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Experimental and numerical study of SiON microresonators with air and polymer cladding

A systematic experimental and numerical study of the device performance of waveguide-coupled SiON microresonators with air and polymer cladding is presented. Values of device parameters like propagation losses of the microresonator modes, the off-resonance insertion losses, and the straight waveguide to microresonator coupling are determined by applying a detailed fitting procedure to the experimental results and compared to results of detailed numerical simulations. By comparing the propagation losses of the fundamental TE polarized microresonator mode obtained by fitting to the measured spectra to the also experimentally determined propagation losses in the adjacent straight waveguide and the materials losses, it is possible to identify the loss mechanisms in the microresonator. By comparing experimental results for microresonators with air and polymethylmethacrylate cladding and a detailed numerical study, the influence of the cladding index on the bend losses is evaluated. It is demonstrated that the presence of an upper cladding can, under the right conditions, actually be beneficial for loss reduction

Flow dynamics of Byrd Glacier, East Antarctica

Force-balance calculations on Byrd Glacier, East Antarctica, reveal large spatial variations in the along-flow component of driving stress with corresponding sticky spots that are stationary over time. On the large scale, flow resistance is partitioned between basal (�80%) and lateral (�20%) drag. Ice flow is due mostly to basal sliding and concentrated vertical shear in the basal ice layers, indicating the bed is at or close to the pressure-melting temperature. There is a significant component of driving stress in the across-flow direction resulting in nonzero basal drag in that direction. This is an unrealistic result and we propose that there are spatial variations of bed features resulting in small-scale flow disturbances. The grounding line of Byrd Glacier is located in a region where the bed slopes upward. Nevertheless, despite a 10% increase in ice discharge between December 2005 and February 2007, following drainage of two subglacial lakes in the catchment area, the position of the grounding line has not retreated significantly and the glacier has decelerated since then. During the speed-up event, partitioning of flow resistance did not change, suggesting the increase in velocity was caused by a temporary decrease in basal effective pressure

The role of arginine 47 in the cyclization and coupling reactions of cyclodextrin glycosyltransferase from Bacillus circulans strain 251 - Implications for product inhibition and product specificity

Cyclodextrin glycosyltransferase (CGTase) (EC 2.4.1.19) is used for the industrial production of cyclodextrins. Its application, however, is hampered by the limited cyclodextrin product specificity and the strong inhibitory effect of cyclodextrins on CGTase activity. Recent structural studies have identified Arg47 in the Bacillus circulans strain 251 CGTase as an active-site residue interacting with cyclodextrins, but not with linear oligosaccharides. Arg47 thus may specifically affect CGTase reactions with cyclic substrates or products. Here we show that mutations in Arg47 (to Leu or Gln) indeed have a negative effect on the cyclization and coupling activities; Arg47 specifically stabilizes the oligosaccharide chain in the transition state for these reactions. As a result, the mutant proteins display a shift in product specificity towards formation of larger cyclodextrins. As expected, both mutants also showed lower affinities for cyclodextrins in the coupling reaction, and a reduced competitive (product) inhibition of the disproportionation reaction by cyclodextrins. Both mutants also provide valuable information about the processes taking place during cyclodextrin production assays. Mutant Arg47-->Leu displayed an increased hydrolyzing activity, causing accumulation of increasing amounts of short oligosaccharides in the reaction mixture, which resulted in lower final amounts of cyclodextrins produced from starch. Interestingly, mutant Arg47-->Gln displayed an increased ratio of cyclization/coupling and a decreased hydrolyzing activity. Due to the decreased coupling activity, which especially affects the production of larger cyclodextrins, this CGTase variant produced the various cyclodextrins in a stable ratio in time. This feature is very promising for the industrial application of CGTase enzymes with improved product specificity

Sensory processing deficiencies in patients with borderline personality disorder who experience auditory verbal hallucinations

Auditory verbal hallucinations (AVH) are common in patients with borderline personality disorder (BPD). We examined two candidate mechanisms of AVH in patients with BPD, suggested to underlie sensory processing systems that contribute to psychotic symptoms in patients with schizophrenia; sensory gating (P50 ratio and P50 difference) and change detection (mismatch negativity; MMN). Via electroencephalographic recordings P50 amplitude, P50 ratio, P50 difference and MMN amplitude were compared between 23 borderline patients with and 25 without AVH, and 26 healthy controls. Borderline patients with AVH had a significantly lower P50 difference compared with healthy controls, whereas no difference was found between borderline patients without AVH and healthy controls. The groups did not differ on MMN amplitude. The impaired sensory gating in patients with borderline personality disorder who experience AVH implies that P50 sensory gating deficiencies may underlie psychotic vulnerability in this specific patient group. Patients with borderline personality disorder with or without AVH did not have problems with auditory change detection. This may explain why they are spared from the poor outcome associated with negative symptoms and symptoms of disorganization in patients with chronic schizophrenia

Electronic origins of photocatalytic activity in d0 metal organic frameworks

Metal-organic frameworks (MOFs) containing d0 metals such as NH2-MIL-125(Ti), NH2-UiO-66(Zr) and NH2-UiO-66(Hf) are among the most studied MOFs for photocatalytic applications. Despite structural similarities, we demonstrate that the electronic properties of these MOFs are markedly different. As revealed by quantum chemistry, EPR measurements and transient absorption spectroscopy, the highest occupied and lowest unoccupied orbitals of NH2-MIL-125(Ti) promote a long lived ligand-to-metal charge transfer upon photoexcitation, making this material suitable for photocatalytic applications. In contrast, in case of UiO materials, the d-orbitals of Zr and Hf, are too low in binding energy and thus cannot overlap with the π* orbital of the ligand, making both frontier orbitals localized at the organic linker. This electronic reconfiguration results in short exciton lifetimes and diminishes photocatalytic performance. These results highlight the importance of orbital contributions at the band edges and delineate future directions in the development of photo-active hybrid solids

Generation of Variants in Listeria monocytogenes Continuous-Flow Biofilms Is Dependent on Radical-Induced DNA Damage and RecA-Mediated Repair

The food-borne pathogen Listeria monocytogenes is a Gram-positive microaerophilic facultative anaerobic rod and the causative agent of the devastating disease listeriosis. L. monocytogenes is able to form biofilms in the food processing environment. Since biofilms are generally hard to eradicate, they can function as a source for food contamination. In several occasions biofilms have been identified as a source for genetic variability, which potentially can result in adaptation of strains to food processing or clinical conditions. However, nothing is known about mutagenesis in L. monocytogenes biofilms and the possible mechanisms involved. In this study, we showed that the generation of genetic variants was specifically induced in continuous-flow biofilms of L. monocytogenes, but not in static biofilms. Using specific dyes and radical inhibitors, we showed that the formation of superoxide and hydroxyl radicals was induced in continuous-flow biofilms, which was accompanied with in an increase in DNA damage. Promoter reporter studies showed that recA, which is an important component in DNA repair and the activator of the SOS response, is activated in continuous-flow biofilms and that activation was dependent on radical-induced DNA damage. Furthermore, continuous-flow biofilm experiments using an in-frame recA deletion mutant verified that RecA is required for induced generation of genetic variants. Therefore, we can conclude that generation of genetic variants in L. monocytogenes continuous-flow biofilms results from radical-induced DNA damage and RecA-mediated mutagenic repair of the damaged DNA

TNF- α augments intratumoural concentrations of doxorubicin in TNF- α -based isolated limb perfusion in rat sarcoma models and enhances anti-tumour effects

We have shown previously that isolated limb perfusion (ILP) in sarcoma-bearing rats results in high response rates when melphalan is used in combination with tumour necrosis factor alpha (TNF-α). This is in line with observations in patients. Here we show that ILP with doxorubicin in combination with TNF-α has comparable effects in two different rat sarcoma tumour models. The addition of TNF-α exhibits a synergistic anti-tumour effect, resulting in regression of the tumour in 54% and 100% of the cases for the BN175-fibrosarcoma and the ROS-1 osteosarcoma respectively. The combination is shown to be mandatory for optimal tumour response. The effect of high dose TNF-α on the activity of cytotoxic agents in ILP is still unclear. We investigated possible modes by which TNF-α could modulate the activity of doxorubicin. In both tumour models increased accumulation of doxorubicin in tumour tissue was found: 3.1-fold in the BN175 and 1.8-fold in the ROS-1 sarcoma after ILP with doxorubicin combined with TNF-α in comparison with an ILP with doxorubicin alone. This increase in local drug concentration may explain the synergistic anti-tumour responses after ILP with the combination. In vitro TNF-α fails to augment drug uptake in tumour cells or to increase cytotoxicity of the drug. These findings make it unlikely that TNF-α directly modulates the activity of doxorubicin in vivo. As TNF-α by itself has no or only minimal effect on tumour growth, an increase in local concentrations of chemotherapeutic drugs might well be the main mechanism for the synergistic anti-tumour effects. © 2000 Cancer Research Campaig

Glaciological and marine geological controls on terminus dynamics of Hubbard Glacier, southeast Alaska

An edited version of this paper was published by AGU. Copyright (2015) American Geophysical Union.Hubbard Glacier, located in southeast Alaska, is the world's largest nonpolar tidewater glacier. It has been steadily advancing since it was first mapped in 1895; occasionally, the advance creates an ice or sediment dam that blocks a tributary fjord (Russell Fiord). The sustained advance raises the probability of long-term closure in the near future, which will strongly impact the ecosystem of Russell Fiord and the nearby community of Yakutat. Here, we examine a 43 year record of flow speeds and terminus position to understand the large-scale dynamics of Hubbard Glacier. Our long-term record shows that the rate of terminus advance has increased slightly since 1895, with the exception of a slowed advance between approximately 1972 and 1984. The short-lived closure events in 1986 and 2002 were not initiated by perturbations in ice velocity or environmental forcings but were likely due to fluctuations in sedimentation patterns at the terminus. This study points to the significance of a coupled system where short-term velocity fluctuations and morainal shoal development control tidewater glacier terminus position

Routine versus on demand removal of the syndesmotic screw; a protocol for an international randomised controlled trial (RODEO-trial)

Background: Syndesmotic injuries are common and their incidence is rising. In case of surgical fixation of the syndesmosis a metal syndesmotic screw is used most often. It is however unclear whether this screw needs to be removed routinely after the syndesmosis has healed. Traditionally the screw is removed after six to 12 weeks as it is thought to hamper ankle functional and to be a source of pain. Some studies however suggest this is only the case in a minority of patients. We therefore aim to investigate the effect of retaining the syndesmotic screw on functional outcome. Design: This is a pragmatic international multicentre randomised controlled trial in patients with an acute syndesmotic injury for which a metallic syndesmotic screw was placed. Patients will be randomised to either routine removal of the syndesmotic screw or removal on demand. Primary outcome is functional recovery at 12 months measured with the Olerud-Molander Score. Secondary outcomes are quality of life, pain and costs. In total 194 patients will be needed to demonstrate non-inferiority between the two interventions at 80% power and a significance level of 0.025 including 15% loss to follow-up. Discussion: If removal on demand of the syndesmotic screw is non-inferior to routine removal in terms of functional outcome, this will offer a strong argument to adopt this as standard practice of care. This means that patients will not have to undergo a secondary procedure, leading to less complications and subsequent lower costs.Peer reviewe