A system model for water management

Although generally accepted as a necessary step to improve water management and planning, integrated water resources management (IWRM) methodology does not provide a clear definition of what should be integrated. The various water-related issues that IWRM might encompass are well documented in the literature, but they are generally addressed separately. Therefore, water management lacks a holistic, systems-based description, with a special emphasis on the interrelations between issues. This article presents such a system model for water management, including a graphical representation and textual descriptions of the various water issues, their components, and their interactions. This model is seen as an aide-memoire and a generic reference, providing background knowledge helping to elicit actual system definitions, in possible combination with other participatory systems approaches. The applicability of the model is demonstrated through its application to two test case studies

Incentives for Human Agents to Share Security Information: a Model and an Empirical Test

In this paper, we investigate the role of incentives for Security Information Sharing (SIS) between human agents working in institutions. We present an incentive-based SIS system model that is empirically tested with an exclusive dataset. The data was collected with an online questionnaire addressed to all participants of a deployed Information Sharing and Analysis Center (ISAC) that operates in the context of critical infrastructure protection (N=262). SIS is measured with a multidimensional approach (intensity, frequency) and regressed on five specific predicators (reciprocity, value of information, institutional barriers, reputation, trust) that are measured with psychometric scales. We close an important research gap by providing, to the best of our knowledge, the first empirical analysis on previous theoretical work that assumes SIS to be beneficial. Our results show that institutional barriers have a strong influence on our population, i.e., SIS decision makers in Switzerland. This lends support to a better institutional design of ISACs and the formulation of incentive-based policies that can avoid non-cooperative and free-riding behaviours. Both frequency and intensity are influenced by the extent to which decision makers expect to receive valuable information in return for SIS, which supports the econometric structure of our multidimensional model. Finally, our policy recommendations support the view that the effectiveness of mandatory security-breach reporting to authorities is limited. Therefore, we suggest that a conducive and lightly regulated SIS environment – as in Switzerland – with positive reinforcement and indirect suggestions can “nudge” SIS decision makers to adopt a productive sharing behaviour

To share or not to share: A behavioral perspective on human participation in security information sharing

Security information sharing (SIS) is an activity whereby individuals exchange information that is relevant to analyze or prevent cybersecurity incidents. However, despite technological advances and increased regulatory pressure, individuals still seem reluctant to share security information. Few contributions have addressed this conundrum to date. Adopting an interdisciplinary approach, our study proposes a behavioral framework that theorizes how and why human behav- ior and SIS may be associated. We use psychometric methods to test these associations, analyzing a unique sample of human Information Sharing and Analysis Center members who share real se- curity information. We also provide a dual empirical operationalization of SIS by introducing the measures of SIS frequency and intensity. We find significant associations between human behavior and SIS. Thus, the study contributes to clarifying why SIS, while beneficial, is underutil- ized by pointing to the pivotal role of human behavior for economic outcomes. It therefore extends the growing field of the economics of information security. By the same token, it informs managers and regulators about the significance of human behavior as they propagate goal alignment and shape institutions. Finally, the study defines a broad agenda for future research on SIS

Dosage Compensation in the Mouse Balances Up-Regulation and Silencing of X-Linked Genes

Dosage compensation in mammals involves silencing of one X chromosome in XX females and requires expression, in cis, of Xist RNA. The X to be inactivated is randomly chosen in cells of the inner cell mass (ICM) at the blastocyst stage of development. Embryonic stem (ES) cells derived from the ICM of female mice have two active X chromosomes, one of which is inactivated as the cells differentiate in culture, providing a powerful model system to study the dynamics of X inactivation. Using microarrays to assay expression of X-linked genes in undifferentiated female and male mouse ES cells, we detect global up-regulation of expression (1.4- to 1.6-fold) from the active X chromosomes, relative to autosomes. We show a similar up-regulation in ICM from male blastocysts grown in culture. In male ES cells, up-regulation reaches 2-fold after 2–3 weeks of differentiation, thereby balancing expression between the single X and the diploid autosomes. We show that silencing of X-linked genes in female ES cells occurs on a gene-by-gene basis throughout differentiation, with some genes inactivating early, others late, and some escaping altogether. Surprisingly, by allele-specific analysis in hybrid ES cells, we also identified a subgroup of genes that are silenced in undifferentiated cells. We propose that X-linked genes are silenced in female ES cells by spreading of Xist RNA through the X chromosome territory as the cells differentiate, with silencing times for individual genes dependent on their proximity to the Xist locus

Tono-Pen XL tonometry during application of a suction ring in rabbits

<p>Abstract</p> <p>Background</p> <p>The purpose of this study is to evaluate the use of Tono-Pen XL in measuring IOP during the application of a suction ring in rabbit eyes with manometrically controlled IOP.</p> <p>Methods</p> <p>Tono-Pen XL was calibrated against direct manometry in 10 rabbit eyes. A suction ring was then applied in 4 rabbit eyes and the IOP was determined manometrically during suction ring application at 350 mmHg vacuum pressure. Finally, in 6 catheterized rabbit eyes the IOP was measured with Tono-Pen XL during suction ring application at suction vacuum from 350 to 650 mmHg, while keeping actual IOP stable at 30 mmHg and 60 mmHg.</p> <p>Results</p> <p>Linear regression analysis revealed that the Tono-pen XL was reliable for IOPs between 10 and 70 mmHg (R²= 0.9855). Direct manometry during suction ring application showed no statistically significant variation of Tono-Pen XL readings when the incanulation manometry intraocular pressure changed from 30 mmHg to 60 mmHg and no statistically significant correlation between suction vacuum and IOP measurements.</p> <p>Conclusion</p> <p>Tono-Pen XL measurements are unreliable during the application of a suction ring on living rabbit eyes even when the actual IOP is forced to be within the validated range of Tono-Pen XL measurements. This inaccuracy is probably related to altered corneal and scleral geometry and stress.</p

X Chromosome Inactivation and Differentiation Occur Readily in ES Cells Doubly-Deficient for MacroH2A1 and MacroH2A2

Macrohistones (mH2As) are unusual histone variants found exclusively in vertebrate chromatin. In mice, the H2afy gene encodes two splice variants, mH2A1.1 and mH2A1.2 and a second gene, H2afy2, encodes an additional mH2A2 protein. Both mH2A isoforms have been found enriched on the inactive X chromosome (Xi) in differentiated mammalian female cells, and are incorporated into the chromatin of developmentally-regulated genes. To investigate the functional significance of mH2A isoforms for X chromosome inactivation (XCI), we produced male and female embryonic stem cell (ESC) lines with stably-integrated shRNA constructs that simultaneously target both mH2A1 and mH2A2. Surprisingly, we find that female ESCs deficient for both mH2A1 and mH2A2 readily execute and maintain XCI upon differentiation. Furthermore, male and female mH2A-deficient ESCs proliferate normally under pluripotency culture conditions, and respond to several standard differentiation procedures efficiently. Our results show that XCI can readily proceed with substantially reduced total mH2A content

Early Loss of Xist RNA Expression and Inactive X Chromosome Associated Chromatin Modification in Developing Primordial Germ Cells

The inactive X chromosome characteristic of female somatic lineages is reactivated during development of the female germ cell lineage. In mouse, analysis of protein products of X-linked genes and/or transgenes located on the X chromosome has indicated that reactivation occurs after primordial germ cells reach the genital ridges.We present evidence that the epigenetic reprogramming of the inactive X-chromosome is initiated earlier than was previously thought, around the time that primordial germ cells (PGCs) migrate through the hindgut. Specifically, we find that Xist RNA expression, the primary signal for establishment of chromosome silencing, is extinguished in migrating PGCs. This is accompanied by displacement of Polycomb-group repressor proteins Eed and Suz(12), and loss of the inactive X associated histone modification, methylation of histone H3 lysine 27.We conclude that X reactivation in primordial germ cells occurs progressively, initiated by extinction of Xist RNA around the time that germ cells migrate through the hindgut to the genital ridges. The events that we observe are reminiscent of X reactivation of the paternal X chromosome in inner cell mass cells of mouse pre-implantation embryos and suggest a unified model in which execution of the pluripotency program represses Xist RNA thereby triggering progressive reversal of epigenetic silencing of the X chromosome

Gene processing control loops suggested by sequencing, splicing, and RNA folding

Abstract Background Small RNAs are known to regulate diverse gene expression processes including translation, transcription, and splicing. Among small RNAs, the microRNAs (miRNAs) of 17 to 27 nucleotides (nts) undergo biogeneses including primary transcription, RNA excision and folding, nuclear export, cytoplasmic processing, and then bioactivity as regulatory agents. We propose that analogous hairpins from RNA molecules that function as part of the spliceosome might also be the source of small, regulatory RNAs (somewhat smaller than miRNAs). Results Deep sequencing technology has enabled discovery of a novel 16-nt RNA sequence in total RNA from human brain that we propose is derived from RNU1, an RNA component of spliceosome assembly. Bioinformatic alignments compel inquiring whether the novel 16-nt sequence or its precursor have a regulatory function as well as determining aspects of how processing intersects with the miRNA biogenesis pathway. Specifically, our preliminary in silico investigations reveal the sequence could regulate splicing factor Arg/Ser rich 1 (SFRS1), a gene coding an essential protein component of the spliceosome. All 16-base source sequences in the UCSC Human Genome Browser are within the 14 instances of RNU1 genes listed in wgEncodeGencodeAutoV3. Furthermore, 10 of the 14 instances of the sequence are also within a common 28-nt hairpin-forming subsequence of RNU1. Conclusions An abundant 16-nt RNA sequence is sourced from a spliceosomal RNA, lies in a stem of a predicted RNA hairpin, and includes reverse complements of subsequences of the 3'UTR of a gene coding for a spliceosome protein. Thus RNU1 could function both as a component of spliceosome assembly and as inhibitor of production of the essential, spliceosome protein coded by SFRS1. Beyond this example, a general procedure is needed for systematic discovery of multiple alignments of sequencing, splicing, and RNA folding data

Analyses of In Vivo Interaction and Mobility of Two Spliceosomal Proteins Using FRAP and BiFC

U1-70K, a U1 snRNP-specific protein, and serine/arginine-rich (SR) proteins are components of the spliceosome and play critical roles in both constitutive and alternative pre-mRNA splicing. However, the mobility properties of U1-70K, its in vivo interaction with SR proteins, and the mobility of the U1-70K-SR protein complex have not been studied in any system. Here, we studied the in vivo interaction of U1-70K with an SR protein (SR45) and the mobility of the U1-70K/SR protein complex using bimolecular fluorescence complementation (BiFC) and fluorescence recovery after photobleaching (FRAP). Our results show that U1-70K exchanges between speckles and the nucleoplasmic pool very rapidly and that this exchange is sensitive to ongoing transcription and phosphorylation. BiFC analyses showed that U1-70K and SR45 interacted primarily in speckles and that this interaction is mediated by the RS1 or RS2 domain of SR45. FRAP analyses showed considerably slower recovery of the SR45/U1-70K complex than either protein alone indicating that SR45/U1-70K complexes remain in the speckles for a longer duration. Furthermore, FRAP analyses with SR45/U1-70K complex in the presence of inhibitors of phosphorylation did not reveal any significant change compared to control cells, suggesting that the mobility of the complex is not affected by the status of protein phosphorylation. These results indicate that U1-70K, like SR splicing factors, moves rapidly in the nucleus ensuring its availability at various sites of splicing. Furthermore, although it appears that U1-70K moves by diffusion its mobility is regulated by phosphorylation and transcription