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Obesity impairs tissue insulin sensitivity and signaling, promoting type-2 diabetes. Although improving insulin signaling is key to reversing diabetes, the multi-organ mechanisms regulating this process are poorly defined. Here, we screen the secretome and receptome in Drosophila to identify the hormonal crosstalk affecting diet-induced insulin resistance and obesity. We discover a complex interplay between muscle, neuronal, and adipose tissues, mediated by Bone Morphogenetic Protein (BMP) signaling and the hormone Bursicon, that enhances insulin signaling and sugar tolerance. Muscle-derived BMP signaling, induced by sugar, governs neuronal Bursicon signaling. Bursicon, through its receptor Rickets, a Leucine-rich-repeat-containing G-protein coupled receptor (LGR), improves insulin secretion and insulin sensitivity in adipose tissue, mitigating hyperglycemia. In mouse adipocytes, loss of the Rickets ortholog LGR4 blunts insulin responses, showing an essential role of LGR4 in adipocyte insulin sensitivity. Our findings reveal a muscle-neuronal-fat-tissue axis driving metabolic adaptation to high-sugar conditions, identifying LGR4 as a critical mediator in this regulatory network., (© 2024. The Author(s).)

General interest in the deployment of molten salt reactors (MSRs) is growing, while the available data on uranium-containing fuel salt candidates remains scarce. Thermophysical data are one of the key parameters for reactor design and understanding reactor operability. Hence, filling in the gap of the missing data is crucial to allow for the advancement of MSRs. This study provides novel data for two eutectic compositions within the NaF-KF-UF 4 ternary system which serve as potential fuel candidates for MSRs. Experimental measurements include their melting point, density, fusion enthalpy, and vapor pressure. Additionally, their boiling point was extrapolated from the vapor pressure data, which were, at the same time, used to determine the enthalpy of vaporization. The obtained thermodynamic values were compared with available data from the literature but also with results from thermochemical equilibrium calculations using the JRCMSD database, finding a good correlation, which thus contributed to database validation. Preliminary thoughts on fluoride salt reactor operability based on the obtained results are discussed in this study.

The corrosion behavior of alloy Ni 201 in molten sodium hydroxide (NaOH) at 600 °C was investigated at varying basicity levels of the molten NaOH. The ability for Ni 201 to form passivating oxides was investigated after immersion tests varying from 70 to 340 h under atmospheres of argon and argon with different partial pressure of water. Morphology and thicknesses of the corrosion products were characterized by Scanning Electron Microscopy (SEM) and crystallography of the corrosion products by X-ray Diffraction (XRD). Dynamic polarizations were made to investigate the effects of basicity and electrochemical potential. The results showed that Ni 201 corroded at a reduced rate in molten acidic NaOH compared to neutral NaOH due to the formation of NiO. The oxide scales formed on Ni 201 in acidic NaOH were shown to grow non-parabolically and did not result in full corrosion protection as the oxide scales showed crack development over time., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Birgitte stoffersen reports financial support was provided by Seaborg Technologies Aps. Birgitte stoffersen reports a relationship with Seaborg Technologies Aps that includes: employment. Daniel John Cooper reports a relationship with Seaborg Technologies Aps that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Functionalizing single-walled carbon nanotubes (SWCNTs) in a robust way that does not affect the sp 2 carbon framework is a considerable research challenge. Here we describe how triiodide salts of positively charged macrocycles can be used not only to functionalize SWCNTs from the outside, but simultaneously from the inside. We employed disulfide exchange in aqueous solvent to maximize the solvophobic effect and therefore achieve a high degree of macrocycle immobilization. Characterization by Raman spectroscopy, EDX-STEM and HR-TEM clearly showed that serendipitously this wet-chemical functionalization procedure also led to the encapsulation of polyiodide chains inside the nanotubes. The resulting three-shell composite materials are redox-active and experience an intriguing interplay of electrostatic, solvophobic and mechanical effects that could be of interest for applications in energy storage., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

HLA-DRB1*08:112 differs from HLA-DRB1*08:01 in exon 2 at amino acid 62; asparagine to lysine substitution., (© 2022 The Authors. HLA: Immune Response Genetics published by John Wiley & Sons Ltd.)

HLA-DQA1*01:65 differs from HLA-DQA1*01:03 in exon 1 at amino acid -7 a valine to methionine substitution., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

HLA-DPA1*01:46 differs from HLA-DPA1*01:03 in exon 2 at amino acid 85; Aspartate to Asparagine substitution., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Genetic studies of Neolithic and Bronze Age skeletons from Europe have provided evidence for strong population genetic changes at the beginning and the end of the Neolithic period. To further understand the implications of these in Southern Central Europe, we analyze 96 ancient genomes from Switzerland, Southern Germany, and the Alsace region in France, covering the Middle/Late Neolithic to Early Bronze Age. Similar to previously described genetic changes in other parts of Europe from the early 3rd millennium BCE, we detect an arrival of ancestry related to Late Neolithic pastoralists from the Pontic-Caspian steppe in Switzerland as early as 2860-2460 calBCE. Our analyses suggest that this genetic turnover was a complex process lasting almost 1000 years and involved highly genetically structured populations in this region.

Sparse sound-field reconstruction methods based on compressive sensing and the equivalent source method have gained a lot of interest in recent years, offering a wide frequency range. An irregular array must be employed, and the sound field must be representable by a sparse vector of source-model amplitudes. With few and concentrated physical sources, the sparsity assumption can be fulfilled, but distributed sources cause problems. Several methods have therefore been introduced to support sparse representation of distributed sources. One set of such methods represents the amplitude vector as a linear combination of modal amplitude distributions. In that case, the coefficient vector just has to be sparse. The present paper gives an overview of such methods, and the performance of the methods is compared based on a set of simulated measurements. Overall the modal representations work well if the true source distribution can be represented by relatively few modes. The results show that even for a vibrating plate this may not be the case if the source model size does not match the plate size and/or if a non-central plate excitation is applied. If, in addition, there are also compact sources, then the basic method without modes may be the best choice.

We report on double-resonant highly efficient sum-frequency generation in the blue range. The system consists of a 10-mm-long periodically poled KTP crystal placed in a double-resonant bow-tie cavity and pumped by a fiber laser at 1064.5 nm and a Ti:sapphire laser at 849.2 nm. An optical power of 375 mW at 472.4 nm in a TEM 00 mode was generated with pump powers of 250 mW at 849.2 nm and 200 mW at 1064.5 nm coupled into the double-resonant ring resonator with 88% mode-matching. The resulting internal conversion efficiency of 95(±3)% of the photons mode-matched to the cavity constitutes, to the best of our knowledge, the highest overall achieved quantum conversion efficiency using continuous-wave pumping. Very high conversion efficiency is rendered possible due to very low intracavity loss on the level of 0.3% and high nonlinear conversion coefficient up to 0.045(0.015) W -1 . Power stability measurements performed over one hour show a stability of 0.8%. The generated blue light can be tuned within 5 nm around the center wavelength of 472.4 nm, limited by the phase-matching of our nonlinear crystal. This can however be expanded to cover the entire blue spectrum (420 nm to 510 nm) by proper choice of nonlinear crystals and pump lasers. Our experimental results agree very well with analytical and numerical simulations taking into account cavity impedance matching and depletion of the pump fields.

HLA-C*07:780 differs from HLA-C*07:04:01:01 in exon 2 at amino acid 49; alanine to threonine substitution., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Disturbing noise in microphone signals is an often occurring problem. The present paper has a main focus on measurements with microphone arrays in wind tunnels, where flow noise will be generated in the individual microphones. Considering stationary operational conditions, the cross-spectral matrix (CSM) is first averaged. Subsequently it is applied for aerodynamic noise-source mapping on a vehicle in the flow using one of several possible array processing algorithms. Several methods exist to suppress the flow-noise effects. Long-time averaging will gradually concentrate the flow-noise contributions on the CSM diagonal, and some array processing algorithms can avoid use of the diagonal. Other algorithms need the diagonal. Denoising methods that subtract a maximum of signal power from the diagonal, while retaining all off-diagonal elements unchanged and the matrix positive semidefinite, have been shown to be limited by remaining off-diagonal flow-noise contributions. A couple of algorithms exist that can overcome that limitation by supporting modifications outside the diagonal, but these methods seem to be limited by high computational cost or difficult parameter selection. The present paper introduces a unique canonical-coherence-based method, which is computationally very fast and with automated parameter selection. The performance is investigated through simulated and real measurements.

Small additions of boron can remarkably improve the long-term creep resistance of 9-12% Cr steels. The improvement has been attributed to boron segregation to grain boundaries during quenching, and subsequent boron incorporation into certain families of precipitates during tempering. However, the detailed mechanisms are not yet fully understood. Atom probe tomography (APT) is an excellent technique for gaining insights into boron distribution, however, in order to acquire accurate analysis of boron in 9-12% Cr steels using APT, there are several key challenges. In order to better understand and address these challenges, we developed a novel method for site-specific APT specimen preparation, which enables convenient preparation of specimens containing specifically selected grain boundaries positioned approximately perpendicular to the axis of the APT tip. Additionally, when analyzing boron at boundaries and in carbides (as diluted solute) and borides, a widening of the profile of boron distribution compared to other elements was repeatedly observed. This phenomenon is particularly analyzed and discussed in light of the evaporation field of different elements. Finally, the possible effects of detector dead-time on quantitative analysis of boron in metal borides are discussed. A simple method using 10B correction was used to obtain good quantification.

During the past decade, several publications have described the use of compressive sensing principles to extend the frequency range supported by a given irregular microphone array for near-field acoustic holography. The applied numerical source model has typically been of the type used for the equivalent source method, i.e., a mesh of point sources, and a one-norm regularized inverse problem has been solved using a very stable, but slow interior-point optimization algorithm. A few publications have investigated the use of simpler and faster iterative algorithms. The present paper gives a brief description of five such iterative algorithms, and it compares their performances with that of the interior-point algorithm based on a set of simulated measurements. A particular focus is on the suitability for industrial applications. Finally, an optimal choice of methodology is discussed based on the presented limited set of simulated tests.

Background: To date, the traditional approach to intraspinal tumors has been open laminectomy or laminoplasty followed by microsurgical tumor resection. Recently, however, minimally invasive approaches have been attempted by some., Objective: To investigate the feasibility and safety of minimally invasive surgery (MIS) for primary intradural spinal tumors., Methods: Medical charts of 83 consecutive patients treated with MIS for intradural spinal tumors were reviewed. Patients were followed up during the study year, 2015, by either routine history/physical examination or by telephone consultation, with a focus on tumor status and surgery-related complications., Results: Mean age at surgery was 53.7 yr and 52% were female. There were 49 schwannomas, 18 meningeomas, 10 ependymomas, 2 hemangioblastomas, 1 neurofibroma, 1 paraganglioma, 1 epidermoid cyst, and 1 hemangiopericytoma. The surgical mortality was 0%. In 87% of cases, gross total resection was achieved. The complication rate was 11%, including 2 cerebrospinal fluid leakages, 1 asymptomatic pseudomeningocele, 2 superficial surgical site infections, 1 sinus vein thrombosis, and 4 cases of neurological deterioration. There were no postoperative hematomas, and no cases of deep vein thrombosis or pulmonary embolism. Ninety-three percent of patients were ambulatory and able to work at the time of follow-up., Conclusion: This study both demonstrates that it is feasible and safe to remove select, primary intradural spinal tumors using MIS, and augments the previous literature in favor of MIS for these tumors.

Objective: To characterize the EndoC-βH1 cell line as a model for human beta cells and evaluate its beta cell functionality, focusing on insulin secretion, proliferation, apoptosis and ER stress, with the objective to assess its potential as a screening platform for identification of novel anti-diabetic drug candidates., Methods: EndoC-βH1 was transplanted into mice for validation of in vivo functionality. Insulin secretion was evaluated in cells cultured as monolayer and as pseudoislets, as well as in diabetic mice. Cytokine induced apoptosis, glucolipotoxicity, and ER stress responses were assessed. Beta cell relevant mRNA and protein expression were investigated by qPCR and antibody staining. Hundreds of proteins or peptides were tested for their effect on insulin secretion and proliferation., Results: Transplantation of EndoC-βH1 cells restored normoglycemia in streptozotocin induced diabetic mice. Both in vitro and in vivo, we observed a clear insulin response to glucose, and, in vitro, we found a significant increase in insulin secretion from EndoC-βH1 pseudoislets compared to monolayer cultures for both glucose and incretins. Apoptosis and ER stress were inducible in the cells and caspase 3/7 activity was elevated in response to cytokines, but not affected by the saturated fatty acid palmitate. By screening of various proteins and peptides, we found Bombesin (BB) receptor agonists and Pituitary Adenylate Cyclase-Activating Polypeptides (PACAP) to significantly induce insulin secretion and the proteins SerpinA6, STC1, and APOH to significantly stimulate proliferation. ER stress was readily induced by Tunicamycin and resulted in a reduction of insulin mRNA. Somatostatin (SST) was found to be expressed by 1% of the cells and manipulation of the SST receptors was found to significantly affect insulin secretion., Conclusions: Overall, the EndoC-βH1 cells strongly resemble human islet beta cells in terms of glucose and incretin stimulated insulin secretion capabilities. The cell line has an active cytokine induced caspase 3/7 apoptotic pathway and is responsive to ER stress initiation factors. The cells' ability to proliferate can be further increased by already known compounds as well as by novel peptides and proteins. Based on its robust performance during the functionality assessment assays, the EndoC-βH1 cell line was successfully used as a screening platform for identification of novel anti-diabetic drug candidates., (Copyright © 2017 Novo Nordisk A/S. Published by Elsevier GmbH.. All rights reserved.)

Atrial fibrillation (AF) is a chronic disease with an incidence increasing steeply by age and affecting more than 11 million patients in Europe and the United States. Diagnosing AF is essential for the prevention of stroke by oral anticoagulation. Opportunistic screening for AF in patients ≥65 years of age is recommended by the European and Danish Societies of Cardiology. The study aim was to examine the detection rate of AF in consecutively screened patients in the primary care setting in Denmark. In an open, non-interventional, cluster, multicenter, cross-sectional, observational study patients ≥65 years of age entering consecutively into general practice clinics were invited to nurse-assisted opportunistic screening for AF. The General Practice (GP) clinics participating were randomized to patient inclusion in three age groups: 65-74, 75-84, and ≥85 years respectively. All patients underwent pulse palpation followed by 12-led electrocardiogram in case of irregular pulse. Two cardiologists validated all electrocardiogram examinations. Forty-nine general practice clinics recruited in total 970 patients split into three age groups; 480 patients (65-74 years), 372 (75-84 years), and 118 patients ≥85 years of age. Co-morbidities increased by age with hypertension being most frequent. Eighty-seven patients (9%) were detected with an irregular pulse, representing 4.4%, 10.5% and 22.9%, respectively in the three age groups. Assessment of electrocardiograms by the GP showed suspicion of AF in 13 patients with final verification of electrocardiograms by cardiologists revealing 10 AF-patients. The highest detection rate of AF was found in the ≥85 age group (3.39%) followed by the 65-74 age group (0.83%) and the 75-84 age group (0.54%). Opportunistic screening of AF in primary care is feasible and do result in the detection of new AF-patients. Close collaboration with cardiologists is advisable to avoid false positive screening results.

When interacting with people with aphasia, communication partners use a range of subtle strategies to scaffold, or facilitate, expression and comprehension. The present article analyses the unintended effects of these ostensibly helpful acts. Twenty people with aphasia and their main communication partners (n = 40) living in the UK were video recorded engaging in a joint task. Three analyses reveal that: (1) scaffolding is widespread and mostly effective, (2) the conversations are dominated by communication partners, and (3) people with aphasia both request and resist help. We propose that scaffolding is inherently paradoxical because it has contradictory effects. While helping facilitates performing an action, and is thus enabling, it simultaneously implies an inability to perform the action independently, and thus it can simultaneously mark the recipient as disabled. Data are in British English.

Measured cross-spectral matrices (CSMs) from a microphone array will in some cases be contaminated by severe incoherent noise signals in the individual channels. A typical example is flow noise generated in the individual microphones when measuring in a wind tunnel. Assuming stationary signals and performing long-time averaging, the contamination will be concentrated on the CSM diagonal. When the CSM is used for traditional frequency-domain beamforming, diagonal removal (DR) will avoid use of the diagonal. DR is effective at suppressing the contamination effects, but it also has some side effects. With other beamforming algorithms and in connection with acoustic holography, however, the diagonal of the CSM is needed. The present paper describes a method for removal of incoherent noise contamination from the CSM diagonal. The method formulates the problem as a semidefinite program, which is a convex optimization problem that can be solved very efficiently and with guaranteed convergence properties. A first numerical study investigates the question, whether the semidefinite program formulation will provide in all cases the desired output. A second numerical study investigates the limitations introduced by off-diagonal noise contributions due to finite averaging time. The results of that study are backed up by results from a practical measurement.

Background: Seizure outcome following surgery in pharmacoresistant temporal lobe epilepsy patients with normal magnetic resonance imaging and normal or non-specific histopathology is not sufficiently presented in the literature., Methods: In a retrospective design, we reviewed data of 263 patients who had undergone temporal lobe epilepsy surgery and identified 26 (9.9%) who met the inclusion criteria. Seizure outcomes were determined at 2-year follow-up. Potential predictors of Engel class I (satisfactory outcome) were identified by logistic regression analyses., Results: Engel class I outcome was achieved in 61.5% of patients, 50% being completely seizure free (Engel class IA outcome). The strongest predictors of satisfactory outcome were typical ictal seizure semiology (p = 0.048) and localised ictal discharges on scalp EEG (p = 0.036)., Conclusion: Surgery might be an effective treatment choice for the majority of these patients, although outcomes are less favourable than in patients with magnetic resonance imaging-defined lesional temporal lobe epilepsy. Typical ictal seizure semiology and localised ictal discharges on scalp EEG were predictors of Engel class I outcome.

Young people's need for sexual counseling is well documented, and both website and hotline-based services have been established as means of health promotion in this field. Such measures, however, are rarely evaluated, so this article offers data from the world's presumably oldest sexuality helpline aimed at young people. With an observation time of two decades and a total of 42,325 questions asked, the study provides a unique glance into the sexual landscapes of Danish youth. It shows an overall male predominance among callers and reveals that the counseling themes change over time and differ between both age groups and genders. The article suggests that telephone counseling-although more resource demanding than online alternatives-provides a secure, anonymous, and dialogue-based arena for discussing delicate sexual issues and therefore may constitute a viable supplement to web-based media for young people with the need to talk rather than just chat.

We demonstrate a significant improvement in the performance of a fiber-based frequency comb when a GPS-disciplined Rb clock is replaced with an acetylene-stabilized laser as the frequency reference. We have developed a compact, maintenance-free acetylene-stabilized fiber laser with a sub-kHz short-term linewidth and an Allan deviation below 3×10 -13 for integration times above 1 s. Switching the comb reference from the Rb clock to the acetylene-stabilized laser improves both comb tooth linewidth and Allan deviation by about two orders of magnitude. Furthermore, long-term measurements of the acetylene-stabilized laser frequency with reference to the GPS-disciplined clock indicate a potential relative frequency uncertainty of 2 × 10 -12 .

During embryonic development, endocrine cells of the pancreas are specified from multipotent progenitors. The transcription factor Neurogenin 3 (NEUROG3) is critical for this development and it has been shown that all endocrine cells of the pancreas arise from endocrine progenitors expressing NEUROG3. A thorough understanding of the role of NEUROG3 during development, directed differentiation of pluripotent stem cells and in models of cellular reprogramming, will guide future efforts directed at finding novel sources of β-cells for cell replacement therapies. In this article, we review the expression and function of NEUROG3 in both mouse and human and present the further characterization of a monoclonal antibody directed against NEUROG3. This antibody has been previously been used for detection of both mouse and human NEUROG3. However, our results suggest that the epitope recognized by this antibody is specific to mouse NEUROG3. Thus, we have also generated a monoclonal antibody specifically recognizing human NEUROG3 and present the characterization of this antibody here. Together, these antibodies will provide useful tools for future studies of NEUROG3 expression, and the data presented in this article suggest that recently described expression patterns of NEUROG3 in human foetal and adult pancreas should be re-examined., (© 2016 John Wiley & Sons Ltd.)

Patch near-field acoustical holography methods like statistically optimized near-field acoustical holography and equivalent source method are limited to relatively low frequencies, where the average array-element spacing is less than half of the acoustic wavelength, while beamforming provides useful resolution only at medium-to-high frequencies. With adequate array design, both methods can be used with the same array. But for holography to provide good low-frequency resolution, a small measurement distance is needed, whereas beamforming requires a larger distance to limit sidelobe issues. The wideband holography method of the present paper was developed to overcome that practical conflict. Only a single measurement is needed at a relatively short distance and a single result is obtained covering the full frequency range. The method uses the principles of compressed sensing: A sparse sound field representation is assumed with a chosen set of basis functions, a measurement is taken with an irregular array, and the inverse problem is solved with a method that enforces sparsity in the coefficient vector. Instead of using regularization based on the 1-norm of the coefficient vector, an iterative solution procedure is used that promotes sparsity. The iterative method is shown to provide very similar results in most cases and to be computationally much more efficient.

We demonstrate a compact fibre-based laser system at 2.05 microns stabilized to a CO 2 transition using frequency modulation spectroscopy of a gas-filled hollow-core fibre. The laser exhibits an absolute frequency accuracy of 5 MHz, a frequency stability noise floor of better than 7 kHz or 5 × 10 -11 and is tunable within ±200 MHz from the molecular resonance frequency while retaining roughly this stability and accuracy.

Background: The area of predominant perifocal [(18)F]fluorodeoxyglucose ((18)F-FDG) hypometabolism and reduced [(11)C]flumazenil ((11)C-FMZ) -binding on PET scans is currently considered to contain the epileptogenic zone and corresponds anatomically to the area localizing epileptogenicity in patients with temporal lobe epilepsy (TLE). The question is whether the volume of the perifocal pre-operative PET abnormalities, the extent of their resection, and the volume of the non-resected abnormalities affects the post-operative seizure outcome., Methods: The sample group consisted of 32 patients with mesial temporal sclerosis who underwent anteromedial temporal lobe resection for refractory TLE. All patients had pathologic perifocal findings on both of the PET modalities as well as on the whole-brain MRI. The volumetric data of the PET and MRI abnormalities within the resected temporal lobe were estimated by automated quantitative voxel-based analysis. The obtained volumetric data were investigated in relation to the outcome subgroups of patients (Engel classification) determined at the 2-year post-operative follow-up., Results: The mean volume of the pre-operative perifocal (18)F-FDG- and (11)C-FMZ PET abnormalities in the volumes of interest (VOI) of the epileptogenic temporal lobe, the mean resected volume of these PET abnormalities, the mean volume of the non-resected PET abnormalities, and the mean MRI-derived resected volume were not significantly related to the outcome subgroups and had a low prediction for individual freedom from seizures., Conclusions: The extent of pre-surgical perifocal PET abnormalities, the extent of their resection, and the extent of non-resected abnormalities were not useful predictors of individual freedom from seizures in patients with TLE.

Background: The existing literature on recurrence rates and long-term clinical outcome after resection of intraspinal nerve sheath tumors is limited., Objective: To evaluate progression-free survival, overall survival, and long-term clinical outcome in a consecutive series of 131 patients with symptomatic intraspinal nerve sheath tumors., Methods: Medical charts were retrospectively reviewed. Surviving patients voluntarily participated in a clinical history and physical examination that focused on neurological function and current tumor status., Results: Follow-up data are 100% complete; median follow-up time was 6.1 years. All patients (100%) had surgery as the first line of treatment; gross total resection was performed in 112 patients (85.5%) and subtotal resection in 19 patients (14.5%). Five-year progression-free survival was 89%. The following risk factors for recurrence were identified: neurofibroma, malignant peripheral nerve sheath tumor, subtotal resection, neurofibromatoses/schwannomatosis, and advancing age at diagnosis. More than 95% of patients had neurological function compatible with an independent life at follow-up. The rate of tumor recurrence in nonneurofibromatosis patients undergoing total resection of a single schwannoma was 3% (3/93), in comparison with a recurrence rate of 32% (12/38) in the remaining patients., Conclusion: Gross total resection is the gold standard treatment for patients with intraspinal nerve sheath tumors. In a time of limited health care resources, we recommend that follow-up be focused on the subgroup of patients with a high risk of recurrence. The benefit of long-term, yearly magnetic resonance imaging follow-up with respect to recurrence in nonneurofibromatosis patients undergoing gross total resection of a single schwannoma is, in our opinion, questionable. 1NF2, neurofibromatosis 2NST, nerve sheath tumorOS, overall survivalPFS, progression-free survivalSTR, subtotal resectionWHO, World Health Organization.

The localization of sound sources with delay-and-sum (DAS) beamforming is limited by a poor spatial resolution-particularly at low frequencies. Various methods based on deconvolution are examined to improve the resolution of the beamforming map, which can be modeled by a convolution of the unknown acoustic source distribution and the beamformer's response to a point source, i.e., point-spread function. A significant limitation of deconvolution is, however, an additional computational effort compared to beamforming. In this paper, computationally efficient deconvolution algorithms are examined with computer simulations and experimental data. Specifically, the deconvolution problem is solved with a fast gradient projection method called Fast Iterative Shrikage-Thresholding Algorithm (FISTA), and compared with a Fourier-based non-negative least squares algorithm. The results indicate that FISTA tends to provide an improved spatial resolution and is up to 30% faster and more robust to noise. In the spirit of reproducible research, the source code is available online.

Background and Purpose: HYPRFlow is a novel imaging strategy that provides fast, high-resolution contrast-enhanced time-resolved images and measurement of the velocity of the entire cerebrovascular system. Our hypothesis was that the images obtained with this strategy are of adequate diagnostic image quality to delineate the major components of AVMs., Materials and Methods: HYPRFlow and 3D TOF scans were obtained in 21 patients with AVMs with correlative DSA examinations in 14 patients. The examinations were scored for image quality and graded by using the Spetzler-Martin criteria. Mean arterial transit time and overlap integrals were calculated from the dynamic image data. Volume flow rates in normal arteries and AVM feeding arteries were measured from the phase contrast data., Results: HYPRFlow was equivalent to 3D-TOF in delineating normal arterial anatomy, arterial feeders, and nidus size and was concordant with DSA for AVM grading and venous drainage in 13 of the 14 examinations. Mean arterial transit time on the AVM side was 0.49 seconds, and on the normal contralateral side, 2.53 seconds with P < .001. Across all 21 subjects, the mean arterial volume flow rate in the M1 segment ipsilateral to the AVM was 4.07 ± 3.04 mL/s; on the contralateral M1 segment, it was 2.09 ± 0.64 mL/s. The mean volume flow rate in the largest feeding artery to the AVM was 3.86 ± 2.74 mL/s., Conclusions: HYPRFlow provides an alternative approach to the MRA evaluation of AVMs, with the advantages of increased coverage, 0.75-second temporal resolution, 0.68-mm isotropic spatial resolution, and quantitative measurement of flow in 6 minutes., (© 2015 by American Journal of Neuroradiology.)

Gas-filled hollow-core photonic crystal fibers are used to stabilize a fiber laser to the 13C2H2 P(16) (ν1+ν3) transition at 1542 nm using saturated absorption. Four hollow-core fibers with different crystal structure are compared in terms of long term lock-point repeatability and fractional frequency instability. The locked fiber laser shows a fractional frequency instability below 4 × 10(-12) for averaging time up to 10(4) s. The lock-point repeatability over more than 1 year is 1.3 × 10(-11), corresponding to a standard deviation of 2.5 kHz. A complete experimental investigation of the light-matter interaction between the spatial modes excited in the fibers and the frequency of the locked laser is presented. A simple theoretical model that explains the interaction is also developed.

Statistically Optimized Near-field Acoustic Holography (SONAH) is a Patch Holography method, meaning that it can be applied in cases where the measurement area covers only part of the source surface. The method performs projections directly in the spatial domain, avoiding the use of spatial discrete Fourier transforms and the associated errors. First, an inverse problem is solved using regularization. For each calculation point a multiplication must then be performed with two transfer vectors--one to get the sound pressure and the other to get the particle velocity. Considering SONAH based on sound pressure measurements, existing derivations consider only pressure reconstruction when setting up the inverse problem, so the evanescent wave amplification associated with the calculation of particle velocity is not taken into account in the regularized solution of the inverse problem. The present paper introduces a scaling of the applied plane wave functions that takes the amplification into account, and it is shown that the previously published virtual source-plane retraction has almost the same effect. The effectiveness of the different solutions is verified through a set of simulated measurements.

Mice genetically deficient in the glucagon receptor (Gcgr(-/-)) show improved glucose tolerance, insulin sensitivity, and α-cell hyperplasia. In addition, Gcgr(-/-) mice do not develop diabetes after chemical destruction of β-cells. Since fibroblast growth factor 21 (FGF21) has insulin-independent glucose-lowering properties, we investigated whether FGF21 was contributing to diabetes resistance in insulin-deficient Gcgr(-/-) mice. Plasma FGF21 was 25-fold higher in Gcgr(-/-) mice than in wild-type mice. FGF21 was found to be expressed in pancreatic β- and α-cells, with high expression in the hyperplastic α-cells of Gcgr(-/-) mice. FGF21 expression was also significantly increased in liver and adipose tissue of Gcgr(-/-) mice. To investigate the potential antidiabetic actions of FGF21 in insulin-deficient Gcgr(-/-) mice, an FGF21-neutralizing antibody was administered prior to oral glucose tolerance tests (OGTTs). FGF21 neutralization caused a decline in glucose tolerance in insulin-deficient Gcgr(-/-) mice during the OGTT. Despite this decline, insulin-deficient Gcgr(-/-) mice did not develop hyperglycemia. Glucagon-like peptide 1 (GLP-1) also has insulin-independent glucose-lowering properties, and an elevated circulating level of GLP-1 is a known characteristic of Gcgr(-/-) mice. Neutralization of FGF21, while concurrently blocking the GLP-1 receptor with the antagonist Exendin 9-39 (Ex9-39), resulted in significant hyperglycemia in insulin-deficient Gcgr(-/-) mice, while blocking with Ex9-39 alone did not. In conclusion, FGF21 acts additively with GLP-1 to prevent insulinopenic diabetes in mice lacking glucagon action.

This study provides data on prevalence of Staphylococcus aureus in oropharynx, rhinopharynx and vestibulum nasi. Specimens were taken from these three pharyngeal sites in 346 patients and analysed for S. aureus. Abnormal pharyngeal findings and patient histories were recorded. S. aureus was found in 8.1%, 7.2% and 20.2% of all specimens from oropharynx, rhinopharynx and vestibulum nasi, respectively. A strong association between colonization of oropharynx and rhinopharynx was found, especially when vestibulum nasi was not colonized. These findings can be used in development of more effective meticillin-resistant Staphylococcus aureus decolonization regimes., (Copyright © 2013 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: Chronic subdural haematoma (CSDH) is a common entity in neurosurgery with a considerable postoperative recurrence rate. Computerised tomography (CT) scanning remains the most important diagnostic test for this disorder. The aim of this study was to characterise the relationship between the recurrence of CSDH after treatment with burr-hole irrigation and closed-system drainage technique and CT scan features of these lesions to assess whether CT findings can be used to predict recurrence., Methods: We investigated preoperative and postoperative CT scan features and recurrence rate of 107 consecutive adult surgical cases of CSDH and assessed any relationship with univariate and multivariate regression analyses., Results: Seventeen patients (15.9 %) experienced recurrence of CSDH. The preoperative haematoma volume, the isodense, hyperdense, laminar and separated CT densities and the residual total haematoma cavity volume on the 1st postoperative day after removal of the drainage were identified as radiological predictors of recurrence. If the preoperative haematoma volume was under 115 ml and the residual total haematoma cavity volume postoperatively was under 80 ml, the probability of no recurrence was very high (94.4 % and 97.4 % respectively)., Conclusions: These findings from CT imaging may help to identify patients at risk for postoperative recurrence.

Objective: Growing evidence suggests that a phenotypic switch converting pancreatic acinar cells to duct-like cells can lead to pancreatic intraepithelial neoplasia and eventually to invasive pancreatic ductal adenocarcinoma. Histologically, the onset of this switch is characterised by the co-expression of acinar and ductal markers in acini, a lesion called acinar-to-ductal metaplasia (ADM). The transcriptional regulators required to initiate ADM are unknown, but need to be identified to characterise the regulatory networks that drive ADM. In this study, the role of the ductal transcription factors hepatocyte nuclear factor 6 (HNF6, also known as Onecut1) and SRY-related HMG box factor 9 (Sox9) in ADM was investigated., Design: Expression of HNF6 and Sox9 was measured by immunostaining in normal and diseased human pancreas. The function of the factors was tested in cultured cells and in mouse models of ADM by a combination of gain and loss of function experiments., Results: Expression of HNF6 and Sox9 was ectopically induced in acinar cells in human ADM as well as in mouse models of ADM. HNF6 and, to a lesser extent, Sox9 were required for repression of acinar genes, for modulation of ADM-associated changes in cell polarity and for activation of ductal genes in metaplastic acinar cells., Conclusions: HNF6 and Sox9 are new biomarkers of ADM and constitute candidate targets for preventive treatment in cases when ADM may lead to cancer. This work also shows that ectopic activation of transcription factors may underlie metaplastic processes occurring in other organs.

Aims/hypothesis: The aim of the study was to identify surface bio-markers and corresponding antibody tools that can be used for the imaging and immunoisolation of the pancreatic beta cell and its progenitors. This may prove essential to obtain therapeutic grade human beta cells via stem cell differentiation., Methods: Using bioinformatics-driven data mining, we generated a gene list encoding putative plasma membrane proteins specifically expressed at distinct stages of the developing pancreas and islet beta cells. In situ hybridisation and immunohistochemistry were used to further prioritise and identify candidates., Results: In the developing pancreas seizure related 6 homologue like (SEZ6L2), low density lipoprotein receptor-related protein 11 (LRP11), dispatched homologue 2 (Drosophila) (DISP2) and solute carrier family 30 (zinc transporter), member 8 (SLC30A8) were found to be expressed in early islet cells, whereas discoidin domain receptor tyrosine kinase 1 (DDR1) and delta/notch-like EGF repeat containing (DNER) were expressed in early pancreatic progenitors. The expression pattern of DDR1 overlaps with the early pancreatic and duodenal homeobox 1 (PDX1)⁺/NK6 homeobox 1 (NKX6-1)⁺ multipotent progenitor cells from embryonic day 11, whereas DNER expression in part overlaps with neurogenin 3 (NEUROG3)⁺ cells. In the adult pancreas SEZ6L2, LRP11, DISP2 and SLC30A8, but also FXYD domain containing ion transport regulator 2 (FXYD2), tetraspanin 7 (TSPAN7) and transmembrane protein 27 (TMEM27), retain an islet-specific expression, whereas DDR1 is undetectable. In contrast, DNER is expressed at low levels in peripheral mouse and human islet cells. Re-expression of DDR1 and upregulation of DNER is observed in duct-ligated pancreas. Antibodies to DNER and DISP2 have been successfully used in cell sorting., Conclusions/interpretation: Extracellular epitopes of SEZ6L2, LRP11, DISP2, DDR1 and DNER have been identified as useful tags by applying specific antibodies to visualise pancreatic cell types at specific stages of development. Furthermore, antibodies recognising DISP2 and DNER are suitable for FACS-mediated cell purification.

The binaural auralization of a 3D sound field using spherical-harmonics beamforming (SHB) techniques was investigated and compared with the traditional method using a head-and-torso simulator (HATS). The new procedure was verified by comparing simulated room impulse responses with measured ones binaurally. The objective comparisons show that there is good agreement in the frequency range between 0.1 and 6.4 kHz. A listening experiment was performed to validate the SHB method subjectively and to compare it to the HATS method. Two musical excerpts, pop and classical, were used. Subjective responses were collected in two head rotation conditions (fixed and rotating) and six spatial reproduction modes, including phantom mono, stereo, and surround sound. The results show that subjective scales of width, spaciousness, and preference based on the SHB method were similar to those obtained for the HATS method, although the width and spaciousness of the stimuli processed by the SHB method were judged slightly higher than the ones using the HATS method in general. Thus, binaural synthesis using SHB may be a useful tool to reproduce a 3D sound field binaurally, while saving considerably on measurement time because head rotation can be simulated based on a single recording., (© 2011 Acoustical Society of America)

Type 1 diabetes (T1D) is a complex disease characterized by the loss of insulin-secreting β-cells. Although the disease has a strong genetic component, and several loci are known to increase T1D susceptibility risk, only few causal genes have currently been identified. To identify disease-causing genes in T1D, we performed an in silico "phenome-interactome analysis" on a genome-wide linkage scan dataset. This method prioritizes candidates according to their physical interactions at the protein level with other proteins involved in diabetes. A total of 11 genes were predicted to be likely disease genes in T1D, including the INS gene. An unexpected top-scoring candidate gene was huntingtin-interacting protein (HIP)-14/ZDHHC17. Immunohistochemical analysis of pancreatic sections demonstrated that HIP14 is almost exclusively expressed in insulin-positive cells in islets of Langerhans. RNAi knockdown experiments established that HIP14 is an antiapoptotic protein required for β-cell survival and glucose-stimulated insulin secretion. Proinflammatory cytokines (IL-1β and IFN-γ) that mediate β-cell dysfunction in T1D down-regulated HIP14 expression in insulin-secreting INS-1 cells and in isolated rat and human islets. Overexpression of HIP14 was associated with a decrease in IL-1β-induced NF-κB activity and protection against IL-1β-mediated apoptosis. Our study demonstrates that the current network biology approach is a valid method to identify genes of importance for T1D and may therefore embody the basis for more rational and targeted therapeutic approaches.

We present the first experimental determination of the electric-dipole forbidden (3s3p)³P₂→(3s²)¹S₀ (M2) transition rate in ²⁴Mg and compare to state-of-the-art theoretical predictions. Our measurement exploits a magnetic trap isolating the sample from perturbations and a magneto-optical trap as an amplifier converting each ³P₂→¹S₀ decay event into millions of photons readily detected. The transition rate is determined to be (4.87 ± 0.3)×10⁻⁴  s⁻¹ corresponding to a ³P₂ lifetime of 2050(-110)(+140) sec. This value is in agreement with recent theoretical predictions, and to our knowledge the longest lifetime ever determined in a laboratory environment.

Objectives: To establish the prevalence of protrusio acetabuli (PA) in adults fulfilling the Ghent criteria for Marfan syndrome (MFS), and in a normal adult population., Methods: 105 adults with probable MFS and 107 controls were included. CT of the hips was obtained. A qualitative assessment of PA was performed. A new method for estimating the degree of PA was introduced with measurement of the parameter CWD (circle-wall distance). Results were compared to an alternative method based on MRI [1]., Results: 87 of the study group fulfilled the Ghent criteria of MFS (Ghent positives), and 18 did not (Ghent negatives). PA was diagnosed qualitatively in 74.7% of Ghent positive persons, in 27.8% of Ghent negative persons, and in 3.7% of the controls. CWD was significantly different between the three groups (p < 0.001). A slight but significant gender difference was found in Ghent positive persons only. The alternative method did not differentiate between the groups with respect to PA, but showed a significant difference between genders., Conclusions: PA was found significantly more often in MFS persons than in controls. Our method was found to be robust and highly reproducible, giving a direct measurement of pelvic protrusion irrespective of pelvic shape.

Spherical near field acoustic holography (spherical NAH) is a technique that makes it possible to reconstruct the sound field inside and just outside a spherical surface on which the sound pressure is measured with an array of microphones. This is potentially very useful for source identification. The sphere can be acoustically transparent or it can be rigid. A rigid sphere is somewhat more practical than an open sphere. However, spherical NAH based on a rigid sphere is only valid if it can be assumed that the sphere has a negligible influence on the incident sound field, and this is not necessarily a good assumption when the sphere is very close to a radiating surface. This Letter examines the matter through simulations and experiments., (© 2011 Acoustical Society of America)

A 32 mW fiber laser is stabilized to the (13)C(2)H(2) P(16) (ν1 + ν3) transition at 1542 nm using saturated absorption. The short-term shot-noise limited fractional frequency instability is 5.0 × 10(-13)(τ/s)-½ for averaging times τ up to about 100 s. The relative lock-point repeatability over 2½ month is 4.3 × 10(-13) corresponding to 83 Hz. The simple setup includes a 21 cm long gas cell, but it does not require an enhancement cavity or external modulators. The spectroscopic lineshape is analyzed with respect to optical power and acetylene pressure. Narrow linewidths of 300 kHz FWHM are observed with a signal to noise ratio of 35 dB in a 9 Hz bandwidth.

Objective: To evaluate progression-free survival, overall survival (OS) and long-term clinical outcome in a consecutive series of 86 patients with intraspinal ependymomas., Methods: Medical charts were retrospectively reviewed. Surviving patients voluntarily participated in a clinical history and physical examination that focused on neurological function and current tumor status., Results: Follow-up data are nearly 100% complete; mean follow-up time was 82 months. Eighty-five patients (99%) had surgery as a first-line treatment; 14 (17%) of these patients received adjuvant radiotherapy. Of the 85 patients who underwent primary surgery, gross total resection was performed in 60 patients (71%) and subtotal resection in 25 patients (29%). Ten-year progression-free survival rate was 75%; 5-year OS, 97%; and 10-year OS, 91%. Reduced preoperative neurological function and older age at diagnosis were significantly associated with increased risk of death. At follow-up, spontaneous regression of residual tumor after primary surgery may have occurred in 7 of 19 patients (37%). More than 75% of patients had neurological function compatible with an independent life at follow-up. Good preoperative neurological function was significantly associated with favorable outcome. It was not possible to evaluate the effect of radiotherapy on progression-free survival and OS., Conclusion: Gross total resection remains the optimal treatment for patients with spinal ependymoma. Patients should be monitored with a clinical examination and magnetic resonance imaging at regular intervals up to 10 years after surgery.

The transmission properties of five types of hollow-core photonic bandgap fibers (HC-PBFs) are characterized in the telecom wavelength range around 1.5 microm. The variations in optical transmission are measured as a function of laser frequency over a 2 GHz scan range as well as a function of time over several hours. The influence of these variations on spectroscopy of molecules in a HC-PBF is simulated.

The aim of this study was to characterize two monoclonal antibodies (F6A11 and F109-D12) generated against Pdx1 (pancreatic and duodenal homeobox-1), a homeodomain transcription factor, which is critical for pancreas formation as well as for normal pancreatic beta cell function. For production of monoclonal antibodies, we immunized Robertsonian POSF (RBF)mice with a GST-Pdx1 fusion protein containing a 68-amino acid C-terminal fragment of rat Pdx1. These monoclonal antibodies detect Pdx1 by western blotting and allow immunohistochemical detection of Pdx1 in both mouse and rat tissue. F6A11 and F109-D12 produce IHC staining patterns indistinguishable from that obtained with highly specific polyclonal Pdx1 antisera raised in rabbits and goats, when applied to embryonic or adult mouse pancreatic tissue. In contrast to previously generated polyclonal anti-Pdx1 antisera, we also demonstrate that F6A11 works for intracellular fluorescence activated cell sorting (FACS) staining of Pdx1. By using F6A11, we characterize the induction of Pdx1 in the Doxycycline (DOX) inducible insulinoma cell line INSralphabeta-Pdx1 and follow the reduction of Pdx1 after removing Dox. Finally, we show that induction of exogenous Pdx1 leads to a reduction in endogenous Pdx1 levels, which suggests that a negative feedback loop is involved in maintaining correct levels of Pdx1 in the cell.

We have demonstrated microwave optical double resonance spectroscopy of the nu(1) + nu(3) and nu(1) + 2nu(4) bands of ammonia in a hollow-core photonic bandgap fiber. Signal strength and lineshapes are analyzed. Spectroscopic assignments of previously assigned lines and previously proposed assignments have been confirmed and new assignments have been made. Several microwave transitions in the excited vibrational states have been measured for the first time.

G protein-coupled receptor (GPR)-39 is a seven-transmembrane receptor expressed mainly in endocrine and metabolic tissues that acts as a Zn(++) sensor signaling mainly through the G(q) and G(12/13) pathways. The expression of GPR39 is regulated by hepatocyte nuclear factor (HNF)-1alpha and HNF-4alpha, and in the present study, we addressed the importance of GPR39 for glucose homeostasis and pancreatic islets function. The expression and localization of GPR39 were characterized in the endocrine pancreas and pancreatic cell lines. Gpr39(-/-) mice were studied in vivo, especially in respect of glucose tolerance and insulin sensitivity, and in vitro in respect of islet architecture, gene expression, and insulin secretion. Gpr39 was down-regulated on differentiation of the pluripotent pancreatic cell line AR42J cells toward the exocrine phenotype but was along with Pdx-1 strongly up-regulated on differentiation toward the endocrine phenotype. Immunohistochemistry demonstrated that GRP39 is localized selectively in the insulin-storing cells of the pancreatic islets as well as in the duct cells of the exocrine pancreas. Gpr39(-/-) mice displayed normal insulin sensitivity but moderately impaired glucose tolerance both during oral and iv glucose tolerance tests, and Gpr39(-/-) mice had decreased plasma insulin response to oral glucose. Islet architecture was normal in the Gpr39 null mice, but expression of Pdx-1 and Hnf-1alpha was reduced. Isolated, perifused islets from Gpr39 null mice secreted less insulin in response to glucose stimulation than islets from wild-type littermates. It is concluded that GPR39 is involved in the control of endocrine pancreatic function, and it is suggested that this receptor could be a novel potential target for the treatment of diabetes.

To avoid the requirement set by standard near-field acoustical holography (NAH) to measure an area that fully covers the source, a set of so-called patch NAH methods has been introduced. One such method is the statistically optimized NAH (SONAH). In this method, the acoustic quantities on a mapping surface near the measurement surface are calculated by using a transfer matrix defined in such a way that all propagating waves and a weighted set of evanescent waves are projected with optimal average accuracy. The present paper gives an overview of the basic theory of SONAH, including a description of phenomena such as spatial aliasing and wave-number domain leakage. A revised and generalized mathematical formulation is given, covering the calculation of all three components of particle velocity and the use of up to six virtual source planes. A set of formulas for the inherent estimation error level of the method is derived and used to visualize the regions of validity of the SONAH predictions for some typical microphone array geometries. The sensitivity of the inherent error level distribution to changes in the parameters of the SONAH algorithm is also investigated.

The spherical wave expansion with a single origin is sometimes used in connection with near-field acoustical holography to determine the sound field on the surface of a source. The radiated field is approximated by a truncated expansion, and the expansion coefficients are determined by matching the sound field model to the measured pressure close to the source. This problem is ill posed, and therefore regularization is required. The present paper investigates the consequence of using only the expansion truncation as regularization approach and compares it with results obtained when additional regularization (the truncated singular value decomposition) is introduced. Important differences between applying the method when using a microphone array surrounding the source completely and an array covering only a part of the source are described. Another relevant issue is the scaling of the wave functions. It is shown that it is important for the additional regularization to work properly that the wave functions are scaled in such a way that their magnitude on the measurement surface decreases with the order. Finally, the method is applied on nonspherical sources using a vibrating plate in both simulations and an experiment, and the performance is compared with the equivalent source method.