AGS slow extracted beam improvement

The Brookhaven AGS is a strong focusing accelerator which is used to accelerate protons and various heavy ion species to an equivalent proton energy of 29 GeV. Since the late 1960`s it has been serving high energy physics (HEP - proton beam) users of both slow and fast extracted beams. The AGS fixed target program presently uses primary proton and heavy ion beams (HIP) in slowly extracted fashion over spill lengths of 1.5 to 4.0 seconds. Extraction is accomplished by flattoping the main and extraction magnets and exciting a third integer resonance in the AGS. Over the long spill times, control of the subharmonic amplitude components up to a frequency of 1 kilohertz is very crucial. One of the most critical contributions to spill modulation is due to the AGS MMPS. An active filter was developed to reduce these frequencies and it`s operation is described in a previous paper. However there are still frequency components in the 60-720 Hz sub-harmonic ripple range, modulating the spill structure due to extraction power supplies and any remaining structures on the AGS MMPS. A recent scheme is being developed to use the existing tune-trim control horizontal quadrupole magnets and power supply to further reduce these troublesome noise sources. Feedback from an external beam sensor and overcoming the limitations of the quadrupole system by lead/lag compensation techniques will be described

Test fast kicker pulser

In this paper, a test pulser of the Brookhaven AGS Booster extraction fast kicker is described. The pulser is projected for both proton and heavy ion operation. A load of total inductance 2.15 /mu/H is used for the test pulser. The PFN voltage is required to be below 40 kV for operation in air. Rise time of the pulse for proton extraction operation is about 120ns up to 97% of full current (1000A), and, for heavy ion extraction, 160ns up to 98% of full current (1615A). R-C compensation networks are used for pulse front edge sharpening. The flexibility of operation is obtained basically by switching an energy dumping resistor to match or mismatch the PFN impedance. Some comments on stray capacitance and stray inductance effects are included. 3 refs., 10 figs., 2 tabs

Limits on the production of neutral penetrating states in a beam dump

We present limits on the production of neutral penetrating states produced in 28 GeV proton nucleus collisions. We obtain limits for light, heavy and unstable neutral states. For light stable states our limit [sigma]I[sigma]P-69cm4/nucleon2 is more than a factor of 5.5 better than previous limits. Time of flight techniques are used to study heavy states. We have poor sensitivity to short-lived states.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24349/1/0000616.pd

Role of Receptor-Interacting Protein 140 in human fat cells

<p>Abstract</p> <p>Background</p> <p>Mice lacking <it>Receptor-interacting protein 140 (RIP140) </it>have reduced body fat which at least partly is mediated through increased lipid and glucose metabolism in adipose tissue. In humans, <it>RIP140 </it>is lower expressed in visceral white adipose tissue (WAT) of obese versus lean subjects. We investigated the role of <it>RIP140 </it>in human subcutaneous WAT, which is the major fat depot of the body.</p> <p>Methods</p> <p>Messenger RNA levels of <it>RIP140 </it>were measured in samples of subcutaneous WAT from women with a wide variation in BMI and in different human WAT preparations. <it>RIP140 </it>mRNA was knocked down with siRNA in <it>in vitro </it>differentiated adipocytes and the impact on glucose transport and mRNA levels of target genes determined.</p> <p>Results</p> <p><it>RIP140 </it>mRNA levels in subcutaneous WAT were decreased among obese compared to lean women and increased by weight-loss, but did not associate with mitochondrial DNA copy number. <it>RIP140 </it>expression increased during adipocyte differentiation <it>in vitro </it>and was higher in isolated adipocytes compared to corresponding pieces of WAT. Knock down of <it>RIP140 </it>increased basal glucose transport and mRNA levels of <it>glucose transporter 4 </it>and <it>uncoupling protein-1</it>.</p> <p>Conclusions</p> <p>Human <it>RIP140 </it>inhibits glucose uptake and the expression of genes promoting energy expenditure in the same fashion as the murine orthologue. Increased levels of human <it>RIP140 </it>in subcutaneous WAT of lean subjects may contribute to economize on energy stores. By contrast, the function and expression pattern does not support that <it>RIP140 </it>regulate human obesity.</p

Heterogeneity in the physiological states and pharmacological responses of differentiating 3T3-L1 preadipocytes

A systems biology–based analysis shows that differentiating adipocytes look very different at the single-cell level and form distinct cellular subpopulations

A MicroRNA Linking Human Positive Selection and Metabolic Disorders

Postponed access: the file will be accessible after 2021-10-14Positive selection in Europeans at the 2q21.3 locus harboring the lactase gene has been attributed to selection for the ability of adults to digest milk to survive famine in ancient times. However, the 2q21.3 locus is also associated with obesity and type 2 diabetes in humans, raising the possibility that additional genetic elements in the locus may have contributed to evolutionary adaptation to famine by promoting energy storage, but which now confer susceptibility to metabolic diseases. We show here that the miR-128-1 microRNA, located at the center of the positively selected locus, represents a crucial metabolic regulator in mammals. Antisense targeting and genetic ablation of miR-128-1 in mouse metabolic disease models result in increased energy expenditure and amelioration of high-fat-diet-induced obesity and markedly improved glucose tolerance. A thrifty phenotype connected to miR-128-1-dependent energy storage may link ancient adaptation to famine and modern metabolic maladaptation associated with nutritional overabundance.acceptedVersio

PKCε Stimulated Arginine Methylation of RIP140 for Its Nuclear-Cytoplasmic Export in Adipocyte Differentiation

Receptor interacting protein 140 (RIP140) is a versatile transcriptional co-repressor that plays roles in diverse metabolic processes including fat accumulation in adipocytes. Previously we identified three methylated arginine residues in RIP140, which rendered its export to the cytoplasm; but it was unclear what triggered RIP140 arginine methylation.In this study, we determined the activated PKCepsilon as the specific trigger for RIP140 arginine methylation and its subsequent export. We identified two PKCepsilon-phosphorylated residues of RIP140, Ser-102 and Ser-1003, which synergistically stimulated direct binding of RIP140 by 14-3-3 that recruited protein arginine methyl transferase 1 to methylate RIP140. The methylated RIP140 then preferentially recruited exportin 1 for nuclear export. As a result, the nuclear gene-repressive activity of RIP140 was reduced. In RIP140 null adipocyte cultures, the defect in fat accumulation was effectively rescued by the phosphorylation-deficient mutant RIP140 that resided predominantly in the nucleus, but less so by the phospho-mimetic RIP140 that was exported to the cytoplasm.This study uncovers a novel means, via a cascade of protein modifications, to inactivate, or suppress, the nuclear action of an important transcription coregulator RIP140, and delineates the first specific phosphorylation-arginine methylation cascade that could alter protein subcellular distribution and biological activity

Comprehensive Gene-Expression Survey Identifies Wif1 as a Modulator of Cardiomyocyte Differentiation

During chicken cardiac development the proepicardium (PE) forms the epicardium (Epi), which contributes to several non-myocardial lineages within the heart. In contrast to Epi-explant cultures, PE explants can differentiate into a cardiomyocyte phenotype. By temporal microarray expression profiles of PE-explant cultures and maturing Epi cells, we identified genes specifically associated with differentiation towards either of these lineages and genes that are associated with the Epi-lineage restriction. We found a central role for Wnt signaling in the determination of the different cell lineages. Immunofluorescent staining after recombinant-protein incubation in PE-explant cultures indicated that the early upregulated Wnt inhibitory factor-1 (Wif1), stimulates cardiomyocyte differentiation in a similar manner as Wnt stimulation. Concordingly, in the mouse pluripotent embryogenic carcinoma cell line p19cl6, early and late Wif1 exposure enhances and attenuates differentiation, respectively. In ovo exposure of the HH12 chicken embryonic heart to Wif1 increases the Tbx18-positive cardiac progenitor pool. These data indicate that Wif1 enhances cardiomyogenesis