On the Change in Archivability of Websites Over Time

As web technologies evolve, web archivists work to keep up so that our digital history is preserved. Recent advances in web technologies have introduced client-side executed scripts that load data without a referential identifier or that require user interaction (e.g., content loading when the page has scrolled). These advances have made automating methods for capturing web pages more difficult. Because of the evolving schemes of publishing web pages along with the progressive capability of web preservation tools, the archivability of pages on the web has varied over time. In this paper we show that the archivability of a web page can be deduced from the type of page being archived, which aligns with that page's accessibility in respect to dynamic content. We show concrete examples of when these technologies were introduced by referencing mementos of pages that have persisted through a long evolution of available technologies. Identifying these reasons for the inability of these web pages to be archived in the past in respect to accessibility serves as a guide for ensuring that content that has longevity is published using good practice methods that make it available for preservation.Comment: 12 pages, 8 figures, Theory and Practice of Digital Libraries (TPDL) 2013, Valletta, Malt

Delivering multiple gene products in the brain from a single adeno-associated virus vector

For certain gene therapy applications, the simultaneous delivery of multiple genes would allow for novel therapies. In the case of adeno-associated virus (AAV) vectors, the limited packaging capacity greatly restricts current methods of carrying multiple transgene cassettes. To address this issue, a recombinant AAV (rAAV) vector was designed such that a furin proteolytic cleavage site (RKRRKR) was placed between the coding sequences of two genes (green fluorescent protein (GFP) and galanin), to allow cleavage of the chimeric protein into two fragments. In addition, these constructs contained the fibronectin secretory signal sequence that causes the gene products to be constitutively secreted from transduced cells. In vitro studies show that after transfection of HEK293 cells, the appropriate cleavage and constitutive secretion occurred regardless of the order of the genes in the transgene cassette. In vivo, infusion of rAAV vectors into the piriform cortex resulted in both GFP expression and significant galanin attenuation of kainic acid-induced seizure activity. Thus, the present results establish the utility of a proteolytic approach for the expression and secretion of multiple gene products from a single AAV vector transgene cassette

Human annexin A6 interacts with influenza a virus protein M2 and negatively modulates infection

Copyright © 2012, American Society for Microbiology. All Rights ReservedThe influenza A virus M2 ion channel protein has the longest cytoplasmic tail (CT) among the three viral envelope proteins and is well conserved between different viral strains. It is accessible to the host cellular machinery after fusion with the endosomal membrane and during the trafficking, assembly, and budding processes. We hypothesized that identification of host cellular interactants of M2 CT could help us to better understand the molecular mechanisms regulating the M2-dependent stages of the virus life cycle. Using yeast two-hybrid screening with M2 CT as bait, a novel interaction with the human annexin A6 (AnxA6) protein was identified, and their physical interaction was confirmed by coimmunoprecipitation assay and a colocalization study of virus-infected human cells. We found that small interfering RNA (siRNA)-mediated knockdown of AnxA6 expression significantly increased virus production, while its overexpression could reduce the titer of virus progeny, suggesting a negative regulatory role for AnxA6 during influenza A virus infection. Further characterization revealed that AnxA6 depletion or overexpression had no effect on the early stages of the virus life cycle or on viral RNA replication but impaired the release of progeny virus, as suggested by delayed or defective budding events observed at the plasma membrane of virus-infected cells by transmission electron microscopy. Collectively, this work identifies AnxA6 as a novel cellular regulator that targets and impairs the virus budding and release stages of the influenza A virus life cycle.This work was supported by the Research Fund for the Control of Infectious Disease (project 09080892) of the Hong Kong Government, the Area of Excellence Scheme of the University Grants Committee (grant AoE/M-12/-06 of the Hong Kong Special Administrative Region, China), the French Ministry of Health, the RESPARI Pasteur Network

The influence of epileptic neuropathology and prior peripheral immunity on CNS transduction by rAAV2 and rAAV5

Adeno-associated virus (AAV) provides a promising platform for clinical treatment of neurological disorders owing to its established efficacy and lack of apparent pathogenicity. To use viral vectors in treating neurological disease, however, transduction must occur under neuropathological conditions. Previous studies in rodents have shown that AAV5 more efficiently transduces cells in the hippocampus and piriform cortex than AAV2. Using the kainic acid (KA) model of temporal lobe epilepsy and AAV2 and 5 carrying a hybrid chicken β-actin promoter driving green fluorescent protein (GFP), we found that limbic seizure activity caused substantial neuropathology and resulted in a significant reduction in subsequent AAV5 transduction. Nonetheless, this reduced transduction still was greater than AAV2 transduction in control rats. Although KA seizures compromise blood–brain barrier function, potentially increasing exposure of target tissue to circulating neutralizing antibodies, we observed no interaction between KA seizure-induced damage and immunization status on AAV transduction. Finally, while we confirmed the near total neuronal-specific transgene expression for both serotypes in control rats, AAV5–GFP expression was increasingly localized to astrocytes in seizure-damaged areas. Thus, the pathological milieu of the injured brain can reduce transduction efficacy and alter viral tropism- both relevant concerns when considering viral vector gene therapy for neurological disorders

Role of modelling in improving nutrient efficiency in cropping systems

The applicability of models in addressing resource management issues in agriculture has been widely promoted by the research community, yet examples of real impacts of such modelling efforts on current farming practices are rare. Nevertheless, simulation models can compliment traditional field experimentation in researching alternative management options. The first objective of this paper is, therefore, to provide four case study examples of where models were used to help research issues relating to improved nutrient efficiency in low-input cropping systems. The first two cases addressed strategies of augmenting traditional farming practices with small applications of chemical fertilizer (N and P). The latter two cases explicitly addressed the question of what plant genetic traits can be beneficial in low-nutrient farming systems. In each of these case studies, the APSIM (Agricultural Production Systems Simulator) systems model was used to simulate the impacts of alternative crop management systems. The question of whether simulation models can assist the research community in contributing to purposeful change in farming practice is also addressed. Recent experiences in Australia are reported where simulation models have contributed to practice change by farmers. Finally, current initiatives aimed at testing whether models can also contribute to improving the nutrient efficiency of smallholder farmers in the SAT are discussed

Overexpression of the Steroidogenic Enzyme Cytochrome P450 Side Chain Cleavage in the Ventral Tegmental Area Increases 3 ,5 -THP and Reduces Long-Term Operant Ethanol Self-Administration

Neuroactive steroids are endogenous neuromodulators capable of altering neuronal activity and behavior. In rodents, systemic administration of endogenous or synthetic neuroactive steroids reduces ethanol self-administration. We hypothesized this effect arises from actions within mesolimbic brain regions that we targeted by viral gene delivery. Cytochrome P450 side chain cleavage (P450scc) converts cholesterol to pregnenolone, the rate-limiting enzymatic reaction in neurosteroidogenesis. Therefore, we constructed a recombinant adeno-associated serotype 2 viral vector (rAAV2), which drives P450scc expression and neuroactive steroid synthesis. The P450scc-expressing vector (rAAV2-P450scc) or control GFP-expressing vector (rAAV2-GFP) were injected bilaterally into the ventral tegmental area (VTA) or nucleus accumbens (NAc) of alcohol preferring (P) rats trained to self-administer ethanol. P450scc overexpression in the VTA significantly reduced ethanol self-administration by 20% over the 3 week test period. P450scc overexpression in the NAc, however, did not alter ethanol self-administration. Locomotor activity was unaltered by vector administration to either region. P450scc overexpression produced a 36% increase in (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP, allopregnanolone)-positive cells in the VTA, but did not increase 3α,5α-THP immunoreactivity in NAc. These results suggest that P450scc overexpression and the resultant increase of 3α,5α-THP-positive cells in the VTA reduces ethanol reinforcement. 3α,5α-THP is localized to neurons in the VTA, including tyrosine hydroxylase neurons, but not astrocytes. Overall, the results demonstrate that using gene delivery to modulate neuroactive steroids shows promise for examining the neuronal mechanisms of moderate ethanol drinking, which could be extended to other behavioral paradigms and neuropsychiatric patholog

A Forecasting Model to Predict the Demand of Roses in an Ecuadorian Small Business Under Uncertain Scenarios

[EN] Ecuador is worldwide considered as one of the main natural flower producers and exporters ¿being roses the most salient ones. Such a fact has naturally led the emergence of small and medium sized companies devoted to the production of quality roses in the Ecuadorian highlands, which intrinsically entails resource usage optimization. One of the first steps towards optimizing the use of resources is to forecast demand, since it enables a fair perspective of the future, in such a manner that the in-advance raw materials supply can be previewed against eventualities, resources usage can be properly planned, as well as the misuse can be avoided. Within this approach, the problem of forecasting the supply of roses was solved into two phases: the first phase consists of the macro-forecast of the total amount to be exported by the Ecuadorian flower sector by the year 2020, using multi-layer neural networks. In the second phase, the monthly demand for the main rose varieties offered by the study company was micro-forecasted by testing seven models. In addition, a Bayesian network model is designed, which takes into consideration macroeconomic aspects, the level of employability in Ecuador and weather-related aspects. This Bayesian network provided satisfactory results without the need for a large amount of historical data and at a low-computational cost.Authors of this publication acknowledge the contribution of the Project 691249, RUC-APS ¿Enhancing and implementing Knowledge based ICT solutions within high Risk and Uncertain Conditions for Agriculture Production Systems¿ (www.ruc-aps.eu), funded by the European Union under their funding scheme H2020-MSCA-RISE-2015. In addition, the authors are greatly grateful by the support given by the SDAS Research Group (www.sdas-group.com)Herrera-Granda, ID.; Lorente-Leyva, LL.; Peluffo-Ordóñez, DH.; Alemany Díaz, MDM. (2021). 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Genetic variances and relationship among traits of an early maturing maize population under drought-stress and low nitrogen environments

Article purchasedDrought and low soil nitrogen (low N) are major causes of low grain yield of maize (Zea mays L.) in sub-Saharan Africa (SSA). An early maturing maize population, TZE-Y Pop DT STR, had undergone four cycles of selection for drought tolerance, followed by four selection cycles for resistance to Striga hermonthica (Del.) Benth., which is normally conducted under low N (about 30 kg N ha-1). The objectives of this study were to estimate residual genetic variances, predict future gains from selection, and investigate inter-trait relationships in the population under drought-stress, low N and across research environments. North Carolina Design I was used to develop 250 full-sib progenies from the improved population, which were evaluated in three drought-stress and two low N environments in Nigeria, 2011 to 2013. Additive genetic variances were not significant for most traits under the research conditions. The predicted gains from selection for grain yield were 5.3, 8.5 and 7.5% cycle-1 under drought, low N, and across environments. These results suggested the absence of substantial genetic variability in the population to ensure progress from selection. Ears per plant (EPP), ear aspect (EASP), plant aspect (PASP), and stay green characteristic (STGR) were consistently identified as important secondary traits under both research conditions. We concluded that there is need to introgress new sources of favorable alleles for drought-stress and low N tolerance into the population for guaranteed progress from selection, using EPP, EASP, PASP, and STGR in combination with yield in a selection index under drought-stress and low N

Cell-wall synthesis and ribosome maturation are co-regulated by an RNA switch in Mycobacterium tuberculosis

The success of Mycobacterium tuberculosis relies on the ability to switch between active growth and non-replicating persistence, associated with latent TB infection. Resuscitation promoting factors (Rpfs) are essential for the transition between these states. Rpf expression is tightly regulated as these enzymes are able to degrade the cell wall, and hence potentially lethal to the bacterium itself. We have identified a regulatory element in the 5' untranslated region (UTR) of rpfB. We demonstrate that this element is a transcriptionally regulated RNA switch/riboswitch candidate, which appears to be restricted to pathogenic mycobacteria, suggesting a role in virulence. We have used translation start site mapping to re-annotate the RpfB start codon and identified and validated a ribosome binding site that is likely to be targeted by an rpfB antisense RNA. Finally, we show that rpfB is co-transcribed with ksgA and ispE downstream. ksgA encodes a universally conserved methyltransferase involved in ribosome maturation and ispE encodes an essential kinase involved in cell wall synthesis. This arrangement implies co-regulation of resuscitation, cell wall synthesis and ribosome maturation via the RNA switch

Free will and mental disorder: Exploring the relationship

A link between mental disorder and freedom is clearly present in the introduction of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). It mentions “an important loss of freedom” as one of the possible defining features of mental disorder. Meanwhile, it remains unclear how “an important loss of freedom” should be understood. In order to get a clearer view on the relationship between mental disorder and (a loss of) freedom, in this article, I will explore the link between mental disorder and free will. I examine two domains in which a connection between mental disorder and free will is present: the philosophy of free will and forensic psychiatry. As it turns out, philosophers of free will frequently refer to mental disorders as conditions that compromise free will and reduce moral responsibility. In addition, in forensic psychiatry, the rationale for the assessment of criminal responsibility is often explained by referring to the fact that mental disorders can compromise free will. Yet, in both domains, it remains unclear in what way free will is compromised by mental disorders. Based on the philosophical debate, I discuss three senses of free will and explore their relevance to mental disorders. I conclude that in order to further clarify the relationship between free will and mental disorder, the accounts of people who have actually experienced the impact of a mental disorder should be included in future research