Observation of Efficient Lower Hybrid Current Drive at High Density in Diverted Plasmas on the Alcator C-Mod Tokamak.

Efficient lower hybrid current drive (LHCD) is demonstrated at densities up to n[over ¯]_{e}≈1.5×10^{20} m^{-3} in diverted plasmas on the Alcator C-Mod tokamak by operating at increased plasma current-and therefore reduced Greenwald density fraction. This density exceeds the nominal "LH density limit" at n[over ¯]_{e}≈1.0×10^{20} m^{-3} reported previously, above which an anomalous loss of current drive efficiency was observed. The recovery of current drive efficiency to a level consistent with engineering scalings is correlated with a reduction in density shoulders and turbulence levels in the far scrape-off layer. Concurrently, rf wave interaction with the edge and/or scrape-off-layer plasma is reduced, as indicated by a minimal broadening of the wave frequency spectrum measured at the plasma edge. These results have important implications for sustaining steady-state tokamak operation and indicate a pathway forward for implementing efficient LHCD in a reactor.

Human xylosyltransferase-I - a new marker for myofibroblast differentiation in skin fibrosis.

Skin fibrosis is a severe type of fibrotic disorder emerging in terms of hypertrophic scars or systemic sclerosis. Key event of fibrogenesis is the transition of fibroblasts to matrix-producing myofibroblasts. In the presence of fibrotic triggers, for instance secretion of profibrotic growth factors like transforming growth factor-ß1 (TGF-ß1) or mechanical strain, myofibroblasts persist. Current research focuses on discovering innovative myofibroblast biomarkers which are regulated in fibrotic development and accessible for antifibrotic inhibition. Here, we consider the suitability of xylosyltransferase-I (XT-I) as a myofibroblast biomarker in skin fibrosis. XT-I catalyzes the initial step of glycosaminoglycan biosynthesis. Its increase in enzymatic activity is known to refer only to manifested diseases which are characterized by an abnormal rate of proteoglycan biosynthesis. In this study, treatment of normal human dermal fibroblasts (NHDF) with TGF-ß1 was followed by increased relative XYLT1 mRNA expression. Remarkably, this upregulation was strongly dependent on myofibroblast content, increasing during fibrogenesis. Moreover, XT activity increased time-dependently in response to progressive myofibroblast transformation. XYLT1 expression was inhibited by TGF-ß receptor I (ALK5) inhibitor SB431542. In contrast, XYLT2 expression was only marginally affected by TGF-ß1 as well as ALK5 inhibition. Our results strengthen the significance of XT expression and activity in fibrotic remodeling. Therefore, we propose XT activity, in addition to α-SMA expression, as a new biomarker for myofibroblast differentiation and fibrotic development. Further studies are now needed to evaluate the option to control and inhibit fibrotic remodeling by interfering with XT expression.

Adipose tissue regeneration following lipectomy.

Surgical removal of subcutaneous fat depots in weanling rats leads to a regenerative response. If the rats are fed a diet high in fat, adipose mass and adipocyte number are precisely restored within 7 months of surgery. Thus, under appropriate experimental circumstances, compensatory hyperplasia will occur in adipose tissues of the rat.

Surgical removal of adipose tissue alters feeding behavior and the development of obesity in rats.

Lipectomized and sham-operated rats were fed a high-fat diet to induce hyperphagia and rapid fat accumulation. Lipectomized rats with 25% fewer adipocytes were less hyperphagic and accumulated less fat, but their adipocytes remained equal in size to adipocytes of controls. A role for adipocyte size in fat storage regulation and food intake control is postulated.

A virally induced obesity syndrome in mice.

An obesity syndrome was found in a number of mice infected as young adults with canine distemper virus, a morbillivirus antigenically related to measles. Body weights of obese animals 16 to 20 weeks after infection were comparable to those reported for genetically obese mice and for mice rendered obese by hypothalamic lesions. The total number of adipocytes in specific fat deposits was greater in obese animals than in their lean littermates. This hyperplasia was accompanied by moderate cell enlargement. Pancreatic islet tissue was also hypercellular in the obese mice. Brain tissue from the obese mice showed no overt pathology, and immunofluorescence staining for viral antigens was negative. There may be a selective, virus-induced disruption of critical brain catecholamine pathways.

Heart Transplantation in Systemic Sclerosis: New Impulses for Conventional Scleroderma Transplantation Regimen and Scleroderma Diagnostic Monitoring: 2 Case Reports.

BACKGROUND: Although low (but increasing) rates of lung/lung-heart transplantations of scleroderma (systemic sclerosis [SSc]) patients have been reported, exclusive heart transplantation is a rare approach for treatment of heart failure due to SSc. CASES: We report on 2 cases of SSc patients receiving a heart transplantation (HTx) due to severe and progressive right heart failure without pulmonary artery hypertension. One patient received a hepatitis C virus (HCV)-positive donor heart and recovered excellently from viral transmission after administration of a direct-acting antiviral (DAA) regimen. This is the first published case of an SSc patient who underwent HTx using an HCV-positive donor heart. The clinical course of both patients was monitored by different serum SSc biomarkers. Only xylosyltransferase activity proved to be a promising biomarker for disease stage determination and therapeutic monitoring, precisely reflecting fibrotic remodeling and successful organ recovery. CONCLUSIONS: Successful implementation of the 2 cases described here demonstrates that HTx is a safe and effective therapeutic option for defined SSc sub-patient groups despite the progressive character of the underlying disease. In the future, xylosyltransferase activity might be conducive to simplify the identification of patients with low systemic involvement but a strong indication for single heart transplantation. Finally, we demonstrate that treatment of HCV viral transmission from HCV-positive donor to organ recipient using DAA gives us new opportunities to consider HCV-positive donor organs for HTx and might reveal new possibilities to ease the lack of donor organs.

Occupational risk factors for acute leukaemia: a case-control study.

A case-control study has been performed for occupational risk factors of acute leukaemia, based on 185 cases more than 30 years old and 513 matched controls. There was a significant excess of polyvalent farming and electronic engineers among professions of cases, and, in addition of metal workers when considering the professions pursued for more than 5 years. The corresponding exposures were analysed through a detailed questionnaire, and assessed by an industrial hygienist after blinding the case-control status. The odds ratios (OR) were computed after adjustment on matching variables and prior chemo- or radiotherapy treatment, and after stratification for the level and total duration of exposure. There was no excess of professional exposure to ionizing radiation among cases. A significant relationship was observed between acute leukaemia and high or medium exposure to benzene, as well as over 10 years high or medium exposure to exhaust gas. In addition a significant relationship was observed with exposure to pesticides--insecticides and/or weed killers--and to electric and magnetic fields (EMF). The relationship with pesticides was significant when considering high or medium exposure to weed killers and more than 10 years exposure to both subtypes of pesticides. The relationship with pesticides and EMF remained significant when confounding factors were taken into consideration and after adjustment on co-exposure to benzene. The cytological studies showed that acute leukaemias following exposure to benzene (high or medium) and to EMF were only of myelogenous subtypes, whereas those following exposure to pesticides were divided between lymphoblastic and myeloblastic subtypes. Cytogenetic studies failed to show increased frequency of chromosomal abnormalities, as described in acute leukaemias secondary to anti-cancer treatments. Our study adds credence to the hypothesis that pesticides and EMF are leukaemogenic agents, together with benzene.

Effects of castration on adipose tissue growth and regrowth in the male rat.

Adipose tissue has been found to regrow in the male rat following surgical removal (lipectomy) of inguinal subcutaneous depots, but the degree of regrowth has varied widely across experiments. It is possible that at least part of the disparity of previous findings occurred because of differences among the experiments in the testicular integrity of experimental animals. To address this possibility, the present study examined effects of castration on adipose tissue regrowth in rats treated either as weanlings or as young adults. Male Sprague-Dawley rats, at either 4 or 15 weeks of age, were subjected to one of four surgical procedures: bilateral lipectomy of the inguinal subcutaneous depots; castration; lipectomy and weight gain, but castrated rats achieved a higher ratio of adipose weight to body weight than noncastrated rats. In rats lipectomized but not castrated at 15 weeks of age, partial regeneration and a small increase in growth of noninguinal subcutaneous adipose tissue combined to produce substantial restoration of adipose mass. The same surgery in 4-week-old rats did not result in significant restoration because growth of noninguinal subcutaneous adipose tissue was reduced. In rats that were both castrated and lipectomized, regrowth of adipose tissue was substantial regardless of age at time of surgery. Thus, castration is seen to impede body weight gain while sparing ordinary growth of adipose tissue and facilitating regrowth of adipose tissue following lipectomy. Since adipose tissue regrowth varied with age only in noncastrated rats, it appears to be facilitated as well by testicular maturation.

Effects of palatable diets on body weight and adipose tissue cellularity in the adult obese female Zucker rat (fa/fa).

Obese 7-8 mo-old female Zucker rats (fa/fa) and their lean littermates (Fa/-) exhibited the same percentage increase in body weight during a 50-day period when both groups of animals were fed a highly palatable snack food diet (SF). A subsequent 50-day period of refeeding with standard laboratory chow caused rats of both genotypes to shed the excess weight gained on SF. These findings suggest that lean and obese Zucker female rats are comparably responsive to a highly palatable diet. When a second group of female fa/fa rats were fed either SF or another palatable, semipurified high fat diet for 135 days, beginning at 2-3 mo of age, they were found to have substantially more fat cells in all depots studied than did female (fa/fa) rats that had been fed only chow. Thus, the obese Zucker rat is also comparable to normal rats with respect to the phenomenon of diet-induced adipocyte hyperplasia.

Meal-taking behavior is related to predisposition to dietary obesity in the rat.

The hypothesis that early nutritional experience can determine endogenous patterns of meal-taking behavior and thereby affect predisposition to dietary obesity was tested by raising male Sprague-Dawley rats in litters of 4, 8, and 20, and examining their meal patterns and responsiveness to a high-fat, high-sugar (HFS) diet in adulthood. At 9 months of age, half the rats from each litter size group were given the HFS diet for 16 weeks, while the other half were continued on laboratory chow. As expected, HFS-fed rats gained more weight and developed larger fat depots and more and larger fat cells than did chow-fed controls. Analysis of meal-taking behavior just prior to the introduction of HFS-feeding allowed some of the rats to be classified as "gorgers" or "nibblers" according to their average daily meal size. While on lab chow, gorgers and nibblers showed no differences in body weight gain, but upon being switched to the HFS diet, gorgers gained significantly more weight than did nibblers, and showed a greater degree of fat depot enlargement. These findings suggest that patterns of meal-taking behavior can predict the magnitude of and may contribute to the development of dietary obesity.

High-resolution tangential absolute extreme ultraviolet arrays for radiated power density measurements on NSTX-U.

The radiated-power-density diagnostic on the equatorial midplane for the NSTX-U tokamak will be upgraded to measure the radial structure of the photon emissivity profile with an improved radial resolution. This diagnostic will enhance the characterization and studies of power balance, impurity transport, and MHD. The layout and response expected of the new system is shown for different plasma conditions and impurity concentrations. The effect of toroidal rotation driving poloidal asymmetries in the core radiation from high-Z impurities is also addressed.

Two-dimensional AXUV-based radiated power density diagnostics on NSTX-U.

A new set of radiated-power-density diagnostics for the National Spherical Torus Experiment Upgrade (NSTX-U) tokamak have been designed to measure the two-dimensional poloidal structure of the total photon emissivity profile in order to perform power balance, impurity transport, and magnetohydrodynamic studies. Multiple AXUV-diode based pinhole cameras will be installed in the same toroidal angle at various poloidal locations. The local emissivity will be obtained from several types of tomographic reconstructions. The layout and response expected for the new radially viewing poloidal arrays will be shown for different impurity concentrations to characterize the diagnostic sensitivity. The radiated power profile inverted from the array data will also be used for estimates of power losses during transitions from various divertor configurations in NSTX-U. The effect of in-out and top/bottom asymmetries in the core radiation from high-Z impurities will be addressed.

Nutrition and the fat cell.

Nutrition and adipose cellularity are considered in terms of possible effects of nutrition on the fat cell and of the fat cell in nutrition. Studies are reported from which it is concluded that change in dietary energy intake occuring in response to a change in the palatability or accessability of diet may be a function of both fat cell number and fat cell size. It is possible that excessive fat cell production is a device used for coping with some disorder. But in cases where diet is the likely cause of excessive fat cell production it may be possible eventually to isolate components of the diet as responsible rather than ordering restriction of total energy intake.

Alterations in rat adipose tissue morphology induced by a low-temperature environment.

Rats raised in the cold showed an unusual pattern of adipose tissue morphology. Male Sprague-Dawley rats were maintained in a 5 degrees C environment for up to 24 wk and the cellularity of their major adipose depots was determined. Normal age-related increases in adipocyte number were absent in two major fat depots (retroperitoneal and inguinal), whereas there was a supranormal increase in a third (epididymal). This pattern of hyperplasia contrasts sharply with that seen in rats fed highly palatable high-fat or high-carbohydrate diets in which retroperitoneal depots show the most hyperplasia and epididymal pads the least. Such variations of response across depots suggest that the features of adipose tissue responsible for adipocyte proliferation in the various depots may not be homogeneous both in their nature and in their distribution.

Effects of diet and environment on adipocyte development.

Induction of adipocyte hyperplasia in the rat is dependent on factors such as hormones, circulating metabolic substrates, fat cell size, and qualitative aspects of the cells in a given depot. Analysis of the specific factors which promote hyperplasia under the different circumstances of diet and environment are discussed and may help towards an understanding of the hyperplastic process in man which may eventually lead to the possibility of intervention.

Resistance to adipocyte hyperplasia in ground squirrels given high-fat diets.

Mammalian hibernators prepare for the winter by depositing fat in existing fat cells. There is little, if any, production of new fat cells. This is curious because equivalent fat deposition in rats is associated with substantial fat cell production. To determine whether degree of weight gain, diet composition, or some special mechanism militating against adipocyte hyperplasia may underlie the absence of adipocyte hyperplasia in hibernators, male Richardson's ground squirrels, Spermophilus richardsonii, were fed a fattening high-fat diet for either 5 mo or 1 yr. The 5-mo high-fat feeding period caused peak body weights to increase 36% relative to the peak body weights seen in control animals fed ordinary chow. Despite this increase, there was no apparent increment in fat cell number in any of the major fat depots. Animals fed the diet for 1 yr reached body weights similar to those of the 5-mo group but showed significant adipocyte hyperplasia in all fat depots studied. Thus adult ground squirrels are clearly capable of enlarging their pool of mature fat cells, but they fail to do so, at least at certain times, in response to conditions of weight gain that cause considerable adipocyte hyperplasia in rats.

Cycles of body fat in hibernators.

This paper reviews data on seasonal changes in body fat of mammalian hibernators. It then presents data on the fat cell number and size in the retroperitoneal and gonadal fat depots of dormice, Glis glis, over the course of their body weight cycles. Enlargement of fat cell size is the principal way that hibernators get fat. The hibernator cycle may provide a way of discovering whether regulation of fat level is achieved through regulation of total mass of fat or through regulation of the size of existing adipocytes.