Search

Most existing autoscaling approaches help to avoid violating the performance-related Service Level Objectives (SLO). However, these solutions do not aim to recover the SLO. The proposed novel autoscaling solution covers both SLO violation avoidance and recovery. The SLO failure avoidance part of the solution aims to avoid SLO violations by adjusting autoscaling thresholds based on compliance with SLO. It also dynamically selects the required CPU threshold, cooldown intervals and the number of replicas based on load velocity. The recovery part of the solution aims to recover SLO by additional resource provisioning if SLO is violated due to a delay or resource underestimation. The proposed implementation of the solution targets embarrassingly parallel workloads. It is compared with two autoscaling solutions in five workload scenarios, evaluating the ability of the solution to operate close to the defined SLO values. The results show that the proposed solution provides sufficient resources to support or recover performance-based SLOs. [ABSTRACT FROM AUTHOR]

As cloud data centers are dramatically growing, various applications are moved to cloud data centers owing to cost benefits for maintenance and hardware resources. However, latency-critical workloads among them suffer from some problems to fully achieve the cost-effectiveness. The latency-critical workloads should show latencies in a stable manner, to be predicted, for strictly meeting QoSs. However, if they are executed with other workloads to save the cost, they experience QoS violation due to the contention for the hardware resources shared with co-location workloads. In order to guarantee QoSs and to improve the hardware resource utilization, we proposed a memory bandwidth management method with an effective prediction model using machine learning. The prediction model estimates the amount of memory bandwidth that will be allocated to the latency-critical workload based on a REP decision tree. To construct this model, we first collect data and train the model with the data. The generated model can estimate the amount of memory bandwidth for meeting the SLO of the latency-critical workload no matter what batch processing workloads are collocated. The use of our approach achieves up to 99% SLO assurance and improves the server utilization up to 6.8 × on average. [ABSTRACT FROM AUTHOR]

Slo3 is a pH-sensitive and weakly voltage-sensitive potassium channel that is essential for male fertility in mouse and whose expression is regarded as sperm-specific. These properties have proposed Slo3 as a candidate target for male contraceptive drugs. Nonetheless, the tissue distribution of Slo3 expression has not been rigorously studied yet. Applying computational and RT-PCR approaches, we identified expression of two short Slo3 isoforms in somatic mouse tissues such as brain, kidney and eye. These isoforms, which seem to result of transcription starting sites between exons 20 and 21, have an identical open reading frame, both encoding the terminal 381 amino acids of the cytosolic Slo3 domain. We corroborated the expression of these isoforms in mouse brain and testis by Western-blot. The complete isoform encoding the Slo3 ion channel was uniquely detected in testis, both at transcript and protein level. Although the functional role of the cytosolic Slo3 isoforms remains to be established, we propose that they may have a functional effect by modulating Slo channels trafficking and/or activity. This study confirms that expression of full-length Slo3 is sperm-specific but warns against developing contraceptive drugs targeting the C-terminal tail of Slo3 channels. [ABSTRACT FROM AUTHOR]

Latency-critical workloads such as web search engines, social networks and finance market applications are sensitive to tail latencies for meeting service level objectives (SLOs). Since unexpected tail latencies are caused by sharing hardware resources with other co-executing workloads, a service provider executes the latency-critical workload alone. Thus, the data center for the latency-critical workloads has exceedingly low hardware resource utilization. For improving hardware resource utilization, the service provider has to co-locate the latency-critical workloads and other batch processing ones. However, because the memory bandwidth cannot be provided in isolation unlike the cores and cache memory, the latency-critical workloads experience poor performance isolation even though the core and cache memory are allocated in isolation to the workloads. To solve this problem, we propose an optimized memory bandwidth management approach for ensuring quality of service (QoS) and high server utilization. By providing isolated shared resources including the memory bandwidth to the latency-critical workload and co-executing batch processing ones, firstly, our proposed approach performs few pre-profilings under the assumption that memory bandwidth contention is the worst with a divide and conquer method. Second, we predict the memory bandwidth to meet the SLO for all queries per seconds (QPSs) based on results of the pre-profilings. Then, our approach allocates the amount of the isolated memory bandwidth that guarantees the SLO to the latency-critical workload and the rest of the memory bandwidth to co-executing batch processing ones. It is experimentally found that our proposed approach can achieve up to 99% SLO assurance and improve the server utilization up to 6.5×. [ABSTRACT FROM AUTHOR]

The pay-as-you-go pricing model and the illusion of unlimited resources in the Cloud initiate the idea to provision services elastically. Elastic provisioning of services allocates/de-allocates resources dynamically in response to the changes of the workload. It minimizes the service provisioning cost while maintaining the desired service level objectives (SLOs). Model-predictive control is often used in building such elasticity controllers that dynamically provision resources. However, they need to be trained, either online or offline, before making accurate scaling decisions. The training process involves tedious and significant amount of work as well as some expertise, especially when the model has many dimensions and the training granularity is fine, which is proved to be essential in order to build an accurate elasticity controller. In this paper, we present OnlineElastMan, which is a self-trained proactive elasticity manager for cloud-based storage services. It automatically evolves itself while serving the workload. Experiments using OnlineElastMan with Cassandra indicate that OnlineElastMan continuously improves its provision accuracy, i.e., minimizing provisioning cost and SLO violations, under various workload patterns. [ABSTRACT FROM AUTHOR]

The retinal vasculature is an extremely complex system that is adapted to support the metabolic demands of the retinal structures, but on the other hand maintain the optimal optical qualities of this tissue. Through histological studies and clinical studies using fluorescein angiography we have learned a lot about the retinal vasculature in its physiological state and in different diseases, but both of these study methods have serious limitations that limit their extensive application in healthy subjects or in patients with early disease. In this current review we will present early observations about the retinal vasculature from several novel noninvasive imaging modalities like adaptive optics SLO, retinal functional imager, adaptive optics OCT and Doppler OCT. Some of these instruments allow a more detailed in vivo examination of the retinal vasculature than fluorescein angiography without its potentially serious side effects, thus better allowing us to further study retinal vascular homeostasis in healthy subjects and to identify preclinical changes in early disease stages. [ABSTRACT FROM AUTHOR]

Copyright of Der Ophthalmologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Deep cerebellar nuclear neurons (DCNs) display characteristic electrical properties, including spontaneous spiking and the ability to discharge narrow spikes at high frequency. These properties are thought to be relevant to processing inhibitory Purkinje cell input and transferring well-timed signals to cerebellar targets. Yet, the underlying ionic mechanisms are not completely understood. BK and Kv3.1 potassium channels subserve similar functions in spike repolarization and fast firing in many neurons and are both highly expressed in DCNs. Here, their role in the abovementioned spiking characteristics was addressed using whole-cell recordings of large and small putative-glutamatergic DCNs. Selective BK channel block depolarized DCNs of both groups and increased spontaneous firing rate but scarcely affected evoked activity. After adjusting the membrane potential to control levels, the spike waveforms under BK channel block were indistinguishable from control ones, indicating no significant BK channel involvement in spike repolarization. The increased firing rate suggests that lack of DCN-BK channels may have contributed to the ataxic phenotype previously found in BK channel-deficient mice. On the other hand, block of Kv3.1 channels with low doses of 4-aminopyridine (20 μM) hindered spike repolarization and severely depressed evoked fast firing. Therefore, I propose that despite similar characteristics of BK and Kv3.1 channels, they play different roles in DCNs: BK channels control almost exclusively spontaneous firing rate, whereas DCN-Kv3.1 channels dominate the spike repolarization and enable fast firing. Interestingly, after Kv3.1 channel block, BK channels gained a role in spike repolarization, demonstrating how the different function of each of the two channels is determined in part by their co-expression and interplay. [ABSTRACT FROM AUTHOR]

Copyright of Der Ophthalmologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Large conductance Ca2+-activated BK channels are important regulators of action potential duration and firing frequency in many neurons. As the pore-forming subunits of BK channels are encoded by a single gene, channel diversity is mainly generated by alternative splicing and interaction with auxiliary β-subunits (BKβ1-4). In hypothalamic neurons several BK channel subtypes have been described electrophysiologically; however, the distribution of BKβ subunits is unknown so far. Therefore, an antibody against the large extracellular loop of the BKβ1 subunit was raised, freed from cross-reactivity against BKβ2-4 and affinity-purified. The resulting polyclonal monospecific BKβ1 antibody was characterized by Western blot analysis, ELISA techniques and immunocytochemical staining of BKβ1-4-transfected CHO and COS-1 cells. Regional and cellular distribution in the rat hypothalamus was analysed by immunocytochemistry and in situ hybridization experiments. Immunocytochemical staining of rat hypothalamic neurons indicates strong BKβ1 expression in the supraoptic nucleus and the magno- and parvocellular parts of the paraventricular nucleus. Lower expression was found in periventricular nucleus, the arcuate nucleus and in the median eminence. Immunostaining was predominantly localized to somata. In addition, pericytes and ependymal epithelial cells showed BKβ1 labelling. In all cases immunocytochemical results were supported by in situ hybridization. [ABSTRACT FROM AUTHOR]

Ca2+/calmodulin-dependent protein kinase II (CaMKII) and the BK channel are enriched at the presynaptic nerve terminal, where CaMKII associates with synaptic vesicles whereas the BK channel colocalizes with voltage-sensitive Ca2+ channels in the plasma membrane. Mounting evidence suggests that these two proteins play important roles in controlling neurotransmitter release. Presynaptic BK channels primarily serve as a negative regulator of neurotransmitter release. In contrast, presynaptic CaMKII either enhances or inhibits neurotransmitter release and synaptic plasticity depending on experimental or physiological conditions and properties of specific synapses. The different functions of presynaptic CaMKII appear to be mediated by distinct downstream proteins, including the BK channel. [ABSTRACT FROM AUTHOR]

Copyright of Der Ophthalmologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Extracellular ATP is an important regulator of transepithelial transport in a number of tissues. In pancreatic ducts, we have shown that ATP modulates epithelial K+ channels via purinergic receptors, most likely the P2Y2 and P2Y4 receptors, but the identity of the involved K+ channels was not clear. In this study, we show by RT-PCR analysis that rat pancreatic ducts express Ca2+-activated K+ channels of intermediate conductance (IK) and big conductance (BK), but not small conductance (SK). Possible interactions between P2Y receptors and these Ca2+-activated K+ channels were examined in co-expression experiments in Xenopus laevis oocytes. K+ channel activity was measured electrophysiologically in oocytes stimulated with UTP (0.1 mM). UTP stimulation of oocytes expressing P2Y4 receptors and BK channels resulted in a 30% increase in the current through the expressed channels. In contrast, stimulation of P2Y2 receptors led to a 20% inhibition of co-expressed BK channel activity, a response that was sensitive to TEA. Furthermore, co-expression of IK channels with P2Y4 and P2Y2 receptors resulted in a large hyperpolarization and 22-fold and 5-fold activation of currents by UTP, respectively. Taken together, this study shows that there are different interactions between the subtypes of P2Y purinergic receptors and different Ca2+-activated K+ channels. [ABSTRACT FROM AUTHOR]

Copyright of Der Ophthalmologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Potassium currents play a critical role in action potential repolarization, setting of the resting membrane potential, control of neuronal firing rates, and regulation of neurotransmitter release. The diversity of the potassium channels that generate these currents is nothing less than staggering. This diversity is generated by multiple genes (as many as 100 and perhaps more in some creatures) encoding the pore-forming channel α subunits, alternative splicing of channel gene transcripts, formation of heteromultimeric channels, participation of auxiliary (non-pore-forming) β and other subunits, and modulation of channel properties by post-translational modifications and other mechanisms. Prominent among the potassium channels are several families of calcium activated potassium channels, which are highly selective for potassium ions as their charge carrier, and require intracellular calcium for channel gating. The modulation of one of these families, that of the large conductance calcium activated and voltage-dependent potassium channels, has been especially widely studied. In this review we discuss a few selected examples of the modulation of these channels, to illustrate some of the molecular mechanisms and physiological consequences of ion channel modulation. [ABSTRACT FROM AUTHOR]