A Knowledge Representation Model for Massive Open Online Course Platforms

This paper describes a knowledge model for the design of Massive Open Online Course (MOOC) platforms. It is based on our generic instructional engineering method called Knowledge Field of Educational Environment with Competence Boundary Conditions (KFEEC). KFEEC uses the ontology as a foundation for the knowledge representation model. It provides a flexible structure to the various self-paced e-learning system designs but appears to be overcomplicated for the MOOC platform. This paper describes the KFEEC method, the steps of adapting the KFEEC to the MOOC platform design, and the specification of the resulting knowledge model. This model is a core of the MOOC platform that will be developed in future work

Non-uniqueness of weak solutions for the fractal Burgers equation

The notion of Kruzhkov entropy solution was extended by the first author in 2007 to conservation laws with a fractional laplacian diffusion term; this notion led to well-posedness for the Cauchy problem in the $L^\infty$-framework. In the present paper, we further motivate the introduction of entropy solutions, showing that in the case of fractional diffusion of order strictly less than one, uniqueness of a weak solution may fail.Comment: 23 page

A Note on the Regularity of Inviscid Shell Model of Turbulence

In this paper we continue the analytical study of the sabra shell model of energy turbulent cascade initiated in \cite{CLT05}. We prove the global existence of weak solutions of the inviscid sabra shell model, and show that these solutions are unique for some short interval of time. In addition, we prove that the solutions conserve the energy, provided that the components of the solution satisfy $|{u_n}| \le C k_n^{-1/3} (\sqrt{n} \log(n+1))^{-1}$, for some positive absolute constant $C$, which is the analogue of the Onsager's conjecture for the Euler's equations. Moreover, we give a Beal-Kato-Majda type criterion for the blow-up of solutions of the inviscid sabra shell model and show the global regularity of the solutions in the ``two-dimensional'' parameters regime

Atomic Mechanisms of Timothy Syndrome-Associated Mutations in Calcium Channel Cav1.2

Timothy syndrome (TS) is a very rare multisystem disorder almost exclusively associated with mutations G402S and G406R in helix IS6 of Cav1.2. Recently, mutations R518C/H in helix IIS0 of the voltage sensing domain II (VSD-II) were described as a cause of cardiac-only TS. The three mutations are known to decelerate voltage-dependent inactivation (VDI). Here, we report a case of cardiac-only TS caused by mutation R518C. To explore possible impact of the three mutations on interdomain contacts, we modeled channel Cav1.2 using as templates Class Ia and Class II cryo-EM structures of presumably inactivated channel Cav1.1. In both models, R518 and several other residues in VSD-II donated H-bonds to the IS6-linked α1-interaction domain (AID). We further employed steered Monte Carlo energy minimizations to move helices S4–S5, S5, and S6 from the inactivated-state positions to those seen in the X-ray structures of the open and closed NavAb channel. In the open-state models, positions of AID and VSD-II were similar to those in Cav1.1. In the closed-state models, AID moved along the β subunit (Cavβ) toward the pore axis and shifted AID-bound VSD-II. In all the models R518 retained strong contacts with AID. Our calculations suggest that conformational changes in VSD-II upon its deactivation would shift AID along Cavβ toward the pore axis. The AID-linked IS6 would bend at flexible G402 and G406, facilitating the activation gate closure. Mutations R518C/H weakened the IIS0-AID contacts and would retard the AID shift. Mutations G406R and G402S stabilized the open state and would resist the pore closure. Several Cav1.2 mutations associated with long QT syndromes are consistent with this proposition. Our results provide a mechanistic rationale for the VDI deceleration caused by TS-associated mutations and suggest targets for further studies of calcium channelopathies

Preclinical Evaluation of a Replication-Deficient Intranasal ΔNS1 H5N1 Influenza Vaccine

We developed a novel intranasal influenza vaccine approach that is based on the construction of replication-deficient vaccine viruses that lack the entire NS1 gene (ΔNS1 virus). We previously showed that these viruses undergo abortive replication in the respiratory tract of animals. The local release of type I interferons and other cytokines and chemokines in the upper respiratory tract may have a “self-adjuvant effect”, in turn increasing vaccine immunogenicity. As a result, ΔNS1 viruses elicit strong B- and T- cell mediated immune responses.), one dose of vaccine delivered intranasally was sufficient for the induction of antibodies against homologous A/Vietnam/1203/04 and heterologous A/Indonesia/5/05 H5N1 strains.Our findings show that intranasal immunization with the replication deficient H5N1 ΔNS1 vaccine candidate is sufficient to induce a protective immune response against H5N1 viruses. This approach might be attractive as an alternative to conventional influenza vaccines. Clinical evaluation of ΔNS1 pandemic and seasonal influenza vaccine candidates are currently in progress

Singular Cucker-Smale Dynamics

The existing state of the art for singular models of flocking is overviewed, starting from microscopic model of Cucker and Smale with singular communication weight, through its mesoscopic mean-filed limit, up to the corresponding macroscopic regime. For the microscopic Cucker-Smale (CS) model, the collision-avoidance phenomenon is discussed, also in the presence of bonding forces and the decentralized control. For the kinetic mean-field model, the existence of global-in-time measure-valued solutions, with a special emphasis on a weak atomic uniqueness of solutions is sketched. Ultimately, for the macroscopic singular model, the summary of the existence results for the Euler-type alignment system is provided, including existence of strong solutions on one-dimensional torus, and the extension of this result to higher dimensions upon restriction on the smallness of initial data. Additionally, the pressureless Navier-Stokes-type system corresponding to particular choice of alignment kernel is presented, and compared - analytically and numerically - to the porous medium equation

Single HA2 Mutation Increases the Infectivity and Immunogenicity of a Live Attenuated H5N1 Intranasal Influenza Vaccine Candidate Lacking NS1

Our finding suggests that an efficient intranasal vaccination with a live attenuated H5N1 virus may require a certain level of pH and temperature stability of HA in order to achieve an optimal virus uptake by the nasal epithelial cells and induce a sufficient immune response. The pH of the activation of the H5 HA protein may play a substantial role in the infectivity of HPAIVs for mammals