Erratum: Rotationally Cold OH

This corrects the article DOI: 10.1103/PhysRevLett.119.073001.

Dianion diagnostics in DESIREE: High-sensitivity detection of Cn2- from a sputter ion source.

A sputter ion source with a solid graphite target has been used to produce dianions with a focus on carbon cluster dianions, Cn2-, with n = 7-24. Singly and doubly charged anions from the source were accelerated together to kinetic energies of 10 keV per atomic unit of charge and injected into one of the cryogenic (13 K) ion-beam storage rings of the Double ElectroStatic Ion Ring Experiment facility at Stockholm University. Spontaneous decay of internally hot Cn2- dianions injected into the ring yielded Cn- anions with kinetic energies of 20 keV, which were counted with a microchannel plate detector. Mass spectra produced by scanning the magnetic field of a 90° analyzing magnet on the ion injection line reflect the production of internally hot C72- - C242- dianions with lifetimes in the range of tens of microseconds to milliseconds. In spite of the high sensitivity of this method, no conclusive evidence of C62- was found while there was a clear C72- signal with the expected isotopic distribution. This is consistent with earlier experimental studies and with theoretical predictions. An upper limit is deduced for a C62- signal that is two orders-of-magnitude smaller than that for C72-. In addition, CnO2- and CnCu2- dianions were detected.

Rotationally Cold OH

We apply near-threshold laser photodetachment to characterize the rotational quantum level distribution of OH^{-} ions stored in the cryogenic ion-beam storage ring DESIREE at Stockholm University. We find that the stored ions relax to a rotational temperature of 13.4±0.2 K with 94.9±0.3% of the ions in the rotational ground state. This is consistent with the storage ring temperature of 13.5±0.5 K as measured with eight silicon diodes but in contrast to all earlier studies in cryogenic traps and rings where the rotational temperatures were always much higher than those of the storage devices at their lowest temperatures. Furthermore, we actively modify the rotational distribution through selective photodetachment to produce an OH^{-} beam where 99.1±0.1% of approximately one million stored ions are in the J=0 rotational ground state. We measure the intrinsic lifetime of the J=1 rotational level to be 145±28 s.

Storing keV negative ions for an hour: the lifetime of the metastable

We use a novel electrostatic ion storage ring to measure the radiative lifetime of the upper level in the 3p^{5} ^{2}P_{1/2}^{o}→3p^{5} ^{2}P_{3/2}^{o} spontaneous radiative decay in ^{32}S^{-} to be 503±54 sec. This is by orders of magnitude the longest lifetime ever measured in a negatively charged ion. Cryogenic cooling of the storage ring gives a residual-gas pressure of a few times 10^{-14} mbar at 13 K and storage of 10 keV sulfur anions for more than an hour. Our experimental results differ by 1.3σ from the only available theoretical prediction [P. Andersson et al., Phys. Rev. A 73, 032705 (2006)].

Waist circumference to assess reversal of insulin resistance following weight reduction after bariatric surgery: cohort and cross-sectional studies.

OBJECTIVE: To validate the use of waist circumference to assess reversal of insulin resistance after weight loss induced by bariatric surgery. DESIGN: In cross-sectional studies, threshold values for insulin resistance were determined with homeostasis model assessment of insulin resistance (HOMA-IR) (algorithm based on fasting plasma glucose and insulin) in 1018 lean subjects and by hyperinsulinemic euglycemic clamp (clamp) in 26 lean women. In a cohort study on 211 patients scheduled for bariatric surgery, HOMA-IR and waist circumference were measured before and 1.5-3 years after weight reduction. In a subgroup of 53 women, insulin sensitivity was also measured using clamp. RESULTS: The threshold for insulin resistance (90th percentile) was 2.21 (mg dl(-1) fasting glucose × mU l(-1) fasting insulin divided by 405) for HOMA-IR and 6.118 (mg glucose per kg body weight per minute) for clamp. Two methods to assess reversal of insulin resistance by measuring waist circumference were used. A single cutoff value to <100 cm for waist circumference was associated with reversal of insulin resistance with an odds ratio (OR) of 49; 95% confidence interval (CI)=7-373 and P=0.0002. Also, a diagram based on initial and weight loss-induced changes in waist circumference in patients turning insulin sensitive predicted reversal of insulin resistance following bariatric surgery with a very high OR (32; 95% CI=4-245; P=0.0008). Results with the clamp cohort were similar as with HOMA-IR analyses. CONCLUSIONS: Reversal of insulin resistance could either be assessed by a diagram based on initial waist circumference and reduction of waist circumference, or by using 100 cm as a single cutoff for waist circumference after weight reduction induced by bariatric surgery.

First storage of ion beams in the Double Electrostatic Ion-Ring Experiment: DESIREE.

We report on the first storage of ion beams in the Double ElectroStatic Ion Ring ExpEriment, DESIREE, at Stockholm University. We have produced beams of atomic carbon anions and small carbon anion molecules (C(n)(-), n = 1, 2, 3, 4) in a sputter ion source. The ion beams were accelerated to 10 keV kinetic energy and stored in an electrostatic ion storage ring enclosed in a vacuum chamber at 13 K. For 10 keV C2 (-) molecular anions we measure the residual-gas limited beam storage lifetime to be 448 s ± 18 s with two independent detector systems. Using the measured storage lifetimes we estimate that the residual gas pressure is in the 10(-14) mbar range. When high current ion beams are injected, the number of stored particles does not follow a single exponential decay law as would be expected for stored particles lost solely due to electron detachment in collision with the residual-gas. Instead, we observe a faster initial decay rate, which we ascribe to the effect of the space charge of the ion beam on the storage capacity.

Visceral fat cell lipolysis and cardiovascular risk factors in obesity.

Visceral fat accumulation relates to cardiovascular risk factors, but the underlying mechanisms are not well understood. We investigated the role of visceral adipocyte triglyceride breakdown (lipolysis) for several risk factors of cardiovascular disease. In 73 obese women, fat mass and distribution, blood pressure, blood samples for cardiometabolic risk factors, and whole-body insulin sensitivity were determined. A subcutaneous and a visceral fat biopsy were taken. Fat cell glycerol release after stimulation with a major lipolytic hormone, noradrenaline, was measured. In simple regression analysis, visceral fat cell lipolysis, but not subcutaneous adipocyte lipolysis was related to components of the metabolic syndrome. Moreover, subjects in the highest quartile of catecholamine-induced visceral lipolysis had higher levels of systolic blood pressure, estimated liver fat, plasma levels of glucose, insulin, cholesterol, LDL-cholesterol, triglycerides and apolipoprotein B and lower whole-body insulin sensitivity than those in the lowest quartile (p=0.0004-0.048). Among subjects with the metabolic syndrome, visceral fat cell lipolysis was 40% higher than in the remaining subjects (p=0.0052). Catecholamine-activated lipolysis in visceral but not subcutaneous fat cells is associated with cardiovascular risk factors in obesity.

The double electrostatic ion ring experiment: a unique cryogenic electrostatic storage ring for merged ion-beams studies.

We describe the design of a novel type of storage device currently under construction at Stockholm University, Sweden, using purely electrostatic focussing and deflection elements, in which ion beams of opposite charges are confined under extreme high vacuum cryogenic conditions in separate "rings" and merged over a common straight section. The construction of this double electrostatic ion ring experiment uniquely allows for studies of interactions between cations and anions at low and well-defined internal temperatures and centre-of-mass collision energies down to about 10 K and 10 meV, respectively. Position sensitive multi-hit detector systems have been extensively tested and proven to work in cryogenic environments and these will be used to measure correlations between reaction products in, for example, electron-transfer processes. The technical advantages of using purely electrostatic ion storage devices over magnetic ones are many, but the most relevant are: electrostatic elements which are more compact and easier to construct; remanent fields, hysteresis, and eddy-currents, which are of concern in magnetic devices, are no longer relevant; and electrical fields required to control the orbit of the ions are not only much easier to create and control than the corresponding magnetic fields, they also set no upper mass limit on the ions that can be stored. These technical differences are a boon to new areas of fundamental experimental research, not only in atomic and molecular physics but also in the boundaries of these fields with chemistry and biology. For examples, studies of interactions with internally cold molecular ions will be particular useful for applications in astrophysics, while studies of solvated ionic clusters will be of relevance to aeronomy and biology.

Role of fat cell size for plasma leptin in a large population based sample.

Earlier studies suggest that fat mass is the only important factor predicting the circulating leptin level in humans. In this population based cross sectional study on 447 women and 158 men total fasting plasma leptin was related to adipose tissue mass and fat cell size to investigate the importance of adipose tissue cellularity. An abdominal subcutaneous fat biopsy was obtained and mean fat cell volume and mean fat cell weight and size were determined. Fasting serum Leptin and Leptin secretion in vitro was also measured. Body fat mass was measured by bioimpedance. Adipose tissue mass and fat cell size independently associated with leptin levels. Partial correlation coefficients were 0.6 (p<0.001) and 0.3 (p<0.01) for fat mass and fat cell size, respectively. Together they explained 2/3 of leptin variance (i. e., adjusted r (2)). Fat mass was a stronger regressor than fat cell volume. The relationship was independent of age, gender and adipocyte secretion of leptin (the latter determined in a subgroup of 391 individuals). In conclusion, although total fat mass is the strongest predictor of circulating leptin, adipose tissue cellularity play an additional independent and important role.

Lipolysis index: evaluation of a new tool for metabolic assessment in epidemiological studies on obesity.

Lipid mobilization through adipocyte lipolysis is central for energy metabolism and is decreased in obesity. However, the factors of importance for lipolytic activity in the general population are not known. To further examine this we performed a cross-sectional study on teenagers and adults. We constructed and evaluated a simple index of lipolytic activity (ratio of fasting p-glycerol and body fat %) in population based samples in 316 teenagers (BMI 16-51 kg/m (2)) and 3,039 adults (BMI 16-70 kg/m (2)). In the adults, multiple regression analysis showed that waist and BMI but not age, plasma insulin, plasma noradrenaline or waist-to-hip ratio contributed independently and inversely to lipolytic activity (partial r=-0.37 and -0.28, respectively, p<0.0001). Together waist and BMI explained about 45% of the variability of lipolysis. Waist was a stronger factor than BMI in stepwise regression. The same analysis in teenagers showed that only BMI contributed independently and inversely to lipolytic activity (partial r=-0.90, p<0.0001) and explained about 55% of lipolysis variation. BMI had the strongest effect on lipolysis in lean teenagers. The results were the same for men and women. At all levels of lipolytic activity plasma fatty acid levels were elevated in obese subjects (p<0.0001). We conclude that during adolescence BMI is the major factor negatively influencing lipolytic activity, in particular among lean young subjects. In adulthood central fat accumulation together with increasing BMI decreases lipolysis. In spite of low lipolytic activity circulating fatty acid levels are increased in obesity, probably due to an adipose mass effect.

Regional impact of adipose tissue morphology on the metabolic profile in morbid obesity.

AIMS/HYPOTHESIS: The aim of this study was to determine whether the mean size of fat cells in either visceral or subcutaneous adipose tissue has an impact on the metabolic and inflammatory profiles in morbid obesity. METHODS: In 80 morbidly obese women, mean visceral (omental) and subcutaneous fat cell sizes were related to in vivo markers of inflammation, glucose metabolism and lipid metabolism. RESULTS: Visceral, but not subcutaneous, adipocyte size was significantly associated with plasma apolipoprotein B, total cholesterol, LDL-cholesterol and triacylglycerols (p ranging from 0.002 to 0.015, partial r ranging from 0.3 to 0.4). Subcutaneous, but not visceral, adipocyte size was significantly associated with plasma insulin and glucose, insulin-induced glucose disposal and insulin sensitivity (p ranging from 0.002 to 0.005, partial r ranging from -0.34 to 0.35). The associations were independent of age, BMI, body fat mass or body fat distribution. Adipose tissue hyperplasia (i.e. many small adipocytes) in both regions was significantly associated with better glucose, insulin and lipid profiles compared with adipose hypertrophy (i.e. few large adipocytes) in any or both regions (p ranging from <0.0001 to 0.04). Circulating inflammatory markers were not associated with fat cell size or corresponding gene expression in the fat cell regions examined. CONCLUSIONS/INTERPRETATION: In morbidly obese women region-specific variations in mean adipocyte size are associated with metabolic complications but not systemic or adipose inflammation. Large fat cells in the visceral region are linked to dyslipidaemia, whereas large subcutaneous adipocytes are important for glucose and insulin abnormalities. Hyperplasia (many small adipocytes) in both adipose regions may be protective against lipid as well as glucose/insulin abnormalities in obesity.

Beta3-adrenoceptor function and long-term changes in body weight.

BACKGROUND: The endogenous factors contributing to long-term changes in body weight are not known but the regulation of energy metabolism by different beta-adrenoceptors (beta(1)-AR, beta(2)-AR, beta(3)-AR) or alpha-adrenoceptors (alpha(2)-AR) may play a role. METHODS: In a prospective study, we investigated beta-AR and alpha(2)-AR subtype function in subcutaneous fat cells of 85 healthy, non-obese women by using a standardized bioassay of lipolysis. Of these 73 were re-investigated on an average 10 years later to compare baseline function of beta(1)-AR, beta(2)-AR, beta(3)-AR and alpha(2)-AR with longitudinal weight changes. RESULTS: Weight change over time was normally distributed ranging from-4 kg/m(2) to +6 kg/m(2) in body mass index. Long-term changes in body weight correlated inversely with beta(3)-AR function at base line (r=0.5, P=0.001). Those with low beta(3)-AR function gained weight, whereas the opposite was observed with those who had a high beta(3)-AR function. Nineteen percent of weight changes could be explained by beta(3)-AR status. No relationship with weight changes was observed as regards the function of alpha(2)-AR, beta(1)-AR or beta(2)-AR function. CONCLUSIONS: Beta(3)-ARs are important for long-term changes in body weight putting energy metabolism in adipose tissue in frontline among endogenous factors that regulate body weight in adulthood.

Impaired subcutaneous adipocyte lipogenesis is associated with systemic insulin resistance and increased apolipoprotein B/AI ratio in men and women.

OBJECTIVES: To study the association between subcutaneous fat cell lipogenesis and components of the metabolic syndrome (systemic insulin resistance, dyslipidaemia and hypertension). DESIGN AND SETTING: A university hospital-based cross-sectional study of 383 subjects (303 women and 80 men) with a wide range of BMI (18-53 kg m(-2)). RESULTS: Strong negative correlations between in vitro fat cell lipogenesis (basal and after maximal insulin stimulation) and HOMA-IR were present in both genders (r = -0.42 to -0.56, P < 0.0001 and r = -0.37 to -0.44, P < 0.001, for women and men respectively). Insulin sensitivity measured using the insulin tolerance test (K(ITT)) was also correlated with adipocyte lipogenesis (r = 0.47-0.57, P < 0.0001, women, r = 0.52-0.70, P < 0.001, men). Plasma apolipoprotein B/AI-ratio negatively associated with fat cell lipogenesis in women (r = -0.41 to-0.51, P < 0.0001,) and men (r = -0.49 to -0.55, P < 0.0001). The negative relationship of fat cell lipogenesis with blood pressure was significant in women (r = -0.27 to -0.28, P < 0.0002,) but not in men (P = 0.08-0.09). All correlations remained significant after adjusting for differences in fat cell volume, body mass index, waist- to hip- ratio or age (P < 0.01). CONCLUSIONS: Subcutaneous adipocyte lipogenesis is negatively associated with systemic insulin resistance, plasma apolipoprotein B/AI-ratio and blood pressure supporting the view that impaired fat cell function per se may contribute to the development of the metabolic syndrome.

No difference in lipolysis or glucose transport of subcutaneous fat cells between moderate-fat and low-fat hypocaloric diets in obese women.

The objective of the present study was to evaluate the effect of two different diets on lipolysis and lipogenesis in subcutaneous fat cells from obese women. In a ten-week nutritional intervention study, forty women were randomly assigned to a hypoenergetic-2,514 kJ (- 600 kcal/day) diet of either moderate-fat/moderate-carbohydrate or low-fat/high-carbohydrate content. Body weight was equally reduced by approximately 7.5 % in both diet groups (p = 0.58). A subcutaneous adipose tissue biopsy was obtained for subsequent measurement of triglyceride breakdown (lipolysis) using drugs active at different steps of the lipolytic signaling cascade, and lipid synthesis (glucose transport) before and after intervention. No difference was found between the two diet groups at the maximum rate of either lipolysis or adrenoceptor sensitivity (p-values: 0.14 - 0.97). Inhibition of lipolysis by insulin was also similar in both diet groups before and after intervention. Finally, insulin-stimulated glucose transport did not show any changes that could be attributed to the type of diet. In conclusion, our data suggest that macronutrient diet composition has no major influence on glucose transport or mobilization of triglycerides in human subcutaneous fat cells of obese women.

Prospective and controlled studies of the actions of insulin and catecholamine in fat cells of obese women following weight reduction.

AIMS/HYPOTHESIS: Enlarged fat cells from obese subjects are characterised by insulin resistance and abnormal adrenergic regulation of lipolysis. The aim of the present study was to examine whether these aberrations return to normal following weight reduction. MATERIALS AND METHODS: Obese women (n=25) were investigated before and 3+/-1 years (mean+/-SD) after steady-state weight reduction and compared with control women who were matched to the cases at re-examination in terms of age and BMI. Adipocyte volume, lipogenesis and lipolysis were determined in isolated subcutaneous fat cells following stimulation or inhibition at different steps of the lipolytic cascade. RESULTS: Weight reduction decreased fat cell volume and basal and adrenergic-regulated lipolysis rates to values that were 20-40% lower than those in control women (p=0.0002-0.03), despite the fact that percentage body fat was almost identical in the two groups of women. Fat cell volume was directly proportional to lipolysis in obese subjects, both before and after weight reduction, and in control subjects. Insulin-induced antilipolysis and lipogenesis were completely normalised after weight reduction. CONCLUSIONS/INTERPRETATION: Body-weight-reduced obese women had low basal and catecholamine-stimulated adipocyte lipolysis, presumably due to adipose tissue hyperplasia. This could make an important contribution to body weight gain following weight loss. Adipocyte insulin resistance is secondary to obesity.

Evidence for an important role of perilipin in the regulation of human adipocyte lipolysis.

AIMS/HYPOTHESIS: We investigated the role of the adipocyte-specific protein perilipin for lipolysis in humans. METHODS: Perilipin protein content and lipolysis rates were measured in human subcutaneous fat cells of non-obese (n=10) and obese (n=117) women. Single nucleotide polymorphisms in the perilipin gene were examined in obese subjects. RESULTS: Basal and noradrenaline-induced rates of lipolysis were two to fourfold increased (p<0.01) and perilipin protein content decreased 50% (p=0.005) in adipocytes of the obese women. In subjects matched for body mass index and fat-cell volume, a high rate of lipolysis was associated with a low adipocyte content of perilipin (p=0.01). Adipocyte content of perilipin was inversely correlated with the circulating concentrations of glycerol (r=0.62) and non-esterified fatty acids (n=0.49). A gene polymorphism (rs891460 A/G) in intron 6 was common. In AA subjects basal and noradrenaline induced lipolysis were 50 to 100% times more rapid (p

Polymorphism in the Calpain 10 gene influences glucose metabolism in human fat cells.

AIMS/HYPOTHESIS: A common G to A polymorphism ( UCSNP-43) in the Calpain 10 gene was recently found to be associated with Type II (non-insulin-dependent) diabetes mellitus and variations in post-absorptive and insulin stimulated glucose metabolism in vivo. We aimed to study the influence of Calpain 10 polymorphism on insulin action in fat cells. METHODS: Calpain 10 polymorphism ( UCSNP-19, -43 or -63) were set in relation to lipolysis and lipogenesis in isolated subcutaneous adipocytes of 46 apparently healthy non-obese subjects. RESULTS: For UCSNP-43 the G/G genotype had twofold higher basal and insulin stimulated rates as compared with AA/AG genotypes. However, there was no genotype effect on basal or insulin inhibited lipolysis rates in fat cells. The protein amount of GLUT 4 in adipocytes was not influenced by the polymorphism. Fat cells expressed mRNA for the Calpain 10 gene at a relatively high concentration, about 4 amol/microg RNA, which is similar to that of uncoupling protein-2. Neither a UCSNP-19 nor a UCSNP-63 polymorphism in the Calpain 10 gene was found to be associated with basal or insulin-induced adipocyte lipolysis and lipogenesis. None of the polymorphisms influenced body mass index or fasting plasma concentrations of insulin and glucose in 693 non-obese healthy subjects. CONCLUSIONS/INTERPRETATION: The Calpain 10 gene could be involved in the regulation of glucose metabolism but not lipolysis in human fat cells, although it does not involve adipocyte GLUT-4 protein content. It is possible that the Calpain 10 gene predisposes to diabetes by influencing the glucose metabolism.

Secretion of tumor necrosis factor-alpha shows a strong relationship to insulin-stimulated glucose transport in human adipose tissue.

Some animal models suggest that tumor necrosis factor (TNF)-alpha is a key component in obesity-linked insulin resistance because it inhibits insulin receptor signaling and glucose transport in insulin-sensitive tissues. However, in vivo data in humans have given conflicting results regarding the relationship between circulating TNF-alpha levels and insulin sensitivity. In the present study, the potential local role of TNF-alpha on insulin action in human subcutaneous adipose tissue was studied in 42 obese women (BMI 39+/-10 kg/m2). We found a strong inverse correlation between adipose TNF-alpha secretion and maximum insulin-stimulated glucose transport in adipocytes that was independent of fat cell volume, age, and BMI (P < 0.001, r = 0.58). As much as one-third of the variation in insulin-stimulated glucose transport could be accounted for by variations in TNF-alpha secretion. There was no significant correlation (r = 0.11) between secretion of adipose plasminogen activator inhibitor 1 and glucose transport. Furthermore, subcutaneous adipose tissue of 4 obese women (BMI 40+/-4) incubated with TNF-A for 24 h showed a one-third concentration-dependent inhibition of insulin-stimulated glucose transport (P < 0.01). In conclusion, adipose TNF-alpha may be an important specific and local factor in adipose tissue that influences the ability of insulin to stimulate glucose transport in human fat cells, at least in obese women.

Technical aspects of left-sided pancreatic resection for cancer.

Adenocarcinoma of the pancreas that originates to the left of the portal vein, i.e. in the body or tail of the pancreas, is seen in approximately one third of all cases with exocrine pancreatic cancer. Except for symptoms of pain and weight loss, these patients usually appear normal upon physical examination. In 5-10% of cases, the tumor is resectable by standard surgical procedures. Unresectability is due to local spread (30-40%) or distant metastases (50-65%). The technique of distal pancreatic resection was outlined by Mayo in 1913. The intimate relationship of the splenic artery and vein to the body of the pancreas makes en bloc mobilization of the spleen and pancreatic tail a safe option; the splenic artery and vein being ligated near their origin and termination. Although the spleen can frequently be preserved when performing a distal pancreatectomy for benign disease, splenic artery preservation is hazardous for oncologic radicality when resection is performed for cancer. Therefore, splenectomy is routine in distal pancreatectomy - in Mayo's and all subsequent descriptions - with the splenic artery being ligated early in the procedure. Recent reports from specialized centers indicate that the procedure is associated with a decrease in mortality rate, often zero or less than a few percent.

Adsorption and coadsorption of water and glycine on TiO2.

Adsorption of water, ions, and biomolecules constitutes the first events occurring at biomaterial-biosystem interfaces. In this work, the adsorption and coadsorption of water and glycine on TiO2 were studied by thermal desorption spectroscopy (TDS). The first water monolayer desorbs in three peaks around 180K, 300K, and 400K, which are assigned to water molecularly adsorbed at oxygen sites, at Ti4+ sites, and to recombination of dissociated water, respectively. A fourth desorption peak (160K), appearing at coverages > 0.8 monolayer, is attributed to water clusters and multilayers. The water-TiO2 interaction is changed if the surface is annealed in vacuum, which leads to increased hydroxylation. Desorption spectra from glycine overlayers evaporated on TiO2 in situ show that around 40% of the first monolayer desorbs as intact molecules ( approximately 300-450 K) and the remainder as dissociation fragments and surface reaction products around 600 K. At coverages > 0.6 monolayers, intact molecules desorbing from cluster multilayers at 310 K are detected. The glycine desorption spectra are unaffected by coadsorbed water. In contrast, coadsorption of glycine displaces water from more strongly bound states in the monolayer to more weakly bound states and clusters, making the surface more hydrophobic. The study shows that TDS is a powerful method for characterizing biomaterial surfaces with regard to their interaction with biologically relevant molecules.