Surface wave modelling and simulation for wave tanks and coastal areas

For testing ships and offshore structures in hydrodynamic laboratories, the sea and ocean states should be represented as realistic as possible in the wave tanks in which the scaled experiments are executed. To support efficient testing, accurate software that determines and translates the required wave maker motion into the downstream waves is very helpful. This paper describes an efficient hybrid spatial-spectral code that can deal with simulations above flat and varying bottom. The accuracy of the code will be illustrated by presenting comparisons of simulations with experimental data for various different type of non-breaking waves, from dispersive focussing waves to irregular wave fields with freak waves; the very broad-band spectra of such waves provide the main challeng

Up Close and Personal : Ethical issues in genomic testing

__Abstract__ Achilles was foretold to die young. When he was still a baby, his mother Thetis took him to the river Styx, which separated the world of the living from the realm of Hades. The waters of the Styx were known to bring invulnerability to those who were touched by them. Thetis bathed the infant in the magical Styx. After that, Achilles lived, grew and flourished. As he came of age, Achilles became a fearless warrior and a leader in the Trojan War, during which he acquired a reputation of unassailability. Until, in the midst of battle, a poisonous arrow pierced through Achilles’ heel, and killed him... Thetis had held her baby by the heel when she submerged him in the Styx. The waters had left only Achilles’ heel vulnerable

PuFFIN--a parameter-free method to build nucleosome maps from paired-end reads.

BackgroundWe introduce a novel method, called PuFFIN, that takes advantage of paired-end short reads to build genome-wide nucleosome maps with larger numbers of detected nucleosomes and higher accuracy than existing tools. In contrast to other approaches that require users to optimize several parameters according to their data (e.g., the maximum allowed nucleosome overlap or legal ranges for the fragment sizes) our algorithm can accurately determine a genome-wide set of non-overlapping nucleosomes without any user-defined parameter. This feature makes PuFFIN significantly easier to use and prevents users from choosing the "wrong" parameters and obtain sub-optimal nucleosome maps.ResultsPuFFIN builds genome-wide nucleosome maps using a multi-scale (or multi-resolution) approach. Our algorithm relies on a set of nucleosome "landscape" functions at different resolution levels: each function represents the likelihood of each genomic location to be occupied by a nucleosome for a particular value of the smoothing parameter. After a set of candidate nucleosomes is computed for each function, PuFFIN produces a consensus set that satisfies non-overlapping constraints and maximizes the number of nucleosomes.ConclusionsWe report comprehensive experimental results that compares PuFFIN with recently published tools (NOrMAL, TEMPLATE FILTERING, and NucPosSimulator) on several synthetic datasets as well as real data for S. cerevisiae and P. falciparum. Experimental results show that our approach produces more accurate nucleosome maps with a higher number of non-overlapping nucleosomes than other tools

Access to Non-reimbursed Expensive Cancer Treatments:A Justice Perspective

When the cost-effectiveness of newly approved cancer treatments is insufficient or unclear, they may not (immediately) be eligible for reimbursement through basic health insurance in publicly funded healthcare systems. Patients may seek access to non-reimbursed treatment through other channels, including individual funding requests made to hospitals, health insurers, or pharmaceutical companies. Alternatively, they may try to pay out of pocket for non-reimbursed treatments. While currently little is known of these practices, they run counter to a deeply held egalitarian ethos that is prevalent in many publicly funded healthcare systems. In this article, we investigate to what extent this ethos can be grounded in theories of justice, notably egalitarianism and prioritarianism. We argue that allowing out-of-pocket payments by patients themselves, in principle, is not unjust from the perspective of either of these theories, provided that it does not raise in-practice justice-based concerns, for instance by displacing more cost-effective care, to the detriment of other patients, or by failing to treat patients equally. In contrast, we conclude that the practice of making exceptions for individual patients by health insurers or healthcare providers does run counter to the justice-based requirements of equal treatment.</p

Can Voluntary Health Insurance for Non-reimbursed Expensive New Treatments Be Just?

Public healthcare systems are increasingly refusing (temporarily) to reimburse newly approved medical treatments of insufficient or uncertain cost-effectiveness. As both patient demand for these treatments and their list prices increase, a market might arise for voluntary additional health insurance (VHI) that covers effective but (very) expensive medical treatments. In this paper, we evaluate such potential future practices of VHI in public healthcare systems from a justice perspective. We find that direct (telic) egalitarian objections to unequal access to expensive treatments based on different ability to afford VHI do not stand up to scrutiny. However, such unequal access might lead to loss of self-respect among individuals, or loss of fraternity within society, rendering it more difficult for citizens to interact on equal moral footing. This would be problematic from a relational egalitarian perspective. Moreover, the introduction of VHI might turn out to have negative consequences for the comprehensiveness and/or the quality of the public healthcare services that are offered to all patients equally through basic health insurance. These consequences must be weighed against potential health gains and the value of liberty. We conclude that governments should be careful when considering the introduction of VHI in public healthcare systems.</p

The mRNA-bound proteome of the human malaria parasite Plasmodium falciparum.

BackgroundGene expression is controlled at multiple levels, including transcription, stability, translation, and degradation. Over the years, it has become apparent that Plasmodium falciparum exerts limited transcriptional control of gene expression, while at least part of Plasmodium's genome is controlled by post-transcriptional mechanisms. To generate insights into the mechanisms that regulate gene expression at the post-transcriptional level, we undertook complementary computational, comparative genomics, and experimental approaches to identify and characterize mRNA-binding proteins (mRBPs) in P. falciparum.ResultsClose to 1000 RNA-binding proteins are identified by hidden Markov model searches, of which mRBPs encompass a relatively large proportion of the parasite proteome as compared to other eukaryotes. Several abundant mRNA-binding domains are enriched in apicomplexan parasites, while strong depletion of mRNA-binding domains involved in RNA degradation is observed. Next, we experimentally capture 199 proteins that interact with mRNA during the blood stages, 64 of which with high confidence. These captured mRBPs show a significant overlap with the in silico identified candidate RBPs (p &lt; 0.0001). Among the experimentally validated mRBPs are many known translational regulators active in other stages of the parasite's life cycle, such as DOZI, CITH, PfCELF2, Musashi, and PfAlba1-4. Finally, we also detect several proteins with an RNA-binding domain abundant in Apicomplexans (RAP domain) that is almost exclusively found in apicomplexan parasites.ConclusionsCollectively, our results provide the most complete comparative genomics and experimental analysis of mRBPs in P. falciparum. A better understanding of these regulatory proteins will not only give insight into the intricate parasite life cycle but may also provide targets for novel therapeutic strategies

Nascent RNA sequencing reveals mechanisms of gene regulation in the human malaria parasite Plasmodium falciparum.

Gene expression in Plasmodium falciparum is tightly regulated to ensure successful propagation of the parasite throughout its complex life cycle. The earliest transcriptomics studies in P. falciparum suggested a cascade of transcriptional activity over the course of the 48-hour intraerythrocytic developmental cycle (IDC); however, the just-in-time transcriptional model has recently been challenged by findings that show the importance of post-transcriptional regulation. To further explore the role of transcriptional regulation, we performed the first genome-wide nascent RNA profiling in P. falciparum. Our findings indicate that the majority of genes are transcribed simultaneously during the trophozoite stage of the IDC and that only a small subset of genes is subject to differential transcriptional timing. RNA polymerase II is engaged with promoter regions prior to this transcriptional burst, suggesting that Pol II pausing plays a dominant role in gene regulation. In addition, we found that the overall transcriptional program during gametocyte differentiation is surprisingly similar to the IDC, with the exception of relatively small subsets of genes. Results from this study suggest that further characterization of the molecular players that regulate stage-specific gene expression and Pol II pausing will contribute to our continuous search for novel antimalarial drug targets

Exploring the Ethics of Implementation of Epigenomics Technologies in Cancer Screening:A Focus Group Study

New epigenomics technologies are being developed and used for the detection and prediction of various types of cancer. By allowing for timely intervention or preventive measures, epigenomics technologies show promise for public health, notably in population screening. In order to assess whether implementation of epigenomics technologies in population screening may be morally acceptable, it is important to understand – in an early stage of development – ethical and societal issues that may arise. We held 3 focus groups with experts in science and technology studies (STS) (n = 13) in the Netherlands, on 3 potential future applications of epigenomic technologies in screening programmes of increasing scope: cervical cancer, female cancers and ‘global’ cancer. On the basis of these discussions, this paper identifies ethical issues pertinent to epigenomics-based population screening, such as risk communication, trust and public acceptance; personal responsibility, stigmatisation and societal pressure, and data protection and data governance. It also points out how features of epigenomics (eg, modifiability) and changing concepts (eg, of cancer) may challenge the existing evaluative framework for screening programmes. This paper aims to anticipate and prepare for future ethical challenges when epigenomics technologies can be tested and introduced in public health settings