About the computation of the signature of surface singularities z^N+g(x,y)=0

In this article we describe our experiences with a parallel SINGULAR-implementation of the signature of a surface singularity defined by z^N+g(x,y)=0.Comment: 6 page

Experimental investigation of collagen waviness and orientation in the arterial adventitia using confocal laser scanning microscopy

Mechanical properties of the adventitia are largely determined by the organization of collagen fibers. Measurements on the waviness and orientation of collagen, particularly at the zero-stress state, are necessary to relate the structural organization of collagen to the mechanical response of the adventitia. Using the fluorescence collagen marker CNA38-OG488 and confocal laser scanning microscopy, we imaged collagen fibers in the adventitia of rabbit common carotid arteries ex vivo. The arteries were cut open along their longitudinal axes to get the zero-stress state. We used semi-manual and automatic techniques to measure parameters related to the waviness and orientation of fibers. Our results showed that the straightness parameter (defined as the ratio between the distances of endpoints of a fiber to its length) was distributed with a beta distribution (mean value 0.72, variance 0.028) and did not depend on the mean angle orientation of fibers. Local angular density distributions revealed four axially symmetric families of fibers with mean directions of 0°, 90°, 43° and −43°, with respect to the axial direction of the artery, and corresponding circular standard deviations of 40°, 47°, 37° and 37°. The distribution of local orientations was shifted to the circumferential direction when measured in arteries at the zero-load state (intact), as compared to arteries at the zero-stress state (cut-open). Information on collagen fiber waviness and orientation, such as obtained in this study, could be used to develop structural models of the adventitia, providing better means for analyzing and understanding the mechanical properties of vascular wal

Prolonged Fasting Identifies Skeletal Muscle Mitochondrial Dysfunction as Consequence Rather Than Cause of Human Insulin Resistance

OBJECTIVE-Type 2 diabetes and insulin resistance have been associated with mitochondrial dysfunction, but it is debated whether this is a primary factor in the pathogenesis of the disease. To test the concept that mitochondrial dysfunction is secondary to the development of insulin resistance, we employed the unique model of prolonged fasting in humans. Prolonged fasting is a physiologic condition in which muscular insulin resistance develops in the presence of increased free fatty acid (FFA) levels, increased fat oxidation and low glucose and insulin levels. It is therefore anticipated that skeletal muscle mitochondrial function is maintained to accommodate increased fat oxidation unless factors secondary to insulin resistance exert negative effects on mitochondrial function. RESEARCH DESIGN AND METHODS-While in a respiration chamber, twelve healthy males were subjected to a 60 h fast and a 60 h normal fed condition in a randomized crossover design. Afterward, insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp, and mitochondrial function was quantified ex vivo in permeabilized muscle fibers using high-resolution respirometry. RESULTS-Indeed, FFA levels were increased approximately ninefold after 60 h of fasting in healthy male subjects, leading to elevated intramuscular lipid levels and decreased muscular insulin sensitivity. Despite an increase in whole-body fat oxidation, we observed an overall reduction in both coupled state 3 respiration and maximally uncoupled respiration in permeabilized skeletal muscle fibers, which could not be explained by changes in mitochondrial density. CONCLUSIONS-These findings confirm that the insulin-resistant State has secondary negative effects on mitochondrial function. Given the low insulin and glucose levels after prolonged fasting, hyperglycemia and insulin action per se can be excluded as underlying mechanisms, pointing toward elevated plasma FFA and/or intramuscular fat accumulation as possible causes for the observed reduction in mitochondrial capacity. Diabetes 59: 2117-2125, 201

Ca2+-binding protein 2 inhibits Ca2+-channel inactivation in mouse inner hair cells

Ca2+ channels mediate excitation-secretion coupling and show little inactivation at sensory ribbon synapses, enabling reliable synaptic information transfer during sustained stimulation. Studies of Ca2+-channel complexes in HEK293 cells indicated that Ca2+-binding proteins (CaBPs) antagonize their calmodulin-dependent inactivation. Although human mutations affecting CABP2 were shown to cause hearing impairment, the role of CaBP2 in auditory function and the precise disease mechanism remained enigmatic. Here, we disrupted CaBP2 in mice and showed that CaBP2 is required for sound encoding at inner hair cell synapses, likely by suppressing Ca2+-channel inactivation. We propose that the number of activatable Ca2+ channels at the active zone is reduced when CaBP2 is lacking, as is likely the case with the newly described human CABP2 mutation

An open-source approach to automation in organic synthesis: The flow chemical formation of benzamides using an inline liquid-liquid extraction system and a homemade 3-axis autosampling/product-collection device

Several open-source hardware and software technologies (RAMPS, Python, PySerial, OpenCV) were used to control an automated flow chemical synthesis system. The system was used to effect the synthesis of a series of benzamides. An inexpensive Raspberry Pi single board computer provided an electronic interface between the control computer and the RAMPS motor driver boards

Sn diffusion during Ni germanide growth on Ge1– xSnx

We report on the redistribution of Sn during Ni germanide formation on Ge1– x Sn x /〈Ge(100)〉 and its influence on the thin film growth and properties. These results show that the reaction involves the formation of Ni5Ge3 and NiGe. Sn redistributes homogenously in both phases, in which the Sn/Ge ratio retains the ratio of the as-deposited Ge1– x Sn x film. Sn continues to diffuse after full NiGe formation and segregates in two regions: (1) at the interface between the germanide and Ge1– x Sn x and (2) at the surface, which has major implications for the thin film and contact properties

Resonant infrared irradiation of CO and CH3OH interstellar ices

Solid-phase photo-processes involving icy dust grains greatly affect the chemical evolution of the interstellar medium by leading to the formation of complex organic molecules and by inducing photodesorption. So far, the focus of laboratory studies has been mainly on the impact of energetic ultraviolet (UV) photons on ices, but direct vibrational excitation by infrared (IR) photons is expected to influence the morphology and content of interstellar ices as well. However, little is still known about the mechanisms through which this excess vibrational energy is dissipated, and its implications on the structure and ice photochemistry. In this work, we present a systematic investigation of the behavior of interstellar relevant CO and CH3OH ice analogues upon resonant excitation of vibrational modes using tunable infrared radiation, leading to both the quantification of infrared-induced photodesorption and insights in the impact of vibrational energy dissipation on ice morphology. We utilize an ultrahigh vacuum setup at cryogenic temperatures to grow pure CO and CH3OH ices, as well as mixtures of the two. We expose the ices to intense, near-monochromatic mid-infrared free-electron-laser radiation to selectively excite the species. The dissipation of vibrational energy is observed to be highly dependent on the excited mode and the chemical environment of the ice. All amorphous ices undergo some degree of restructuring towards a more organized configuration upon on-resonance irradiation. Moreover, IR-induced photodesorption is observed to occur for both pure CO and CH3OH ices, with interstellar photodesorption efficiencies of the order of 10 molecules cm-2 s-1 (i.e., comparable to or higher than UV-induced counterparts). Indirect photodesorption of CO upon vibrational excitation of CH3OH in ice mixtures is also observed to occur, particularly in environments rich in methanol.Comment: Accepted for publication in A&A. 19 pages, 14 figures, 2 table

Four novel UCP3 gene variants associated with childhood obesity: effect on fatty acid oxidation and on prevention of triglyceride storage

The objective of the study was to look for uncoupling protein 3 (UCP3) gene variants in early-onset severe childhood obesity and to determine their effect on long-chain fatty acid oxidation and triglyceride storage

Reduced incorporation of Fatty acids into triacylglycerol in myotubes from obese individuals with type 2 diabetes.

Altered skeletal muscle lipid metabolism is a hallmark feature of type 2 (T2D). Here we investigated muscle lipid turnover in T2D versus BMI- controls and examined if putative in vivo differences would be preserved myotubes.Male obese T2D individuals (T2D) (n=6) and their BMI-matched (C) (n=6) underwent a hyperinsulinemic-euglycemic clamp, VO2max test, underwater weighing and muscle biopsy of v. lateralis. 14C-palmitate and 14C-oleate oxidation rates and incorporation into lipids were measured tissue, as well as in primary myotubes.Palmitate oxidation (C: 0.99 +/- T2D: 0.53 +/- 0.07nmol/mg protein; P=0.03) and incorporation of fatty into triacylglycerol (TAG) (C: 0.45 +/- 0.13, T2D: 0.11 +/- 0.02nmol/mg P=0.047) were significantly reduced in muscle homogenates of T2D. These reductions were not retained for palmitate oxidation in primary myotubes (P=0.38); however, incorporation of FAs into TAG was lower in T2D oleate and P=0.11 for palmitate), with a strong correlation of TAG between muscle tissue and primary myotubes (r=0.848, P=0.008).Our data that the ability to incorporate FAs into TAG is an intrinsic feature of muscle cells that is reduced in individuals with T2D

Relationship between de novo lipogenesis and serum sex hormone binding globulin in humans

Objective Obesity and liver fat are associated with decreased levels of serum sex hormone binding globulin (SHBG). Laboratory studies suggest that hepatic de novo lipogenesis (DNL) is involved in the downregulation of SHBG synthesis. The aim of the present study was to address the role of DNL on serum SHBG in humans. Design A cross-sectional study examining the association between DNL, measured by stable isotopes, and serum SHBG, stratified by sex. Participants Healthy men (n = 34) and women (n = 21) were combined from two cross-sectional studies. Forty-two per cent of participants had hepatic steatosis, and the majority were overweight (62%) or obese (27%). Results DNL was inversely associated with SHBG in women (beta: -0.015, 95% CI: -0.030; 0.000), but not in men (beta: 0.007, 95% CI: -0.005; 0.019) (p for interaction = .068). Adjustment for study population, age and body mass index did not materially change these results, although statistical significance was lost after adjustment for serum insulin. Conclusions An inverse association between DNL and SHBG may explain the decreased SHBG levels that are observed in obesity, at least in women.Peer reviewe