Pump Channel Research Articles

The Impact of Chronic Magnesium Deficiency on Excitable Tissues-Translational Aspects.

Neuromuscular excitability is a vital body function, and Mg2+ is an essential regulatory cation for the function of excitable membranes. Loss of Mg2+ homeostasis disturbs fluxes of other cations across cell membranes, leading to pathophysiological electrogenesis, which can eventually cause vital threat to the patient. Chronic subclinical Mg2+ deficiency is an increasingly prevalent condition in the general population. It is associated with an elevated risk of cardiovascular, respiratory and neurological conditions and an increased mortality. Magnesium favours bronchodilation (by antagonizing Ca2+ channels on airway smooth muscle and inhibiting the release of endogenous bronchoconstrictors). Magnesium exerts antihypertensive effects by reducing peripheral vascular resistance (increasing endothelial NO and PgI2 release and inhibiting Ca2+ influx into vascular smooth muscle). Magnesium deficiency disturbs heart impulse generation and propagation by prolonging cell depolarization (due to Na+/K+ pump and Kir channel dysfunction) and dysregulating cardiac gap junctions, causing arrhythmias, while prolonged diastolic Ca2+ release (through leaky RyRs) disturbs cardiac excitation-contraction coupling, compromising diastolic relaxation and systolic contraction. In the brain, Mg2+ regulates the function of ion channels and neurotransmitters (blocks voltage-gated Ca2+ channel-mediated transmitter release, antagonizes NMDARs, activates GABAARs, suppresses nAChR ion current and modulates gap junction channels) and blocks ACh release at neuromuscular junctions. Magnesium exerts multiple therapeutic neuroactive effects (antiepileptic, antimigraine, analgesic, neuroprotective, antidepressant, anxiolytic, etc.). This review focuses on the effects of Mg2+ on excitable tissues in health and disease. As a natural membrane stabilizer, Mg2+ opposes the development of many conditions of hyperexcitability. Its beneficial recompensation and supplementation help treat hyperexcitability and should therefore be considered wherever needed.

Chapter 9 - Familial hemiplegic migraine

Hemiplegic migraine consists of attacks of migraine with aura that includes reversible motor weakness. It is classified as familial or sporadic depending on the involvement or not of a first or second degree relative. The most described subtypes of familial hemiplegic migraine include FHM1, FHM2, and FHM3. These have been demonstrated to have a mutation in either CACNA1A, ATP1A2 or SCN1A, which encode different subunits of channels, involving P/Q-type calcium channel, Na/K pump and Na channel, respectively, located in neurons and glial cells. Mutations localized in different genes are defined as "other loci." Patients with a known mutation can have different genetic penetrance, and may present a more complex and disabling phenotype that develops earlier in life. The clinical manifestations can be similar in the three mutations, including neurologic comorbidities other than muscular weakness, such as episodes of loss of consciousness, epilepsy, gait or limb ataxia or movement disorders, among others. Treatment includes antiepileptics such as lamotrigine, valproate or topiramate, calcium blockers such as flunarizine or verapamil and acetazolamide.

Amplification of Long-Wave Infrared Pulses in a Multicolor Non-Collinearly Pumped OPCPA for High-Energy Output

Non-collinearly-seeded, KTA-based NOPCPA is used to generate multicolor, angularly separated pump pulses above 2 μm wavelength. These multicolor pump channels are used to amplify LWIR pulses in a non-collinearly-pumped ZGP NOPCPA to sub-mJ level, with potential scalability beyond 10 mJ. © 2024 The Authors.

Longitudinal diffusion barriers imposed by myofilaments and mitochondria in murine cardiac myocytes.

Using optical and electrical methods, we document that diffusion in the cytoplasm of BL6 murine cardiomyocytes becomes restricted >20-fold as molecular weight increases from 30 to 2,000, roughly as expected for pores with porin channel dimensions. Bodipy-FL ATP diffuses >40-fold slower than in free water at 25°C. From several fluorophores analyzed, bound fluorophore fractions range from 0.1 for a 2 kD FITC-labeled polyethylene glycol to 0.93 for sulforhodamine. Unbound fluorophores diffuse at 0.5-8 × 10-7 cm2/s (5-80 μm2/s). Analysis of Na/K pump and veratridine-modified Na channel currents suggests that Na diffusion is nearly unrestricted at 35°C (time constant for equilibration with the pipette tip, ∼20 s). Using multiple strategies, we estimate that at 35°C, ATP diffuses four to eight times slower than in free water. To address whether restrictions are caused more by protein or membrane networks, we verified first that a protein gel, 10 g% gelatin, restricts diffusion with strong dependence on molecular weight. Solute diffusion in membrane-extracted cardiac myofilaments, confined laterally by suction into large-diameter pipette tips, is less restricted than in intact myocytes. Notably, myofilaments extracted similarly from skeletal (diaphragm) myocytes are less restrictive. Solute diffusion in myocytes with sarcolemma permeabilized by β-escin (80 µM) is similar to diffusion in intact myocytes. Restrictions are strain-dependent, being twofold greater in BL6 myocytes than in CD1/J6/129svJ myocytes. Furthermore, longitudinal diffusion is 2.5-fold more restricted in CD1/J6/129svJ myocytes lacking the mitochondrial porin, VDAC1, than in WT CD1/J6/129svJ myocytes. Thus, mitochondria networks restrict long-range diffusion while presumably optimizing nucleotide transfer between myofilaments and mitochondria. We project that diffusion restrictions imposed by both myofilaments and the outer mitochondrial membrane are important determinants of total free cytoplasmic AMP and ADP (∼10 μM). However, the capacity of diffusion to deliver ATP to myofilaments remains ∼100-fold greater than ATP consumption.

Electromagnetic pump with rotating permanent magnets operation at low inlet pressures

This study aimed to investigate the performance of an electromagnetic induction pump with rotating permanent magnets under different inlet pressure conditions. The tested cylindrical-type pump was placed in the test loop to test its parameters while pumping liquid sodium. The measurements of the pump characteristics were carried out at the different inlet pressure values. The inlet pressure was varied, changing initial overpressure in the loop's expansion tank from 0,1 to 1,75 bars. Inlet pressure influenced the cavitation occurrence in the pump channel, and thus, the maximal flow rate varied from 15,2 to 73 l/s. In addition to the pressure-flow rate characteristics, various data were collected during the experiments, such as drive unit power, vibration data, and acoustic signals. Analysis of these parameters showed a clear correlation between the inlet pressure and the apparent cavitation process in the pump channel. This study aimed to establish the operational limits for the electromagnetic induction pump with rotating permanent magnets. The results indicate that the pump can safely operate within the range of inlet pressure values of 0,6 bar and cavitation number values of 3,2.

Spectral characterization and energy transfer study of Nd3+/Yb3+ in borosilicate glasses

Very sharp emission in near infrared region is observed for Nd3+/Yb3+ codoped 60B2O3-10SiO2-5PbO-10Al2O3-10Li2O-5ZnO (BSPbLAZ) glasses which were prepared by melt-quenching method along with Nd3+ doped BSPbLAZ glass. Photoluminescence excitation (PLE) spectra of 1 mol% of Nd2O3 doped BSPbLAZ glass shows intense band at 584 nm at an emission wavelength of 1062 nm. Photoluminescence emission (PL) spectra for 1 mol% of Nd2O3 doped BSPbLAZ glass at an excitation wavelength of 584 nm shows three characteristics emission bands in NIR range, 4F3/2→4I9/2, 4I11/2 and 4I13/2, most intense among these being the one at 1062 nm corresponding to 4F3/2→4I11/2. In the codoped system (Nd2O3/Yb2O3), prominent emission bands for Nd3+ are observed at 887, 1062 and 1336 nm corresponding to 4F3/2→4I9/2, 4I11/2 and 4I13/2 respectively, while for Yb3+ ions transition is observed at 980 nm corresponding to 2F5/2→2F7/2. Detailed investigation of characteristics like NIR emission, lifetime and energy transfer efficiency on increment of Yb2O3 doping concentration helps in understanding the utility of these glasses in the fields like photonic and optical devices. In BSPbLAZ glass Yb3+ can be easily sensitized by Nd3+ ions on account of its 4f-4f transitions. These factors provide healthy possibility for usage of Nd3+/Yb3+codoped BSPbLAZ glasses as multiple pump channel sources for laser fiber system based on Yb3+ ions.

INCREASED IONIZED CALCIUM-MAGNESIUM RATIO IN ELDERLY HYPERTENSIVES

Objective: Alterations in the metabolism of calcium and the biofactor magnesium can be involved in the pathogenesis of essential hypertension. Serum magnesium concentrations only insufficiently reflect disorders in magnesium handling in humans, as only about 1% of total body magnesium stores are in blood. The calcium and magnesium flux across the external membrane is regulated by a calcium pump (calcium-magnesium-ATPase), calcium and magnesium (TRPM 6 and 7) channels and a sodium magnesium antiport. An increased calcium-magnesium ratio is known to be involved in the development of atherosclerosis. Early onset of this disorders are known in hypertension. Design and method: We present a study in 18 hypertensive elderly concerning ionized magnesium concentrations and ionized calcium-magnesium ratio in blood measured by a Prime Plus apparatus by NOVA Medical, Andover, USA. Results: In 18 elderly hypertensives (9 male/9 female with normal renal function) ionized magnesium was measured 0.55 +/- 0.04 mmol/l (normal range: 0.54 - 0.80 mmol/l). The ionized calcium-magnesium ratio was 2.33 +/- 0.18 (normal range below 2.40)(p< 0.05). Data are means +/- SD. ANOVA was used for statistical evaluation. About 40% of elderly hypertensives showed an significantly increased ratio of ionized calcium and magnesium, which is well known to be a marker for the development of arteriosclerosis. Conclusions: As described earlier, a deficiency in the biofactor magnesium can be involved in the pathogenesis of essential hypertension. Ionized magnesium data, as presented here, are rare, but ionized magnesium is the active magnesium in the body regulating about 600 enzymatic reactions. The significantly increased ratio of ionized calcium and magnesium is important in the development of arteriosclerosis often resulting in stroke or heart insufficiency in hypertension.

PREVELANCE OF CARBAPENEMASE PRODUCING ORGANISMS AND MOLECULAR RAPID DETECTION OF DIFFERENT GENES FROM VARIOUS CLINICAL ISOLATES IN PATIENTS ADMITTED AT TERTIARY CARE HOSPITALS OF VADODARA

Introduction- Carbapenemase-producing organisms (CPO) have been identied as an urgent healthcare threat. The spread of carbapenemase-producing Enterobacterales (CPE) is a global health problem of great concern. Rapid detection of carbapenemase-producing organisms is clinically desirable for hospital infection control and antibiotic stewardship. Recently, an on-demand polymerase chain reaction (PCR) assay, namely, the Xpert CarbaR assay, that requires less than an hour of turnaround time, had been developed for CPO detection in clinical samples to identify and guide infection control programs to contain the spread of CPO within a hospital. Objective- Carba-R assay is a qualitative multiplex real-time PCR method that qualitatively detects and differentiates ve common carbapenemase genes blaKPC, blaNDM, blaVIM, blaOXA-48, and blaIMP) directly from clinical samples or puried colonies within approximately 1 hour. This benets hospitals and patients by facilitating timely Infection Prevention & Control measures, thereby reducing risk of exposure, transmission and bed-days lost. Materials & Methods- In this study, the Xpert Carba-R assay was evaluated for detection of the ve carbapenemase genes (blaKPC, blaNDM, blaIMP, blaOXA-48, and blaVIM) in total of 40 non duplicate various clinical samples of admitted patients in tertiary care hospitals of Vadodara. Result- We performed Carba-R on 40 isolates: 18 blood samples, 06 urine, 05 rectal swabs, 03 Endotracheal secretion, 03 Pus, 02 wound discharge, 01 Bronchoalveolar lavage uid, 01 sputum, and 01 ERCP stent isolates. 36/40 (90%) isolates had one or more carbapenemase genes. They were as follows: 19/40 (47.5%) both OXA48 and NDM , 12/40 (30%) NDM and 05/40(12.5%) OXA-48. There were 04/40 (10 %) isolates which were Carbapenem resistant on disc diffusion & VITEK but none of the resistant genes were detected possibly due to other resistant mechanism like efux pump and porin channels. Klebsiella pneumoniae was the most common isolate with CR, 34/40 (85%). The most frequent genes encountered in Klebsiella pneumoniae were both OXA48 and NDM, 19/34 (55.88%), NDM 08/34 (23.53%) followed by OXA 48, 05/34 (14.71%) and Out of 34 Klebsiella isolates, 02 isolates failed to detect any of these ve carbapenemase genes. Conclusion- Xpert Carba-R assay provides good reliable results for detection and differentiation of ve carbapenemase genes in clinical isolates. Compared to bacterial culture followed by PCR identication of resistance genes from colonies, the Carba-R assay reduced turnaround time from 48 to 72 hours to less than 1 hour. Carbapenemase genes were detected by the Carba-R assay in Klebsiella pneumoniae (34/40), Escherichia coli (5/40), Acinetobacter spp (1/40). The Carba-R assay detected 19 both OXA48 and NDM (47.5%), 12 blaNDM (30% and 05 blaOXA-48 (12.5%) genes. Laboratory detection of these genes may help improve patient outcomes by tailoring therapy. This study was conducted for understanding the molecular epidemiology of Carbapenemase producing Enterobacteriaceae in a tertiary care hospital. The combined use of the Xpert Carba-R assay and culture produces rapid and reliable results for the active surveillance of CPO in patients

A systematic investigation on flow characteristics of needle-ring-net electrohydrodynamic gas pump

In this study, a two-dimensional numerical simulation is conducted to investigate the characteristics of gas flow induced by an electrohydrodynamic (EHD) pump with needle-ring-net electrodes. A needle electrode and a ring electrode are used as the high-voltage electrode, and a net electrode is used as the grounding one. The electric field distribution, space charge distribution, and flow field distribution behaviors were simulated and analyzed in detail. The simulation results were in good agreement with the experimentally measured data. The influence of key parameters, including applied voltage, electrode configurations, and channel diameter, on the flow characteristics and energy efficiency of an EHD pump was studied systematically. The results showed that the most pronounced electric field strength locates at the region around the needle tip and the edge of the ring electrode, while there is no obvious evidence showing more space charge located at the vicinity of the ring electrode. The airflow velocity at the net pores is higher than that at the central circular hole. Flow velocity and energy conversion efficiency of the pump monotonically increase with applied voltage. A combinational effect of tip-ring distance, ring inner diameter, and pump channel size should be considered to design the EHD pump to achieve maximum efficiency. The results also showed that an optimal energy conversion efficiency of 4.26% can be achieved, which is higher than most of the other EHD pumps (0.11–2.56%). The proposed model can serve as an efficient tool for the design and optimization of the needle-ring-net EHD gas pumps.

Transcriptional Basis of Ca2+ Remodeling Reversal Induced by Polyamine Synthesis Inhibition in Colorectal Cancer Cells.

Colorectal cancer (CRC) is associated with mutations in APC/Wnt leading to c-myc activation and the overexpression of ODC1, the limiting step in polyamine synthesis. CRC cells also display a remodeling of intracellular Ca2+ homeostasis that contributes to cancer hallmarks. As polyamines may modulate Ca2+ homeostasis during epithelial tissue repair, we investigated whether polyamine synthesis inhibition may reverse Ca2+ remodeling in CRC cells and, if so, the molecular basis for this reversal. To this end, we used calcium imaging and transcriptomic analysis in normal and CRC cells treated with DFMO, an ODC1 suicide inhibitor. We found that polyamine synthesis inhibition partially reversed changes in Ca2+ homeostasis associated with CRC, including a decrease in resting Ca2+ and SOCE along with an increased Ca2+ store content. We also found that polyamine synthesis inhibition reversed transcriptomic changes in CRC cells without affecting normal cells. Specifically, DFMO treatment enhanced the transcription of SOCE modulators CRACR2A; ORMDL3; and SEPTINS 6, 7, 8, 9, and 11, whereas it decreased SPCA2, involved in store-independent Orai1 activation. Therefore, DFMO treatment probably decreased store-independent Ca2+ entry and enhanced SOCE control. Conversely, DFMO treatment decreased the transcription of the TRP channels TRPC1 and 5, TRPV6, and TRPP1 while increasing TRPP2, thus probably decreasing Ca2+ entry through TRP channels. Finally, DFMO treatment enhanced the transcription of the PMCA4 Ca2+ pump and mitochondrial channels MCU and VDAC3 for enhanced Ca2+ extrusion through the plasma membrane and mitochondria. Collectively, these findings suggested the critical role of polyamines in Ca2+ remodeling in colorectal cancer.

Analysis And Comparison Of Ventricular Cardiac Arrhythmia Classification Using Sodium Potassium Pump Channel Parameters With ANN And KNN Classifier

Aim: The intent of this research is to analyze and compare ventricular cardiac arrhythmia classification using sodium potassium pump (Na+/K+) channel parameters with Artificial Neural Network (ANN) and K-Nearest Neighbor (KNN) classifiers. Materials and Methods: P.J.Noble and A.V.Panfilov model (PJAV) is used for human ventricular study based on the action potential distance. PJAV uses alternative methods of computer simulations which include major ions, pumps and exchangers. Sample was calculated by keeping threshold 0.05, G Power 80%, confidence interval 95% and enrolment ratio as 1. Number of samples considered is 20. According to these data the accuracy is obtained from the classifiers by training novel ANN and KNN classifiers by alternating the Cross fold validation to obtain 20 different samples. These samples are imported to Statistical Package for the Social Science (SPSS) software for graphical representation and overall accuracy. Result: The concluded results shows that ANN has accuracy of 12.25% with standard deviation (4.0911) and Standard error mean (0.9148). Similarly KNN produces an accuracy value of 4.54 % with standard deviation (2.5732) and Standard error mean (0.5754). Conclusion: As of the results, it clearly shows that ANN has better accuracy for classification than KNN.

Neuron populations use variable combinations of short-term feedback mechanisms to stabilize firing rate.

Neurons tightly regulate firing rate and a failure to do so leads to multiple neurological disorders. Therefore, a fundamental question in neuroscience is how neurons produce reliable activity patterns for decades to generate behavior. Neurons have built-in feedback mechanisms that allow them to monitor their output and rapidly stabilize firing rate. Most work emphasizes the role of a dominant feedback system within a neuronal population for the control of moment-to-moment firing. In contrast, we find that respiratory motoneurons use 2 activity-dependent controllers in unique combinations across cells, dynamic activation of an Na+ pump subtype, and rapid potentiation of Kv7 channels. Both systems constrain firing rate by reducing excitability for up to a minute after a burst of action potentials but are recruited by different cellular signals associated with activity, increased intracellular Na+ (the Na+ pump), and membrane depolarization (Kv7 channels). Individual neurons do not simply contain equal amounts of each system. Rather, neurons under strong control of the Na+ pump are weakly regulated by Kv7 enhancement and vice versa along a continuum. Thus, each motoneuron maintains its characteristic firing rate through a unique combination of the Na+ pump and Kv7 channels, which are dynamically regulated by distinct feedback signals. These results reveal a new organizing strategy for stable circuit output involving multiple fast activity sensors scaled inversely across a neuronal population.

Phenylalanine-arginine β-naphthylamide could enhance neomycin-sensitivity on Riemerella anatipestifer in vitro and in vivo.

Riemerella anatipestifer is an important duck pathogen responsible for septicemia and infectious serositis, which has caused great economic losses to the duck industry. Phenylalanine-arginine β-naphthylamide (PAβN) is an efflux pump inhibitor, which mainly reduces the efflux effect by competing with antibiotics for efflux pump channels. Here, we found that R. anatipestifer strain GD2019 showed resistances to gentamicin, amikacin, kanamycin, and neomycin. Notably, PAβN could significantly reduce the Minimal inhibitory concentrations (MICs) of neomycin on the GD2019 strain. Moreover, PAβN combined with neomycin significantly decreased bacterial loads, relieved pathological injury and increase survival rate (p < 0.05) for the ducks lethally challenged by the GD2019 strain. Therefore, our results suggested, in vitro and in vivo, PAβN could reduce neomycin-resistant of R. anatipestifer. Importantly, finding of this study provide a new approach for treating antibiotic-resistant R. anatipestifer infection.

Pharmacological Basis of Rumex hastatus D. Don in Gastrointestinal Diseases with Focusing Effects on H+/K+-ATPase, Calcium Channels Inhibition and PDE Mediated Signaling: Toxicological Evaluation on Vital Organs.

This present study aimed to delineate Rumex hastatus D. Don crude extract (Rh.Cr), n-Hexane, ethyl acetate, aqueous fractions (Rh.n-Hex, Rh.ETAC, Rh.Aq) and rutin for antidiarrheal, antisecretory effects, anti-spasmodic, gastrointestinal transient time, anti H. pylori, antiulcer effects, and toxicology. The preliminary phytochemical analysis of Rumex hastatus showed different phytoconstituents and shows different peaks in GC-MC chromatogram. Rumex hastatus crude extract (Rh.Cr), fractions, and rutin attributed dose-dependent (50–300 mg/kg) protection (0–100%) against castor oil-induced diarrhea and dose-dependently inhibited intestinal fluid secretions in mice. They decreased the distance traversed by charcoal in the gastrointestinal transit model in rats. In rabbit jejunum preparations, Rh.Cr and Rh.ETAC caused a concentration-dependent relaxation of both spontaneous and K+ (80 mM)-induced contractions at a similar concentration range, whereas Rh.n-Hex, rutin, and verapamil were relatively potent against K+-induced contractions and shifted the Ca2+ concentration–response curves (CRCs) to the right, Rh.Cr (0.3–1 mg/mL) and Rh.ETAC (0.1–0.3 mg/mL) shifted the isoprenaline-induced inhibitory CRCs to the left. Rh.n-Hex, Rh.ETAC and rutin showed anti-H. pylori effect, also shows an inhibitory effect against H+/K+-ATPase. Rumex hastatus showed gastroprotective and antioxidant effects. Histopathological evaluation showed improvement in cellular architecture and a decrease in the expression of inflammatory markers such as, cyclooxygenase (COX-2), tumor necrosis factor (TN,F-α) and phosphorylated nuclear factor kappa B (p-NFƙB), validated through immunohistochemistry and ELISA techniques. In RT-PCR it decreases H+/K+-ATPase mRNA levels. Rumex hastatus was found to be safe to consume up to a dose of 2000 mg/kg in a comprehensive toxicity profile. Docking studies revealed that rutin against H+/K+-ATPase pump and voltage-gated L-type calcium channel showed E-values of −8.7 and −9.4 Kcal/mol, respectively. MD simulations Molecular Mechanics Poisson Boltzmann surface area and molecular mechanics Generalized Born surface area (MMPBSA/GBSA) findings are consistent with the in-vitro, in-vivo and docking results.

A magnetorheological flap valve micropump for drug delivery applications

In this paper, we propose a flap valve micro-fluidic pump that relies on an electromagnetic actuation mechanism. We employed a multiphysics-based simulation methodology to prove the proposed concept. More specifically, the complex and fully coupled magneto-solid-fluid interaction analyses were carried out via a two-dimensional, time-dependent computational model to determine the deformation of the upper wall of the pump chamber and the velocity field inside the pump channel. The simulations were performed in COMSOL Multiphysics software. The simulation approach was verified through a validity check study by replicating an existing study in the literature. Once verified, the full simulations were performed for the proposed concept. The performance characteristics of the pump were presented and discussed. In addition, a parametric study was conducted to see the effects of important design parameters on the net pumped volume, results of which were also presented and discussed. The proposed micropump can transfer 1.9 µL of fluid in one pumping cycle, which is almost two times the other micropump models. Also, the proposed flap valve can reduce the backflow up to 10 times during the expansion phase in comparison with the no valve model. The parametric studies demonstrated that the net pumped volume of the fluid is directly proportional to the channel height and valve spacing distance and is inversely proportional to the upper wall thickness, elastic modulus of the pump structure, width, height, and Poisson ratio of the valves. The proposed micropump could potentially be used in a broad range of applications, such as an insulin dosing system for Type 1 Diabetic patients, artificial organs to transport blood, organ-on-chip applications, and so on.

Dual Optomechanical Cavities for All-Optical Actuation and Sensing of Mechanical Motion

Cavity optomechanics in the photonic devices enables a light-matter interaction in the chip-scale systems via the optical force driven mechanical motion. In this paper, a pump-probe scheme consisting of dual optomechanical cavities is proposed for the first time, where one optical cavity driven by a high input power act as a pump channel and the other one is used as a probe channel to detect the dynamical motion of mechanical resonator. Moreover, modulation of the optical force in the pump channel is achieved to observe the amplification of mechanical motions. As the light input of the pump channel increases, the dynamical displacement of the mechanical resonator is theoretically actuated to 4.8 nm <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$/\!\sqrt {\text{Hz}} $</tex-math></inline-formula> at the pump power of 0.75 mW. This all-optical amplification of mechanical motion based on the pump-probe scheme potentially paves the way for the development of optomechanical actuation and switch for the photonic integrated circuits.

INCREASED IONIZED CALCIUM-MAGNESIUM-RATIO IN ELDERLY HYPERTENSIVES - RELATIONSHIP TO ARTHERIOSCLEROSIS

Objective: Changes in calcium and magnesium metabolism are involved in the pathogenesis of primary hypertension. The calcium and magnesium flux across the external membrane is regulated by a calcium pump (calcium-magnesium-ATPase), calcium and magnesium channels (TRPM 6 and 7) and a sodium-magnesium-antiport. An increased calcium-magnesium-ratio is known to be involved in the development of atherosclerosis. Early onset of these disorders are known in hypertension. In earlier animal studies this phenomenon has been described, too. Design and method: Our study was performed in 18 elderly hypertensives (9 male/9 female, with normal renal function, age beyond 60 years). No patient had diabetes mellitus, no diuretic therapy for at least 4 weeks before entry in study and no magnesium supplementation. In each patient ionized calcium and magnesium was measured and the calcium-magnesium-ratio was calculated. Measurements were performed by a Prime Plus Apparatus by NOVA Medical, Rödermark, Germany. Results: Ionized magnesium was measured 0.55 + /-0.04 mmol/L, normal range 0.54–0.80 mmol/L) in patients. The ionized calcium-magnesium-ratio was 2.33+/-0.18 (normal range below 2.40). About 40% of elderly hypertensives showed an increased ratio of ionized calcium and magnesium, which is known to be a marker for the development of artheriosclerosis. Conclusions: As described earlier, a magnesium deficiency can be involved in the pathogenesis of hypertension and in elderly. The increased calcium-magnesium-ratio is also a pathogenetic factor for artheriosclerosis often found in elderly hypertensives with vascular damage, e.g. stroke, renal insufficiency or heart disease.

Testing and validation of reciprocating positive displacement pump for benchtop pulsating flow model of cerebrospinal fluid production and other physiologic systems.

BackgroundThe flow of physiologic fluids through organs and organs systems is an integral component of their function. The complex fluid dynamics in many organ systems are still not completely understood, and in-vivo measurements of flow rates and pressure provide a testament to the complexity of each flow system. Variability in in-vivo measurements and the lack of control over flow characteristics leave a lot to be desired for testing and evaluation of current modes of treatments as well as future innovations. In-vitro models are particularly ideal for studying neurological conditions such as hydrocephalus due to their complex pathophysiology and interactions with therapeutic measures. The following aims to present the reciprocating positive displacement pump, capable of inducing pulsating flow of a defined volume at a controlled beat rate and amplitude. While the other fluidic applications of the pump are currently under investigation, this study was focused on simulating the pulsating cerebrospinal fluid production across profiles with varying parameters.MethodsPumps were manufactured using 3D printed and injection molded parts. The pumps were powered by an Arduino-based board and proprietary software that controls the linear motion of the pumps to achieve the specified output rate at the desired pulsation rate and amplitude. A range of 0.01 to 0.7 was tested to evaluate the versatility of the pumps. The accuracy and precision of the pumps’ output were evaluated by obtaining a total of 150 one-minute weight measurements of degassed deionized water per output rate across 15 pump channels. In addition, nine experiments were performed to evaluate the pumps’ control over pulsation rate and amplitude.ResultsVolumetric analysis of a total of 1200 readings determined that the pumps achieved the target output volume rate with a mean absolute error of -0.001034283 across the specified domain. It was also determined that the pumps can maintain pulsatile flow at a user-specified beat rate and amplitude.ConclusionThe validation of this reciprocating positive displacement pump system allows for the future validation of novel designs to components used to treat hydrocephalus and other physiologic models involving pulsatile flow. Based on the promising results of these experiments at simulating pulsatile CSF flow, a benchtop model of human CSF production and distribution could be achieved through the incorporation of a chamber system and a compliance component.

Dissecting the Component Parts of the Excitation‐Contraction Coupling Machinery in Drosophila melanogaster

The Drosophila neuromuscular system is widely used to characterize synaptic development and function. However, little is known about how specific synaptic and muscular alterations effect neuromuscular transduction and muscle contractility that ultimately dictate behavioral output. Here a system developed to characterize excitation‐contraction coupling at Drosophila larval neuromuscular junctions (NMJs) was exploited to examining how specific neuronal, synaptic, and muscle manipulations disrupt muscle contractility and locomotion. Increases in motor neuron stimulation frequency and duration increased muscle force in a predictable fashion, but show considerable plasticity between 5–40 Hz and saturating above 50 Hz. Fictive contraction recordings from larvae with CNS intact revealed motor neuron burst frequencies of 20‐30 Hz, consistent with the endogenous machinery operating within the range of contractility of greatest plasticity. Experimental parameters such as saline composition (e.g. calcium and magnesium) temperature, larval size and orientation, were explored to examine their impacts on muscle force production. Subsequently, genetic and pharmacological approaches were taken to dissect several molecular pathways which contribute to muscle contraction and modulation of force. First, well‐established calcium regulation pathways were manipulated via application of ryanodine, caffeine, thapsigargin, and felodipine to demonstrate the role of the ryanodine receptors, SERCA pump, and postsynaptic calcium channels in modulating the magnitude and time‐course of muscle contractions. Presynaptic calcium channels and ryanodine receptor expression were genetically altered to further examine their role in muscle force production. Next using both null and knock‐down (Gal4/UAS system) approaches combined with tissue‐specific expression of drivers, screens for motor, synaptic, and muscle proteins contributing to excitation‐contraction coupling (ECC) were conducted. Altering the expression of the motor proteins kinesin, dynein or dynactin all resulted in a significant reduction in muscle force production. Critical synaptic proteins like synaptotagmin, complexin, cacophony, gbb (homolog of BMP), significantly impacted ECC in Drosophila larvae. Several critical muscle‐specific proteins alter the magnitude and time‐course of muscle contractions when altering their expression in a sub‐set of muscle fibers. Lastly a screen for modulators of muscle contractility led to identification and characterization of the molecular and cellular pathway by which the FMRFa peptide, TPAEDFMRFa, increases muscle performance. These findings indicate Drosophila NMJs provide a robust system to correlate synaptic dysfunction, regulation, and modulation, to alterations in excitation‐contraction coupling.

Mechanisms of energy conversion in induction magnetohydrodynamic pumps for transporting conducting liquids

Efficiency of energy conversion in magnetohydrodynamic (MHD) pumps is relatively lower compared with conventional mechanical pumps. The processes of energy conversion in an induction MHD pump are identified and the energy efficiencies of the processes are evaluated based on the numerical simulations. Two numerical models with different geometrical dimensions are built to simulate all involved processes. The results illustrate that vortices suddenly occur in the pump channel when the flow rate reduces below a critical value. The size and scale of the vortices are dependent on the modeling dimension. By analyzing the energy conversion among different forms of energy, it is demonstrated that the energy conversion is strongly correlated with the vortex flow. The appearing vortices at low flow rates result in both large Ohmic dissipation and negative power of Lorentz force, which are the main obstructions for energy transfer from the input power to the fluid pressure energy. In addition, the overall efficiency of this machine is estimated using the model containing external components (e.g., coils, stators and ducts). It is found that the energy dissipation in the external components plays an increasing role of reducing the energy efficiency with the increasing flow rate.