Practical Large-Scale Proof-of-Stake Asynchronous Total-Order Broadcast

We present simple and practical protocols for generating randomness as used by asynchronous total-order broadcast. The protocols are secure in a proof-of-stake setting with dynamically changing stake. They can be plugged into existing protocols for asynchronous total-order broadcast and will turn these into asynchronous total-order broadcast with dynamic stake. Our contribution relies on two important techniques. The paper ``Random Oracles in Constantinople: Practical Asynchronous Byzantine Agreement using Cryptography\u27\u27 [Cachin, Kursawe, and Shoup, PODC 2000] has influenced the design of practical total-order broadcast through its use of threshold cryptography. However, it needs a setup protocol to be efficient. In a proof-of-stake setting with dynamic stake this setup would have to be continually recomputed, making the protocol impractical. The work ``Asynchronous Byzantine Agreement with Subquadratic Communication\u27\u27 [Blum, Katz, Liu-Zhang, and Loss, TCC 2020] showed how to use an initial setup for broadcast to asymptotically efficiently generate sub-sequent setups. The protocol, however, resorted to fully homomorphic encryption and was therefore not practically efficient. We adopt their approach to the proof-of-stake setting with dynamic stake, apply it to the Constantinople paper, and remove the need for fully homomorphic encryption. This results in simple and practical proof-of-stake protocols. We discuss how to use the new coin-flip protocols together with DAG rider [Keidar et al., PODC 2021] and create a variant which works for dynamic proof of stake. Our method can be employed together with many further asynchronous total-order broadcast protocols

Protocol for an individual patient data meta-analysis on blood pressure targets after cardiac arrest

Background Hypotension is common after cardiac arrest (CA), and current guidelines recommend using vasopressors to target mean arterial blood pressure (MAP) higher than 65 mmHg. Pilot trials have compared higher and lower MAP targets. We will review the evidence on whether higher MAP improves outcome after cardiac arrest. Methods This systematic review and meta-analysis will be conducted based on a systematic search of relevant major medical databases from their inception onwards, including MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL), as well as clinical trial registries. We will identify randomised controlled trials published in the English language that compare targeting a MAP higher than 65-70 mmHg in CA patients using vasopressors, inotropes and intravenous fluids. The data extraction will be performed separately by two authors (a third author will be involved in case of disagreement), followed by a bias assessment with the Cochrane Risk of Bias tool using an eight-step procedure for assessing if thresholds for clinical significance are crossed. The outcomes will be all-cause mortality, functional long-term outcomes and serious adverse events. We will contact the authors of the identified trials to request individual anonymised patient data to enable individual patient data meta-analysis, aggregate data meta-analyses, trial sequential analyses and multivariable regression, controlling for baseline characteristics. The certainty of the evidence will be assessed by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. We will register this systematic review with Prospero and aim to redo it when larger trials are published in the near future. Conclusions This protocol defines the performance of a systematic review on whether a higher MAP after cardiac arrest improves patient outcome. Repeating this systematic review including more data likely will allow for more certainty regarding the effect of the intervention and possible sub-groups differences.Peer reviewe

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

SBML Level 3: an extensible format for the exchange and reuse of biological models

Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction-based models and packages that extend the core with features suited to other model types including constraint-based models, reaction-diffusion models, logical network models, and rule-based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single-cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution

Regulation and Function of the Human Leukotriene D4 Receptor CysLT1 in Epithelial Cells and Colon Cancer

The pro-inflammatory mediators leukotrienes have shown to be important players in the pathogenesis of diseases like asthma and inflammatory bowel disease (IBD). Patients suffering from IBD have been found to have an increased risk of developing colon cancer. Since leukotrienes have been shown in increased concentrations in stools of IBD patients we hypothesise that LTD4 can play a role in the development of colon cancer. In order to induce its effects on the intestinal epithelial cells, LTD4 binds to its receptor CysLT1R. We therefore chose to study CysLT1 in colon cancer specimens and in non-transformed and colon cancer cell lines. Our results show that CysLT1R can be found in increased levels in colon cancer enterocytes (50% of 84 patients) and that high expression of this receptor in Dukes`B staged tumours predicts a poor disease outcome. Furthermore, we observed that CysLT1R is located in the plasma membrane and in the outer nuclei membrane. We identified a putative nuclear localisation sequence in CysLT1R, which is crucial for the LTD4, induced internalisation of the receptor. Interestingly, stimulation of CysLT1R located in the nuclei induced the activation of ERK1/2, an enzyme which have been shown to mediate LTD4 induced proliferation. When studying the LTD4 induced signalling pathways we found that CysLT1R mediated stress fibre formation and a calcium response through two heterotrimeric G-proteins, Ga12 and Gai3, respectively and that the LTD4 induced calcium response is dependent on PKCe. Taken together we have shown that LTD4 might have an impact on tumour development through the regulation of CysLT1R and its downstream signalling pathways

Practical Large-Scale Proof-Of-Stake Asynchronous Total-Order Broadcast

We present simple and practical protocols for generating randomness as used by asynchronous total-order broadcast. The protocols are secure in a proof-of-stake setting with dynamically changing stake. They can be plugged into existing protocols for asynchronous total-order broadcast and will turn these into asynchronous total-order broadcast with dynamic stake. Our contribution relies on two important techniques. The paper "Random Oracles in Constantinople: Practical Asynchronous Byzantine Agreement using Cryptography" [Cachin, Kursawe, and Shoup, PODC 2000] has influenced the design of practical total-order broadcast through its use of threshold cryptography. However, it needs a setup protocol to be efficient. In a proof-of-stake setting with dynamic stake this setup would have to be continually recomputed, making the protocol impractical. The work "Asynchronous Byzantine Agreement with Subquadratic Communication" [Blum, Katz, Liu-Zhang, and Loss, TCC 2020] showed how to use an initial setup for broadcast to asymptotically efficiently generate sub-sequent setups. The protocol, however, resorted to fully homomorphic encryption and was therefore not practically efficient. We adopt their approach to the proof-of-stake setting with dynamic stake, apply it to the Constantinople paper, and remove the need for fully homomorphic encryption. This results in simple and practical proof-of-stake protocols