Regioselective synthesis of antiparallel loops on a macrocyclic scaffold constrained by oxazoles and thiazoles

[GRAPHICS] The regioselective syntheses and structures are reported for two tris-macrocylic compounds, each possessing two antiparallel loops on a macrocyclic scaffold constrained by two oxazoles and two thiazoles. NMR solution structures show the loops projecting from the same face of the macrocycle. Such molecules are shown to be prototypes for mimicking multiple loops of proteins.

Synthesis, stability, antiviral activity, and protease-bound structures of substrate-mimicking constrained macrocyclic inhibitors of HIV-1 protease

Three new peptidomimetics (1-3) have been developed with highly stable and conformationally constrained macrocyclic components that replace tripeptide segments of protease substrates. Each compound inhibits both HIV-1 protease and viral replication (HIV-I, HIV-2) at nanomolar concentrations without cytotoxicity to uninfected cells below 10 mu M. Their activities against HIV-1 protease (K-i 1.7 nM (1), 0.6 nM (2), 0.3 nM (3)) are 1-2 orders of magnitude greater than their antiviral potencies against HIV-1-infected primary peripheral blood mononuclear cells (IC50 45 nM (1), 56 nM (2), 95 nM (3)) or HIV-1-infected MT2 cells (IC50 90 nM (1), 60 nM (2)), suggesting suboptimal cellular uptake. However their antiviral potencies are similar to those of indinavir and amprenavir under identical conditions. There were significant differences in their capacities to inhibit the replication of HIV-1 and HIV-2 in infected MT2 cells, 1 being ineffective against HIV-2 while 2 was equally effective against both virus types. Evidence is presented that 1 and 2 inhibit cleavage of the HIV-1 structural protein precursor Pr55(gag) to p24 in virions derived from chronically infected cells, consistent with inhibition of the viral protease in cells. Crystal structures refined to 1.75 Angstrom (1) and 1.85 Angstrom (2) for two of the macrocyclic inhibitors bound to HIV-1 protease establish structural mimicry of the tripeptides that the cycles were designed to imitate. Structural comparisons between protease-bound macrocyclic inhibitors, VX478 (amprenavir), and L-735,524 (indinavir) show that their common acyclic components share the same space in the active site of the enzyme and make identical interactions with enzyme residues. This substrate-mimicking minimalist approach to drug design could have benefits in the context of viral resistance, since mutations which induce inhibitor resistance may also be those which prevent substrate processing.

CP properties of symmetry-constrained two-Higgs-doublet models

The two-Higgs-doublet model can be constrained by imposing Higgs-family symmetries and/or generalized CP symmetries. It is known that there are only six independent classes of such symmetry-constrained models. We study the CP properties of all cases in the bilinear formalism. An exact symmetry implies CP conservation. We show that soft breaking of the symmetry can lead to spontaneous CP violation (CPV) in three of the classes.

Network air gap controller

As ameaças à segurança da informação, (INFOSEC) atentam contra a perda da respectiva confidencialidade, integridade e disponibilidade, pelo que as organizações são impelidas a implementar políticas de segurança, quer ao nível físico quer ao nível lógico, utilizando mecanismos específicos de defesa. O projecto Network Air Gap Controller (NAGC) foi concebido no sentido de contribuir para as questões da segurança, designadamente daquelas que se relacionam directamente com a transferência de informação entre redes de classificação de segurança diferenciadas ou de sensibilidades distintas, sem requisitos de comunicação em tempo real, e que mereçam um maior empenho nas condições de robustez, de disponibilidade e de controlo. Os organismos que, em razão das atribuições e competências cometidas, necessitam de fazer fluir informação entre este tipo de redes, são por vezes obrigados a realizar a transferência de dados com recurso a um processo manual, efectuado pelo homem e não pela máquina, que envolve dispositivos amovivéis, como sejam o CD, DVD, PEN, discos externos ou switches manuais. Neste processo, vulgarmente designado por Network Air Gap (NAG), o responsável pela transferência de dados deverá assumir de forma infalível, como atribuições intrínsecas e inalienáveis da função exercida, as garantias do cumprimento de um vasto conjunto de normas regulamentares. As regras estabelecidas desdobram-se em ferramentas e procedimentos que se destinam, por exemplo, à guarda em arquivo de todas as transferências efectuadas; à utilização de ferramentas de segurança (ex: antivírus) antes da colocação da informação na rede de classificação mais elevada; ao não consentimento de transferência de determinados tipos de ficheiro (ex: executáveis) e à garantia de que, em consonância com a autonomia que normalmente é delegada no elemento responsável pela operação das comunicações, apenas se efectuam transferências de informação no sentido da rede de classificação inferior para a rede de classificação mais elevada. Face ao valor da informação e do impacto na imagem deste tipo de organizações, o operador de comunicações que não cumpra escrupulosamente o determinado é inexoravelmente afastado dessas funções, sendo que o processo de apuramento de responsabilidades nem sempre poderá determinar de forma inequívoca se as razões apontam para um acto deliberado ou para factores não intencionais, como a inépcia, o descuido ou a fadiga. Na realidade, as actividades periódicas e rotineiras, tornam o homem propenso à falha e poderão ser incontornavelmente asseguradas, sem qualquer tipo de constrangimentos ou diminuição de garantias, por soluções tecnológicas, desde que devidamente parametrizadas, adaptadas, testadas e amadurecidas, libertando os recursos humanos para tarefas de manutenção, gestão, controlo e inspecção. Acresce que, para este tipo de organizações, onde se multiplicam o número de redes de entrada de informação, com diferentes classificações e actores distintos, e com destinatários específicos, a utilização deste tipo de mecanismos assume uma importância capital. Devido a este factor multiplicativo, impõe-se que o NAGC represente uma opção válida em termos de oferta tecnológica, designadamente para uma gama de produtos de baixíssimo custo e que possa desenvolver-se por camadas de contributo complementar, em função das reais necessidades de cada cenário.

Unit Commitment in a Competitive and Emission Constrained Environment

This paper is on the unit commitment problem, considering not only the economic perspective, but also the environmental perspective. We propose a bi-objective approach to handle the problem with conflicting profit and emission objectives. Numerical results based on the standard IEEE 30-bus test system illustrate the proficiency of the proposed approach.

Coordination between mid-term maintenance outage decisions and short-term security-constrained scheduling in smart distribution systems

Distribution systems are the first volunteers experiencing the benefits of smart grids. The smart grid concept impacts the internal legislation and standards in grid-connected and isolated distribution systems. Demand side management, the main feature of smart grids, acquires clear meaning in low voltage distribution systems. In these networks, various coordination procedures are required between domestic, commercial and industrial consumers, producers and the system operator. Obviously, the technical basis for bidirectional communication is the prerequisite of developing such a coordination procedure. The main coordination is required when the operator tries to dispatch the producers according to their own preferences without neglecting its inherent responsibility. Maintenance decisions are first determined by generating companies, and then the operator has to check and probably modify them for final approval. In this paper the generation scheduling from the viewpoint of a distribution system operator (DSO) is formulated. The traditional task of the DSO is securing network reliability and quality. The effectiveness of the proposed method is assessed by applying it to a 6-bus and 9-bus distribution system.

A Sensorless PMDC Motor Speed Controller with a Logical Overcurrent Protection

A method to control the speed or the torque of a permanent-magnet direct current motor is presented. The rotor speed and the external torque estimation are simultaneously provided by appropriate observers. The sensorless control scheme is based on current measurement and switching states of power devices. The observer’s performances are dependent on the accurate machine parameters knowledge. Sliding mode control approach was adopted for drive control, providing the suitable switching states to the chopper power devices. Despite the predictable chattering, a convenient first order switching function was considered enough to define the sliding surface and to correspond with the desired control specifications and drive performance. The experimental implementation was supported on a single dsPIC and the controller includes a logic overcurrent protection.

Derivative-free optimization and filter methods to solve nonlinear constrained problems

In real optimization problems, usually the analytical expression of the objective function is not known, nor its derivatives, or they are complex. In these cases it becomes essential to use optimization methods where the calculation of the derivatives, or the verification of their existence, is not necessary: the Direct Search Methods or Derivative-free Methods are one solution. When the problem has constraints, penalty functions are often used. Unfortunately the choice of the penalty parameters is, frequently, very difficult, because most strategies for choosing it are heuristics strategies. As an alternative to penalty function appeared the filter methods. A filter algorithm introduces a function that aggregates the constrained violations and constructs a biobjective problem. In this problem the step is accepted if it either reduces the objective function or the constrained violation. This implies that the filter methods are less parameter dependent than a penalty function. In this work, we present a new direct search method, based on simplex methods, for general constrained optimization that combines the features of the simplex method and filter methods. This method does not compute or approximate any derivatives, penalty constants or Lagrange multipliers. The basic idea of simplex filter algorithm is to construct an initial simplex and use the simplex to drive the search. We illustrate the behavior of our algorithm through some examples. The proposed methods were implemented in Java.

Dimensionless analysis of constrained damping treatments

One of the most effective ways of controlling vibrations in plate or beam structures is by means of constrained viscoelastic damping treatments. Contrary to the unconstrained configuration, the design of constrained and integrated layer damping treatments is multifaceted because the thickness of the viscoelastic layer acts distinctly on the two main counterparts of the strain energy the volume of viscoelastic material and the shear strain field. In this work, a parametric study is performed exploring the effect that the design parameters, namely the thickness/length ratio, constraining layer thickness, material modulus, natural mode and boundary conditions have on these two counterparts and subsequently, on the treatment efficiency. This paper presents five parametric studies, namely, the thickness/length ratio, the constraining layer thickness, material properties, natural mode and boundary conditions. The results obtained evidence an interesting effect when dealing with very thin viscoelastic layers that contradicts the standard treatment efficiency vs. layer thickness relation; hence, the potential optimisation of constrained and integrated viscoelastic treatments through the use of properly designed thin multilayer configurations is justified. This work presents a dimensionless analysis and provides useful general guidelines for the efficient design of constrained and integrated damping treatments based on single or multi-layer configurations. (C) 2012 Elsevier Ltd. All rights reserved.

Sensing Cloud Optimization applied to a non-convex constrained economical dispatch

Conferência: 39th Annual Conference of the IEEE Industrial-Electronics-Society (IECON) - NOV 10-14, 2013

LNT: a logical neighbor tree secure group communication scheme for wireless sensor networks

Secure group communication is a paradigm that primarily designates one-to-many communication security. The proposed works relevant to secure group communication have predominantly considered the whole network as being a single group managed by a central powerful node capable of supporting heavy communication, computation and storage cost. However, a typical Wireless Sensor Network (WSN) may contain several groups, and each one is maintained by a sensor node (the group controller) with constrained resources. Moreover, the previously proposed schemes require a multicast routing support to deliver the rekeying messages. Nevertheless, multicast routing can incur heavy storage and communication overheads in the case of a wireless sensor network. Due to these two major limitations, we have reckoned it necessary to propose a new secure group communication with a lightweight rekeying process. Our proposal overcomes the two limitations mentioned above, and can be applied to a homogeneous WSN with resource-constrained nodes with no need for a multicast routing support. Actually, the analysis and simulation results have clearly demonstrated that our scheme outperforms the previous well-known solutions.

RiSeG: a ring based secure group communication protocol for resource-constrained wireless sensor networks

Securing group communication in wireless sensor networks has recently been extensively investigated. Many works have addressed this issue, and they have considered the grouping concept differently. In this paper, we consider a group as being a set of nodes sensing the same data type, and we alternatively propose an efficient secure group communication scheme guaranteeing secure group management and secure group key distribution. The proposed scheme (RiSeG) is based on a logical ring architecture, which permits to alleviate the group controller’s task in updating the group key. The proposed scheme also provides backward and forward secrecy, addresses the node compromise attack, and gives a solution to detect and eliminate the compromised nodes. The security analysis and performance evaluation show that the proposed scheme is secure, highly efficient, and lightweight. A comparison with the logical key hierarchy is preformed to prove the rekeying process efficiency of RiSeG. Finally, we present the implementation details of RiSeG on top of TelosB sensor nodes to demonstrate its feasibility.

A preliminary idea for an 8-competitive, log2 DMAX + log2 log2 1/U asymptotic-space, interface generation algorithm for two-level hierarchical scheduling of constrained-deadline sporadic tasks on a uniprocessor

Consider a single processor and a software system. The software system comprises components and interfaces where each component has an associated interface and each component comprises a set of constrained-deadline sporadic tasks. A scheduling algorithm (called global scheduler) determines at each instant which component is active. The active component uses another scheduling algorithm (called local scheduler) to determine which task is selected for execution on the processor. The interface of a component makes certain information about a component visible to other components; the interfaces of all components are used for schedulability analysis. We address the problem of generating an interface for a component based on the tasks inside the component. We desire to (i) incur only a small loss in schedulability analysis due to the interface and (ii) ensure that the amount of space (counted in bits) of the interface is small; this is because such an interface hides as much details of the component as possible. We present an algorithm for generating such an interface.

A 12*(1+|R|/(4m))-speed algorithm for scheduling constrained-deadline sporadic real-time tasks on a multiprocessor comprising m processors where a task may request one of |R| sequentially-reusable shared resources

We present a 12*(1+|R|/(4m))-speed algorithm for scheduling constrained-deadline sporadic real-time tasks on a multiprocessor comprising m processors where a task may request one of |R| sequentially-reusable shared resources.

The utilization bound of non-preemptive rate-monotonic scheduling in controller area networks is 25%

Consider a distributed computer system comprising many computer nodes, each interconnected with a controller area network (CAN) bus. We prove that if priorities to message streams are assigned using rate-monotonic (RM) and if the requested capacity of the CAN bus does not exceed 25% then all deadlines are met.