211 research outputs found

    Application of a Machine Learning Algorithm in a Multi Stage Production System

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    This paper examines a permutation flow-shop scheduling problem, which is a complex combinatorial problem encountered in many practical applications. The objective of the research is to reduce the maximum completion time, i.e., the makespan of all jobs. In order to increase productivity and to meet the demand, manufacturers are continuously under pressure to attain the shortest possible completion time. Estimation of accurate cycle time can tremendously help production planning and scheduling in manufacturing industries. Since production planning is characterised by NP-hardness and a wide range, traditional optimization methods and heuristic rules are unable to find satisfactory solutions. Q-learning, a type of reinforcement learning algorithm, is used in this paper to find a solution that is close to being optimal. Q-learning is a branch of machine learning referring to the way an intelligent agent should act in order to maximize the concept of cumulative reward in a given environment. To validate the performance of the algorithm, Taillard’s benchmark problems were solved and compared with the upper bound value. The results showed that the performance of the algorithm is better and has low computational time. Based on the performance of the proposed algorithm, two case studies were done and the solutions are compared with the performance of a metaheuristic algorithm. The result shows that the proposed algorithm can effectively and efficiently solve the problem stated above and that it is an interesting solution to resolving complex scheduling problems

    Should reporting of peri-neural invasion and extra prostatic extension be mandatory in prostate cancer biopsies? Correlation with outcome in biopsy cases treated conservatively

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    The identification of perineural invasion (PNI) and extraprostatic extension (ECE) in prostate cancer (PC) biopsies is time consuming and can be difficult. Although this is required information in many datasets, there is little evidence on their effect on outcome in patients treated conservatively. Cases of PC were identified from three cancer registries in the UK from men with clinically localized prostate cancer diagnosed by needle biopsy from 1990-2003. The endpoint was prostate cancer death (DOD). Patients treated radically within 6 months, those with objective evidence of metastases or who had prior hormone therapy were excluded. Follow-up was through cancer registries up until 2012. Deaths were divided into those from PC and those from other causes, according to WHO criteria. 988 biopsy cases (6522 biopsy cores) were centrally reviewed by three uropathologists and assigned a Gleason score and Grade Group (GG). The presence of both PNI and ECE was recorded. Of 988 patients, PNI was present in 288 (DOD = 75) and ECE in 23 (DOD = 5). On univariable analysis PNI was highly significantly associated with DOD (hazard ratio [HR] 2.28, 95% CI: 1.68, 3.1, log-rank test p-value = 4.8 × 10-8), but ECE was not (log-rank test p-value = 0.334). On multivariable analysis with GG, serum PSA (per 10%), clinical stage and extent of disease (per 10%), PNI lost significance (HR 1.16, 95% CI: 0.83, 1.63, likelihood ratio test p-value = 0.371). The utility of routinely examining prostate biopsies for ECE and PNI is doubtful as it is not independently associated with higher grade, stage or prognosis.</p

    Coherence Potentials Encode Simple Human Sensorimotor Behavior

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    Recent work has shown that large amplitude negative periods in the local field potential (nLFPs) are able to spread in saltatory manner across large distances in the cortex without distortion in their temporal structure forming ‘coherence potentials’. Here we analysed subdural electrocorticographic (ECoG) signals recorded at 59 sites in the sensorimotor cortex in the left hemisphere of a human subject performing a simple visuomotor task (fist clenching and foot dorsiflexion) to understand how coherence potentials arising in the recordings relate to sensorimotor behavior. In all behaviors we found a particular coherence potential (i.e. a cascade of a particular nLFP wave pattern) arose consistently across all trials with temporal specificity. During contrateral fist clenching, but not the foot dorsiflexion or ipsilateral fist clenching, the coherence potential most frequently originated in the hand representation area in the somatosensory cortex during the anticipation and planning periods of the trial, moving to other regions during the actual motor behavior. While these ‘expert’ sites participated more consistently, other sites participated only a small fraction of the time. Furthermore, the timing of the coherence potential at the hand representation area after onset of the cue predicted the timing of motor behavior. We present the hypothesis that coherence potentials encode information relevant for behavior and are generated by the ‘expert’ sites that subsequently broadcast to other sites as a means of ‘sharing knowledge’

    Transcriptome Analysis of Synaptoneurosomes Identifies Neuroplasticity Genes Overexpressed in Incipient Alzheimer's Disease

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    In Alzheimer's disease (AD), early deficits in learning and memory are a consequence of synaptic modification induced by toxic beta-amyloid oligomers (oAβ). To identify immediate molecular targets downstream of oAβ binding, we prepared synaptoneurosomes from prefrontal cortex of control and incipient AD (IAD) patients, and isolated mRNAs for comparison of gene expression. This novel approach concentrates synaptic mRNA, thereby increasing the ratio of synaptic to somal mRNA and allowing discrimination of expression changes in synaptically localized genes. In IAD patients, global measures of cognition declined with increasing levels of dimeric Aβ (dAβ). These patients also showed increased expression of neuroplasticity related genes, many encoding 3′UTR consensus sequences that regulate translation in the synapse. An increase in mRNA encoding the GluR2 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) was paralleled by elevated expression of the corresponding protein in IAD. These results imply a functional impact on synaptic transmission as GluR2, if inserted, maintains the receptors in a low conductance state. Some overexpressed genes may induce early deficits in cognition and others compensatory mechanisms, providing targets for intervention to moderate the response to dAβ

    Gradients and Modulation of K+ Channels Optimize Temporal Accuracy in Networks of Auditory Neurons

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    Accurate timing of action potentials is required for neurons in auditory brainstem nuclei to encode the frequency and phase of incoming sound stimuli. Many such neurons express “high threshold” Kv3-family channels that are required for firing at high rates (>∼200 Hz). Kv3 channels are expressed in gradients along the medial-lateral tonotopic axis of the nuclei. Numerical simulations of auditory brainstem neurons were used to calculate the input-output relations of ensembles of 1–50 neurons, stimulated at rates between 100–1500 Hz. Individual neurons with different levels of potassium currents differ in their ability to follow specific rates of stimulation but all perform poorly when the stimulus rate is greater than the maximal firing rate of the neurons. The temporal accuracy of the combined synaptic output of an ensemble is, however, enhanced by the presence of gradients in Kv3 channel levels over that measured when neurons express uniform levels of channels. Surprisingly, at high rates of stimulation, temporal accuracy is also enhanced by the occurrence of random spontaneous activity, such as is normally observed in the absence of sound stimulation. For any pattern of stimulation, however, greatest accuracy is observed when, in the presence of spontaneous activity, the levels of potassium conductance in all of the neurons is adjusted to that found in the subset of neurons that respond better than their neighbors. This optimization of response by adjusting the K+ conductance occurs for stimulus patterns containing either single and or multiple frequencies in the phase-locking range. The findings suggest that gradients of channel expression are required for normal auditory processing and that changes in levels of potassium currents across the nuclei, by mechanisms such as protein phosphorylation and rapid changes in channel synthesis, adapt the nuclei to the ongoing auditory environment

    Selective Cholinergic Depletion in Medial Septum Leads to Impaired Long Term Potentiation and Glutamatergic Synaptic Currents in the Hippocampus

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    Cholinergic depletion in the medial septum (MS) is associated with impaired hippocampal-dependent learning and memory. Here we investigated whether long term potentiation (LTP) and synaptic currents, mediated by alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors in the CA1 hippocampal region, are affected following cholinergic lesions of the MS. Stereotaxic intra-medioseptal infusions of a selective immunotoxin, 192-saporin, against cholinergic neurons or sterile saline were made in adult rats. Four days after infusions, hippocampal slices were made and LTP, whole cell, and single channel (AMPA or NMDA receptor) currents were recorded. Results demonstrated impairment in the induction and expression of LTP in lesioned rats. Lesioned rats also showed decreases in synaptic currents from CA1 pyramidal cells and synaptosomal single channels of AMPA and NMDA receptors. Our results suggest that MS cholinergic afferents modulate LTP and glutamatergic currents in the CA1 region of the hippocampus, providing a potential synaptic mechanism for the learning and memory deficits observed in the rodent model of selective MS cholinergic lesioning
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