYGMMamide) is revised in structure from the original sequence by a single site substitution (Asn/Asp at position 6), and (Thr)11-hylambatin, a novel tachykinin, differs in structure from hylambatin by a single Thr/Met substitution. (Thr)11-hylambatin is five- to ten-fold more abundant than hylambatin in secretions. Synthetic replicates of both peptides were active in smooth muscle preparations including the rat tail artery, rat ileum and bovine trachea. While hylambatin displayed activity consistent with an NK1-receptor ligand, (Thr)11-hylambatin was more active than either substance P or neurokinin A in both NK1- and NK-2 receptor rich preparations. Incorporation of a threoninyl residue rather than the canonical leucyl residue at the penultimate position in both substance P and neurokinin A, generated active ligands in both arterial and intestinal smooth muscle preparations. Hylambatin precursor cDNAs, designated HYBN-1 and HYBN-2, respectively, were cloned from a skin library by 3'- and 5'-RACE reactions. Both were highly-homologous containing open-reading frames of 66 amino acids encoding single copies of either hylambatin or (Thr)11-hylambatin. These data reveal a hitherto unrecognized structure/activity attribute of mammalian tachykinin receptors revealed though discovery of a novel amphibian skin-derived, site-substituted peptide ligand.
Resumo:
In this study, the physicochemical properties and preliminary in vivo clinical performance of formulations containing hydroxyethylcellulose (HEC; 3, 5, 10% w/w, poly(vinylpyrrolidone) (PVP; 3, 5% w/w), polycarbophil (PC; 1, 3, 5% w/w), and flurbiprofen (5% w/w) were examined. Flurbiprofen release into PBS pH 7.4 was performed at 37 degrees C. The mechanical properties (hardness, compressibility, adhesiveness, initial stress) and syringeability of formulations were determined using a texture analyzer in texture profile analysis (TPA) and compression modes, respectively. In general, the time required for release of 10 and 30% of the original mass of flurbiprofen (t(10%), t(30%)) increased as the concentration of each polymeric component increased. However, in the presence of either 5 or 10% HEC and 5% PC, increased PVP concentration decreased both t(10%), t(30%) due to excessive swelling land disintegration) of these formulations. Increased concentrations of HEC, PVP, and PC significantly increased formulation hardness, compressibility, work of syringe expression, and initial stress due to the effects of these polymers on formulation viscoelasticity. Similarly, increased concentrations of PC (primarily), HEC, and PVP increased formulation adhesiveness-due to the known bioadhesive properties of these polymers. Clinical efficacies of formulations containing 3% HEC, 3% PVP, 3% PC, and either 0% (control) of 5% (test) flurbiprofen, selected to offer optimal drug release and mechanical properties, were evaluated and clinically compared in an experimental gingivitis model. The test (flurbiprofen-containing) formulation significantly reduced gingival inflammation, as evaluated using the gingival index, and the gingival crevicular fluid volume, whereas, these clinical parameters were generally increased in volunteers who had received the control formulation. There were no observed differences in the plaque indices of the two subject groups, confirming that the observed differences in gingival inflammation could not be accredited to differences in plaque accummulation. This study has shown both the applicability of the in vitro methods used, particularly TPA, for the rational selection of formulations for clinical evaluation and, additionally, the clinical benefits of the topical application of a bioadhesive semisolid flurbiprofen-containing formulation for the treatment of experimental gingivitis.
Resumo:
The various steps of monoterpene indole alkaloid (MIA) biosynthesis are known to occur in specialized cell types and subcellular compartments. Numerous MIAs display powerful biological activities that have led to their use as pharmaceutical treatments for cancer, hypertension and malaria. Many of these compounds accumulate on the leaf surface of medicinally important Apocynaceae plants, which led to the recent discovery and characterization of an ABC transporter (CrTPT2) that was shown to mobilize catharanthine from its site of biosynthesis in epidermal cells to the leaf surface of Catharanthus roseus. Bioinformatic analysis of transcriptomes from several geographically distant MIA-producing species led to the identification of proteins with high amino acid sequence identity to CrTPT2. Molecular cloning of a similar transporter (VmTPT2) from Vinca minor was carried out and expressed in a yeast heterologous system for transport experiments and functional characterization. In planta studies involved transcript expression analysis of the early MIA biosynthetic gene VmTDC and putative transporter VmTPT2, and alkaloid profile analyses. RT-qPCR results showed that VmTPT2 expression increased 15-fold between the first two leaf pairs, and high levels were maintained across older leaves. The alkaloid accumulation profile on leaf surfaces matched that of VmTPT2 expression, especially for the MIAs vincadifformine and vincamine. Gene expression and alkaloid profile analyses suggest that the functional protein may act as a similar transporter to CrTPT2. However, although VmTPT2 had 88.4% identity at the amino acid level to CrTPT2, it displayed an altered expression pattern in planta across developing leaves, and functional characterization using a previously developed yeast heterologous system was unsuccessful due to difficulties with reproducibility of transport assays.
Resumo:
Land snail middens occur widely throughout the circum-Mediterranean, particularly in the Maghreb and Libya, but are relatively understudied when compared with the better known coastal marine middens. The site of Taforalt (Grotte des Pigeons) in north east Morocco contains thick ashy deposits with considerable numbers of land snails, dating between 13,000 and 11,000 BP. The site has been excavated periodically since its discovery in 1908, but little attention has been paid to the land snail component. Recent excavations at the site as part of the Cemeteries and Sedentism Project has facilitated reinvestigation of the Iberomaurusian layers, including the upper ashy midden unit. This investigation addresses questions surrounding chronological variation in the lithic assemblage, subsistence strategies, population health and mortuary practices. Preliminary work on the land snails has identified a low species diversity in the grey series midden layers, characterised by the large edible species Alabastrina alabastrites, Helix cf aspersa, Dupotetia dupotetiana, Otala punctata and Cernuella sp, which appear to represent an abrupt intensification in the use of land snails as a food source. Significant quantities of associated plant material and animal bone suggest that land snails are part of a broader based diet which is adopted from around 13,000 BP.