Artemisinins act through at least two targets in a yeast model

Artemisinin and related compounds are potent and widely used antimalarial drugs but their biochemical mode of action is not clear. There is strong evidence that ATP-dependent calcium transporters are a key target in the malarial parasite. However, work using Saccharomyces cerevisiae suggests that disruption of mitochondrial function is critical in the cell killing activity of these compounds. Here it is shown that, in the absence of reducing agents, artemisinin and artesunate targeted the S. cerevisiae calcium channels Pmr1p and Pmc1p. Both compounds affected the growth of yeast on fermentable and nonfermentable media. This growth inhibition was not seen in a yeast strain in which the genes encoding both calcium channels were deleted. In the presence of reducing agents, which break the endoperoxide bridge in the drugs, growth inhibition was only observed in nonfermentable media. This inhibition could be partially relieved by the addition of a free radical scavenger. These results suggest that the drugs have two biochemical modes of action - one acting by specific binding to calcium channels and one involving free radical production in the mitochondria.

Simulação de processos de adsorção recorrendo ao Aspen Chromatography

As operações de separação por adsorção têm vindo a ganhar importância nos últimos anos, especialmente com o desenvolvimento de técnicas de simulação de leitos móveis em colunas, tal como a cromatografia de Leito Móvel Simulado (Simulated Moving Bed, SMB). Esta tecnologia foi desenvolvida no início dos anos 60 como método alternativo ao processo de Leito Móvel Verdadeiro (True Moving Bed, TMB), de modo a resolver vários dos problemas associados ao movimento da fase sólida, usuais nestes métodos de separação cromatográficos de contracorrente. A tecnologia de SMB tem sido amplamente utilizada em escala industrial principalmente nas indústrias petroquímica e de transformação de açúcares e, mais recentemente, na indústria farmacêutica e de química fina. Nas últimas décadas, o crescente interesse na tecnologia de SMB, fruto do alto rendimento e eficiente consumo de solvente, levou à formulação de diferentes modos de operação, ditos não convencionais, que conseguem unidades mais flexíveis, capazes de aumentar o desempenho de separação e alargar ainda mais a gama de aplicação da tecnologia. Um dos exemplos mais estudados e implementados é o caso do processo Varicol, no qual se procede a um movimento assíncrono de portas. Neste âmbito, o presente trabalho foca-se na simulação, análise e avaliação da tecnologia de SMB para dois casos de separação distintos: a separação de uma mistura de frutose-glucose e a separação de uma mistura racémica de pindolol. Para ambos os casos foram considerados e comparados dois modos de operação da unidade de SMB: o modo convencional e o modo Varicol. Desta forma, foi realizada a implementação e simulação de ambos os casos de separação no simulador de processos Aspen Chromatography, mediante a utilização de duas unidades de SMB distintas (SMB convencional e SMB Varicol). Para a separação da mistura frutose-glucose, no quediz respeito à modelização da unidade de SMB convencional, foram utilizadas duas abordagens: a de um leito móvel verdadeiro (modelo TMB) e a de um leito móvel simulado real (modelo SMB). Para a separação da mistura racémica de pindolol foi considerada apenas a modelização pelo modelo SMB. No caso da separação da mistura frutose-glucose, procedeu-se ainda à otimização de ambas as unidades de SMB convencional e Varicol, com o intuito do aumento das suas produtividades. A otimização foi realizada mediante a aplicação de um procedimento de planeamento experimental, onde as experiências foram planeadas, conduzidas e posteriormente analisadas através da análise de variância (ANOVA). A análise estatística permitiu selecionar os níveis dos fatores de controlo de modo a obter melhores resultados para ambas as unidades de SMB.

A novel voltage step-down/up ZCS-PWM Zeta converter

This paper presents an analysis of a novel pulse-width-modulated (PWM) voltage step-down/up Zeta converter, featuring zero-current-switching (ZCS) at the active switches. The applications in de to de and ac to de (rectifier) operation modes are used as examples to illustrate the performance of this new ZCS-PWM Zeta converter. Regarding to the new ZCS-PWM Zeta rectifier proposed, it should be noticed that the average-current mode control is used in order to obtain a structure with high power-factor (HPF) and low total harmonic distortion (THD) at the input current.Two active switches (main and auxiliary transistors), two diodes, two small resonant inductors and one small resonant capacitor compose the novel ZCS-PWM soft-commutation cell, used in these new ZCS-PWM Zeta converters. In this cell, the turn-on of the active switches occurs in zero-current (ZC) and their turn-off in zero-current and zero-voltage (ZCZV). For the diodes, their turn-on process occurs in zero-voltage (ZV) and their reverse-recovery effects over the active switches are negligible. These characteristics make this cell suitable for Insulated-Gate Bipolar Transistors (IGBTs) applications.The main advantages of these new Zeta converters, generated from the new soft-commutation cell proposed, are possibility of obtaining isolation (through their accumulation inductors), and high efficiency, at wide load range. In addition, for the rectifier application, a high power factor and low THD in the input current ran be obtained, in agreement with LEC 1000-3-2 standards.The principle of operation, the theoretical analysis and a design example for the new de to de Zeta converter operating in voltage step-down mode are presented. Experimental results are obtained from a test unit with 500W output power, 110V(dc) output voltage, 220V(dc) input voltage, operating at 50kHz switching frequency. The efficiency measured at rated toad is equal to 97.3%for this new Zeta converter.Finally, the new Zeta rectifier is analyzed, and experimental results from a test unit rated at 500W output power, 110V(dc) output voltage, 220V(rms) input voltage, and operating at 50kHz switching frequency, are presented. The measured efficiency is equal to 96.95%, the power-factor is equal to 0.98, and the input current THD is equal to 19.07%, for this new rectifier operating at rated load.

Quality of performance of the operation of sugarcane mechanized planting in day and night shifts

The sugarcane mechanized planting is becoming increasingly widespread in Brazil due to a higher operability and better working conditions offered to workers compared to other types of planting. Studies related to this topic are insufficient or scarce in Brazil. In this context, the aim of this study was to evaluate the operation quality of sugarcane mechanized planting in two operation shifts, by means of statistical process control. The mechanized planting was held on March 2012 and statistical design was completely randomized with two treatments, totaling 40 replications for the day shift and 40 replications for the night shift. The variables evaluated were: speed, engine rotation, engine oil pressure, water temperature of the engine, effective field capacity and the time consumption hourly and effective fuel. The use of statistical control charts showed that random intrinsic do not cause this process. The tractor alignment error showed outliers in the day and night shifts operations, indicating a possible delay in receiving the signal. The water temperature of the engine and the effective fuel consumption showed lower variability in nighttime operation with average values of 81°C and 22.66 L ha-1, respectively. The hourly fuel consumption had greater variability and consequently lower quality during the night of the operation, with an average consumption of 25.46 L h-1 while the day shift showed 26.86 L h-1.

Kinetic parameters and monomeric conversion of different dental composites using standard and soft-start photoactivation modes

This paper evaluates the photopolymerization kinetics and degree of conversion of different commercial dental composites when photoactivated by a LED curing unit using two different modes (standard and soft-start mode). The investigation was performed on with RelyX ARC (dual-cured), Filtek Z-350 (Nanocomposite), Filtek Z-250 (Hybrid), and Filtek Z-350flow (Flowable) resin composites. The analysis used was attenuated total reflection with a Fourier transform infrared (ATR-FTIR). The RelyX ARC resin demonstrated the highest degree of conversion with both LED photoactivation modes. For this resin a 28% decrease in maximum rate was observed and the time to reach its highest rate was almost 2.3 times higher than when the soft-start photoactivation light curing was used. Z-350flow resin recorder a higher maximum rate using the soft-start mode rather than the standard mode. In contrast, the Z-250 showed a higher value using the standard mode. Although Z-250 and Z-350 showed a higher total degree of conversion effectiveness using the soft-start mode, RelyX and Z-350flow achieved a higher value using the standard mode.

Convective instabilities in two superposed horizontal liquid layers heated laterally.

This work is devoted to the theoretical study of the stability of two superposed horizontal liquid layers bounded by two solid planes and subjected to a horizontal temperature gradient. The liquids are supposed to be immiscible with a nondeformable interface. The forces acting on the system are buoyancy and interfacial tension. Four different flow patterns and temperature profiles are found for the basic state. A linear perturbative analysis with respect to two- and three-dimensional perturbations reveals the existence of three kinds of patterns. Depending on the relative height of both liquids several situations are predicted: either wave propa- gation from cold to the hot regions, or waves propagating in the opposite direction or still stationary longitu- dinal rolls. The behavior of three different pairs of liquids which have been used in experiments on bilayers under vertical gradient by other authors have been examined. The instability mechanisms are discussed and a qualitative interpretation of the different behaviors exhibited by the system is provided. In some configurations it is possible to find a codimension-two point created by the interaction of two Hopf modes with different frequencies and wave numbers. These results suggest to consider two liquid layers as an interesting prototype ? nard-Marangoni problem.

Analysis of mode competition in a monolithic master- oscillator power‐amplifier emitting at 1.5 μm

The optical and radio-frequency spectra of a monolithic master-oscillator power-amplifier emitting at 1.5 ?m have been analyzed in a wide range of steady-state injection conditions. The analysis of the spectral maps reveals that, under low injection current of the master oscillator, the device operates in two essentially different operation modes depending on the current injected into the amplifier section. The regular operation mode with predominance of the master oscillator alternates with lasing of the compound cavity modes allowed by the residual reflectance of the amplifier front facet. The quasi-periodic occurrence of these two regimes as a function of the amplifier current has been consistently interpreted in terms of a thermally tuned competition between the modes of the master oscillator and the compound cavity modes.

Norepinephrine transporters have channel modes of conduction.

Neurotransmitter transporters couple to existing ion gradients to achieve reuptake of transmitter into presynaptic terminals. For coupled cotransport, substrates and ions cross the membrane in fixed stoichiometry. This is in contrast to ion channels, which carry an arbitrary number of ions depending on the channel open time. Members of the gamma-aminobutyric acid transporter gene family presumably function with fixed stoichiometry in which a set number of ions cotransport with one transmitter molecule. Here we report channel-like events from a presumably fixed stoichiometry [norepinephrine (NE)+, Na+, and Cl-], human NE (hNET) in the gamma-aminobutyric acid transporter gene family. These events are stimulated by NE and by guanethidine, an hNET substrate, and they are blocked by cocaine and the antidepressant desipramine. Voltage-clamp data combined with NE uptake data from these same cells indicate that hNETs have two functional modes of conduction: a classical transporter mode (T-mode) and a novel channel mode (C-mode). Both T-mode and C-mode are gated by the same substrates and antagonized by the same blockers. T-mode is putatively electrogenic because the transmitter and cotransported ions sum to one net charge. However, C-mode carries virtually all of the transmitter-induced current, even though it occurs with low probability. This is because each C-mode opening transports hundreds of charges per event. The existence of a channel mode of conduction in a previously established fixed-stoichiometry transporter suggests the appearance of an aqueous pore through the transporter protein during the transport cycle and may have significance for transporter regulation.

Semiconductor optical amplifier-based nonlinear optical-loop mirror with feedback

The behavior of a semiconductor optical amplifier (SOA)-based nonlinear loop mirror with feedback has been investigated as a potential device for all-optical signal processing. In the feedback device, input signal pulses (ones) are injected into the loop, and amplified reflected pulses are fed back into the loop as switching pulses. The feedback device has two stable modes of operation - block mode, where alternating blocks of ones and zeros are observed, and spontaneous clock division mode, where halving of the input repetition rate is achieved. Improved models of the feedback device have been developed to study its performance in different operating conditions. The feedback device could be optimized to give a choice of either of the two stable modes by shifting the arrival time of the switching pulses at the SOA. Theoretically, it was found possible to operate the device at only tens of fJ switching pulse energies if the SOA is biased to produce very high gain in the presence of internal loss. The clock division regime arises from the combination of incomplete SOA gain recovery and memory of the startup sequence that is provided by the feedback. Clock division requires a sufficiently high differential phase shift per unit differential gain, which is related to the SOA linewidth enhancement factor.

Directionality based preventive link maintenance scheme for mobile ad hoc networks

The purpose of this study was to design a preventive scheme using directional antennas to improve the performance of mobile ad hoc networks. In this dissertation, a novel Directionality based Preventive Link Maintenance (DPLM) Scheme is proposed to characterize the performance gain [JaY06a, JaY06b, JCY06] by extending the life of link. In order to maintain the link and take preventive action, signal strength of data packets is measured. Moreover, location information or angle of arrival information is collected during communication and saved in the table. When measured signal strength is below orientation threshold , an orientation warning is generated towards the previous hop node. Once orientation warning is received by previous hop (adjacent) node, it verifies the correctness of orientation warning with few hello pings and initiates high quality directional link (a link above the threshold) and immediately switches to it, avoiding a link break altogether. The location information is utilized to create a directional link by orienting neighboring nodes antennas towards each other. We call this operation an orientation handoff, which is similar to soft-handoff in cellular networks. ^ Signal strength is the indicating factor, which represents the health of the link and helps to predict the link failure. In other words, link breakage happens due to node movement and subsequently reducing signal strength of receiving packets. DPLM scheme helps ad hoc networks to avoid or postpone costly operation of route rediscovery in on-demand routing protocols by taking above-mentioned preventive action. ^ This dissertation advocates close but simple collaboration between the routing, medium access control and physical layers. In order to extend the link, the Dynamic Source Routing (DSR) and IEEE 802.11 MAC protocols were modified to use the ability of directional antennas to transmit over longer distance. A directional antenna module is implemented in OPNET simulator with two separate modes of operations: omnidirectional and directional. The antenna module has been incorporated in wireless node model and simulations are performed to characterize the performance improvement of mobile ad hoc networks. Extensive simulations have shown that without affecting the behavior of the routing protocol noticeably, aggregate throughput, packet delivery ratio, end-to-end delay (latency), routing overhead, number of data packets dropped, and number of path breaks are improved considerably. We have done the analysis of the results in different scenarios to evaluate that the use of directional antennas with proposed DPLM scheme has been found promising to improve the performance of mobile ad hoc networks. ^

Comparing exercise prescribed with exercise completed : effects of gender and mode of exercise

The purpose of this study was to compare the amount of exercise prescribed with the amount completed between two different modes of training intervention and between the sexes. Thirty-two men (mean age = 39.1 years, body mass index = 32.9 kg · m-2) and women (mean age = 39.6 years, body mass index = 32.1 kg · m-2) were prescribed traditional resistance training or light-resistance circuit training for 16 weeks. Lean mass and fat mass were determined by dual-energy X-ray absorptiometry at weeks 1 and 16. A completion index was calculated to provide a measure of the extent to which participants completed exercise training relative to the amount of exercise prescribed. The absolute amount of exercise completed by the circuit training group was significantly greater than the amount prescribed (P < 0.0001). The resistance training group consistently under-completed relative to the amount prescribed, but the difference was not significant. The completion index for the circuit training group (26 ± 21.7%) was significantly different from that of the resistance training group (-7.4 ± 3.0%). The completion index was not significantly different between men and women in either group. These data suggest that overweight and obese individuals participating in light-resistance circuit training complete more exercise than is prescribed. Men and women do not differ in the extent to which they over- or under-complete prescribed exercise.

Raman microscopy study of tyrolite : a multi-anion arsenate mineral

The Raman spectrum of tyrolite, CaCu5(AsO4)2(CO3)(OH) 4.6H2O, from Brixlegg, Tyrol, Austria, is reported. Comparison with copper hydroxy-arsenate and basic carbonates was used to achieve assignments of the observed bands. The AsO43- group is characterized by two υ4 modes around 433 and 480 cm-1 plus a broad band around 840 cm-1 as the υ overlapping with the υ. The υ3 mode is observed as a single band around 355 cm -1. The CO32- υ1 mode is observed around 1035 and 1088 cm-1, although this assignment is difficult because of the in-plane OH bending vibrations at similar frequencies. Two υ4 modes are assigned to the 717 and 755 cm-1 bands. The υ3 mode is present as three bands at 1431, 1463, and 1498 cm-1. A large split caused by bridging carbonates may explain the band at 1370 cm -1. The H2O bending region shows two bands at 1635 and 1667 cm-1 together with stretching modes around 3204 and 3303 cm-1, the first associated with adsorbed H2O, while the second indicates more strongly bonded H2O. Three bands around 3534, 3438, and 3379 cm -1 are assigned to OH stretching modes of the OH groups in the crystal structure. The 202, 262, 301, 524, and 534 cm-1 bands are assigned to Cu-OH bending and stretching modes, whereas the bands around 179, 202, and 217 cm-1 are ascribed to O-(Ca, Cu)-O(H) with the O(H) at much greater distance from the cation. The bands around 503, 570, and 598 cm-1 are ascribed to the Cu-O stretching modes.

To bound or not to bound: preliminary Theory of Time Bounds Specification in strategic alliances

This article augments Resource Dependence Theory with Real Options reasoning in order to explain time bounds specification in strategic alliances. Whereas prior work has found about a 50/50 split between alliances that are time bound and those that are open-ended, their substantive differences and antecedents are ill understood. To address this, we suggest that the two alliance modes present different real options trade-offs in adaptation to environmental uncertainty: ceteris paribus, time-bound alliances are likely to provide abandonment options over open-ended alliances, but require additional investments to extend the alliance when this turns out to be desirable after formation. Open-ended alliances are likely to provide growth options over open-ended alliances, but they demand additional effort to abandon the alliance if post-formation circumstances so desire. Therefore, we expect time bounds specification to be a function of environmental uncertainty: organizations in more uncertain environments will be relatively more likely to place time bounds on their strategic alliances. Longitudinal archival and survey data collected amongst 39 industry clusters provides empirical support for our claims, which contribute to the recent renaissance of resource dependence theory by specifying the conditions under which organizations choose different time windows in strategic partnering.

Project management governance : a situational approach

The purpose of this paper is to show how project management governance is addressed through the use of a specific meta-method. Governance is defined here on two criteria: accountability and performance. Accountability is promoted through transparency and performance is promoted by responsive and responsible decision-making. According to a systemic perspective, transparency and decision-making involve having information, tacit or explicit knowledge, as well as understanding of the context, the different parameters and variables, their interaction and conditions of change. Although this method of methods was built according a heuristic process involving 25 years of various researches and consulting activities, it seems appropriate to draw its foundations. I clarify first my epistemological position and the notion of project and project management, as Art and Science. This lead me to define a "Be" / "Have" posture to this regards. Then, the main theoretical roots of MAP Method are exposed: Boisot' s Social Learning Cycle, Praxeology and Theory of Convention. Then we introduced the main characteristics of the method and the 17 methods and tools constituting MAP "tool box", thus with regard to the project management governance perspective. Finally, I discuss the integration of two managerial modes (operational and project modes) and the consequence in term of governance in a specific socio-techno-economic project/context ecosystem.

A New DER coordination in LV network based on the concept of distributed control

Given the paradigm of smart grid as the promising backbone for future network, this paper uses this paradigm to propose a new coordination approach for LV network based on distributed control algorithm. This approach divides the LV network into hierarchical communities where each community is controlled by a control agent. Different level of communication has been proposed for this structure to control the network in different operation modes.