A unique role for Kv3 voltage-gated potassium channels in starburst amacrine cell signaling in mouse retina

Direction-selective retinal ganglion cells show an increased activity evoked by light stimuli moving in the preferred direction. This selectivity is governed by direction-selective inhibition from starburst amacrine cells occurring during stimulus movement in the opposite or null direction. To understand the intrinsic membrane properties of starburst cells responsible for direction-selective GABA release, we performed whole-cell recordings from starburst cells in mouse retina. Voltage-clamp recordings revealed prominent voltage-dependent K+ currents. The currents were mostly blocked by 1 mm TEA, activated rapidly at voltages more positive than -20 mV, and deactivated quickly, properties reminiscent of the currents carried by the Kv3 subfamily of K+ channels. Immunoblots confirmed the presence of Kv3.1 and Kv3.2 proteins in retina and immunohistochemistry revealed their expression in starburst cell somata and dendrites. The Kv3-like current in starburst cells was absent in Kv3.1-Kv3.2 knock-out mice. Current-clamp recordings showed that the fast activation of the Kv3 channels provides a voltage-dependent shunt that limits depolarization of the soma to potentials more positive than -20 mV. This provides a mechanism likely to contribute to the electrical isolation of individual starburst cell dendrites, a property thought essential for direction selectivity. This function of Kv3 channels differs from that in other neurons where they facilitate high-frequency repetitive firing. Moreover, we found a gradient in the intensity of Kv3.1b immunolabeling favoring proximal regions of starburst cells. We hypothesize that this Kv3 channel gradient contributes to the preference for centrifugal signal flow in dendrites underlying direction-selective GABA release from starburst amacrine cells.

Effects of verapamil and ryanodine on activity of the embryonic chick heart during anoxia and reoxygenation.

Perturbations of the trans-sarcolemmal and sarcoplasmic Ca2+ transport contribute to the abnormal myocardial activity provoked by anoxia and reoxygenation. Whether Ca2+ pools of the extracellular compartment and sarcoplasmic reticulum (SR) are involved to the same extent in the dysfunction of the anoxic-reoxygenated immature heart has not been investigated. Spontaneously contracting hearts isolated from 4-day-old chick embryos were submitted to repeated anoxia (1 min) followed by reoxygenation (5 min). Heart rate, atrioventricular propagation velocity, ventricular shortening, velocities of contraction and relaxation, and incidence of arrhythmias were studied, recorded continuously. Addition of verapamil (10 nM), which blocks selectively sarcolemmal L-type Ca2+ channels, was expected to protect against excessive entry of extracellular Ca2+, whereas addition of ryanodine (10 nM), which opens the SR Ca2+ release channel, was expected to increase cytosolic Ca2+ concentration. Verapamil (a) had no dromotropic effect by contrast to adult heart, (b) attenuated ventricular contracture induced by repeated anoxia, (c) shortened cardioplegia induced by reoxygenation, and (d) had remarkable antiarrhythmic properties during reoxygenation specially. On the other hand, ryanodine potentiated markedly arrhythmias both during anoxia and at reoxygenation. Thus despite its immaturity, the SR seems to be functional early in the developing chick heart and involved in the reversible dysfunction induced by anoxia-reoxygenation. Moreover, Ca2+ entry through L-type channels appears to worsen arrhythmias especially during reoxygenation. These findings show that the Ca2+-handling systems involved in irregular activity in immature heart, such as the embryonic chick heart, may differ from those in the adult.

Identification of neuronal network properties from the spectral analysis of calcium imaging signals in neuronal cultures

Neuronal networks in vitro are prominent systems to study the development of connections in living neuronal networks and the interplay between connectivity, activity and function. These cultured networks show a rich spontaneous activity that evolves concurrently with the connectivity of the underlying network. In this work we monitor the development of neuronal cultures, and record their activity using calcium fluorescence imaging. We use spectral analysis to characterize global dynamical and structural traits of the neuronal cultures. We first observe that the power spectrum can be used as a signature of the state of the network, for instance when inhibition is active or silent, as well as a measure of the network's connectivity strength. Second, the power spectrum identifies prominent developmental changes in the network such as GABAA switch. And third, the analysis of the spatial distribution of the spectral density, in experiments with a controlled disintegration of the network through CNQX, an AMPA-glutamate receptor antagonist in excitatory neurons, reveals the existence of communities of strongly connected, highly active neurons that display synchronous oscillations. Our work illustrates the interest of spectral analysis for the study of in vitro networks, and its potential use as a network-state indicator, for instance to compare healthy and diseased neuronal networks.

Effets des supplémentations en calcium et vitamine D sur la maladie cardiovasculaire. [Effects of calcium and vitamin D supplementations on cardiovascular disease: review article].

Studies exploring the effect of calcium supplementation on cardiovascular risk suggest that systolic blood pressure decreases with supplementation. A lower calcium intake has been associated with an increased risk of stroke. By contrast, calcium supplementation may increase the risk of myocardial infarction. The effect of vitamin D supplementation on blood pressure is still unclear and no effect of vitamin D supplementation on coronary heart disease or stroke has been clearly demonstrated. There is a lack of randomized clinical trials primarily addressing the effect of these parameters on CVD. Currently, the use of calcium and vitamin D supplementations for the prevention of cardiovascular disease is not justified.

Dysregulation of voltage-gated sodium channels by ubiquitin ligase NEDD4-2 in neuropathic pain.

Peripheral neuropathic pain is a disabling condition resulting from nerve injury. It is characterized by the dysregulation of voltage-gated sodium channels (Navs) expressed in dorsal root ganglion (DRG) sensory neurons. The mechanisms underlying the altered expression of Navs remain unknown. This study investigated the role of the E3 ubiquitin ligase NEDD4-2, which is known to ubiquitylate Navs, in the pathogenesis of neuropathic pain in mice. The spared nerve injury (SNI) model of traumatic nerve injury-induced neuropathic pain was used, and an Nav1.7-specific inhibitor, ProTxII, allowed the isolation of Nav1.7-mediated currents. SNI decreased NEDD4-2 expression in DRG cells and increased the amplitude of Nav1.7 and Nav1.8 currents. The redistribution of Nav1.7 channels toward peripheral axons was also observed. Similar changes were observed in the nociceptive DRG neurons of Nedd4L knockout mice (SNS-Nedd4L-/-). SNS-Nedd4L-/- mice exhibited thermal hypersensitivity and an enhanced second pain phase after formalin injection. Restoration of NEDD4-2 expression in DRG neurons using recombinant adenoassociated virus (rAAV2/6) not only reduced Nav1.7 and Nav1.8 current amplitudes, but also alleviated SNI-induced mechanical allodynia. These findings demonstrate that NEDD4-2 is a potent posttranslational regulator of Navs and that downregulation of NEDD4-2 leads to the hyperexcitability of DRG neurons and contributes to the genesis of pathological pain.

Association of calcemia and serum vitamin D with 24H-urinary calcium excretion in a swiss population-based study

Background: Elevated urinary calcium excretion is associated with reduced bone mineral density. Population-based data on urinary calcium excretion are scarce. We explored the association of serum calcium and circulating levels of vitamin D (including 25(OH)D2 and 25(OH)D3) with urinary calcium excretion in men and women in a population-based study. Methods: We used data from the "Swiss Survey on Salt" conducted between 2010 and 2012 and including people aged 15 years and over. Twenty-four hour urine collection, blood analysis, clinical examination and anthropometric measures were collected in 11 centres from the 3 linguistic regions of Switzerland. Vitamin D was measured centrally using liquid chromatography - tandem mass spectrometry. Hypercalciuria was defined as urinary calcium excretion >0.1 mmol/kg/24h. Multivariable linear regression was used to explore factors associated with 24-hour urinary calcium excretion (mmol/24h) squared root transformed, taken as the dependant variable. Vitamin D was divided into monthspecific tertiles with the first tertile having the lowest value and the third tertile having the highest value. Results: The 669 men and 624 women had mean (SD) age of 49.2 (18.1) and 47 (17.9) years and a prevalence of hypercalciuria of 8.9% and 8.0%, respectively. In adjusted models, the association of urinary calcium excretion with protein-corrected serum calcium was (β coefficient } standard error, according to urinary calcium squared root transformed) 1.125 } 0.184 mmol/L per square-root (mmol/24h) (P<0.001) in women and 0.374 } 0.224 (P=0.096) in men. Men in the third month-specific vitamin D tertile had higher urinary calcium excretion than men in the first tertile (0.170 } 0.05 nmol/L per mmol/24h, P=0.001) and the corresponding association was 0.048 } 0.043, P= 0.272 in women. Conclusion: About one in eleven person has hypercalciuria in the Swiss population. The positive association of serum calcium with urinary calcium excretion was steeper in women than in men, independently of menopausal status. Circulating vitamin D was associated positively with urinary calcium excretion only in men. The reasons underlying the observed sex differences in the hormonal control of urinary calcium excretion need to be explored in further studies.

TRPM5-mediated calcium uptake regulates mucin secretion from human colon goblet cells

Mucin 5AC (MUC5AC) is secreted by goblet cells of the respiratory tract and, surprisingly, also expressed de novo in mucus secreting cancer lines. siRNA-mediated knockdown of 7343 human gene products in a human colonic cancer goblet cell line (HT29-18N2) revealed new proteins, including a Ca(2+)-activated channel TRPM5, for MUC5AC secretion. TRPM5 was required for PMA and ATP-induced secretion of MUC5AC from the post-Golgi secretory granules. Stable knockdown of TRPM5 reduced a TRPM5-like current and ATP-mediated Ca(2+) signal. ATP-induced MUC5AC secretion depended strongly on Ca(2+) influx, which was markedly reduced in TRPM5 knockdown cells. The difference in ATP-induced Ca(2+) entry between control and TRPM5 knockdown cells was abrogated in the absence of extracellular Ca(2+) and by inhibition of the Na(+)/Ca(2+) exchanger (NCX). Accordingly, MUC5AC secretion was reduced by inhibition of NCX. Thus TRPM5 activation by ATP couples TRPM5-mediated Na(+) entry to promote Ca(2+) uptake via an NCX to trigger MUC5AC secretion

Role of CLOCK and circadian rhythms in calcium homeostasis

Le maintien d'une concentration sanguine constante de calcium est d'une importance cruciale et trois organes participent à la balance calcique normale : les reins, les intestins et les os. La concentration plasmatique de calcium est strictement régulée par l'hormone parathyroïdienne (PTH) et par la vitamine D. Des variations circadiennes de la PTH, de la vitamine D ainsi que du calcium plasmatique ont été décrites précédemment chez l'humain ainsi que chez le rat. Ces rythmes de PTH dans le sérum sont importants pour la régulation du remodelage de l'os. En effet, il a été montré chez les souris C57BL/6J que des injections de PTH une fois par jour mènent à une augmentation de la densité minérale de l'os alors que l'infusion en continu de PTH est associée à une diminution de cette densité. La vitamine D joue également un rôle fondamental dans la physiologie osseuse, car un déficit en vitamine D peut conduire à une ostéomalacie. Cependant la fonction des oscillations de vitamine D au niveau de l'homéostasie osseuse reste inconnue. L'horloge circadienne est un système interne de contrôle biologique du temps générant des rythmes de 24 heures dans l'expression des gènes, ainsi que dans la physiologie et le comportement. Ce contrôle s'opère par des boucles rétroactives positives et négatives de l'expression de gènes circadiens tels que CLOCK, BMAL1, CRY1 et 2 ou PERI et 2. Dans ce travail, nous avons émis l'hypothèse que l'homéostasie calcique est sous le contrôle de l'horloge circadienne. Dans un premier temps, nous avons montré chez les souris C57BL/6J des variations journalières des concentrations de calcium, de PTH et de vitamine D dans le sang, ainsi que de calcium dans les urines. Nous avons également démontré des changements au niveau de l'expression rénale des gènes importants dans l'homéostasie du calcium, tant au niveau de l'ARN messager que des protéines. Ensuite, pour analyser le rôle du système de l'horloge circadienne dans l'homéostasie du calcium, nous avons étudié des souris dans lesquelles a été supprimé le gène CLOCK crucial pour la fonction de l'horloge et nous avons comparé ces souris à des souris de type sauvage de même portée. Les souris CLOCK-I- étaient hypercalciuriques à chaque moment de la journée. Cependant le rythme circadien de l'excrétion de calcium était préservé. Le taux de calcium plasmatique ne différait pas entre les génotypes, mais les souris CLOCK -/- ne montraient pas de variations journalières de ce paramètre. Une perte du rythme journalier était également observée pour les niveaux de vitamine D, perte qui pourrait être une cause de l'altération de la micro-architecture osseuse révélée chez les souris CLOCK-/-. En effet, ces souris montrent une diminution du nombre de trabécules, de leur volume ainsi que de leur surface, ce qui suggère la présence d'ostéoporose. Nous avons également trouvé que le rythme de l'expression de l'ARN messager de CYP27B1 était aboli dans les reins des souris CLOCK -/-, ce qui peut expliquer l'altération du rythme de la vitamine D. Les taux sanguins de PTH étaient comparables entre les souris CLOCK -/- et de type sauvage. Dans les reins, une augmentation de l'expression de l'ARN messager de TRPV5 et NCX1 a été constatée, ce qui suggérerait une augmentation de la réabsorption de calcium dans le tubule convoluté distal et dans le tubule connecteur. Dans les intestins, la réabsorption calcique était diminuée, chez les souris CLOCK-I-, fait confirmé par une diminution des niveaux d'ARN messager de TRPV6 et PMCAL. En résumé, la suppression du gène CLOCK chez les souris a conduit à une hypercalciurie, une altération du rythme des taux plasmatiques de calcium et de vitamine D et à une détérioration de l'architecture osseuse. Pour conclure, ces résultats montrent que l'horloge circadienne est essentielle à l'homéostasie calcique ainsi qu'à la physiologie des os. - L'ostéoporose affecte environ 22 millions de femmes et 5.5 millions d'hommes en Europe, réduisant significativement leur qualité de vie et a causé 3.5 millions de nouvelles fractures en 2010. Les dépenses totales liées à ces fractures ont atteint 37 milliards d'euro et ce coût devrait augmenter de 25% d'ici à 2025. Le nombre de nouvelles fractures dues à l'ostéoporose à travers le monde est estimé à environ 1000 par heure. Parmi les causes de l'ostéoporose, le déficit én calcium et/ou en vitamine D joue un rôle important, mais il existe également des causes génétiques ou liées à des facteurs comme les hormones sexuelles (estrogènes, testostérone), l'âge, le tabac, le poids corporel, certains médicaments,... La vie est rythmique : ceci est dû à l'alternance naturelle du jour et de la nuit et de ses effets sur le corps. La prise alimentaire, par exemple, est un processus qui a lieu pendant la phase active, qui est prévisible (il se produit toujours au même moment) et qui peut être anticipé par le corps. Pour cela, une horloge interne est présente dans chaque cellule du corps et est synchronisée par la lumière du jour, entre autres stimuli. Cette horloge indique la phase du jour et régule l'expression de gènes impliqués dans les différents processus qui nécessitent une anticipation. Pendant mon travail de thèse, je me suis demandé si des îythmes circadiens (c'est-à-dire d'une durée d'environ 24 heures et indépendants des stimuli externes) étaient observables'pour les gènes régulant les flux de calcium dans le corps et si l'interruption de ces rythmes pouvait mener à des altérations de la qualité de l'os. J'ai d'abord travaillé avec des souris normales et j'ai pu montrer la présence de rythmes au niveau du calcium sanguin et urinaire, mais également au niveau des hormones et gènes qui contrôlent le métabolisme du calcium dans le corps, comme la vitamine D et l'hormone parathyroidienne. De manière intéressante, j'ai observé que la plupart de ces gènes ont un rythme synchronisé. J'ai ensuite utilisé un modèle de souris dans lequel l'horloge interne a été génétiquement invalidée et j'ai montré que ces souris présentent une augmentation de leur excrétion urinaire de calcium et un rythme circadien altéré de la vitamine D dans le sang. Ces souris absorbent aussi moins bien le calcium intestinal et présentent une ostéoporose marquée. Ce travail montre donc que l'horloge interne est nécessaire pour établir un rythme circadiens de certains facteurs influant les flux de calcium dans l'organisme, comme la vitamine D, et que la perturbation de ces rythmes mène à une dérégulation du métabolisme osseux. Ainsi, la perturbation de l'horloge interne peut causer une ostéoporose et une hypercalciurie qui pourraient aboutir à la formation de fractures et de calculs rénaux. L'extrapolation de ces observations chez l'homme ou à des changements plus subtiles des rythmes circadiens, comme le décalage horaire, restent à montrer. Cette recherche a démontré que les rythmes circadiens des mécanismes de régulation des flux de calcium dans l'organisme sont essentiels au maintien d'un squelette normal et suggère que les perturbations des rythmes circadiens pourraient être une nouvelle cause de l'ostéoporose. - Maintaining constant calcium concentration in the plasma is of a crucial importance and three organs participate in normal calcium balance - kidney, gut and bone. Plasma calcium concentration is strictly regulated by parathyroid hormone (PTH) and vitamin D. Circadian variations of PTH, vitamin D and plasma calcium were previously described in humans, as well as in rats. Rhythms in serum PTH are important for balanced bone remodelling. Indeed in C57BL/6J mice, PTH injection once per day leads to an increase in bone mineral density (BMD), whilst continuous infusion is associated with decreased BMD. Vitamin D also plays a crucial role in bone physiology, since the deficiency in vitamin D can lead to rickets/osteomalacia. However, the role of vitamin D rhythms in bone homeostasis remains unknown. The circadian clock is an. internal time-keeping system generating rhythms in gene expression with 24h periodicity, in physiology and in behaviour. It is operated by positive- and negative-feedback loops of circadian genes, such as CLOCK, BMAL1, CRY1 and 2 or PERI and 2. In this work, we hypothesized, that calcium homeostasis is under the control of the circadian clock. First, we showed daily variations in urinary calcium and serum calcium, PTH and l,25(OH)2 vitamin D, together with renal mRNA and protein levels of genes involved in calcium homeostasis in C57BL/6J mice. Second, and to investigate the role of the circadian clock system in calcium handling, we studied mice lacking the gene CLOCK crucial for fonction of the clock system and compared them to the WT littermates. CLOCK-/- mice were hypercalciuric at all timepoints of the day. However, the circadian rhythm of calcium excretion was preserved. Serum calcium levels did not differ between the genotypes, but CLOCK-/- mice did not exhibit daily variation for this parameter. Loss of rhythm was observed also for serum l,25(OH)2 vitamin D levels, which may be one of the causes of altered bone microarchitecture that was revealed in CLOCK-/- mice. They displayed increased trabecular separation and decreased trabecular number, trabecular bone volume and trabecular bone surface, suggestive of osteoporosis. We found that the rhythm of the mRNA expression of CYP27B1 was abolished in the kidney of CLOCK-/- mice, which could induce the altered rhythm of l,25(OH)2 vitamin. Serum PTH levels were comparable between CLOCK-/- and WT mice. In the kidney, increased mRNA expression of TRPV5 and NCX1 suggests increased calcium reabsorption in the distal convoluted and connecting tubule. In the gut, intestinal calcium absorption was decreased in CLOCK¬/- mice, confirmed by decreased mRNA levels of TRPV6 and PMCA1. In summary, deletion of the CLOCK gene in mice conducts to hypercalciuria, alteration of the rhythm in serum calcium and l,25(OH)2D levels, and impainnent of their bone microarchitecture. In conclusion, these data show that the circadian clock system is essential in calcium homeostasis and bone physiology.

Alkaline mineral water lowers bone resorption even in calcium sufficiency: alkaline mineral water and bone metabolism.

BACKGROUND: Dietary acid charge enhances bone loss. Bicarbonate or alkali diet decreases bone resorption in humans. We compared the effect of an alkaline mineral water, rich in bicarbonate, with that of an acid one, rich in calcium only, on bone markers, in young women with a normal calcium intake. METHODS: This study compared water A (per litre: 520 mg Ca, 291 mg HCO(3)(-), 1160 mg SO(4)(-), Potential Renal Acid load (PRAL) +9.2 mEq) with water B (per litre: 547 mg Ca, 2172 mg HCO(3)(-), 9 mg SO(4)(-), PRAL -11.2 mEq). 30 female dieticians aged 26.3 yrs (SD 7.3) were randomized into two groups, followed an identical weighed, balanced diet (965 mg Ca) and drank 1.5 l/d of the assigned water. Changes in blood and urine electrolytes, C-telopeptides (CTX), urinary pH and bicarbonate, and serum PTH were measured after 2 and 4 weeks. RESULTS: The two groups were not different at baseline, and showed a similar increase in urinary calcium excretion. Urinary pH and bicarbonate excretion increased with water B, but not with water A. PTH (p=0.022) and S-CTX (p=0.023) decreased with water B but not with water A. CONCLUSION: In calcium sufficiency, the acid calcium-rich water had no effect on bone resorption, while the alkaline water rich in bicarbonate led to a significant decrease of PTH and of S-CTX.

Intracellular thiol-mediated modulation of epithelial sodium channel activity.

The epithelial sodium channel ENaC is physiologically important in the kidney for the regulation of the extracellular fluid volume, and in the lungs for the maintenance of the appropriate airway surface liquid volume that lines the pulmonary epithelium. Besides the regulation of ENaC by hormones, intracellular factors such as Na(+) ions, pH, or Ca(2+) are responsible for fast adaptive responses of ENaC activity to changes in the intracellular milieu. In this study, we show that ENaC is rapidly and reversibly inhibited by internal sulfhydryl-reactive molecules such as methanethiosulfonate derivatives of different sizes, the metal cations Cd(2+) and Zn(2+), or copper(II) phenanthroline, a mild oxidizing agent that promotes the formation of disulfide bonds. At the single channel level, these agents applied intracellularly induce the appearance of long channel closures, suggesting an effect on ENaC gating. The intracellular reducing agent dithiothreitol fully reverses the rundown of ENaC activity in inside-out patches. Our observations suggest that changes in intracellular redox potential modulate ENaC activity and may regulate ENaC-mediated Na(+) transport in epithelia. Finally, substitution experiments reveal that multiple cysteine residues in the amino and carboxyl termini of ENaC subunits are responsible for this thiol-mediated inhibition of ENaC.

Selection of common bean lines with high agronomic performance and high calcium and iron concentrations

The objective of this work was to evaluate the genetic variability of common bean lines for cycle, weight of 100 grains, grain yield, cooking time, and grain calcium and iron concentrations. Twenty-four common bean lines were evaluated in two crop cycles (2010 and 2011). The ¯Z index was used for the selection of superior lines for most of the traits. The DF 06-19, DF 06-03, DF 06-17, DF 06-20, DF 06-11, DF 06-14, DF 06-01, DF 06-08, DF 06-22, and DF 06-04 lines showed high grain yield. All lines were of semi-early cycle and of fast cooking. The DF 06-08 and DF 06-23 lines showed high calcium concentration in grains (>1.4 g kg-1 dry matter - DM), and the DF 06-09, DF 06-03, DF 06-04, and DF 06-06 lines presented high iron concentration in grains (>0.95 g kg-1 DM) in the two crop cycles. The DF 06-09 and DF 06-03 carioca lines present high agronomic performance and high iron concentration in grains. The DF 06-17 and DF 06-08 black lines present high agronomic performance and high calcium concentration in grains. The selection of the DF 06-09, DF 06-03, DF 06-17, and DF 06-08 lines is recommended.

Capacity of MIMO Channels: asymptotic evaluation under correlated fading

This paper investigates the asymptotic uniform power allocation capacity of frequency nonselective multiple-inputmultiple-output channels with fading correlation at either thetransmitter or the receiver. We consider the asymptotic situation,where the number of inputs and outputs increase without boundat the same rate. A simple uniparametric model for the fadingcorrelation function is proposed and the asymptotic capacity perantenna is derived in closed form. Although the proposed correlationmodel is introduced only for mathematical convenience, itis shown that its shape is very close to an exponentially decayingcorrelation function. The asymptotic expression obtained providesa simple and yet useful way of relating the actual fadingcorrelation to the asymptotic capacity per antenna from a purelyanalytical point of view. For example, the asymptotic expressionsindicate that fading correlation is more harmful when arising atthe side with less antennas. Moreover, fading correlation does notinfluence the rate of growth of the asymptotic capacity per receiveantenna with high Eb /N0.

Enhanced MDIR receiver for space-time dispersive channels

A particular property of the matched desiredimpulse response receiver is introduced in this paper, namely,the fact that full exploitation of the diversity is obtained withmultiple beamformers when the channel is spatially and timelydispersive. This particularity makes the receiver specially suitablefor mobile and underwater communications. The new structureprovides better performance than conventional and weightedVRAKE receivers, and a diversity gain with no needs of additionalradio frequency equipment. The baseband hardware neededfor this new receiver may be obtained through reconfigurabilityof the RAKE architectures available at the base station. Theproposed receiver is tested through simulations assuming UTRAfrequency-division-duplexing mode.

Joint array combining and MLSE for single-user receivers in multipath Gaussian multiuser channels

The well-known structure of an array combiner along with a maximum likelihood sequence estimator (MLSE) receiveris the basis for the derivation of a space-time processor presentinggood properties in terms of co-channel and intersymbol interferencerejection. The use of spatial diversity at the receiver front-endtogether with a scalar MLSE implies a joint design of the spatialcombiner and the impulse response for the sequence detector. Thisis faced using the MMSE criterion under the constraint that thedesired user signal power is not cancelled, yielding an impulse responsefor the sequence detector that is matched to the channel andcombiner response. The procedure maximizes the signal-to-noiseratio at the input of the detector and exhibits excellent performancein realistic multipath channels.

Mapping out customer segments and marketing channels in the Finnish Homelift market

Työn tavoitteena oli saada selville ketkä ovat uuden tuotteen, eli kotihissin asiakkaat. Mitkä ovat tuotteen mahdollisuudet Suomen markkinoilla ja onko markkinoilla odotettavissa kasvua, sekä miten tähän mahdolliseen kasvuun päästäisiin käsiksi. Kotihissin ominaisuudet vaikuttavat siihen, että se on tarkoitettu asennettavaksi yksityisiin pientaloihin. Uuden tuotteen ansiosta KONE voi liittää nykyiseen vahvaan toimialaansa, eli kerrostaloihin, uuden aluevaltauksen; Pientalot. Tämä 'laajentuminen' tuo mukanaan kuluttajamarkkinoiden haasteet. Markkinatilanteen selvittämiseen käyttin jo olemassa olevaa tietoa hyväkseni; sanomalehdistä markkinatutkimuksiin. Asiakasryhmät kartoitin tutustumalla messutapahtumissa saatuihin kontakteihin. Päätutkimusmenetelmänä käytin haastatteluja. Niihin osallistui kaikkiaan 14 vastaajaa. He vasatsivat kysymyksiin ostomotiiveista ja tuotteesta. Eräs haastattelujen tärkeimmistä teemoista liittyi yhteydenpito- ja jakelukanaviin, joista 12 vastaajaa antoivat mielipiteitään. Työni tulokset viittaavat siihen, että markkinatilanne näyttää positiiviselta KONEen kannalta. Tutkimuksesta sain selville kotihissin asiakassegmentit ja myös miten nämä potentiaaliset asiakkaat saadaan tehokkaimmin tavoitettua.