Intracellular chemical messengers and neuronal function: Two examples

Two distinct classes of neurons have been examined in the nervous system of Aplysia. The membrane properties of these neurons are regulated by intracellular signalling molecules in both a short-term and a long-term fashion.^ The role of the phosphatidylinositol cycle in the control of neuronal properties was studied in a class of bursting pacemaker cells, the left upper-quadrant bursting neurons (cells L2, L3, L4, and L6) of the abdominal ganglion of Aplysia. These cells display a regular burst-firing pattern that is controlled by cyclic changes of intracellular Ca$\sp{2+}$ that occur during the bursting rhythm. The characteristic bursting pattern of these neurons occurs within a range of membrane potentials ($-35$ to $-50$ mV) called the pacemaker range. Intracellular pressure injection of inositol 1,4,5-trisphosphate (IP$\sb3$) altered the bursting rhythm of the bursting cells. Injection of IP$\sb3$ induced a brief depolarization that was followed by a long-lasting (2-15 min) hyperpolarization. When cells were voltage-clamped at potentials within the pacemaker range, injection of IP$\sb3$ generally induced a biphasic response that had a total duration of 2-15 min. An initial inward shift in holding current (I$\sb{\rm in}$), which lasted 5-120 sec, was followed by a slow outward shift in holding current (I$\sb{\rm out}$). At membrane potentials more negative than $-40$ mV, I$\sb{\rm in}$ was associated with a small and relatively voltage-independent increase in membrane conductance. I$\sb{\rm in}$ was not blocked by bath application of TTX or Co$\sp{2+}$. Although I$\sb{\rm in}$ was activated by injection of IP$\sb3$, it was not blocked by iontophoretic injection of ethyleneglycol-bis-(beta-aminoethyl ether), N, N$\sp\prime$-tetraacetic acid (EGTA) sufficient to block the Ca$\sp{2+}$-activated inward tail current (I$\sb{\rm B}$).^ Long-term (lasting at least 24 hours) effects of adenylate cyclase activation were examined in a well characterized class of mechanosensory neurons in Aplysia. The injected cells were analyzed 24 hours later by two-electrode voltage-clamp techniques. We found that K$\sp+$ currents of these cells were reduced 24 hours after injection of cAMP. The currents that were reduced by cAMP were very similar to those found to be reduced 24 hours after behavioral sensitization. These results suggest that cAMP is part of the intracellular signal that induces long-term sensitization in Aplysia. (Abstract shortened with permission of author.) ^

Integrin function in T cell activation recapitulated in tumor growth

An in vitro model using highly purified freshly isolated T cells demonstrated that immobilized ligands for the integrin $\alpha4\beta1$ could cooperate to enhance mitogen signals delivered by coimmobilized anti-CD3 specfic monoclonal antibody OKT3. Costimulation through $\alpha4\beta1$ integrin lead to enhanced proliferation which depended on expression of both IL-2 as well as IL-2 receptor. The transcription factors NF-AT, AP-1, and NF-$\kappa$B, which are involved in the regulation of IL-2 as well as other cytokine genes, were weakly induced by anti-CD3 stimulation alone in electromobility shift assays, but were augmented significantly with $\alpha4\beta1$ costimulation. These results suggested that $\alpha4\beta1$ ligands delivered a growth promoting signal which could synergize with signals induced by engagement of the TCR/CD3 complex, and also suggested a dual function for integrins in both localization and subsequent delivery of a growth promoting signal for T lymphocytes. Integrin involvement in lymphocyte trafficking has been employed as a model for understanding tumor cell metastasis. Therefore we have extended the duality of integrin function in both homing and subsequent delivery of a growth promoting signal to include a role for integrins in providing growth stimulation for tumor cells. Using a gastric derived tumor line, inhibition of adhesion to substrate leads to G0/G1 cell cycle arrest, reduced cyclin A expression, and reduced phospholipid synthesis. This effect could be reversed upon $\alpha2\beta1$ integrin mediated reattachment to collagen. These observations demonstrated a role for an integrin in the growth regulation of a tumor line. The small GTP-binding protein Rho, implicated in phospholipid synthesis, can be inactivated by the ADP-ribosylation exoenzyme C3 from C. botulinum. Addition of C3 to cell cultures inhibited the growth promoting effect due to integrin mediated adhesion. Taken together, these results are consistent with a model for cooperative interaction between integrins and Rho leading to enhanced phospholipid synthesis and mitogen signaling. This model may provide a basis for understanding the phenomena of integrin costimulation in T cell activation. ^

Neuromuscular disuse and atrophy: {\it In vivo\/} magnetic resonance studies of intramuscular lipid metabolism and fluid shift changes

We postulated that neuromuscular disuse results in deleteriously affected tissue-vascular fluid exchange processes and subsequently damages the important oxidative bioenergetic process of intramuscular lipid metabolism. The in-depth research reported in the literature is somewhat limited by the ex vivo nature and sporadic time-course characterization of disuse atrophy and recovery. Thus, an in vivo controlled, localized animal model of disuse atrophy was developed in one of the hindlimbs of laboratory rabbits (employing surgically implanted tetrodotoxin (TTX)-filled mini-osmotic pump-sciatic nerve superfusion system) and tested repeatedly with magnetic resonance (MR) throughout the 2-week period of temporarily induced disuse and during the recovery period (following explantation of the TTX-filled pump) for a period of 3 weeks. Controls consisted of saline/"sham"-implanted rabbit hindlimbs. The validity of this model was established with repeated electrophysiologic nerve conduction testing using a clinically appropriate protocol and percutaneously inserted small needle stimulating and recording electrodes. Evoked responses recorded from proximal (P) and distal (D) sites to the sciatic nerve cuff in the TTX-implanted group revealed significantly decreased (p $<$ 0.001) proximal-to-distal (P/D) amplitude ratios (as much as 50-70% below Baseline/pre-implanted and sham-implanted group values) and significantly increased (p $<$ 0.01) differential latency (PL-DL) values (as much as 1.5 times the pre- and sham-implanted groups). By Day 21 of recovery, observed P/D and PL-DL levels matched Baseline/sham-implemented levels. MRI-determined cross-sectional area (CSA) values of Baseline/pre-implanted, sham- or TTX-implanted, and recovering/explanted and the corresponding contralateral hindlimb tibialis anterior (TA) muscles normalized to tibial bone (TB) CSA (in TA/TB ratios) revealed that there was a significant decline (indicative of atrophic response) from pre- and sham-implanted controls by as much as 20% (p $<$ 0.01) at Day 7 and 50-55% (p $<$ 0.001) at Day 13 of TTX-implantation. In the non-implanted contralaterals, a significant increase (indicative of hypertrophic response) by as much as 10% (p $<$ 0.025) at Day 7 and 27% (p $<$ 0.001) at Day 13 + TTX was found. The induced atrophic/hypertrophic TA muscles were observed to be fully recovered by Day 21 post-explantation as evidenced by image TA/TB ratios. End-point biopsy results from a small group of rabbits revealed comprehensive atrophy of both Type I and Type II fibers, although the heterogeneity of the response supports the use of image-guided, volume-localized proton magnetic resonance spectroscopy (MRS) to noninvasively assess tissue-level metabolic changes. MRS-determined results of a 0.25cc volume of tissue within implanted limb TA muscles under resting/pre-ischemic, ischemic-stressed, and post-ischemic conditions at timepoints during and following disuse atrophy/recovery revealed significantly increased intramuscular spectral lipid levels, as much as 2-3 times (p $<$ 0.01) the Baseline/pre-implanted values at Day 7 and 6-7 times (p $<$ 0.001) at Day 13 + TTX, which approached normal levels (compared to pre- and sham-implanted groups) by Day 21 of post-explanation recovery. (Abstract shortened by UMI.) ^

Sleep respiratory disturbances and arousals at moderate altitude have overlapping electroencephalogram spectral signatures

An ascent to altitude has been shown to result in more central apneas and a shift towards lighter sleep in healthy individuals. This study employs spectral analysis to investigate the impact of respiratory disturbances (central/obstructive apnea and hypopnea or periodic breathing) at moderate altitude on the sleep electroencephalogram (EEG) and to compare EEG changes resulting from respiratory disturbances and arousals. Data were collected from 51 healthy male subjects who spent 1 night at moderate altitude (2590 m). Power density spectra of Stage 2 sleep were calculated in a subset (20) of these participants with sufficient artefact-free data for (a) epochs with respiratory events without an accompanying arousal, (b) epochs containing an arousal and (c) epochs of undisturbed Stage 2 sleep containing neither arousal nor respiratory events. Both arousals and respiratory disturbances resulted in reduced power in the delta, theta and spindle frequency range and increased beta power compared to undisturbed sleep. The similarity of the EEG changes resulting from altitude-induced respiratory disturbances and arousals indicates that central apneas are associated with micro-arousals, not apparent by visual inspection of the EEG. Our findings may have implications for sleep in patients and mountain tourists with central apneas and suggest that respiratory disturbances not accompanied by an arousal may, none the less, impact sleep quality and impair recuperative processes associated with sleep more than previously believed.

A new Bayesian approach to the reconstruction of spectral functions

We present a novel approach for the reconstruction of spectra from Euclidean correlator data that makes close contact to modern Bayesian concepts. It is based upon an axiomatically justified dimensionless prior distribution, which in the case of constant prior function m(ω) only imprints smoothness on the reconstructed spectrum. In addition we are able to analytically integrate out the only relevant overall hyper-parameter α in the prior, removing the necessity for Gaussian approximations found e.g. in the Maximum Entropy Method. Using a quasi-Newton minimizer and high-precision arithmetic, we are then able to find the unique global extremum of P[ρ|D] in the full Nω » Nτ dimensional search space. The method actually yields gradually improving reconstruction results if the quality of the supplied input data increases, without introducing artificial peak structures, often encountered in the MEM. To support these statements we present mock data analyses for the case of zero width delta peaks and more realistic scenarios, based on the perturbative Euclidean Wilson Loop as well as the Wilson Line correlator in Coulomb gauge.

Analysis of p53 function and regulation

p53 is a tumor suppressor gene that is the most frequent target inactivated in cancers. Overexpression of wild-type p53 in rat embryo fibroblasts suppresses foci formation by other cooperating oncogenes. Introduction of wild-type p53 into cells that lack p53 arrests them at the G1/S boundary and reverses the transformed phenotype of some cells. The function of p53 in normal cells is illustrated by the ability of p53 to arrest cells at G1 phase of the cell cycle upon exposure to DNA-damaging agents including UV-irradiation and biosynthesis inhibitors.^ Since the amino acid sequence of p53 suggested that it may function as a transcription factor, we used GAL4 fusion assays to test that possibility. We found that wild-type p53 could specifically activate transcription when anchored by the GAL4 DNA binding domain. Mutant p53s, which have lost the ability to suppress foci formation by other oncogenes, were not able to activate transcription in this assay. Thus, we established a direct correlation between the tumor suppression and transactivation functions of p53.^ Having learned that p53 was a transcriptional activator, we next sought targets of p53 activation. Because many transcription factors regulate their own expression, we tested whether p53 had this autoregulatory property. Transient expression of wild-type p53 in cells increased the levels of endogenous p53 mRNA. Cotransfection of p53 together with a reporter bearing the p53 promoter confirmed that wild-type p53 specifically activates its own promoter. Deletion analysis from both the 5$\sp\prime$ and 3$\sp\prime$ ends of the promoter minimized the region responsible for p53 autoregulation to 45 bp. Methylation interference identified nucleotides involved in protein-DNA interaction. Mutations within this protected site specifically eliminated the response of the promoter to p53. In addition, multiple copies of this element confer responsiveness to wild-type p53 expression. Thus, we identified a F53 responsive element within the p53 promoter.^ The presence of a consensus NF-$\kappa$B site in the p53 promoter suggested that NF-KB may regulate p53 expression. Gel-shift experiments showed that both the p50 homodimer and the p50/p65 heterodimer bind to the p53 promoter. In addition, the p65 subunit of NF-$\kappa$B activates the p53 promoter in transient transfection experiments. TNF $\alpha$, a natural NF-$\kappa$B inducer, also activates the p53 promoter. Both p65 activation and TNF $\alpha$ induction require an intact NF-$\kappa$B site in the p53 promoter. Since NF-$\kappa$B activation occurs as a response to stress and p53 arrests cells in G1/S, where DNA repair occurs, activation of p53 by NF-$\kappa$B could be a mechanism by which cells recover from stress.^ In conclusion, we provided the first data that wild-type p53 functions as a transcriptional activator, whereas mutant p53 cannot. The correlation between growth suppression and transcriptional activation by p53 implies a pathway of tumor suppression. We have analyzed upstream components of the pathway by the identification of both p53 and NF-$\kappa$B as regulators of the p53 promoter. ^

Genetic integration of a nuclear -encoded mitochondrial gene with cardiac function

Cardiovascular disease (CVD) is the leading cause of death in the United States. One manifestation of CVD known to increase mortality is an enlarged, or hypertrophic heart. Hypertrophic cardiomyocytes adapt to increased contractile demand at the genetic level with a re-emergence of the fetal gene program and a downregulation of fatty acid oxidation genes with concomitant increased reliance on glucose-based metabolism. To understand the transcriptional regulatory pathways that implement hypertrophic directives we analyzed the upstream promoter region of the muscle specific isoform of the nuclear-encoded mitochondrial gene, carnitine palmitoyltransferase-1β (CPT-1β) in cultured rat neonatal cardiac myocytes. This enzyme catalyzes the rate-limiting step of fatty acid entry into β-oxidation and is downregulated in cardiac hypertrophy and failure, making it an attractive model for the study of hypertrophic gene regulation and metabolic adaptations. We demonstrate that the muscle-enriched transcription factors GATA-4 and SRF synergistically activate CPT-1β; moreover, DNA binding to cognate sites and intact protein structure are required. This mechanism coordinates upregulation of energy generating processes with activation of the energy consuming contractile promoter for cardiac α-actin. We hypothesized that fatty acid or glucose responsive transcription factors may also regulate CPT-1β. Oleate weakly stimulates CPT-1β activity; in contrast, the glucose responsive Upstream Stimulatory Factors (USF) dramatically depresses the CPT-1β reporter. USF regulates CPT-1β through a novel physical interaction with the cofactor PGC-1 and abrogation of MEF2A/PGC-1 synergistic stimulation. In this way, USF can inversely regulate metabolic gene programs and may play a role in the shift of metabolic substrate preference seen in hypertrophy. Failing hearts have elevated expression of the nuclear hormone receptor COUP-TF. We report that COUP-TF significantly suppresses reporter transcription independent of DNA binding and specific interactions with GATA-4, Nkx2.5 or USF. In summary, CPT-1β transcriptional regulation integrates mitochondrial gene expression with two essential cardiac functions: contraction and metabolic substrate oxidation. ^

hyDRaCAT Spectral Reflectance Library: Hyperspectral Field Spectroscopy and Field Spectro-Goniometry of Siberian and Alaskan Tundra

hyDRaCAT Spectral Reflectance Library for tundra provides the surface reflectance data and the bidirectional reflectance distribution function (BRDF) of important Arctic tundra vegetation communities at representative Siberian and Alaskan tundra sites. The aim of this dataset is the hyperspectral and spectro-directional reflectance characterization as basis for the extraction of vegetation parameters, and the normalization of BRDF effects in off-nadir and multi-temporal remote sensing data. The spectroscopic and field spectro-goniometric measurements were undertaken on the YAMAL2011 expedition of representative Siberian vegetation fields and on the North American Arctic Transect NAAT2012 expedition of Alaskan vegetation fields both belonging to the Greening-of-the-Arctic (GOA) program. For the field spectroscopy each 100 m2 vegetation study grid was divided into quadrats of 1 × 1 m. The averaged reflectance of all quadrats represents the spectral reflectance at the scale of the whole grid at the 10 × 10 m scale. For the surface radiometric measurements two GER1500 portable field spectroradiometers (Spectra Vista Corporation, Poughkeepsie, NY, USA) were used. The GER1500 measures radiance across the wavelength range of 350-1,050 nm, with sampling intervals of 1.5 nm and a radiance accuracy of 1.2 × 10**-1 W/cm**2/nm/sr. In order to increase the signal-to-noise ratio, 32 individual measurements were averaged per one target scan. To minimize variations in the target reflectance due to sun zenith angle changes, all measurements at one study location have been performed under similar sun zenith angles and during clear-sky conditions. The field spectrometer measurements were carried out with a GER1500 UV-VIS spectrometer The spectrogoniometer measurements were carried out with a self-designed spectro-goniometer: the Manual Transportable Instrument platform for ground-based Spectro-directional observations (ManTIS, patent publication number: DE 10 2011 117 713.A1). The ManTIS was equipped with the GER1500 spectrometer allowing spectro-directional measurements with up to 30° viewing zenith angle by full 360° viewing azimuth angles. Measurements in central Yamal (Siberia) at the research site 'Vaskiny Dachi' were carried out in the late summer phenological state from August 12 2011 to August 28 2011. All measurements in Alaska along the North South transect on the North Slope were taken between 29 June and 11 July 2012, ensuring that the vegetation was in the same phenological state near peak growing season.

Fotodiodos basados en (Zn,Mg)O para la detección de luz ultravioleta

La presente tesis fue ideada con el objetivo principal de fabricar y caracterizar fotodiodos Schottky en capas de ZnMgO y en estructuras de pozo cuántico ZnMgO/ZnO para la detección de luz UV. La elección de este material semiconductor vino motivada por la posibilidad que ofrece de detectar y procesar señales simultáneamente, en un amplio margen de longitudes de onda, al igual que su más directo competidor el GaN. En esta memoria se da en primer lugar una visión general de las propiedades estructurales y ópticas del ZnO, prestando especial atención a su ternario ZnMgO y a las estructuras de pozo cuántico ZnMgO/ZnO. Además, se han desarrollado los conocimientos teóricos necesarios para una mejor compresión y discusión de los resultados alcanzados. En lo que respecta a los resultados de esta memoria, en esencia, estos se dividen en dos bloques. Fotodiodos desarrollados sobre capas delgadas de ZnMgO no-polar, y sobre estructuras de pozo cuántico de ZnMgO/ZnO no-polares y semipolares Fotodiodos de capas delgadas de ZnMgO. Es bien conocido que la adición de Mg a la estructura cristalina del ZnO desplaza el borde de absorción hacia energías mayores en el UV. Se ha aprovechado esto para fabricar fotodiodos Schottky sobre capas de ZnMgO crecidas por MOCVD y MBE, los cuales detecten en un ventana de energías comprendida entre 3.3 a 4.6 eV. Sobre las capas de ZnMgO, con diferentes contenidos de Mg(5.6-18.0 %), crecidas por MOCVD se han fabricado fotodiodos Schottky. Se han estudiado en detalle las curvas corrientevoltaje (I-V). Seguidamente, se ha realizado un análisis de la respuesta espectral bajo polarización inversa. Tanto los valores de responsividad obtenidos como el contraste UV/VIS están claramente aumentados por la presencia de ganancia. Paralelamente, se han realizado medidas de espectroscopia de niveles profundos (DLOS), identificándose la presencia de dos niveles profundos de carácter aceptor. El papel desempeñado por estos en la ganancia ha sido analizado meticulosamente. Se ha demostrado que cuando estos son fotoionizados son responsables directos del gran aumento de la corriente túnel que se produce a través de la barrera Schottky, dando lugar a la presencia de la ganancia observada, que además resulta ser función del flujo de fotones incidente. Para extender el rango detección hasta 4.6 eV se fabricaron fotodiodos sobre capas de ZnMgO de altísima calidad cristalina crecidas por MBE. Sobre estos se ha realizado un riguroso análisis de las curvas I-V y de las curvas capacidad-voltaje (CV), para posteriormente identificar los niveles profundos presentes en el material, mediante la técnica de DLOS. Así mismo se ha medido la respuesta espectral de los fotodetectores, la cual muestra un corte abrupto y un altísimo contraste UV/VIS. Además, se ha demostrado como estos son perfectos candidatos para la detección de luz en la región ciega al Sol. Por otra parte, se han fabricado fotodiodos MSM sobre estas mismas capas. Se han estudiado las principales figuras de mérito de estos, observándose unas corrientes bajas de oscuridad, un contraste UV/VIS de 103, y la presencia de fotocorriente persistente. Fotodiodos Schottky de pozos cuánticos de ZnO/ZnMgO. En el segundo bloque de esta memoria, con el objeto final de clarificar el impacto que tiene el tratamiento del H2O2 sobre las características optoelectrónicas de los dispositivos, se ha realizado un estudio detallado, en el que se han analizado por separado fotodiodos tratados y no tratados con H2O2, fabricados sobre pozos cuánticos de ZnMgO/ZnO. Se ha estudiado la respuesta espectral en ambos casos, observándose la presencia de ganancia en los dos. A través de un análisis meticuloso de las características electrónicas y optoeletrónicas de los fotodiodos, se han identificado dos mecanismos de ganancia internos diferentes en función de que la muestra sea tratada o no-tratada. Se han estudiado fotodetectores sensibles a la polarización de la luz (PSPDs) usando estructuras de pozo cuántico no-polares y semipolares sobre sustratos de zafiro y sustratos de ZnO. En lo que respecta a los PSPDs sobre zafiro, en los cuales el pozo presenta una tensión acumulada en el plano, se ha visto que el borde de absorción se desplaza _E _21 meV con respecto a luz linealmente polarizada perpendicular y paralela al eje-c, midiéndose un contraste (RE || c /RE c)max _ 6. Con respecto a los PSPDs crecidos sobre ZnO, los cuales tienen el pozo relajado, se ha obtenido un 4E _30-40, y 21 meV para las heteroestructuras no-polar y semipolar, respectivamente. Además el máximo contraste de responsividad fue de (RE || c /RE c)max _ 6 . Esta sensibilidad a la polarización de la luz ha sido explicada en términos de las transiciones excitónicas entre la banda de conducción y las tres bandas de valencia. ABSTRACT The main goal of the present thesis is the fabrication and characterization of Schottky photodiodes based on ZnMgO layers and ZnMgO / ZnO quantum wells (QWs) for the UV detection. The decision of choosing this semiconductor was mainly motivated by the possibility it offers of detecting and processing signals simultaneously in a wide range of wavelengths like its main competitor GaN. A general overview about the structural and optical properties of ZnO, ZnMgO layers and ZnMgO/ZnO QWs is given in the first part of this thesis. Besides, it is shown the necessary theoretical knowledge for a better understanding of the discussion presented here. The results of this thesis may be divided in two parts. On the one hand, the first part is based on studying non-polar ZnMgO photodiodes. On the other hand, the second part is focused on the characterization of non-polar and semipolar ZnMgO / ZnO QWs Schottky photodiodes. ZnMgO photodiodes. It is well known that the addition of Mg in the crystal structure of ZnO results in a strong blue-shift of the ZnO band-gap. Taking into account this fact Schottky photodiodes were fabricated on ZnMgO layers grown by MOCVD and MBE. Concerning ZnMgO layers grown by MOCVD, a series of Schottky photodiodes were fabricated, by varying the Mg content from 5.6% to 18 %. Firstly, it has been studied in detail the current-voltage curves. Subsequently, spectral response was analyzed at reverse bias voltage. Both the rejection ratio and the responsivity are shown to be largely enhanced by the presence of an internal gain mechanism. Simultaneously, measurements of deep level optical spectroscopy were carried out, identifying the presence of two acceptor-like deep levels. The role played for these in the gain observed was studied in detail. It has been demonstrated that when these are photoionized cause a large increase in the tunnel current through the Schottky barrier, yielding internal gains that are a function of the incident photon flux. In order to extend the detection range up to 4.6 eV, photodiodes ZnMgO grown by MBE were fabricated. An exhaustive analysis of the both I-V and CV characteristics was performed. Once again, deep levels were identified by using the technique DLOS. Furthermore, the spectral response was measured, observing sharp absorption edges and high UV/VIS rejections ratio. The results obtained have confirmed these photodiodes are excellent candidates for the light detection in the solar-blind region. In addition, MSM photodiodes have also been fabricated on the same layers. The main figures of merit have been studied, showing low dark currents, a large UV/VIS rejection ratio and persistent photocurrent. ZnMgO/ZnO QWs photodiodes. The second part was focused on ZnMgO/ ZnO QWs. In order to clarify the impact of the H2O2 treatment on the performance of the Schottky diodes, a comparative study using treated and untreated ZnMgO/ZnO photodiodes has been carried out. The spectral response in both cases has shown the presence of gain, under reverse bias. Finally, by means of the analysis of electronic and optoelectronic characteristics, two different internal gain mechanisms have been indentified in treated and non-treated material. Light polarization-sensitive UV photodetectors (PSPDs) using non-polar and semipolar ZnMgO/ZnO multiple quantum wells grown both on sapphire and ZnO substrates have been demonstrated. For the PSPDs grown on sapphire with anisotropic biaxial in-plain strain, the responsivity absorption edge shifts by _E _21 meV between light polarized perpendicular and parallel to the c-axis, and the maximum responsivity contrast is (RE || c /RE c)max _ 6 . For the PSPDs grown on ZnO, with strain-free quantum wells, 4E _30-40, and 21 meV for non-polar and semipolar heterostructures, and maximum (R /R||)max _10. for non-polar heterostructure was achieved. These light polarization sensitivities have been explained in terms of the excitonic transitions between the conduction and the three valence bands.

Light-Emitting-Diodes based on ordered InGaN nanocolumns emitting in the blue, green and yellow spectral range

The growth of ordered arrays of InGaN/GaN nanocolumnar light emitting diodes by molecular beam epitaxy, emitting in the blue (441 nm), green (502 nm), and yellow (568 nm) spectral range is reported. The device active region, consisting of a nanocolumnar InGaN section of nominally constant composition and 250 to 500 nm length, is free of extended defects, which is in strong contrast to InGaN layers (planar) of similar composition and thickness. The devices are driven under pulsed operation up to 1300 A/cm2 without traces of efficiency droop. Electroluminescence spectra show a very small blue shift with increasing current, (almost negligible in the yellow device) and line widths slightly broader than those of state-of-the-art InGaN quantum wells.

Temporally flat top pulse generation from gain switched semiconductor lasers based on a polarization interferometer with variable transfer function

We propose the use of a polarization based interferometer with variable transfer function for the generation of temporally flat top pulses from gain switched single mode semiconductor lasers. The main advantage of the presented technique is its flexibility in terms of input pulse characteristics, as pulse duration, spectral bandwidth and operating wavelength. Theoretical predictions and experimental demonstrations are presented and the proposed technique is applied to two different semiconductor laser sources emitting in the 1550 nm region. Flat top pulses are successfully obtained with input seed pulses with duration ranging from 40 ps to 100 ps.

A cobalt complex that selectively disrupts the structure and function of zinc fingers

Zinc finger domains are structures that mediate sequence recognition for a large number of DNA-binding proteins. These domains consist of sequences of amino acids containing cysteine and histidine residues tetrahedrally coordinated to a zinc ion. In this report, we present a means to selectively inhibit a zinc finger transcription factor with cobalt(III) Schiff-base complexes. 1H NMR spectroscopy confirmed that the structure of a zinc finger peptide is disrupted by axial ligation of the cobalt(III) complex to the nitrogen of the imidazole ring of a histidine residue. Fluorescence studies reveal that the zinc ion is displaced from the model zinc finger peptide in the presence of the cobalt complex. In addition, gel-shift and filter-binding assays reveal that cobalt complexes inhibit binding of a complete zinc finger protein, human transcription factor Sp1, to its consensus sequence. Finally, a DNA-coupled conjugate of the cobalt complexes selectively inhibited Sp1 in the presence of several other transcription factors.

Mechanisms of spectral tuning in the mouse green cone pigment

Diversification of cone pigment spectral sensitivities during evolution is a prerequisite for the development of color vision. Previous studies have identified two naturally occurring mechanisms that produce variation among vertebrate pigments by red-shifting visual pigment absorbance: addition of hydroxyl groups to the putative chromophore binding pocket and binding of chloride to a putative extracellular loop. In this paper we describe the use of two blue-shifting mechanisms during the evolution of rodent long-wave cone pigments. The mouse green pigment belongs to the long-wave subfamily of cone pigments, but its absorption maximum is 508 nm, similar to that of the rhodopsin subfamily of visual pigments, but blue-shifted 44 nm relative to the human red pigment, its closest homologue. We show that acquisition of a hydroxyl group near the retinylidene Schiff base and loss of the chloride binding site mentioned above fully account for the observed blue shift. These data indicate that the chloride binding site is not a universal attribute of long-wave cone pigments as generally supposed, and that, depending upon location, hydroxyl groups can alter the environment of the chromophore to produce either red or blue shifts.

Mendel’s dwarfing gene: cDNAs from the Le alleles and function of the expressed proteins

The major gibberellin (GA) controlling stem elongation in pea (Pisum sativum L.) is GA1, which is formed from GA20 by 3β-hydroxylation. This step, which limits GA1 biosynthesis in pea, is controlled by the Le locus, one of the original Mendelian loci. Mutations in this locus result in dwarfism. We have isolated cDNAs encoding a GA 3β-hydroxylase from lines of pea carrying the Le, le, le-3, and led alleles. The cDNA sequences from le and le-3 each contain a base substitution resulting in single amino acid changes relative to the sequence from Le. The cDNA sequence from led, a mutant derived from an le line, contains both the le “mutation” and a single-base deletion, which causes a shift in reading frame and presumably a null mutation. cDNAs from each line were expressed in Escherichia coli. The expression product for the clone from Le converted GA9 to GA4, and GA20 to GA1, with Km values of 1.5 μM and 13 μM, respectively. The amino acid substitution in the clone from le increased Km for GA9 100-fold and reduced conversion of GA20 to almost nil. Expression products from le and le-3 possessed similar levels of 3β-hydroxylase activity, and the expression product from led was inactive. Our results suggest that the 3β-hydroxylase cDNA is encoded by Le. Le transcript is expressed in roots, shoots, and cotyledons of germinating pea seedlings, in internodes and leaves of established seedlings, and in developing seeds.