Periodic synchronization of isolated network elements facilitates simulating and inferring gene regulatory networks including stochastic molecular kinetics

Background The temporal progression of many fundamental processes in cells and organisms, including homeostasis, differentiation and development, are governed by gene regulatory networks (GRNs). GRNs balance fluctuations in the output of their genes, which trace back to the stochasticity of molecular interactions. Although highly desirable to understand life processes, predicting the temporal progression of gene products within a GRN is challenging when considering stochastic events such as transcription factor–DNA interactions or protein production and degradation. Results We report a method to simulate and infer GRNs including genes and biochemical reactions at molecular detail. In our approach, we consider each network element to be isolated from other elements during small time intervals, after which we synchronize molecule numbers across all network elements. Thereby, the temporal behaviour of network elements is decoupled and can be treated by local stochastic or deterministic solutions. We demonstrate the working principle of this modular approach with a repressive gene cascade comprising four genes. By considering a deterministic time evolution within each time interval for all elements, our method approaches the solution of the system of deterministic differential equations associated with the GRN. By allowing genes to stochastically switch between on and off states or by considering stochastic production of gene outputs, we are able to include increasing levels of stochastic detail and approximate the solution of a Gillespie simulation. Thereby, CaiNet is able to reproduce noise-induced bi-stability and oscillations in dynamically complex GRNs. Notably, our modular approach further allows for a simple consideration of deterministic delays. We further infer relevant regulatory connections and steady-state parameters of a GRN of up to ten genes from steady-state measurements by identifying each gene of the network with a single perceptron in an artificial neuronal network and using a gradient decent method originally designed to train recurrent neural networks. To facilitate setting up GRNs and using our simulation and inference method, we provide a fast computer-aided interactive network simulation environment, CaiNet. Conclusion We developed a method to simulate GRNs at molecular detail and to infer the topology and steady-state parameters of GRNs. Our method and associated user-friendly framework CaiNet should prove helpful to analyze or predict the temporal progression of reaction networks or GRNs in cellular and organismic biology. CaiNet is freely available at https://gitlab.com/GebhardtLab/CaiNet.

The MMX rover: performing in situ surface investigations on Phobos

The Japanese MMX sample return mission to Phobos by JAXA will carry a rover developed by CNES and DLR that will be deployed on Phobos to perform in situ analysis of the Martian moon’s surface properties. Past images of the surface of Phobos show that it is covered by a layer of regolith. However, the mechanical and compositional properties of this regolith are poorly constrained. In particular, from current remote images, very little is known regarding the particle sizes, their chemical composition, the packing density of the regolith as well as other parameters such as friction and cohesion that influence surface dynamics. Understanding the properties and dynamics of the regolith in the low-gravity environment of Phobos is important to trace back its history and surface evolution. Moreover, this information is also important to support the interpretation of data obtained by instruments onboard the main MMX spacecraft, and to minimize the risks involved in the spacecraft sampling operations. The instruments onboard the Rover are a Raman spectrometer (RAX), an infrared radiometer (miniRad), two forward-looking cameras for navigation and science purposes (NavCams), and two cameras observing the interactions of regolith and the rover wheels (WheelCams). The Rover will be deployed before the MMX spacecraft samples Phobos’ surface and will be the first rover to drive on the surface of a Martian moon and in a very low gravity environment. Graphic Abstract

Can We Make All Legal Norms into Legal Syllogisms and Why is That Important in Times of Artificial Intelligence?

Background: The term ‘hard cases’ trace back to Herbert Lionel Adolphus Hart who was one of the first legal philosophers who directly used it in his works and Ronald Myles Dworkin to whom the development and establishment of this concept in legal language is linked. Even though these two legal philosophers in one of the most famous - The Hart–Dworkin – legal debate couldn’t agree on certain things, they both agreed that when dealing with hard cases, there is a need to act creatively in order to resolve such a case properly. The division of cases into easy ones and hard ones gradually lost its popularity, even in legal theory, but perhaps it can be resurrected and used these challenging times to help meet the challenges prompted by technology? Methods: This paper analyses the dichotomy of hard and easy cases as well as circumstances relating to the courts’ decision-making processes in such cases. The essay examines whether the solutions proposed by legal positivism (such as applying syllogisms and precedents) are sufficient to deal with easy cases. The paper also examines what factors analysed by legal realists have an impact on judges while making decisions in hard cases (for example, psychological factors, such as hindsight bias, intuition, hunches, the anchor effect, laziness, unwillingness to take responsibility, or the gambler’s fallacy, as well as social factors, like upbringing, life experience, social relations, gender, age, education, etc.). Given that the article is theoretical in nature, logical, systemic, teleological methods dominate. Both descriptive method and scientific research method were used as well. Results and Conclusions: The author concludes that easy cases should eventually be delegated to artificial intelligence to resolve, whereas hard cases will remain in the competence of human judges, at least until technological development reaches a certain level.

Une paratextualité émergente dans les tombes privées

In this paper, I investigate the speech captions (the so-called ‘Reden und Rufe’) in the private tombs from the Old Kingdom to the Late Period. I aim to show some of the ways used by the Egyptian scribes and/or artists to formally distinguish these speeches from other captions and inscriptions displayed in private tombs. After presenting the text- image interrelation and the most common speech caption layouts, I turn my attention to the form(s) of these captions and trace back the appearance of discursive marks in Old Kingdom mastaba as first evidence of paratextuality. I then offer a diachronic overview of the other paratextual means used to categorize a caption as a speech or a song: Dd-formulas, the parenthetic in indicating a direct quotation as well as the expression xn n wSb and xn n nhm.

An Applying Colored Petri Net for Computerized Accounting System and Ledger Accounts Instruction

Many learners who are not familiar with the accounting terms find blended learning very complex to understand with respect to the computerized accounting system, the journal entries process, and tracing the accounting transaction flows of accounting system. A simulation-based model is a viable option to help instructors and learners make understanding the accounting system components and monitoring the accounting transactions easier. This paper proposes a [Chanon]CPNcolored Petri net (CPN)-based model for the instruction of an accounting system focused on the journal entries processes, accounting modules, and accounting transaction flows. The CPN-based language and the model checking tool named CPN are used to represent the accounting system components: a chart of accounts, an account mapping profile, the journal and ledgers system, and the financial report creations. We evaluated the designed CPN models by creating the simulation cases from ground truth data of the retail department store system and the mortgage loan system, using the decision-table-based testing technique. The results show that the designed CPN model and provided simulation cases help the learners to animate, verify, trace back accounting [chanon]transaction flowstransactions and data flows, and increase the learner’s understanding.

Intra-Tumoral Nerve-Tracing in a Novel Syngeneic Model of High-Grade Serous Ovarian Carcinoma

Dense tumor innervation is associated with enhanced cancer progression and poor prognosis. We observed innervation in breast, prostate, pancreatic, lung, liver, ovarian, and colon cancers. Defining innervation in high-grade serous ovarian carcinoma (HGSOC) was a focus since sensory innervation was observed whereas the normal tissue contains predominantly sympathetic input. The origin, specific nerve type, and the mechanisms promoting innervation and driving nerve-cancer cell communications in ovarian cancer remain largely unknown. The technique of neuro-tracing enhances the study of tumor innervation by offering a means for identification and mapping of nerve sources that may directly and indirectly affect the tumor microenvironment. Here, we establish a murine model of HGSOC and utilize image-guided microinjections of retrograde neuro-tracer to label tumor-infiltrating peripheral neurons, mapping their source and circuitry. We show that regional sensory neurons innervate HGSOC tumors. Interestingly, the axons within the tumor trace back to local dorsal root ganglia as well as jugular–nodose ganglia. Further manipulations of these tumor projecting neurons may define the neuronal contributions in tumor growth, invasion, metastasis, and responses to therapeutics.

Molecular Variability and Host Distribution of ‘Candidatus Phytoplasma solani’ Strains from Different Geographic Origins

The knowledge of phytoplasma genetic variability is a tool to study their epidemiology and to implement an effective monitoring and management of their associated diseases. ‘Candidatus Phytoplasma solani’ is associated with “bois noir” disease in grapevines, and yellowing and decline symptoms in many plant species, causing serious damages during the epidemic outbreaks. The epidemiology of the diseases associated with this phytoplasma is complex and related to numerous factors, such as interactions of the host plant and insect vectors and spreading through infected plant propagation material. The genetic variability of ‘Ca. P. solani’ strains in different host species and in different geographic areas during the last two decades was studied by RFLP analyses coupled with sequencing on vmp1, stamp, and tuf genes. A total of 119 strains were examined, 25 molecular variants were identified, and the variability of the studied genes was linked to both geographic distribution and year of infection. The crucial question in ‘Ca. P. solani’ epidemiology is to trace back the epidemic cycle of the infections. This study presents some relevant features about differential strain distribution useful for disease monitoring and forecasting, illustrating and comparing the phytoplasma molecular variants identified in various regions, host species, and time periods.

Study on SDN with Security Issues Using Mininet

The internet is faced with many problems daily, one of them is decrement in network bandwidth because of Distributed Denial of Service (DDoS) attack on host server, which deplete host resources. Researchers has been invented many protection mechanisms such as detection, trace back, prevention, reaction, and characterization are in case of DDoS attacks, which will control the number of malicious packets received by the victim. But it does not provide efficient detection technique with high rate in real time network infrastructure. Thus, modern technologies are prepared on Mininet network simulators, which give more impact to simulate the real network. The architecture of Software Defined Networks (SDN) and OpenFlow architecture is used to demonstrate a programmable network model and centralized management of real network. In this research work, we provide design of software defined network (SDN) using mininet simulator and security issues related to the Software Defined Network.

LEONID ANDREYEV’S AND PÄR LAGERKVIST’S WORKS IN THE CONTEXT OF EXPRESSIONISM: THE PROBLEM STATEMENT

The article substantiates the classification of the creative methods of Leonid Andreyev (1871-1917) and Pär Lagerkvist (1891-1974) as expressionistic. Expressionism was the leading art and literature direction in the early XX century. The authors trace back the Russian and foreign academic tradition of viewing certain periods of these writers’ creative career as expressionistic. This tradition is based on some of the characteristics present in their works, such as heightened expression, one-dimensional characters, static scenes, grotesque forms, colour contrasts, the depiction of a chaotic world, and a nervous and alienated person within it. The authors come to the conclusion that the expressionist works of Leonid Andreyev and Pär Lagerkvist can be most effectively compared by employing the historical typological method developed by Victor Zhirmunsky.

An investigation of Aharonov-Bohm effect towards the potential use for the gravitational wave detection

We investigate an alternative way to detect the gravitational wave using the concept of Aharonov-Bohm experiment in curved space-time. Our system consists of an electron beam which is split into two beams passing opposite sides of the solenoid and producing interference patterns. The change in interference patterns can be observed if the system is perturbed by the gravitational wave, and can be used to trace back to the nature of the gravitational wave. This system is described by the cylindrical coordinate in Minkowski space-time where we set the incoming wave propagating in the z-direction, perpendicular to the solenoid’s cross-section. We found that the perturbation on the cross-section area due to gravitational strength is not strong enough to significantly change the phase shift. Contrarily, by changing the magnetic field generated by the current inside the solenoid, the results suggest that the significant phase shift could potentially be detected if the gravitational wave is allowed to propagate in the direction that is perpendicular to z-direction.