Mixed tetraoxanes containing the acetone subunit as antimalarials

Eleven new tetraoxanes possessing cholic acid-derived carrier and isopropylidene moiety were synthesized and were tested in vitro and in vivo. In vitro screening revealed that nine of them were more potent against CQ-resistant W2 than CQ-susceptible D6 strain and that two of them were equally or more potent than artemisinin and mefloquine against multi-drug resistant TM91C235 strain. Amine 8 cured all mice at the dose of 160mg/kg/day, while the anilide 9 exhibited MCD相似文献   

A learning theory for reward-modulated spike-timing-dependent plasticity with application to biofeedback

Reward-modulated spike-timing-dependent plasticity (STDP) has recently emerged as a candidate for a learning rule that could explain how behaviorally relevant adaptive changes in complex networks of spiking neurons could be achieved in a self-organizing manner through local synaptic plasticity. However, the capabilities and limitations of this learning rule could so far only be tested through computer simulations. This article provides tools for an analytic treatment of reward-modulated STDP, which allows us to predict under which conditions reward-modulated STDP will achieve a desired learning effect. These analytical results imply that neurons can learn through reward-modulated STDP to classify not only spatial but also temporal firing patterns of presynaptic neurons. They also can learn to respond to specific presynaptic firing patterns with particular spike patterns. Finally, the resulting learning theory predicts that even difficult credit-assignment problems, where it is very hard to tell which synaptic weights should be modified in order to increase the global reward for the system, can be solved in a self-organizing manner through reward-modulated STDP. This yields an explanation for a fundamental experimental result on biofeedback in monkeys by Fetz and Baker. In this experiment monkeys were rewarded for increasing the firing rate of a particular neuron in the cortex and were able to solve this extremely difficult credit assignment problem. Our model for this experiment relies on a combination of reward-modulated STDP with variable spontaneous firing activity. Hence it also provides a possible functional explanation for trial-to-trial variability, which is characteristic for cortical networks of neurons but has no analogue in currently existing artificial computing systems. In addition our model demonstrates that reward-modulated STDP can be applied to all synapses in a large recurrent neural network without endangering the stability of the network dynamics.     

Translating Service Level Objectives to lower level policies for multi-tier services

Service providers and their customers agree on certain quality of service guarantees through Service Level Agreements (SLA). An SLA contains one or more Service Level Objectives (SLO)s that describe the agreed-upon quality requirements at the service level. Translating these SLOs into lower-level policies that can then be used for design and monitoring purposes is a difficult problem. Usually domain experts are involved in this translation that often necessitates application of domain knowledge to this problem. In this article, we propose an approach that combines performance modeling with regression analysis to solve this problem. We demonstrate that our approach is practical and that it can be applied to different n-tier services. Our experiments show that for a typical 3-tier e-commerce application in a virtualized environment, the SLA can be met while improving CPU utilization by up to 3 times.

Feedback Control of an Achiral Robotic Microswimmer

Magnetic microswimmers are useful for navigating and performing tasks at small scales.To demonstrate effective control over such microswimmers,we implemented feedback control of the three-bead achiral microswimmers in both simulation and experiment.The achiral microswimmers with the ability to swim in bulk fluid are controlled wirelessly using magnetic fields generated from electromagnetic coils.The achirality of the microswimmers introduces unknown handedness resulting in uncertainty in swimming direction.We use a combination of rotating and static magnetic fields generated from an approximate Helmholtz coil system to overcome such uncertainty.There are also movement uncertainties due to environmental factors such as unsteady flow conditions.A kinematic model based feedback controller was created based on data fitting of experimental data.However,the controller was unable to yield satisfactory performance due to uncertainties from environmental factors;i.e.,the time to reach target pose under adverse flow condition is too long.Following the implementation of an integral controller to control the microswimmers' swimming velocity,the microswimmers were able to reach the target in roughly half the time.Through simulation and experiments,we show that the feedback control law can move an achiral microswimmer from any initial conditions to a target pose.     

Fatigue compensation during FES using surface EMG

Muscle fatigue limits the effectiveness of FES when applied to regain functional movements in spinal cord injured (SCI) individuals. The stimulation intensity must be manually increased to provide more force output to compensate for the decreasing muscle force due to fatigue. An artificial neural network (ANN) system was designed to compensate for muscle fatigue during functional electrical stimulation (FES) by maintaining a constant joint angle. Surface electromyography signals (EMG) from electrically stimulated muscles were used to determine when to increase the stimulation intensity when the muscle’s output started to drop.

In two separate experiments on able-bodied subjects seated in hard back chairs, electrical stimulation was continuously applied to fatigue either the biceps (during elbow flexion) or the quadriceps muscle (during leg extension) while recording the surface EMG. An ANN system was created using processed surface EMG as the input, and a discrete fatigue compensation control signal, indicating when to increase the stimulation current, as the output. In order to provide training examples and test the systems’ performance, the stimulation current amplitude was manually increased to maintain constant joint angles. Manual stimulation amplitude increases were required upon observing a significant decrease in the joint angle. The goal of the ANN system was to generate fatigue compensation control signals in an attempt to maintain a constant joint angle.

On average, the systems could correctly predict 78.5% of the instances at which a stimulation increase was required to maintain the joint angle. The performance of these ANN systems demonstrates the feasibility of using surface EMG feedback in an FES control system.     

A validated method for the quantification of pimarane and trachylobane diterpenes in the leaves of Croton zambesicus by capillary gas chromatography

A sensitive and accurate method, combining Soxhlet extraction, solid-phase extraction and capillary gas chromatography, is described for the quantitative determination of four new diterpenes (ent-trachyloban-3beta-ol, ent-18-hydroxy-trachyloban-3-one, ent-trachyloban-3-one and isopimara-7,15-dien-3beta-ol) from the leaves of Croton zambesicus. This is the first method describing the quantification of trachylobane diterpenes in a crude extract. It has been fully validated in order to be able to compare the diterpene composition in other samples of C. zambesicus, which is an important source of trachylobanes.     

Protocadherin alpha3 acts at sites distinct from classic cadherins in rat testis and sperm

The testis expresses a variety of cadherin superfamily members including classic cadherins and protocadherins. This report describes the first localization of a protocadherin protein in testis and sperm. After cloning rat cDNAs for protocadherin alpha3 and alpha4, isoform-specific polyclonal antibodies were generated against protocadherin alpha3. Western blotting of rat testis showed that protocadherin alpha3 was solubilized completely by Triton X-100, in contrast to the adhesion junction components N-cadherin, beta-catenin, and p120 catenin. Corroborating this data, protocadherin alpha3 was immunolocalized to the spermatid acrosomal area, intercellular bridge, and flagellum, but not classic cadherin-based adhesion junctions. Acrosome-associated protocadherin alpha3 was first detected at step 8 of spermiogenesis, and this association remained on cauda epididymal sperm. Acrosome immunostaining was reduced, but present, in acrosome-reacted sperm. Spermatid intercellular bridges became positive for protocadherin alpha3 coincident with the appearance of plectin, occurring at spermiogenic steps 8 to 9, and elongate spermatid bridges remained positive throughout spermatogenesis. The developing flagellum was uniformly immunostained for protocadherin alpha3 up to approximately spermiogenic step 17. Subsequently, flagellar immunostaining was confined to the principal piece, and this pattern continued in cauda epididymal sperm. These data show that protocadherin alpha3 performs functions unique from classic cadherins in spermatogenesis and suggest a role for protocadherin alpha3 in organizing germ cell-specific structures including the intercellular bridge, flagellum, and acrosome.     

Therapy of paretic arm in hemiplegic subjects augmented with a neural prosthesis: a cross-over study

There are indications that both intensive exercise and electrical stimulation have a beneficial effect on arm function in post-stroke hemiplegic patients. We recommend the use of Functional Electrical Therapy (FET), which combines electrical stimulation of the paretic arm and intensive voluntary movement of the arm to exercise daily functions. FET was applied 30 min daily for 3 weeks. Forty-one acute hemiplegics volunteered in the 18-months single blinded cross-over study (CoS). Nineteen patients (Group A) participated in FET during their acute hemiplegia, and 22 patients (Group B) participated in FET during their chronic phase of hemiplegia. Group B patients were controls during FET in acute hemiplegia, and Group A patients were controls during the FET in chronic hemiplegia. Thirty-two patients completed the study. The outcomes of the Upper Extremity Function Test (UEFT) were used to assess the ability of patients to functionally use objects, as were the Drawing Test (DT) (used to assess the coordination of the arm), the Modified Ashworth Scale, the range of movement, and the questionnaire estimating the patients' satisfaction with the usage of the paretic arm. Patients who participated in the FET during the acute phase of hemiplegia (Group A) reached functionality of the paretic arm, on average, in less than 6 weeks, and maintained this near-normal use of the arm and hand throughout the follow-up. The gains in all outcome scores were significantly larger in Group A after FET and at all follow-ups compared with the scores before the treatment. The gains in patients who participated in the FET in the chronic phase of hemiplegia (Group B) were measurable, yet not significant. The speed of recovery was larger during the period of the FET compared with the follow-up period. The gains in Group A were significantly larger compared with the gains in Group B. The FET greatly promotes the recovery of the paretic arm if applied during the acute phase of post-stroke hemiplegia.     

Canonical labeling of proteome maps

We propose a canonical labeling of proteome maps, which enables one to sort and catalog the maps in a simple way. The canonical label of a proteome map is based on the canonical labeling of vertexes of Hasse diagram embedded in the map resulting in the adjacency matrix, the rows of which when viewed as binary numbers are the smallest possible such numbers. The use of the approach in documentation is illustrated with the proteome maps of liver cells of healthy male Fisher F344 rats and the rats treated with different peroxisome proliferators.