High-definition velocity-space tomography of fast-ion dynamics

Velocity-space tomography of the fast-ion distribution function in a fusion plasma is usually a photon-starved tomography method due to limited optical access and signal-to-noise ratio of fast-ion Dα (FIDA) spectroscopy as well as the strive for high-resolution images. In high-definition tomography, prior information makes up for this lack of data. We restrict the target velocity space through the measured absence of FIDA light, impose phase-space densities to be non-negative, and encode the known geometry of neutral beam injection (NBI) sources. We further use a numerical simulation as prior information to reconstruct where in velocity space the measurements and the simulation disagree. This alternative approach is demonstrated for four-view as well as for two-view FIDA measurements. The high-definition tomography tools allow us to study fast ions in sawtoothing plasmas and the formation of NBI peaks at full, half and one-third energy by time-resolved tomographic movies

4D and 5D phase-space tomography using slowing-down physics regularization

We compute reconstructions of 4D and 5D fast-ion phase-space distribution functions in fusion plasmas from synthetic projections of these functions. The fast-ion phase-space distribution functions originating from neutral beam injection (NBI) at TCV and Wendelstein 7-X (W7-X) at full, half, and one-third injection energies can be istinguished and particle densities of each component inferred based on 20 synthetic spectra of projected velocities at TCV and 680 at W7-X. Further, we demonstrate that an expansion into a basis of slowing-down distribution functions is equivalent to regularization using slowing-down physics as prior information. Using this technique in a Tikhonov formulation, we infer the particle density fractions for each NBI energy for each NBI beam from synthetic measurements, resulting in six unknowns at TCV and 24 unknowns at W7-X. Additionally, we show that installing 40 LOS in each of 17 ports at W7-X, providing full beam coverage and almost full angle coverage, produces the highest quality reconstructions

Third party consultation: a method for the study and resolution of conflict

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66597/2/10.1177_002200277201600105.pd

Pulsatility of insulin release – a clinically important phenomenon

The mechanisms and clinical importance of pulsatile insulin release are presented against the background of more than half a century of companionship with the islets of Langerhans. The insulin-secreting β-cells are oscillators with intrinsic variations of cytoplasmic ATP and Ca2+. Within the islets the β-cells are mutually entrained into a common rhythm by gap junctions and diffusible factors (ATP). Synchronization of the different islets in the pancreas is supposed to be due to adjustment of the oscillations to the same phase by neural output of acetylcholine and ATP. Studies of hormone secretion from the perfused pancreas of rats and mice revealed that glucose induces pulses of glucagon anti-synchronous with pulses of insulin and somatostatin. The anti-synchrony may result from a paracrine action of somatostatin on the glucagon-producing α-cells. Purinoceptors have a key function for pulsatile release of islet hormones. It was possible to remove the glucagon and somatostatin pulses with maintenance of those of insulin with an inhibitor of the P2Y1 receptors. Knock-out of the adenosine A1 receptor prolonged the pulses of glucagon and somatostatin without affecting the duration of the insulin pulses. Studies of isolated human islets indicate similar relations between pulses of insulin, glucagon, and somatostatin as found during perfusion of the rodent pancreas. The observation of reversed cycles of insulin and glucagon adds to the understanding how the islets regulate hepatic glucose production. Current protocols for pulsatile intravenous infusion therapy (PIVIT) should be modified to mimic the anti-synchrony between insulin and glucagon normally seen in the portal blood

特別賦金論

Velocity-space tomography has been used to infer 2D fast-ion velocity distribution functions. Here we compare the performance of five different tomographic inversion methods: truncated singular value decomposition, maximum entropy, minimum Fisher information and zerothand first-order Tikhonov regularization. The inversion methods are applied to fast-ion Dα measurements taken just before and just after a sawtooth crash in the ASDEX Upgrade tokamak as well as to synthetic measurements from different test distributions. We find that the methods regularizing by penalizing steep gradients or maximizing entropy perform best. We assess the uncertainty of the calculated inversions taking into account photon noise, uncertainties in the forward model as well as uncertainties introduced by the regularization which allows us to distinguish regions of high and low confidence in the tomographies. In high confidence regions, all methods agree that ions with pitch values close to zero, as well as ions with large pitch values, are ejected from the plasma center by the sawtooth crash, and that this ejection depletes the ion population with large pitch values more strongly

A Drug Delivery System for Administration of Anti–TNF-α Antibody

Purpose To describe the fabrication, evaluation, and preliminary in vivo safety of a new drug delivery system (DDS) for topical anti–TNF-α antibody administration. Methods: A DDS was fabricated using inverse template fabrication of a hydrophobic three-dimensional porous scaffold (100–300 μm in diameter porosity) loaded with 10% polyvinyl alcohol hydrogel carrying 5 mg/ml (weight/volume) of anti–TNF-α antibody. Drug-loaded DDS was sterilized with 25 kGy of gamma irradiation. Long-term in vitro antibody affinity and release was evaluated at room temperature or 37°C using enzyme-linked immunosorbent assay (ELISA) and protein fluorescence. In vivo clinical and histolopathological assessment was performed by subcutaneous implantation in BALB/c mice for 3 months. Results: Gamma irradiation, repeated dry/wet cycles, and storage at room temperature for 1 year or 37°C for 1 month had no deleterious effects on antibody affinity. Anti–TNF-α release was high during the first minutes of aqueous exposure, followed by stabilization and gradual, low-dose, antibody release over the next 30 days. Histopathologic evaluation of explanted DDS showed a fibrous pseudocapsule and a myxoid acute/chronic inflammation without granuloma formation surrounding the implants. Conclusions: Sustained local delivery of anti–TNF-α antibody is feasible using the described DDS, which provides stability of the enclosed antibody for up to 1 year of storage. Preliminary results show good in vivo tolerance following subcutaneous placement for 3 months. The proposed fabrication and sterilization process opens new possibilities for the delivery of biologic agents to the anterior surface of the eye. Translational Relevance The described DDS will facilitate the treatment of ocular surface diseases amenable to biologic therapy

Speech Spectrum's Correlation with Speakers' Eysenck Personality Traits

The current study explored the correlation between speakers' Eysenck personality traits and speech spectrum parameters. Forty-six subjects completed the Eysenck Personality Questionnaire. They were instructed to verbally answer the questions shown on a computer screen and their responses were recorded by the computer. Spectrum parameters of /sh/ and /i/ were analyzed by Praat voice software. Formant frequencies of the consonant /sh/ in lying responses were significantly lower than that in truthful responses, whereas no difference existed on the vowel /i/ speech spectrum. The second formant bandwidth of the consonant /sh/ speech spectrum was significantly correlated with the personality traits of Psychoticism, Extraversion, and Neuroticism, and the correlation differed between truthful and lying responses, whereas the first formant frequency of the vowel /i/ speech spectrum was negatively correlated with Neuroticism in both response types. The results suggest that personality characteristics may be conveyed through the human voice, although the extent to which these effects are due to physiological differences in the organs associated with speech or to a general Pygmalion effect is yet unknown

Protection from Intracellular Oxidative Stress by Cytoglobin in Normal and Cancerous Oesophageal Cells

Cytoglobin is an intracellular globin of unknown function that is expressed mostly in cells of a myofibroblast lineage. Possible functions of cytoglobin include buffering of intracellular oxygen and detoxification of reactive oxygen species. Previous work in our laboratory has demonstrated that cytoglobin affords protection from oxidant-induced DNA damage when over expressed in vitro, but the importance of this in more physiologically relevant models of disease is unknown. Cytoglobin is a candidate for the tylosis with oesophageal cancer gene, and its expression is strongly down-regulated in non-cancerous oesophageal biopsies from patients with TOC compared with normal biopsies. Therefore, oesophageal cells provide an ideal experimental model to test our hypothesis that downregulation of cytoglobin expression sensitises cells to the damaging effects of reactive oxygen species, particularly oxidative DNA damage, and that this could potentially contribute to the TOC phenotype. In the current study, we tested this hypothesis by manipulating cytoglobin expression in both normal and oesophageal cancer cell lines, which have normal physiological and no expression of cytoglobin respectively. Our results show that, in agreement with previous findings, over expression of cytoglobin in cancer cell lines afforded protection from chemically-induced oxidative stress but this was only observed at non-physiological concentrations of cytoglobin. In addition, down regulation of cytoglobin in normal oesophageal cells had no effect on their sensitivity to oxidative stress as assessed by a number of end points. We therefore conclude that normal physiological concentrations of cytoglobin do not offer cytoprotection from reactive oxygen species, at least in the current experimental model

Investigating the Role of Islet Cytoarchitecture in Its Oscillation Using a New β-Cell Cluster Model

The oscillatory insulin release is fundamental to normal glycemic control. The basis of the oscillation is the intercellular coupling and bursting synchronization of β cells in each islet. The functional role of islet β cell mass organization with respect to its oscillatory bursting is not well understood. This is of special interest in view of the recent finding of islet cytoarchitectural differences between human and animal models. In this study we developed a new hexagonal closest packing (HCP) cell cluster model. The model captures more accurately the real islet cell organization than the simple cubic packing (SCP) cluster that is conventionally used. Using our new model we investigated the functional characteristics of β-cell clusters, including the fraction of cells able to burst fb, the synchronization index λ of the bursting β cells, the bursting period Tb, the plateau fraction pf, and the amplitude of intracellular calcium oscillation [Ca]. We determined their dependence on cluster architectural parameters including number of cells nβ, number of inter-β cell couplings of each β cell nc, and the coupling strength gc. We found that at low values of nβ, nc and gc, the oscillation regularity improves with their increasing values. This functional gain plateaus around their physiological values in real islets, at nβ∼100, nc∼6 and gc∼200 pS. In addition, normal β-cell clusters are robust against significant perturbation to their architecture, including the presence of non-β cells or dead β cells. In clusters with nβ>∼100, coordinated β-cell bursting can be maintained at up to 70% of β-cell loss, which is consistent with laboratory and clinical findings of islets. Our results suggest that the bursting characteristics of a β-cell cluster depend quantitatively on its architecture in a non-linear fashion. These findings are important to understand the islet bursting phenomenon and the regulation of insulin secretion, under both physiological and pathological conditions

Association of hypoxia inducible factor-1 alpha gene polymorphism with both type 1 and type 2 diabetes in a Caucasian (Hungarian) sample

BACKGROUND: Hypoxia inducible factor-1 alpha (HIF-1alpha) is a transcription factor that plays an important role in neo-vascularisation, embryonic pancreas beta-cell mass development, and beta cell protection. Recently a non synonymous single nucleotide polymorphism (g.C45035T SNP, rs11549465) of HIF-1alpha gene, resulting in the p.P582S amino acid change has been shown to be associated with type 2 diabetes (T2DM) in a Japanese population. Our aim was to replicate these findings on a Caucasian (Hungarian) population, as well as to study whether this genetic effect is restricted to T2DM or can be expanded to diabetes in general. METHODS: A large Caucasian sample (N = 890) was recruited including 370 T2DM, 166 T1DM and 354 healthy subjects. Genotyping was validated by two independent methods: a restriction fragment analysis (RFLP) and a real time PCR using TaqMan probes. An overestimation of heterozygotes by RFLP was observed as a consequence of a nearby SNP (rs34005929). Therefore genotyping results of the justified TaqMan system were accepted. The measured genotype distribution corresponded to Hardy-Weinberg equilibrium (P = 0.740) RESULTS: As the TT genotype was extremely rare in the population (0.6% in clinical sample and 2.5% in controls), the genotypes were grouped as T absent (CC) and T present (CT and TT). Genotype-wise analysis showed a significant increase of T present group in controls (24.0%) as compared to patients (16.8%, P = 0.008). This genetic effect was demonstrated in the separated samples of type 1 (15.1%, P = 0.020), and also in type 2 (17.6%, P = 0.032) diabetes. Allele-wise analysis gave identical results showing a higher frequency of the T allele in the control sample (13.3%) than in the clinical sample (8.7%, P = 0.002) with similar results in type 1 (7.8%, P = 0.010) and type 2 (9.1%, P = 0.011) diabetes. The odds ratio for diabetes (either type 1 or 2) was 1.56 in the presence of the C allele. CONCLUSION: We confirmed the protective effect of a rare genetic variant of HIF-1alpha gene against type 2 diabetes in a Caucasian sample. Moreover we demonstrated a genetic contribution of the same polymorphism in type 1 diabetes as well, supporting a possible overlap in pathomechanism for T2DM and a T1DM