Voltage-gated calcium channels are required for many key functions in the body. In this review, the different subtypes of voltage-gated calcium channels are described and their physiologic roles and pharmacology are outlined. We describe the current uses of drugs interacting with the different calcium channel subtypes and subunits, as well as specific areas in which there is strong potential for future drug development. Current therapeutic agents include drugs targeting L-type Ca(V)1.2 calcium channels, particularly 1,4-dihydropyridines, which are widely used in the treatment of hypertension. T-type (Ca(V)3) channels are a target of ethosuximide, widely used in absence epilepsy. The auxiliary subunit α2δ-1 is the therapeutic target of the gabapentinoid drugs, which are of value in certain epilepsies and chronic neuropathic pain. The limited use of intrathecal ziconotide, a peptide blocker of N-type (Ca(V)2.2) calcium channels, as a treatment of intractable pain, gives an indication that these channels represent excellent drug targets for various pain conditions. We describe how selectivity for different subtypes of calcium channels (e.g., Ca(V)1.2 and Ca(V)1.3 L-type channels) may be achieved in the future by exploiting differences between channel isoforms in terms of sequence and biophysical properties, variation in splicing in different target tissues, and differences in the properties of the target tissues themselves in terms of membrane potential or firing frequency. Thus, use-dependent blockers of the different isoforms could selectively block calcium channels in particular pathologies, such as nociceptive neurons in pain states or in epileptic brain circuits. Of important future potential are selective Ca(V)1.3 blockers for neuropsychiatric diseases, neuroprotection in Parkinson's disease, and resistant hypertension. In addition, selective or nonselective T-type channel blockers are considered potential therapeutic targets in epilepsy, pain, obesity, sleep, and anxiety. Use-dependent N-type calcium channel blockers are likely to be of therapeutic use in chronic pain conditions. Thus, more selective calcium channel blockers hold promise for therapeutic intervention.

The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential

Numerical Methods for Scientists and Engineers

random data analysis and measurement procedures is available in our digital library an online access to it is set as public so you can get it instantly. Our book servers spans in multiple countries, allowing you to get the most less latency time to download any of our books like this one. Merely said, the random data analysis and measurement procedures is universally compatible with any devices to read.

Random Data Analysis And Measurement Procedures

There has been significant advancement in various aspects of scientific knowledge concerning the role of cerebellum in the etiopathogenesis of autism. In the current consensus paper, we will observe the diversity of opinions regarding the involvement of this important site in the pathology of autism. Recent emergent findings in literature related to cerebellar involvement in autism are discussed, including: cerebellar pathology, cerebellar imaging and symptom expression in autism, cerebellar genetics, cerebellar immune function, oxidative stress and mitochondrial dysfunction, GABAergic and glutamatergic systems, cholinergic, dopaminergic, serotonergic, and oxytocin-related changes in autism, motor control and cognitive deficits, cerebellar coordination of movements and cognition, gene–environment interactions, therapeutics in autism, and relevant animal models of autism. Points of consensus include presence of abnormal cerebellar anatomy, abnormal neurotransmitter systems, oxidative stress, cerebellar motor and cognitive deficits, and neuroinflammation in subjects with autism. Undefined areas or areas requiring further investigation include lack of treatment options for core symptoms of autism, vermal hypoplasia, and other vermal abnormalities as a consistent feature of autism, mechanisms underlying cerebellar contributions to cognition, and unknown mechanisms underlying neuroinflammation.

/pdf/consensus-paper-pathological-role-of-the-cerebellum-in-418xwk2miz.pdf

Consensus Paper: Pathological Role of the Cerebellum in Autism

A review on signal processing techniques utilized in the fault diagnosis of rolling element bearings

This article addresses the way in which we can generate an “acoustically bright zone” in a space. The bright zone is defined as the volume where we can have higher acoustic energy than in other space. A method is proposed to generate the bright zone by controlling multiple monopole sources. Two kinds of cost functions involved with acoustic brightness are defined. One is the ratio of the brightness of a zone to the input power, and the other expresses the “contrast” between the bright zone and the other space. Through eigenvalue analysis, the optimal volume velocity distribution of the monopoles has been obtained.

Generation of an acoustically bright zone with an illuminated region using multiple sources

Helmholtz resonators are often used to reduce noise. They are particularly useful when noise has a narrow frequency band. In this study we aim to broaden its narrow band characteristics by combining many resonators. Serial and parallel arrangements of resonators have been tested to obtain broader impedance mismatch characteristics in the broader band. Theoretical and experimental results explain these characteristics in the absence of mean flow. The serial arrangement mainly increases the peak of TL at the resonance frequency. But the parallel arrangement logarithmically increases the peak of TL and expands the bandwidth. The change of acoustic characteristics is explained by introducing an “equivalent impedance analysis.” This shows that the transmission loss has a maximum value when the distance between resonators is λ∕4 of its wavelength. In this study we propose a novel design method that optimizes the arrangement of resonators while keeping the volume minimized. Various transmission loss characterist...

Silencer design by using array resonators for low-frequency band noise reduction

The rhythmic motor pathway activation by pacemaker neurons or circuits in the brain has been proposed as the mechanism for the timing of motor coordination, and the abnormal potentiation of this mechanism may lead to a pathological tremor. Here, we show that the potentiation of CaV3.1 T-type Ca2+ channels in the inferior olive contributes to the onset of the tremor in a pharmacological model of essential tremor. After administration of harmaline, 4- to 10-Hz synchronous neuronal activities arose from the IO and then propagated to cerebellar motor circuits in wild-type mice, but those rhythmic activities were absent in mice lacking CaV3.1 gene. Intracellular recordings in brain-stem slices revealed that the CaV3.1-deficient inferior olive neurons lacked the subthreshold oscillation of membrane potentials and failed to trigger 4- to 10-Hz rhythmic burst discharges in the presence of harmaline. In addition, the selective knockdown of CaV3.1 gene in the inferior olive by shRNA efficiently suppressed the harmaline-induced tremor in wild-type mice. A mathematical model constructed based on data obtained from patch-clamping experiments indicated that harmaline could efficiently potentiate CaV3.1 channels by changing voltage-dependent responsiveness in the hyperpolarizing direction. Thus, CaV3.1 is a molecular pacemaker substrate for intrinsic neuronal oscillations of inferior olive neurons, and the potentiation of this mechanism can be considered as a pathological cause of essential tremor.

https://www.pnas.org/content/pnas/107/23/10731.full.pdf

CaV3.1 is a tremor rhythm pacemaker in the inferior olive

A personal audio system that does not use earphone or any wire would have great interest and potential impact on the audio industries. In this study, a line array speaker system is used to localize sound in the listening zone. The contrast control [Choi, J.-W. and Kim, Y.-H. (2002). J. Acoust. Soc. Am. 111, 1695-1700] is applied, which is a method to make acoustically bright zone around the user and acoustically dark zone in other regions by maximizing the ratio of acoustic potential energy density between the bright and the dark zone. This ratio is regarded as acoustic contrast, analogous with what is used for optical devices. For the evaluation of the performance of acoustic contrast control, experiments are performed and the results are compared with those of uncontrolled case and time reversal array.

Yang-Hann Kim

Papers

Generation of an acoustically bright zone with an illuminated region using multiple sources

Silencer design by using array resonators for low-frequency band noise reduction

CaV3.1 is a tremor rhythm pacemaker in the inferior olive

A realization of sound focused personal audio system using acoustic contrast control.

A simple model to estimate the impact force induced by piston slap