3,402 research outputs found
Wavelength tunable 10-GHz 3-ps pulse source using a dispersion decreasing fiber-based nonlinear optical loop mirror
No full textWe experimentally demonstrate the use of a dispersion decreasing fiber (DDF)-based nonlinear optical loop mirror (NOLM) for the generation of wavelength tunable soliton-like pulses at a repetition rate of 10 GHz. We compress ~12 ps Gaussian pulses from an electro-absorption modulator (EAM) (followed by 125 m of DCF for preliminary linear dispersion compensation) into 3 ps pedestal-free pulses using both high-order soliton compression and nonlinear switching effects within an 8.5 km DDF-based loop mirror. The output pulses from the DDF-based NOLM show considerable pedestal reduction compared to those obtained by directly compressing the EAM seed pulses via a single passage through the DDF. Wavelength tuning of the compressed pulses over a ~15 nm bandwidth (from 1541 to 1556 nm) is demonstrated without a significant increase in pulse duration or degradation in pulse quality
Player agency in interactive narrative: audience, actor & author
No full textThe question motivating this review paper is, how can
computer-based interactive narrative be used as a constructivist learn-
ing activity? The paper proposes that player agency can be used to
link interactive narrative to learner agency in constructivist theory,
and to classify approaches to interactive narrative. The traditional
question driving research in interactive narrative is, ‘how can an in-
teractive narrative deal with a high degree of player agency, while
maintaining a coherent and well-formed narrative?’ This question
derives from an Aristotelian approach to interactive narrative that,
as the question shows, is inherently antagonistic to player agency.
Within this approach, player agency must be restricted and manip-
ulated to maintain the narrative. Two alternative approaches based
on Brecht’s Epic Theatre and Boal’s Theatre of the Oppressed are
reviewed. If a Boalian approach to interactive narrative is taken the
conflict between narrative and player agency dissolves. The question
that emerges from this approach is quite different from the traditional
question above, and presents a more useful approach to applying in-
teractive narrative as a constructivist learning activity
Charisma and Spirituality in the Early Church: A Study of Messalianism and Pseudo-Macarius
No full textThe thesis is an investigation into the concept of Charisma and Spirituality in the Early Church with particular emphasis upon the writings of Ps-Macarius, and of a group of ascetics known as the Messalians, evident in the late fourth / early fifth centuries. The Macarian writings are
examined to see what they reveal about the experiential pneumatic theology of the Early Church, the relationship between Syrian and Hellenic traditions of Christian Rhetoric, and the relationship between Ps-Macarius and the Cappadocian Circle. The Macarian corpus as a whole is examined to assess its rhetorical influences and style. The rhetoric of the Macarian corpus is seen to illustrate a high degree of sophistication. This study also gives definition to two terms that have become imprecise and diverse in their use: 'enkrateia' (self-control), and
`Syrian Christianity'. By isolating the characteristics of enkratefa the definitive stages of an encratic lifestyle are identified. The breaking down of the term into enkrateia, radical enkrateta and exclusive enkrateta enables a much clearer discussion to take place as to the
nature of the encratic theology of a group or individual. The final element of this study is a consideration of the distinct Macarian imagery that is evident within the corpus. Two images are considered in detail, the 'flight of the soul' and 'sober intoxication'. Overall this study
shows the variety of influences upon Ps-Macarius, and the uniqueness of his expression. The influences upon Ps-Macarius include a context of endemic Syrian spirituality, a radical encratic lifestyle, a Hellenic rhetorical training, and a distinct interpretation of Platonic and Neo-
Platonic images, coupled to the wider Judaic / Mesopotamian influences of his Church. It is shown that Ps-Macarius represents an individual voice that is distinct and recognisable amongst the Fathers of the Church
Nuclear translocation and signalling of L1-CAM in human carcinoma cells requires ADAM10 and presenilin/gamma-secretase activity
No full textL1-CAM (L1 cell-adhesion molecule), or more simply L1, plays an important role in the progression of human carcinoma. Overexpression promotes tumour-cell invasion and motility, growth in nude mice and tumour metastasis. It is feasible that L1-dependent signalling contributes to these effects. However, little is known about its mechanism in tumour cells. We reported previously that L1 is cleaved by ADAM (a disintegrin and metalloprotease) and that the cytoplasmic part is essential for L1 function. Here we analysed more closely the role of proteolytic cleavage in L1-mediated nuclear signalling. Using OVMz carcinoma cells and L1-transfected cells as a model, we found that ADAM10-mediated cleavage of L1 proceeds in lipid raft and non-raft domains. The cleavage product, L1-32, is further processed by PS (presenilin)/gamma-secretase to release L1-ICD, an L1 intracellular domain of 28 kDa. Overexpression of dominantnegative PS1 or use of a specific gamma-secretase inhibitor leads to an accumulation of L1-32. Fluorescence and biochemical analysis revealed a nuclear localization for L1-ICD. Moreover, inhibition of ADAM10 and/or gamma-secretase blocks nuclear translocation of L1-ICD and L1-dependent gene regulation. Overexpression of recombinant L1-ICD mediates gene regulation in a similar manner to full-length L1. Our results establish for the first time that regulated proteolytic processing by ADAM10 and PS/gamma-secretase is essential for the nuclear signalling of L1 in human carcinoma cell lines. Key words: a disintegrin and metalloprotease 10 (ADAM10), L1 cell-adhesion molecule (L1-CAM), nuclear translocation, presenilin (PS)/gamma-secretase activity, raft, signalling
Acute action of rotenone on nigral dopaminergic neurons--involvement of reactive oxygen species and disruption of Ca2+ homeostasis
No full textAbstract
Rotenone is a toxin used to generate animal models of Parkinson’s disease; however, the mechanisms of toxicity in substantia nigra pars compacta (SNc) neurons have not been well characterized. We have investigated rotenone (0.05–1 lm) effects on SNc neurons in acute rat midbrain slices, using whole-cell patch-clamp recording combined with microfluorometry. Rotenone evoked a tolbutamide-sensitive outward current (94 ± 15 pA) associated with increases in intracellular [Ca2+] ([Ca2+]i) (73.8 ± 7.7 nm) and intracellular [Na+] (3.1 ± 0.6 mm) (all with 1 lm). The outward current was not affected by a high ATP level (10 mm) in the patch pipette but was decreased by Trolox. The [Ca2+]i rise was abolished by removing extracellular Ca2+, and attenuated by Trolox and a transient receptor potential M2 (TRPM2) channel blocker, N-(p-amylcinnamoyl) anthranilic acid. Other effects included mitochondrial
depolarization (rhodamine-123) and increased mitochondrial reactive oxygen species (ROS) production (MitoSox), which was also abolished by Trolox. A low concentration of rotenone (5 nm) that, by itself, did not evoke a [Ca2+]i rise resulted in a large (46.6 ± 25.3 nm) Ca2+ response when baseline [Ca2+]i was increased by a ‘priming’ protocol that activated voltage-gated Ca2+ channels. There was also a positive correlation between ‘naturally’ occurring variations in baseline [Ca2+]i and the rotenone-induced [Ca2+]i rise. This correlation was not seen in non-dopaminergic neurons of the substantia nigra pars reticulata (SNr). Our results show that mitochondrial ROS production is a key element in the effect of rotenone on ATP-gated K+ channels and TRPM2-like channels in SNc neurons, and demonstrate, in these neurons (but not in the SNr), a large potentiation of rotenone-induced [Ca2+]i rise by a small
increase in baseline [Ca2+]i
Characterising the molecular mode of action of connexin therapeutics for the treatment of retinal injury and disease
No full textConnexin43 gap junctions are non-selective membrane channels that facilitate cell-to-cell communication. A functional gap junction channel is formed upon docking of two hemichannels, or connexons, but an undocked hemichannel plays a key role in the initial response to cellular injury. In particular Connexin43 hemichannels have been shown to communicate aberrant signals that promote a self-perpetuating cycle involving vascular leak, edema, inflammation and neuronal cell death. Pre-clinical models of central nervous system injuries have demonstrated that systemic delivery of Connexin43 mimetic Peptide5 (VDCFLSRPTEKT, PeptagonTM) significantly improves functional outcomes. Additionally Tonabersat (SB-220453) has been tested in phase II clinical trials to target spreading waves of abnormal activity in cellular injury. Despite the therapeutic potential, the molecular mode of action of these compounds has not yet been described. Therefore, the aim of this thesis is to characterise the molecular mode of action of Peptide5 and Tonabersat to support their clinical progression. An in vitro model of ischemia-reperfusion injury was developed to examine connexin43 hemichannel-mediated ATP release in a human cerebral microvascular endothelial cell (hCMVEC) line. Gap junction channel function was assessed using an established scrapeloading assay and visualised using immunohistochemistry. Modified analogues of Peptide5, including single alanine substituted peptides and truncated, were used to assess the mode of action of Peptide5. The site of action of Peptide5 was tested using extracellular loops in a competition assay. Peptide5 inhibits Connexin43 hemichannel-mediated ATP release in hCMVEC by acting on extracellular loop two of Connexin43. Furthermore, Peptide5 sequence specificity is important for inhibiting hemichannel-mediated ATP release but less so for the uncoupling of gap junctions. The SRPTEKT motif is central to Peptide5 function but on its own is not sufficient to inhibit hemichannels at the concentrations used. Tonabersat exhibits a concentration-dependent response where a low concentration significantly inhibits connexin43 hemichannel-mediated ATP release but relatively higher concentrations uncouple gap junctions, with Connexin43 junction plaques internalised and degraded via the lysosomal pathway. Taken together, this study provides an understanding for the molecular mode of action of Peptide5 and Tonabersat to support their clinical development for the treatment of retinal injury and diseases
LinoSPAD2: A 512×1 linear SPAD camera with system-level 135-ps SPTR and a reconfigurable computational engine for time-resolved single-photon imaging
No full textThe LinoSPAD2 camera combines a 512×1 linear single-photon avalanche diode (SPAD) array with an FPGA-based photon-counting and time-stamping platform, to create a reconfigurable sensing system capable of detecting single photons. The read-out is fully parallel, where each SPAD is connected to a different FPGA input. The hardware can be reconfigured to achieve different functionalities, such as photon counters, time-to-digital converter (TDC) arrays and histogramming units. Time stamping is performed by an array of 64 TDCs, with 20 ps resolution (LSB), serving 256 channels by means of 4:1 sharing. At sensor level, the pixel pitch is 26.2 μm with a fill factor of 25.1%. The median dark count rate of each SPAD at room temperature is below 100 cps at 6V excess bias, the single-photon timing resolution (SPTR) of each channel is 50 ps FWHM, and the peak photon detection probability reaches ~50% at 510 nm at the same excess bias. The fill factor can be increased by 2.3× by means of microlenses, with good spatial uniformity and flat spectral response above 400 nm. At system level, the average instrument response function (IRF) is 135 ps FWHM. The LinoSPAD2 camera enables a wide range of time-of-flight and time-resolved applications, including 3D imaging, fluorescence lifetime imaging microscopy (FLIM), heralded spectroscopy, and compressive Raman imaging, to name a few. Thanks to its features, LinoSPAD2 is a novel generation of reconfigurable single-photon image sensors capable of adapting their read-out and processing to match application-specific requirements, and combining SPAD arrays with advanced, massively-parallel computational functionalities. Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.QCD/DiCarlo La
Synthesis and Characterization of PEO-PS-PEO Triblock Copolymer Conjugated with Ni-NTA for Biosensors, 2018
No full textPoly(ethylene oxide)-poly(styrene)-poly(ethylene oxide) triblock copolymer with di-hydroxyl terminated groups (HO-PEO-PS-PEO-OH) was conjugated with nitrilotriacetic acid (NTA) via esterification reaction using N,N'-Dicyclohexylcarbodiimide (DCC), 4-Dimethylaminopyridine (DMAP) and Dimethylformamide (DMF) as a solvent at 80 ?C. The poly(ethylene oxide)-poly(styrene)-poly(ethylene oxide) with NTA end groups (NTA-PEO-PS-PEO-NTA) was characterized and structure confirmed by 1H NMR, 13C NMR, and FT-IR spectroscopies. Thermogravimetric analysis (TGA) was carried out to investigate the thermal stability of the starting triblock copolymer poly(ethylene oxide)-poly(styrene)-poly(ethylene oxide) with di-hydroxyl terminated groups (HO-PEO-PS-PEO-OH) and the conjugated poly(ethylene oxide)-poly(styrene)-poly(ethylene oxide) functional polymer (NTA-PEO-PS-PEO-NTA). Surface morphologies of the (HO-PEO-PS-PEO-OH) and (NTA-PEO-PS-PEO-NTA) were studied by atomic force microscopy. In addition, the size distributions were determined using dynamic light scattering. The thermal behavior of the (HO-PEO-PS-PEO-OH) and (NTA-PEO-PS-PEO-NTA) were examined by differential scanning calorimetry (DSC). DSC thermograms indicate the formation of a two phase polymer matrix. The poly(ethylene oxide)-poly(styrene)-poly(ethylene oxide) with NTA functionalized end groups (NTA-PEO-PS-PEO-NTA) was bound or chelated with Ni(II) metal ion. The binding studies were carried out by ultraviolet-visible (UV-Vis) spectroscopy. The electronic behaviors of PEO-b-PS-b-PEO/ PS/ NTA-PEO-b-PS-b-PEO-NTA with ratio (1/5/1) and PEO-b-PS-b-PEO/ PS/ NTA-PEO-b-PS-b-PEO-NTA-Ni containing 1% of oxidized single-walled carbon nanotubes (SWCNTs) were investigated by IV plots from Kelvin sensing. The IV plots before sensitizing with protein varied from the IV plots after binding with protein indicating that the composites may be used as active components in biosensors. KEYWORDS: Materials Chemistry, Polymer Chemistr
The contribution shift of ammonia-oxidizing archaea and bacteria to ammoxidation under Ag-NPs/SWCNTs/PS-NPs stressors in constructed wetlands
No full textAmmonia-oxidizing microorganisms (AOMs, archaea (AOA) and bacteria (AOB)) are primarily responsible for the ammoxidation in constructed wetlands (CWs). However, little is known about evaluating the response of AOA and AOB to engineered nanomaterials (ENMs) and quantifying the shift of their contribution to ammoxidation. Herein, we operated a series of CWs exposing to silver nanoparticles (Ag-NPs), single-walled carbon nanotubes (SWCNTs), and polystyrene nano-sized plastics (PS-NPs) with the wastewater-accumulating concentration of ENMs for 180 days. The results showed that the abundance of AOA amoA gene in situ was far lower than that of AOB, while the abundance ratio of AOA to AOB increased by 15 folds after 180-day experiment. Using DNA stable isotope probing (DNA-SIP) experiment, we found that the active AOB microbiota varied substantially but the AOA was more stable across different groups. Furthermore, the co-occurrence analysis proved that ENMs stress increased the negative coexistence pattern of AOA and AOB; predictive functional profiling showed that the ENMs enhanced the functional advantage of AOA by inhibiting AOB (mainly hydroxylamine oxidation process). Finally, the contribution of AOA increased under exposing to SWCNTs (18.35%), PS-NPs (24.92%), and Ag-NPs (32.14%) compared with control group (0.03%) for 180 days. Despite this, AOB was still the primary executant of ammoxidation in CWs. Overall, in our study, the differences in activities and contributions of AOMs were quantified in CWs, and a significantly negative coexistence relationship between AOA and AOB was revealed when exposed to emerging nanomaterials.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Sanitary Engineerin
Dionysios Ps.-Areiopagites im heutigen Forschungsgespräch
No full textThe intention of this paper is to overcome an alarming polarization within the actual academic debate on the writing of the unknown author of the Corpus Areopagiticum. It discusses five exemplary problems: a. unity and diversity in God; b. theurgy in Proklos and Ps.-Dionysios; c. Porphyry, Dionysios and the “anthropological Model” for the solution of the Christological problem; d. ambivalences within the Dionysian corpus; e. the intention of the author. In the introduction the paper also touches – very briefly, it is true – upon the question, if Peter the Iberian could have been the author of that corpus, as – independently from each other – E. Honigmann and S. Nutsubidze once proposed
- …
