Forward Mode Research Articles

Crosslink between calcium and sodium signalling.

What is the topic of this review? This paper overviews the links between Ca2+ and Na+ signalling in various types of cells. What advances does it highlight? This paper highlights the general importance of ionic signalling and overviews the molecular mechanisms linking Na+ and Ca2+ dynamics. In particular, the narrative focuses on the molecular physiology of plasmalemmal and mitochondrial Na+ -Ca2+ exchangers and plasmalemmal transient receptor potential channels. Functional consequences of Ca2+ and Na+ signalling for co-ordination of neuronal activity with astroglial homeostatic pathways fundamental for synaptic transmission are discussed. Transmembrane ionic gradients, which are an indispensable feature of life, are used for generation of cytosolic ionic signals that regulate a host of cellular functions. Intracellular signalling mediated by Ca2+ and Na+ is tightly linked through several molecular pathways that generate Ca2+ and Na+ fluxes and are in turn regulated by both ions. Transient receptor potential (TRP) channels bridge endoplasmic reticulum Ca2+ release with generation of Na+ and Ca2+ currents. The plasmalemmal Na+ -Ca2+ exchanger (NCX) flickers between forward and reverse mode to co-ordinate the influx and efflux of both ions with membrane polarization and cytosolic ion concentrations. The mitochondrial calcium uniporter channel (MCU) and mitochondrial Na+ -Ca2+ exchanger (NCLX) mediate Ca2+ entry into and release from this organelle and couple cytosolic Ca2+ and Na+ fluctuations with cellular energetics. Cellular Ca2+ and Na+ signalling controls numerous functional responses and, in the CNS, provides for fast regulation of astroglial homeostatic cascades that are crucial for maintenance of synaptic transmission.

Sequential forward and reverse transport of the Na+ Ca2+ exchanger generates Ca2+ oscillations within mitochondria

Mitochondrial Ca2+ homoeostasis regulates aerobic metabolism and cell survival. Ca2+ flux into mitochondria is mediated by the mitochondrial calcium uniporter (MCU) channel whereas Ca2+ export is often through an electrogenic Na+–Ca2+ exchanger. Here, we report remarkable functional versatility in mitochondrial Na+–Ca2+ exchange under conditions where mitochondria are depolarised. Following physiological stimulation of cell-surface receptors, mitochondrial Na+–Ca2+ exchange initially operates in reverse mode, transporting cytosolic Ca2+ into the matrix. As matrix Ca2+ rises, the exchanger reverts to its forward mode state, extruding Ca2+. Transitions between reverse and forward modes generate repetitive oscillations in matrix Ca2+. We further show that reverse mode Na+–Ca2+ activity is regulated by the mitochondrial fusion protein mitofusin 2. Our results demonstrate that reversible switching between transport modes of an ion exchanger molecule generates functionally relevant oscillations in the levels of the universal Ca2+ messenger within an organelle.

Secrecy Outage of a Cognitive Radio Network with Selection of Energy Harvesting Relay and Imperfect CSI

This paper investigates the physical layer security of an underlay cognitive radio network with relay selection scheme under threats of an eavesdropper. We consider a set of intermediate relays working in decode and forward mode. The relays harvest energy from radio frequency signal transmission of secondary user (SU) using a time switching relaying. We evaluate the secrecy outage probability (SOP) of secondary relay network assuming that the channel state information (CSI) of the interfering links from both the SU and relay transmitter to primary user (PU) receiver are imperfect. The transmit power of the SU as well as relay is controlled by the maximum tolerable interference at PU because of underlay environment and outage constraint of PU as demanded by quality of service of PU. The impact of several network parameters such as maximum tolerable interference threshold, number of relays, time for energy harvesting, imperfection in CSI and primary outage constraint on the secrecy outage of the SU network is indicated. The influence of relay selection scheme on SOP with energy harvesting and imperfect CSI is indicated.

Phishlimiter: A Phishing Detection and Mitigation Approach Using Software-Defined Networking

Phishing is one of the most harmful social engineering techniques to subdue end users where threat actors find a chance to gain access to critical information systems. A common approach in phishing is through the use of e-mail communication with an embedded hyperlink. The detection and mitigation of phishing attacks are a grand challenge due to the complexity of current phishing attacks. Existing techniques are often too time consuming to be used in the real world in terms of detection and mitigation time. Likewise, they employ static detection rules that are not effective in the real world due to the dynamics of phishing attacks. In this paper, we present PhishLimiter, a new detection and mitigation approach, where we first propose a new technique for deep packet inspection (DPI) and then leverage it with software-defined networking (SDN) to identify phishing activities through e-mail and web-based communication. The proposed DPI approach consists of two components: phishing signature classification and real-time DPI. Based on the programmability of SDN, we develop the store and forward mode and the forward and inspect mode to the direct network traffic by using an artificial neural network model to classify phishing attack signatures and design the real-time DPI so that PhishLimiter can flexibly address the dynamics of phishing attacks in the real world. PhishLimiter also provides better network traffic management for containing phishing attacks since it has the global view of a network through SDN. Furthermore, we evaluate PhishLimiter using a real-world testbed environment and data sets consisting of real-world e-mail with embedded links. Our extensive experimental study shows that PhishLimiter provides an effective and efficient solution to deter malicious activities.

Mitochondrial Substrate-Level Phosphorylation as Energy Source for Glioblastoma: Review and Hypothesis.

Glioblastoma multiforme (GBM) is the most common and malignant of the primary adult brain cancers. Ultrastructural and biochemical evidence shows that GBM cells exhibit mitochondrial abnormalities incompatible with energy production through oxidative phosphorylation (OxPhos). Under such conditions, the mitochondrial F0-F1 ATP synthase operates in reverse at the expense of ATP hydrolysis to maintain a moderate membrane potential. Moreover, expression of the dimeric M2 isoform of pyruvate kinase in GBM results in diminished ATP output, precluding a significant ATP production from glycolysis. If ATP synthesis through both glycolysis and OxPhos was impeded, then where would GBM cells obtain high-energy phosphates for growth and invasion? Literature is reviewed suggesting that the succinate-CoA ligase reaction in the tricarboxylic acid cycle can substantiate sufficient ATP through mitochondrial substrate-level phosphorylation (mSLP) to maintain GBM growth when OxPhos is impaired. Production of high-energy phosphates would be supported by glutaminolysis—a hallmark of GBM metabolism—through the sequential conversion of glutamine → glutamate → alpha-ketoglutarate → succinyl CoA → succinate. Equally important, provision of ATP through mSLP would maintain the adenine nucleotide translocase in forward mode, thus preventing the reverse-operating F0-F1 ATP synthase from depleting cytosolic ATP reserves. Because glucose and glutamine are the primary fuels driving the rapid growth of GBM and most tumors for that matter, simultaneous restriction of these two substrates or inhibition of mSLP should diminish cancer viability, growth, and invasion.

Online control system for EVO 2+4roll bar reducing and sizing mill of Primetals Technologies

The Bar Reducing and Sizing Technology has a core function in the value-chain for the production of rolled Special Bar Quality products. Primetals Technologies has tested industrially the 4roll ultra-sizing concept as a complement to the 2roll reducing and sizing group of stands. As a synthesis of a consolidated know-how, Primetals developed a new mechatronic unit, the EVO 2+4roll mill, based on the compact combination of a 2roll high-reduction module followed by a 4roll low-reduction module for ultra-precise sizing: it is a patented solution of Primetals and a break-through technology for superior metallurgical and technical features of the rolled product, allowing to gain significant technical and economic advantages in the hot- and post-rolling process routes. A control system for this sizing block has been newly designed. RINA Consulting Centro Sviluppo Materiali SpA supported Primetals in the development of algorithms and guidelines for the process control system implementation. The control logic is based on the definition of “sensitivities” or “system derivatives” used, in a feed forward mode, as reference for the online correction and/or regulation of the control parameters, taking into account the small perturbation of the control variables during the rolling, starting from a working point. The conditions, in terms of control variables values, related to the working and “perturbed” points are evaluated using a mill setup model. On the other hand, a feedback module has been implemented, taking into account the online measurements, so calculating the sensitivities on the base of the actual measured quantity.

Fabrication of whole-thermoplastic normally closed microvalve, micro check valve, and micropump

There is a critical need to develop fabrication methods for rapid and cost-effective prototyping of thermoplastics-based microfluidics in academic research laboratories. This paper presents a method for the fabrication of whole-thermoplastic microfluidic functional elements, including a pneumatic (gas-actuated) normally closed microvalve, a micro-check valve, and a pneumatic dual-phase micropump. All devices were made from thermoplastic polyurethane (TPU) and poly(methyl methacrylate) (PMMA). The fabrication process consisted of only laser micromachining and thermal fusion bonding without need to perform any particular chemical treatment or use a master mold. These features enable the widespread adaptation of this method in academic research settings. Characterizations revealed that the fabricated normally closed microvalve could stop liquid flows at pressures lower than 2 psi in its passive operation mode where no pressure was used for valve actuation. The check valve could block liquid flows with liquid pressures of up to 30 psi in its reverse mode of operation while it could allow liquid to pass through in its forward mode. In addition, the micropump, which consisted of two check valves and a pneumatic uni-diaphragm displacement chamber, could pump liquid at an average flow rate of 87.6 ± 5.0 μL/min using an actuation frequency and pressure of 1 Hz and ±5 psi, respectively. Taken together, the developed low-cost whole-thermoplastic microfluidic functional elements could be employed for the fabrication of various lab-on-a-chip applications.

Inherent losses induced absorptive acoustic rainbow trapping with a gradient metasurface

Acoustic rainbow trapping represents the phenomenon of strong acoustic dispersion similar to the optical “trapped rainbow,” which allows spatial-spectral modulation and broadband trapping of sound. It can be realized with metamaterials that provide the required strong dispersion absent in natural materials. However, as the group velocity cannot be reduced to exactly zero before the forward mode being coupled to the backward mode, such trapping is temporary and the local sound oscillation ultimately radiates backward. Here, we propose a gradient metasurface, a rigid surface structured with gradient perforation along the wave propagation direction, in which the inherent thermal and viscous losses inside the holes are considered. We show that the gradually diminished group velocity of the structure-induced surface acoustic waves (SSAWs) supported by the metasurface becomes anomalous at the trapping position, induced by the existence of the inherent losses, which implies that the system's absorption reaches its maximum. Together with the progressively increased attenuation of the SSAWs along the gradient direction, reflectionless spatial-spectral modulation and sound enhancement are achieved in simulation. Such phenomenon, which we call as absorptive trapped rainbow, results from the balanced interplay among the local resonance inside individual holes, the mutual coupling of adjacent unit cells, and the inherent losses due to thermal conductivity and viscosity. This study deepens the understanding of the SSAWs propagation at a lossy metasurface and may contribute to the practical design of acoustic devices for high performance sensing and filtering.

Newton step methods for AD of an objective defined using implicit functions

We consider the problem of computing derivatives of an objective that is defined using implicit functions; i.e., implicit variables are computed by solving equations that are often nonlinear and solved by an iterative process. If one were to apply Algorithmic Differentiation (AD) directly, one would differentiate the iterative process. In this paper we present the Newton step methods for computing derivatives of the objective. These methods make it easy to take advantage of sparsity, forward mode, reverse mode, and other AD techniques. We prove that the partial Newton step method works if the number of steps is equal to the order of the derivatives. The full Newton step method obtains two derivatives order for each step except for the first step. There are alternative methods that avoid differentiating the iterative process; e.g., the method implemented in ADOL-C. An optimal control example demonstrates the advantage of the Newton step methods when computing both gradients and Hessians. We also discuss the Laplace approximation method for nonlinear mixed effects models as an example application.

Enzymatic production of all fourteen partially acetylated chitosan tetramers using different chitin deacetylases acting in forward or reverse mode

Some of the most abundant biomolecules on earth are the polysaccharides chitin and chitosan of which especially the oligomeric fractions have been extensively studied regarding their biological activities. However, most of these studies have not been able to assess the activity of a single, defined, partially acetylated chitosan oligosaccharide (paCOS). Instead, they have typically analyzed chemically produced, rather poorly characterized mixtures, at best with a single, defined degree of polymerization (DP) and a known average degree of acetylation (DA), as no pure and well-defined paCOS are currently available. We here present data on the enzymatic production of all 14 possible partially acetylated chitosan tetramers, out of which four were purified (>95%) regarding DP, DA, and pattern of acetylation (PA). We used bacterial, fungal, and viral chitin deacetylases (CDAs), either to partially deacetylate the chitin tetramer; or to partially re-N-acetylate the glucosamine tetramer. Both reactions proceeded with surprisingly strong and enzyme-specific regio-specificity. These pure and fully defined chitosans will allow to investigate the particular influence of DP, DA, and PA on the biological activities of chitosans, improving our basic understanding of their modes of action, e.g. their molecular perception by patter recognition receptors, but also increasing their usefulness in industrial applications.

Simulating the Canopy Reflectance of Different Eucalypt Genotypes With the DART 3-D Model

Finding suitable models of canopy reflectance in forward simulation mode is a prerequisite for their use in inverse mode to characterize canopy variables of interest, such as leaf area index (LAI) or chlorophyll content. In this study, the accuracy of the three-dimensional reflectance model DART (Discrete Anisotropic Radiative Transfer) was assessed for canopies of different genotypes of Eucalyptus , having distinct biophysical and biochemical characteristics, to improve the knowledge on how these characteristics are influencing the reflectance signal as measured by passive orbital sensors. The first step was to test the model suitability to simulate reflectance images in the visible and near infrared. We parameterized DART model using extensive measurements from Eucalyptus plantations including 16 contrasted genotypes. Forest inventories were conducted and leaf, bark, and forest floor optical properties were measured. Simulation accuracy was evaluated by comparing the mean top of canopy (TOC) bidirectional reflectance of DART with TOC reflectance extracted from a Pleiades very high resolution satellite image. Results showed a good performance of DART with mean reflectance absolute error lower than 2%. Intergenotype reflectance variability was correctly simulated, but the model did not succeed at catching the slight spatial variation for a given genotype, excepted when large gaps appeared due to tree mortality. The second step consisted of sensitivity analysis to explore which biochemical or biophysical characteristics influenced more the canopy reflectance between genotypes. Perspectives for using DART model in inversion mode in these ecosystems were discussed.

Potential of interval partial least square regression in estimating leaf area index

Leaf area index (LAI) is a critical parameter in determining vegetation status and health. In tropical grasslands, reliable determination of LAI, useful in determining above ground biomass, provides a basis for rangeland management, conservation and restoration. In this study, interval partial least square regression (iPLSR) in forward mode was compared to partial least square regression (PLSR) to estimate LAI from in-situ canopy hyperspectral data on a heterogeneous grassland at different periods (onset, mid and end) during summer. The performance of the two techniques was determined using the least relative root mean square error to the mean (nRMSEP) and the highest coefficients of determination (R2p) between the predicted and the measured LAI. Results show that iPLSR models could explain LAI variation with R2p values ranging from 0.81 to 0.93 and low nRMSEP from 9.39% to 24.71%. The highest accuracies for estimates of LAI using iPLSR were at mid- and end of summer (R2p = 0.93 and nRMSEP = 9.39%; R2p = 0.89 and nRMSEP = 10.50%, respectively). Pooling data sets from the three assessed periods yielded the highest prediction error (nRMSEP=24.71%). Results show that iPLSR performed better than PLSR, which yielded R2p and RMSEP values ranging from 0.36 to 0.65 and from 28.44% to 33.47%, respectively. Overall, this study demonstrates the value of iPLSR in predicting LAI and therefore provides a basis for more accurate mapping and monitoring of canopy characteristics of tropical grasslands.
 Significance: 
 
 
 
 The relationship between LAI and canopy reflectance can be used in iPLSR modelling to provide more accurate mapping and monitoring of canopy characteristics for land management and conservation.
 
 

The Effects of SEA0400 on Ca2+ Transient Amplitude and Proarrhythmia Depend on the Na+/Ca2+ Exchanger Expression Level in Murine Models.

Background/Objective: The cardiac Na+/Ca2+ exchanger (NCX) has been identified as a promising target to counter arrhythmia in previous studies investigating the benefit of NCX inhibition. However, the consequences of NCX inhibition have not been investigated in the setting of altered NCX expression and function, which is essential, since major cardiac diseases (heart failure/atrial fibrillation) exhibit NCX upregulation. Thus, we here investigated the effects of the NCX inhibitor SEA0400 on the Ca2+ transient amplitude and on proarrhythmia in homozygous NCX overexpressor (OE) and heterozygous NCX knockout (hetKO) mice compared to corresponding wild-types (WTOE/WThetKO).Methods/Results: Ca2+ transients of field-stimulated isolated ventricular cardiomyocytes were recorded with fluo-4-AM or indo-1-AM. SEA0400 (1 μM) significantly reduced NCX forward mode function in all mouse lines. SEA0400 (1 μM) significantly increased the amplitude of field-stimulated Ca2+ transients in WTOE, WThetKO, and hetKO, but not in OE (% of basal; OE = 98.7 ± 5.0; WTOE = 137.8 ± 5.2*; WThetKO = 126.3 ± 6.0*; hetKO = 140.6 ± 12.8*; *p < 0.05 vs. basal). SEA0400 (1 μM) significantly reduced the number of proarrhythmic spontaneous Ca2+ transients (sCR) in OE, but increased it in WTOE, WThetKO and hetKO (sCR per cell; basal/+SEA0400; OE = 12.5/3.7; WTOE = 0.2/2.4; WThetKO = 1.3/8.8; hetKO = 0.2/5.5) and induced Ca2+ overload with subsequent cell death in hetKO.Conclusion: The effects of SEA0400 on Ca2+ transient amplitude and the occurrence of spontaneous Ca2+ transients as a proxy measure for inotropy and cellular proarrhythmia depend on the NCX expression level. The antiarrhythmic effect of SEA0400 in conditions of increased NCX expression promotes the therapeutic concept of NCX inhibition in heart failure/atrial fibrillation. Conversely, in conditions of reduced NCX expression, SEA0400 suppressed the NCX function below a critical level leading to adverse Ca2+ accumulation as reflected by an increase in Ca2+ transient amplitude, proarrhythmia and cell death. Thus, the remaining NCX function under inhibition may be a critical factor determining the inotropic and antiarrhythmic efficacy of SEA0400.

Computationally relevant generalized derivatives: theory, evaluation and applications

A new method for evaluating generalized derivatives in nonsmooth problems is reviewed. Lexicographic directional (LD-)derivatives are a recently developed tool in nonsmooth analysis for evaluating generalized derivative elements in a tractable and robust way. Applicable to problems in both steady-state and dynamic settings, LD-derivatives exhibit a number of advantages over current theory and algorithms. As highlighted in this article, the LD-derivative approach now admits a suitable theory for inverse and implicit functions, nonsmooth dynamical systems and optimization problems, among others. Moreover, this technique includes an extension of the standard vector forward mode of automatic differentiation (AD) and acts as the natural extension of classical calculus results to the nonsmooth case in many ways. The theory of LD-derivatives is placed in the context of state-of-the-art methods in nonsmooth analysis, with an application in multistream heat exchanger modelling and design used to illustrate the usefulness of the approach.

Interfractional dosimetric study of target volume and organs at risk following intracavitary brachytherapy for cervical cancer

Objective To examine the interfractional dosimetric variations among inverse three-dimensional (3D) plan, forward 3D plan, and two-dimensional (2D) plan of intracavitary brachytherapy for cervical cancer, and to discuss the risk of implementing the interval plan on different implantation applicators at short time intervals. Methods Twenty-five groups of CT-guided intracavitary brachytherapy (two consecutive radiations at ≤4 d apart) plans from 11 cervical cancer patients who received radical radiation therapy in our hospital were reviewed and compared. The dwelling location and time of the first intracavitary brachytherapy plan (Plan-1) were simulated on the CT image of the second intracavitary brachytherapy to form Plan-1-S. The target coverage indices and D 2 cc of organs at risk (OARs) of Plan-1-S and Plan 2(actual plan of the second intracavitary brachytherapy) under the three planning modes were recorded and compared using the paired t-test, Wilcoxon signed rank test, and ANOVA. Results The D90, D100, and V100 of high-risk CTV were significantly lower in Plan-1-S created under the inverse mode in the actual plan (-9.11±13.46%, -13.16±18.79%, and -7.80±13.34%, P=0.002, 0.002, and 0.005, respectively). D90, D100, and V100 of the interval plan had the greatest reduction under the inverse mode (76%, 80%, and 76%, respectively). The maximum reductions in D90, D100, and V100 were 332.14 cGy (2D), 244.12 cGy (forward), and 41.76%(inverse). OAR overdose occurred most frequently under the forward mode; the rates of D90, D100, and V100 reductions accompanied by one OAR overdose were 29.41%, 37.50%, and 25.00%, and the rates of D90, D100, and V100 reductions by two OAR overdoses were 5.88%, 12.50%, and 6.25%, respectively. Overdose occurred most frequently in the small intestine (36%). Comparison of the three planning modes showed that the inverse plan had a greater reduction in each target coverage index than the 2D plan. Conclusions The simulated interval plan can significantly reduce target coverage and increase the risk of OAR overdose regardless of the planning mode and the short time intervals, and is therefore not recommended for clinical application. Key words: Cervical neoplasms/brachytherapy; Interfractional dosimetric; Interval model plan

Light Assisted Electrodeposition for Silicon Solar Cell Copper Metallization

Cu electroplating is of a great deal of interest for the metallization of silicon solar cells due to its comparable resistance with the current silver metallizaion, and its lower cost for both the material and the operation.[1,2] However, the notorious Cu diffusion into Si is of great concern to the devices performance degradation during the life cycle of the cells. Ni silicide and Ni metal layers have been recently reported as part of the integration scheme to enable the Cu metallizaion and greatly improved the solar cell reliability.[3,4] The formation of this Ni silicide and Ni stack structure is to provide a low-resistance contact between the silicon and metal grid, a good adhesion of metal grid, and a diffusion barrier for the Cu. Among them, the Ni silicide formation needs to be well controlled so that it is not too thick to shunt the solar cell. This paper will present the development of light assisted plating processes for the formation of nickel silicide and copper grids on silicon solar cells, including beaker scale, bench top tool, and pilot tool processing[5,6,7]. The solar cell substrates for plating comprise ~ 60 ohm/sq emitter formed by POCl diffusion, PECVD SiN passivation layer, and evaporated Al back surface field. Electrodeposition of Ni and copper was studied on 4 cm x 4 cm solar cells in small scale studies and 6 in x 6 in cells on tools. Figure 1 shows the absorption spectra of different electrolytes for deposition and the relation between the applied potential and the light intensity at different constant current densities. Nickel solution has a strong absorption at wavelength between 350 to 450 nm and between 600 to 800 nm. Two regions of operation were clearly observed with a threshold light intensity when a high intensity wide spectrum halogen light source is used for illumination during electroplating. At high illumination, when enough carriers were generated by the light, the plating occurs at the forward bias mode of the diode. As the light intensity decreases below a threshold value, the potential increases significantly and stays at a high value indicating the diode operates at reverse bias mode. The threshold light intensity is dependent on the illumination energy spectrum, solution absorbance, anode shadowing and applied current density. The learnings from beaker scale experiments were directly used to define the tool requirements and process specifications. REFERENCES D. A. Yates, US Patent 4,609,565 (1986).K. Holdermann, US patent 5,543,333 (1996).J Bartsch, A Mondon, K Bayer, C Schetter, M Horteis, and S W Glunz, J. Electrochem. Soc., 157, H942 (2010).J Bartsch, A Mondon, C Schetter, M Horteis, S W Glunz, IEEE 35th PVSC, Honolulu HI (2010).Q Huang, S S Papa Rao, K. Fisher, ECS J. Solid State Sci. Technol., 4, Q75 (2015).Q Huang, ECS J. Solid State Sci. Technol., 5, P51 (2016).Q Huang, K B Reuter, Y Zhu, V R Deline, ECS J. Solid State Sci. Technol., 5, Q24 (2016). Figure 1

Development of engineering drawing ability for emerging engineering education

Students majoring in engineering is required by the emerging engineering education (3E) in the aspect of their ability of engineering drawing. This paper puts forward training mode of engineering drawing ability for 3E. This mode consists of three kinds of training including training in courses, training in competitions and training in actual demand. We also design the feasible implementation plan and supplies viable references to carry out the mode.

Algorithm 984

A toolbox called ADiGator is described for algorithmically differentiating mathematical functions in MATLAB. ADiGator performs source transformation via operator overloading using forward mode algorithmic differentiation and produces a file that can be evaluated to obtain the derivative of the original function at a numeric value of the input. A convenient by-product of the file generation is the sparsity pattern of the derivative function. Moreover, because both the input and output to the algorithm are source codes, the algorithm may be applied recursively to generate derivatives of any order. A key component of the algorithm is its ability to statically exploit derivative sparsity at the MATLAB operation level to improve runtime performance. The algorithm is applied to four different classes of example problems and is shown to produce runtime efficient derivative code. Due to the static nature of the approach, the algorithm is well suited and intended for use with problems requiring many repeated derivative computations.

Chronic pharmacological blockade of the Na+ /Ca2+ exchanger modulates the growth and development of the Purkinje cell dendritic arbor in mouse cerebellar slice cultures.

The Na+ /Ca2+ exchanger (NCX) is a bidirectional plasma membrane antiporter involved in Ca2+ homeostasis in eukaryotes. NCX has three isoforms, NCX1-3, and all of them are expressed in the cerebellum. Immunostaining on cerebellar slice cultures indicates that NCX is widely expressed in the cerebellum, including expression in Purkinje cells. The pharmacological blockade of the forward mode of NCX (Ca2+ efflux mode) by bepridil moderately inhibited growth and development of Purkinje cell dendritic arbor in cerebellar slice cultures. However, the blockade of the reverse mode (Ca2+ influx mode) by KB-R7943 severely reduced the dendritic arbor and induced a morphological change with thickened distal dendrites. The effect of KB-R7943 on dendritic growth was unrelated to the activity of voltage-gated calcium channels and was also apparent in the absence of bioelectrical activity indicating that it was mediated by NCX expressed in Purkinje cells. We have used additional NCX inhibitors including CB-DMB, ORM-10103, SEA0400, YM-244769, and SN-6 which have higher specificity for NCX isoforms and target either the forward, reverse, or both modes. These inhibitors caused a strong dendritic reduction similar to that seen with KB-R7943, but did not elicit thickening of distal dendrites. Our findings indicate that disturbance of the NCX-dependent calcium transport in Purkinje cells induces a reduction of dendritic arbor, which is presumably caused by changes in the calcium handling, and underline the importance of the calcium equilibrium for the dendritic development in cerebellar Purkinje cells.

Comprehensive Study on the Relation Between Low-Frequency Noise and Asymmetric Parasitic Resistances in a Vertical Pillar-Type FET

The low-frequency noise (LFN) characteristics of a vertical pillar-type FET were investigated in order to observe the different influences of the source resistance ( $R_{S})$ and the drain resistance ( $R_{D})$ . Because of its inherent vertical channel structure, the $R_{S}$ and $R_{D}$ are inevitably different. To observe the effects of the asymmetric $R_{S}$ and $R_{D}$ on LFN, a forward mode (FM) and reverse mode (RM) of voltage sweep were used. In the RM, the correlated mobility fluctuation effect was higher and the power spectral density of resistance fluctuation ( $S_{\mathrm{ RSD}})$ was lower than those in the FM. In addition, $S_{\mathrm{ RSD}}$ was correlated with the $R_{S}$ , but little with the $R_{D}$ . To suppress $S_{\mathrm{ RSD}}$ , it is important to minimize the $R_{S}$ .