Search

Summary Endometritis, which is usually caused by bacterial infection, is characterized by high levels of pro‐inflammatory cytokines and a high infertility rate. Triggering receptor expressed on myeloid cells‐1 (TREM‐1) has been recognized as a potent amplifier of inflammatory reactions. Studies have demonstrated reduced inflammatory responses and mortality rates of animals with bacterial infection due to the blocking of TREM‐1 expression. However, whether TREM‐1 deficiency could alleviate the inflammatory reaction in bacterial endometritis is still unclear. Here, TREM‐1 knock‐out (Trem‐1−/−) mice were used to inhibit TREM‐1 signalling to evaluate its role in inflammatory reactions after a highly pathogenic LPS infection in mice uteri. The results demonstrated that TREM‐1 deficiency attenuated the inflammation in mice uteri; markedly reduced the number of polymorphonuclear neutrophils; and suppressed interleukin‐1β (IL‐1β), IL‐6, and tumour necrosis factor‐α (TNF‐α) concentrations in serum as well as their production in inflamed uteri after LPS stimulation. Our results illustrate an anticipated pathogenic impact of TREM‐1 on endometritis during LPS infection and indicate that blocking of TREM‐1 in LPS‐induced endometritis holds considerable promise for blunting excessive inflammation.

Active vibration control of stable rotating machinery with a time-variant structure is a research priority in the field. Simultaneous perturbation stochastic approximation (SPSA), a model-free active control strategy, has attracted a lot of attention from researchers. This paper studies the cost function of the SPSA algorithm to improve its performance in controlling periodic vibration. After the weight vector being perturbed by a perturbation vector, the existing cost functions of the SPSA algorithm can reveal the overall energy variation but hardly detail the variation of each harmonic wave. Therefore, the adaptive notch filter with the SPSA algorithm using these cost functions shows a low convergence speed and a bad control effect in active periodic disturbance controlling. In order to detail the energy variation of each harmonic, this paper proposes a cost function using the weighted cross correlation function. When the algorithm calculates the energy of each harmonic wave, the disturbances from other harmonics and background noise are reduced. The interference noises in the estimated gradient of the cost function are reduced indirectly. The algorithm convergence performance improves. To illustrate that, the simulations of controlling harmonic waves and the experiments of eliminating the vibration of the pump inlet pipeline are conducted. The results indicate that the adaptive notch filter with the proposed cost function has reached the fastest convergence speed and the best control effect so far among the use of other cost functions mentioned in this paper.

Epidemiological studies have corroborated that respiratory diseases, including lung cancer, are related to fine particulate matter (

Temporal lobe epilepsy (TLE) is characterized by recurrent seizures driven by synchronous neuronal activity. The reorganization of the dentate gyrus (DG) in TLE may create pathological conduction pathways for synchronous discharges in the temporal lobe, though critical microcircuit-level detail is missing from this pathophysiological intuition. In particular, the relative contribution of adult-born (abGC) and mature (mGC) granule cells to epileptiform network events remains unknown. We assess dynamics of abGCs and mGCs during interictal epileptiform discharges (IEDs) in mice with TLE as well as sharp-wave ripples (SPW-Rs) in healthy mice, and find that abGCs and mGCs are desynchronized and differentially recruited by IEDs compared to SPW-Rs. We introduce a neural topic model to explain these observations, and find that epileptic DG networks organize into disjoint, cell-type specific pathological ensembles in which abGCs play an outsized role. Our results characterize identified GC subpopulation dynamics in TLE, and reveal a specific contribution of abGCs to IEDs., The dentate gyrus is involved in synchronous discharges and seizures, but its microcircuit functional organization in TLE is unclear. Here, the authors show that interictal discharges recruit specific granule cell ensembles dominated by adult-born immature neurons.

Temporal lobe epilepsy (TLE) is characterized by recurrent seizures driven by synchronous neuronal activity. The dentate gyrus (DG) region of the hippocampal formation is highly reorganized in chronic TLE; in particular, pathological remodeling of the “dentate gate” is thought to open up pathological conduction pathways for synchronous discharges and seizures in the mesial temporal lobe. However, this pathophysiological framework lacks a mechanistic explanation of how macroscale synchronous dynamics emerge from alterations of the DG at the microcircuit level. In particular, the relative contribution of developmentally defined subpopulations of adult-born (abGCs) and mature (mGCs) granule cells to epileptiform network events remains unknown. To address this question, we optically recorded activity dynamics of identified populations of abGCs and mGCs during interictal epileptiform discharges (IEDs) in mice with chronic TLE. We find that disjoint subsets of IEDs differentially recruit abGC and mGC populations. We used these observations to develop a neural topic modeling framework, under which we find that the epileptic DG network organizes into disjoint, cell-type specific pathological ensembles, a subset of which are recruited by each IED. We found that statistics of this ensemble structure are highly conserved across animals, with abGCs disproportionately driving network activity in the epileptic DG during IEDs. Our results provide the first in vivo characterization of activity dynamics of identified GC subpopulations in the epileptic DG, the first microcircuit-level correlates of IEDs in vivo, and reveal a specific contribution of abGCs to interictal epileptic events.HighlightsWe relate electrographic signatures of epilepsy to microcircuit dynamics at single-cell resolutionThe chronically epileptic dentate gyrus granule cell network is organized in lineage-specific pathological ensemblesA novel generative model framework for ensemble recruitment relates local field potential signatures to microcircuit activation during interictal epileptiform dischargesAdult-born granule cell-dominated ensembles are disproportionately represented among the inferred ensemblesThe most active ensemble during an interictal epileptiform discharge can be decoded directly from the local field potential spectrumThis Latent Ensemble Recruitment model of cell recruitment by interictal events is the first application of Bayesian topic modeling to in vivo two-photon calcium imaging data

Summary DNA vaccines, the third‐generation vaccines, were extensively studied. The attenuated Salmonella choleraesuis (S. choleraesuis) was widely focused as a carrier to deliver DNA vaccines in the chromosome–plasmid balanced‐lethal system. The efficacy of inhibin DNA vaccine delivered by attenuated S. choleraesuis was proved in mice and cows in our previous studies. In this study, the efficacy of inhibin DNA vaccine was confirmed in rhesus monkeys. To further study the biodistribution and safety, the mice were immunized under laboratory conditions. The results of the rhesus monkeys showed the plasma IgA and IgG titres against inhibin were elevated, and the oestradiol (E2) and progesterone (P4) levels were increased with immunizing inhibin DNA vaccine. The biodistribution and safety assessment displayed the body weight, pathological change and haematology indexes where there is no significant difference between vaccinated mice and control. And the genomics analysis showed there was no integration of the inhibin gene into the mouse genome 2 months after immunization. This study indicated the inhibin DNA vaccine delivered by attenuated S. choleraesuis was safe. And this vaccine was a potential means to improve their reproductive traits in primates and other animals.

As an efficient and low-cost adsorbent, biochar has attracted extensive attention and research in the field of heavy metal pollution water treatment due to its superiority in heavy metal adsorption. However, research progress on the physicochemical properties of biochar, adsorption mechanism, modified biochar and the factors affecting the adsorption of heavy metal, there is still a lack of relevant information in the field application of heavy metal polluted water bodies. This review firstly summarizes the effects of physicochemical properties such as pore distribution, element composition, pH value, specific surface area, cation exchange capacity and surface functional groups on the adsorption of heavy metals by biochar under different raw materials and pyrolysis temperatures. The physicochemical properties and effects of biochar improved by physical and chemical modification methods in recent years are discussed, as well as the dosage of biochar, pH value of water, temperature of water, initial concentrations and types of other cations and heavy metals in water, ageing process of biochar and other factors affecting the removal effect of heavy metals. The different mechanisms of heavy metals adsorption by different physicochemical properties are also given, which can be mainly divided into physical adsorption, ion exchange and surface complexation, electrostatic interaction and redox effect, and precipitation effect. Finally, research gaps and uncertainties of biochar in the water treatment of heavy metal polluted water bodies are pointed out, and further research needs and future research directions are proposed.

This paper describes the learning and control capabilities of a biologically constrained bottom-up model of the mammalian cerebellum. Results are presented from six tasks: 1) eyelid conditioning; 2) pendulum balancing; 3) proportional-integral-derivative control; 4) robot balancing; 5) pattern recognition; and 6) MNIST handwritten digit recognition. These tasks span several paradigms of machine learning, including supervised learning, reinforcement learning, control, and pattern recognition. Results over these six domains indicate that the cerebellar simulation is capable of robustly identifying static input patterns even when randomized across the sensory apparatus. This capability allows the simulated cerebellum to perform several different supervised learning and control tasks. On the other hand, both reinforcement learning and temporal pattern recognition prove problematic due to the delayed nature of error signals and the simulator's inability to solve the credit assignment problem. These results are consistent with previous findings which hypothesize that in the human brain, the basal ganglia is responsible for reinforcement learning, while the cerebellum handles supervised learning.

Identification of different neuronal cell types is critical for understanding their contribution to brain functions. Yet, automated and reliable classification of neurons remains a challenge, primarily because of their biological complexity. Typical approaches include laborious and expensive immunohistochemical analysis while feature extraction algorithms based on cellular characteristics have recently been proposed. The former rely on molecular markers, which are often expressed in many cell types, while the latter suffer from similar issues: finding features that are distinctive for each class has proven to be equally challenging. Moreover, both approaches are time consuming and demand a lot of human intervention. In this work we establish the first, automated cell-type classification method that relies on neuronal activity rather than molecular or cellular features. We test our method on a real-world dataset comprising of raw calcium activity signals for four neuronal types. We compare the performance of three different deep learning models and demonstrate that our method can achieve automated classification of neuronal cell types with unprecedented accuracy.

In a nonequilibrium multiphase system, the Marangoni effect has important influence on interphase heat and mass transfer induced by interfacial tension gradient associated with either solutal or thermal gradients in numerous applications. Although the basic knowledge of the Marangoni effect has made great progress, its mechanism is not yet fully recognized. An in-depth understanding of the basic principles of heat and mass transport induced by the Marangoni effect is important for better operation of interphase transfer units. This report aims to provide a systematic study of the mechanisms of the Marangoni effect. Special foci are concentrated on the field of material processing, which encompasses the process wherein the raw materials are transformed into useful engineering products. A series of experimental, theoretical, or simulated results are extracted from the literature to elucidate the mechanism of the Marangoni effect and to rationalize the interphase transport phenomena. We examine the major physical explanations and attempt to distinguish the working principle behind the process. Perspectives are also proposed to trigger further innovative thinking about the topics. This work provides new insight into material processing by taking advantage of the Marangoni effect and has far-reaching implications in the design of future nonequilibrium multiphase system.

Based on the grey correlation analysis method, the chilling damage inducing factors and yield structure traits of rice in different growth stages, and the yield structure traits and final yield of rice were regarded as two grey systems. By seeking the grey relations of the grey systems and using the multi level grey correlation analysis method, the comprehensive assessment model of rice chil-ling damage was constructed, and the comprehensive assessment indices of chilling damages in sepa rate stages were established. The rice chilling damages at 27 stations in Northeast China from 1961 to 2015 were assessed separately. The results showed that there was a good corresponding relationship between the chilling damage and the rice yield. The low temperature during the vegetative growth stage, the vegetative growth and reproductive stage, the pollination stage or the grain filling stage significantly decreased the panicle number per plant, the average panicle grain number or the thousand kernel mass, and increased the empty grain rate. A good correspondence existed between temperature and rice yield in the typical chilling damage years.基于灰色关联分析法，将水稻不同生育期的冷害致灾因子值和产量结构性状、水稻不同生育期的产量结构性状和最终产量分别视作两个灰色系统，通过寻找各个灰色系统的灰映射关系，建立基于多层次灰色关联分析法的水稻低温冷害综合评估模型；并构建了单站各生育期、全生育期的冷害综合评估指数和区域评估指数，对东北水稻主产区27个站1961—2015年水稻冷害进行分生育期评估.结果表明：水稻冷害影响程度与各生育期产量丰歉能够较好对应.营养生长期、营养和生殖生长并进期、授粉结实期或满浆期受到冷害影响时，株穗数、平均穗粒数或千粒重有一定减少，空壳率有所增加.典型冷害年温度与单站或区域产量丰歉有较好的对应关系.

Summary Diverse computations in the neocortex are aided by specialized GABAergic interneurons (INs), which selectively target other INs. However, much less is known about how these canonical disinhibitory circuit motifs contribute to network operations supporting spatial navigation and learning in the hippocampus. Using chronic two-photon calcium imaging in mice performing random foraging or goal-oriented learning tasks, we found that vasoactive intestinal polypeptide-expressing (VIP+), disinhibitory INs in hippocampal area CA1 form functional subpopulations defined by their modulation by behavioral states and task demands. Optogenetic manipulations of VIP+ INs and computational modeling further showed that VIP+ disinhibition is necessary for goal-directed learning and related reorganization of hippocampal pyramidal cell population dynamics. Our results demonstrate that disinhibitory circuits in the hippocampus play an active role in supporting spatial learning. Video Abstract

To reduce heat loss and save cost, a combination decision model of reverb aluminum holding furnace linings in aluminum casting industry was established based on economic thickness method, and was resolved using simulated annealing. Meanwhile, a three-dimensional mathematical model of aluminum holding furnace linings was developed and integrated with user-defined heat load distribution regime model. The optimal combination was as follows: side wall with 80 mm alumino-silicate fiber felts, 232 mm diatomite brick and 116 mm chamotte brick; top wall with 50 mm clay castables, 110 mm alumino-silicate fiber felts and 200 mm refractory concrete; and bottom wall with 232 mm high-alumina brick, 60 mm clay castables and 68 mm diatomite brick. Lining temperature from high to low was successively bottom wall, side wall, and top wall. Lining temperature gradient in increasing order of magnitude was refractory layer and insulation layer. It was indicated that the results of combination optimization of aluminum holding furnace linings were valid and feasible, and its thermo-physical mechanism and cost characteristics were reasonably revealed.

A palladium-catalyzed (3 + 2) cycloaddition of vinyl cyclopropane and α,β-unsaturated imines generated in situ from aryl sulfonyl indoles is reported. The reaction proceeds with high diastereoselectivity to provide the optically enriched spirocyclopentane-1,3'-indolenines in up to 74% yield and with up to 97% ee, which contains an all-carbon quaternary center and two tertiary stereocenters. The reaction involves a first conjugate addition of the carbon anion of zwitterionic π-allylpalladium complex from vinyl cyclopropane to the in situ formed unsaturated imine followed by a palladium-catalyzed intramolecular C3-allylation of indole.

Palladium-catalyzed enantioselective cycloaddition of vinyl cyclopropane dicarbonitriles and nitroolefins was achieved to generate structurally and optically enriched nitrocyclopentanes with three consecutive chiral carbon centers in up to 96 % yield and with up to 92 % ee. The two diastereoisomers produced in each reaction are readily separable by simple chromatography. The present method allows the preparation of both diastereoisomers in optically enriched form.

To achieve high heat efficiency, low pollutant emission and homogeneous melt temperature during thermal process of secondary aluminum, taking into account the features of aluminum alloying process, a CFD process model was developed and integrated with heat load and aluminum temperature control model. This paper presented numerical simulation of aluminum holding furnaces using the customized code based on FLUENT packages. Thermal behaviors of aluminum holding furnaces were investigated by probing into main physical fields such as flue gas temperature, velocity, and concentration, and combustion instability of aluminum holding process was represented by chaos theory. The results show that aluminum temperature uniform coefficient firstly decreases during heating phase, then increases and reduces alternately during holding phase, lastly rises during standing phase. Correlation dimension drops with fuel velocity. Maximal Lyapunov exponent reaches to a maximum when air–fuel ratio is close to 1. It would be a clear comprehension about each phase of aluminum holding furnaces to find new technology, retrofit furnace design, and optimize parameters combination.

It is indispensable for strengthening smelting process and controlling fine to understand metallurgical behaviors and mechanism of production process of aluminum holding furnaces. A CFD (computational fluid dynamics) compressive process model was developed and integrated with energy distribution regime using user subroutines based on FLUENT code. Integrated intelligence ideas with a combination of response surface methodology and uniform design was employed to quantitatively achieve the inherent laws of thermal characteristics and mechanism behind various factors. The optimal scheme obtained from the compromise of the two desirable responses was as follows: flue position of same side, oxidant type of pure oxygen, air preheated temperature of 719 K, natural gas velocity of 108.88 m/s, burner height of 1150 mm, vertical burner angle of 5°, pool depth of 625 mm, horizontal spacing between burners of 2050 mm, height-radius ratio of 0.6, air–fuel ratio of 1.04, and burner load ratio of 1:1. The maximal end aluminum temperature uniform coefficient of 12.85% and minimal energy consumption per ton of aluminum of 0.01092 kg ce/t-Al were obtained. Confirmed experiments demonstrated that such a combination of the CFD, RSM (response surface methodology) and UD (uniform design) is a powerful and useful approach for process optimization of aluminum holding furnaces.

According to the features of melting process of regenerative aluminum melting furnaces, a three-dimensional mathematical model with user-developed melting model, burner reversing and burning capacity model was established. The numerical simulation of melting process of a regenerative aluminum melting furnace was presented using hybrid programming method of FLUENT UDF and FLUENT scheme based on the heat balance test. Burner effects on melting process of aluminum melting furnaces were investigated by taking optimization regulations into account. The change rules of melting time on influence factors are achieved. Melting time decreases with swirl number, vertical angle of burner, air preheated temperature or natural gas flow; melting time firstly decreases with horizontal angle between burners or air-fuel ratio, then increases; melting time increases with the height of burner.

Adult Drosophila melanogaster has long been a popular model for learning and memory studies. Now the larval stage of the fruit fly is also being used in an increasing number of classical conditioning studies. In this study, we employed heat shock as a novel negative reinforcement for larvae and obtained high learning scores following just one training trial. We demonstrated heat-shock conditioning in both reciprocal and non-reciprocal paradigms and observed that the time window of association for the odor and heat shock reinforcement is on the order of a few minutes. This is slightly wider than the time window for electroshock conditioning reported in previous studies, possibly due to lingering effects of the high temperature. To test the utility of this simplified assay for the identification of new mutations that disrupt learning, we examined flies carrying mutations in the dnc gene. While the sensitivity to heat shock, as tested by writhing, was similar for wild type and dnc homozygotes, dnc mutations strongly diminished learning. We confirmed that the learning defect in dnc flies was indeed due to mutation in the dnc gene using non-complementation analysis. Given that heat shock has not been employed as a reinforcement for larvae in the past, we explored learning as a function of heat shock intensity and found that optimal learning occurred around 41 °C, with higher and lower temperatures both resulting in lower learning scores. In summary, we have developed a very simple, robust paradigm of learning in fruit fly larvae using heat shock reinforcement.

Hydraulic system is the important system in plane,hydraulic transmission mainly completes subject components hoisting,actuator manipulation,wheel brake,etc.According to the statistics,the current military aircraft hy-draulic system failure account for about 30% of total failure of mechanical and hydraulic,its system maintenance work load is about 1/3 of total mechanical maintenance.Therefore,keeping the normal operating hydraulic system condition is the important content of maintenance system.There are many hydraulic fault diagnosis and diagnostic methods.In this paper,we briefly describe the aircraft fluid system theory of fault diagnosis and its advantages and disadvantages with the basic theory of traditional hydraulic introduction of fault diagnosis,and put forward a kind of method based on the AHP default tree analysis under plane of hydraulic system failure prevention and eliminate research methods.We hope to provide a scientific management measure method for aircrft maintenance and diagnosis of hydraulic by this method.

Palladium-catalyzed enantioselective cycloaddition of vinyl cyclopropane dicarbonitriles and nitroolefins was achieved to generate structurally and optically enriched nitrocyclopentanes with three consecutive chiral carbon centers in up to 96 % yield and with up to 92 % ee. The two diastereoisomers produced in each reaction are readily separable by simple chromatography. The present method allows the preparation of both diastereoisomers in optically enriched form.

The unsaturated imines, involved in the title [3+2] cycloadditions, are generated in situ from aryl sulfonyl indoles [(I) and (IV)].

The design optimizes, the oil-saving rate of the rare earth permanent magnetism energy conservation strengthened by the electric field is higher than domestic similar ones not adding the electric field and not to optimize the design magnetization. The gantry empirical datum indicated that on the condition that the power is under 42–52 horsepower condition, does not add electric field, saving oil rate is 5.2%-10.5%, after adding the electric field, saving oil rate is 5.7%-11.3%. The gantry experiment indicated that the motive installing this magnetization saving gas oil appliance will have higher operating speed, compared with not installing magnetization saving oil appliance in the same power. This saving oil, volume small, the structure is compact, is easy to operate, designed bravely and innovated, receives the welcome of the users and the factories.

The technology is introduced about mechanical ball milling and liquid phase sintering of machining crumbs of steel based carbide alloy in this article. The materials obtained from machining crumbs of steel-bonded cemented carbide are qualified compared with the conventional steel-bonded cemented carbide materials in the aspects of hardness, wear resistance by using the technology and the process is reasonable and practicable, according to experimental results. It can be extremely important when considering the recycling and make full use of tungsten resources.

The analysis of well-defined behaviors that require the cerebellum has helped reveal many key mechanisms operating in the cerebellum to mediate learning and feed-forward prediction. These systems include eyelid conditioning, adaptation of the vestibuloocular reflex, smooth pursuit eye movements, and arm-reaching tasks. This review focuses specifically on the variety of findings that have come from the use of eyelid conditioning to study the cerebellum. Phenomena discussed include sites and rules for plasticity, temporal coding and mechanisms of timing, cerebellar control of climbing fibers and its role in bidirectional learning, extinction of conditioned responses, and the phenomenon of savings.

With increasing use of various techniques to record optically and electrophysiologically from awake behaving animals and the growing developments of brain-machine interfaces, one might wonder if the use of acute-slice physiology is on its deathbed. Have we actually arrived at a stage where we can abandon the use of acute slices, with most of the information about brain functions coming from in vivo experiments? We do not believe that this is the case, given that our understanding of the nuts and bolts of the nervous system, such as ion channels and transporters in near-native state, neuronal compartmentalization, and single-neuron computation, is far from complete. We believe that in the foreseeable future, questions in these fields will still be best addressed by acute-slice physiology. We approach this review from the perspective of improving acute-slice physiology so it can continue to provide relevant and valuable contributions to neuroscience. We conclude that the death of acute-slice physiology is an obituary prematurely written, merely due to waxing and waning trends in science and the shortsightedness of investigators. Acute-slice physiology has at least one more life to live after the hype around new techniques has passed, but it needs to reinvent itself in light of current knowledge.

Several factors combine to make it feasible to build computer simulations of the cerebellum and to test them in biologically realistic ways. These simulations can be used to help understand the computational contributions of various cerebellar components, including the relevance of the enormous number of neurons in the granule cell layer. In previous work we have used a simulation containing 12000 granule cells to develop new predictions and to account for various aspects of eyelid conditioning, a form of motor learning mediated by the cerebellum. Here we demonstrate the feasibility of scaling up this simulation to over one million granule cells using parallel graphics processing unit (GPU) technology. We observe that this increase in number of granule cells requires only twice the execution time of the smaller simulation on the GPU. We demonstrate that this simulation, like its smaller predecessor, can emulate certain basic features of conditioned eyelid responses, with a slight improvement in performance in one measure. We also use this simulation to examine the generality of the computation properties that we have derived from studying eyelid conditioning. We demonstrate that this scaled up simulation can learn a high level of performance in a classic machine learning task, the cart-pole balancing task. These results suggest that this parallel GPU technology can be used to build very large-scale simulations whose connectivity ratios match those of the real cerebellum and that these simulations can be used guide future studies on cerebellar mediated tasks and on machine learning problems.

Drosophila melanogaster larvae are model systems for studies of development, synaptic transmission, sensory physiology, locomotion, drug discovery, and learning and memory. A detailed behavioral understanding of larvae can advance all these fields of neuroscience. Automated tracking can expand fine-grained behavioral analysis, yet its full potential remains to be implemented for the larvae. All published methods are unable to track the larvae near high contrast objects, including the petri-dish edges encountered in many behavioral paradigms. To alleviate these issues, we enhanced the larval contrast to obtain complete tracks. Our method employed a dual approach of optical-contrast boosting and post-hoc image processing for contrast enhancement. We reared larvae on black food media to enhance their optical contrast through darkening of their digestive tracts. For image processing we performed Frame Averaging followed by Subtraction then Thresholding (FAST). This algorithm can remove all static objects from the movie, including petri-dish edges prior to processing by the image-tracking module. This dual approach for contrast enhancement also succeeded in overcoming fluctuations in illumination caused by the alternating current power source. Our tracking method yields complete tracks, including at the edges of the behavioral arena and is computationally fast, hence suitable for high-throughput fine-grained behavioral measurements.

Drosophila melanogaster has proven to be a useful model system for the genetic analysis of ethanol-associated behaviors. However, past studies have focused on the response of the adult fly to large, and often sedating, doses of ethanol. The pharmacological effects of low and moderate quantities of ethanol have remained understudied. In this study, we tested the acute effects of low doses of ethanol (∼7 mM internal concentration) on Drosophila larvae. While ethanol did not affect locomotion or the response to an odorant, we observed that ethanol impaired associative olfactory learning when the heat shock unconditioned stimulus (US) intensity was low but not when the heat shock US intensity was high. We determined that the reduction in learning at low US intensity was not a result of ethanol anesthesia since ethanol-treated larvae responded to the heat shock in the same manner as untreated animals. Instead, low doses of ethanol likely impair the neuronal plasticity that underlies olfactory associative learning. This impairment in learning was reversible indicating that exposure to low doses of ethanol does not leave any long lasting behavioral or physiological effects.

Enantioselective conjugate addition of diethyl zinc to vinylogous imines generated in situ from sulfonyl indoles was developed. Various sulfonyl indoles reacted with diethyl zinc in the presence of chiral phosphoramidites in combination with copper triflate affording the corresponding indole substituted alkanes in up to 99% yield with moderate to good enanti- oselectivity (up to 80% ee).