Catalytic cyclization and competitive deactivation with Ru(P\u3csup\u3eR\u3c/sup\u3e2N\u3csup\u3eR′\u3c/sup\u3e2) complexes

The first successful use of the PR2NR′2 (1,5-R′-3,7-R-1,5-diaza-3,7-diphosphacyclooctane) ligand family toward an organic synthesis is described. The precatalysts [Ru(Cp)(PR2NBn2)(MeCN)]PF6 are active toward cyclization of 2-ethynylbenzyl alcohol at low catalyst loading and mild temperatures. Catalyst performance however is limited by both low conscription and by competitive deactivation

Catalytic Acceptorless Dehydrogenation of Amines with Ru(P\u3csup\u3eR\u3c/sup\u3e2N\u3csup\u3eR′\u3c/sup\u3e2) and Ru(dppp) Complexes

[Ru(Cp)(PPh2NBn2)(MeCN)]PF6 (1; PPh2NBn2 = 1,5-benzyl-3,7-phenyl-1,5-diaza-3,7-diphosphacyclooctane) and [Ru(Cp)(dppp)(MeCN)]PF6 (2; dppp = 1,3-bis(diphenylphosphino)propane) are both active toward the acceptorless dehydrogenation of benzylamine (BnNH2) and N-heterocycles. The two catalysts have similar activities but different selectivities for dehydrogenation products. Independent synthesis of a [Ru(Cp)(PPh2NBn2)(NH2Bn)]PF6 adduct (3) reveals the presence of a hydrogen bond between the bound amine and the pendent base of the PPh2NBn2 ligand. Preliminary mechanistic studies reveal that the benzylamine adduct is not an on-cycle catalyst intermediate

Phosphine-imine and-enamido ligands for acceptorless dehydrogenation catalysis

A highly tunable phosphine-imine ligand family is introduced. Following metallation with ruthenium, deprotonation of the ligand affords a phosphine-enamido species. Complexes with the ligand in both the imine and enamido forms are active toward acceptorless dehydrogenation reactions

Contact Discontinuities in Models of Contact Binaries Undergoing Thermal Relaxation Oscillations

In this paper we pursue the suggestion by Shu, Lubow & Anderson (1979) and Wang (1995) that contact discontinuity (DSC) may exist in the secondary in the expansion TRO (thermal relaxation oscillation) state. It is demonstrated that there is a mass exchange instability in some range of mass ratio for the two components. We show that the assumption of {\it constant} volume of the secondary should be relaxed in DSC model. For {\it all} mass ratio the secondary alway satisfies the condition that no mass flow returns to the primary through the inner Lagrangian point. The secondary will expand in order to equilibrate the interaction between the common convective envelope and the secondary. The contact discontinuity in contact binary undergoing thermal relaxation does not violate the second law of thermodynamics. The maintaining condition of contact discontinuity is derived in the time-dependent model. It is desired to improve the TRO model with the advanced contact discontinuity layer in future detailed calculations.Comment: 5 pages in emulateapj, 1 figur

Can airborne ultrasound monitor bubble size in chocolate?

Aerated chocolate products consist of solid chocolate with the inclusion of bubbles and are a popular consumer product in many countries. The volume fraction and size distribution of the bubbles has an effect on their sensory properties and manufacturing cost. For these reasons it is important to have an online real time process monitoring system capable of measuring their bubble size distribution. As these products are eaten by consumers it is desirable that the monitoring system is non contact to avoid food contaminations. In this work we assess the feasibility of using an airborne ultrasound system to monitor the bubble size distribution in aerated chocolate bars. The experimental results from the airborne acoustic experiments were compared with theoretical results for known bubble size distributions using COMSOL Multiphysics. This combined experimental and theoretical approach is used to develop a greater understanding of how ultrasound propagates through aerated chocolate and to assess the feasibility of using airborne ultrasound to monitor bubble size distribution in these systems. The results indicated that a smaller bubble size distribution would result in an increase in attenuation through the product

Simon\u27s fundamental rich-get-richer model entails a dominant first-mover advantage

Herbert Simon\u27s classic rich-get-richer model is one of the simplest empirically supported mechanisms capable of generating heavy-tail size distributions for complex systems. Simon argued analytically that a population of flavored elements growing by either adding a novel element or randomly replicating an existing one would afford a distribution of group sizes with a power-law tail. Here, we show that, in fact, Simon\u27s model does not produce a simple power-law size distribution as the initial element has a dominant first-mover advantage, and will be overrepresented by a factor proportional to the inverse of the innovation probability. The first group\u27s size discrepancy cannot be explained away as a transient of the model, and may therefore be many orders of magnitude greater than expected. We demonstrate how Simon\u27s analysis was correct but incomplete, and expand our alternate analysis to quantify the variability of long term rankings for all groups. We find that the expected time for a first replication is infinite, and show how an incipient group must break the mechanism to improve their odds of success. We present an example of citation counts for a specific field that demonstrates a first-mover advantage consistent with our revised view of the rich-get-richer mechanism. Our findings call for a reexamination of preceding work invoking Simon\u27s model and provide an expanded understanding going forward

Dual-5α-Reductase Inhibition Promotes Hepatic Lipid Accumulation in Man

Context: 5α-Reductase 1 and 2 (SRD5A1, SRD5A2) inactivate cortisol to 5α-dihydrocortisol in addition to their role in the generation of DHT. Dutasteride (dual SRD5A1 and SRD5A2 inhibitor) and finasteride (selective SRD5A2 inhibitor) are commonly prescribed, but their potential metabolic effects have only recently been identified. Objective: Our objective was to provide a detailed assessment of the metabolic effects of SRD5A inhibition and in particular the impact on hepatic lipid metabolism. Design: We conducted a randomized study in 12 healthy male volunteers with detailed metabolic phenotyping performed before and after a 3-week treatment with finasteride (5 mg od) or dutasteride (0.5 mg od). Hepatic magnetic resonance spectroscopy (MRS) and two-step hyperinsulinemic euglycemic clamps incorporating stable isotopes with concomitant adipose tissue microdialysis were used to evaluate carbohydrate and lipid flux. Analysis of the serum metabolome was performed using ultra-HPLC-mass spectrometry. Setting: The study was performed in the Wellcome Trust Clinical Research Facility, Queen Elizabeth Hospital, Birmingham, United Kingdom. Main Outcome Measure: Incorporation of hepatic lipid was measured with MRS. Results: Dutasteride, not finasteride, increased hepatic insulin resistance. Intrahepatic lipid increased on MRS after dutasteride treatment and was associated with increased rates of de novo lipogenesis. Adipose tissue lipid mobilization was decreased by dutasteride. Analysis of the serum metabolome demonstrated that in the fasted state, dutasteride had a significant effect on lipid metabolism. Conclusions: Dual-SRD5A inhibition with dutasteride is associated with increased intrahepatic lipid accumulation. - See more at: http://press.endocrine.org/doi/10.1210/jc.2015-2928#sthash.KmmY91Iw.dpu

Abdominal subcutaneous adipose tissue insulin resistance and lipolysis in patients with non-alcoholic steatohepatitis

BACKGROUND: Systemic insulin resistance (IR) is a primary feature in non-alcoholic steatohepatitis (NASH), however, there remain limited data on tissue-specific insulin sensitivity in vivo. METHODS: We examined tissue-specific (adipose, muscle and liver) insulin sensitivity and inflammation in 16 European Caucasian patients with biopsy-confirmed NASH and in 15 healthy controls. All underwent a two-step hyperinsulinaemic euglycaemic clamp incorporating stable isotope measurements of carbohydrate and lipid metabolism with concomitant subcutaneous adipose tissue (SAT) microdialysis. RESULTS: Hepatic and muscle insulin sensitivity were decreased in patients with NASH compared with controls, as demonstrated by reduced suppression of hepatic glucose production and glucose disposal (Gd) rates following insulin infusion. In addition, rates of lipolysis were higher in NASH patients with impaired insulin-mediated suppression of free fatty acid levels. At a tissue specific level, abdominal SAT in patients with NASH was severely insulin resistant, requiring >sixfold more insulin to cause ½-maximal suppression of glycerol release when compared with healthy controls. Furthermore, patients with NASH had significantly higher circulating levels of pro-inflammatory adipocytokines than controls. CONCLUSION: NASH patients have profound IR in the liver, muscle and in particular adipose tissues. This study represents the first in vivo description of dysfunctional SAT in patients with NASH

Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatophepatitis

OBJECTIVE: Insulin resistance and lipotoxicity are pathognomonic in non-alcoholic steatohepatitis (NASH). Glucagon-like peptide-1 (GLP-1) analogues are licensed for type 2 diabetes, but no prospective experimental data exists in NASH. This study determined the effect of a long-acting GLP-1 analogue, liraglutide, on organ-specific insulin sensitivity, hepatic lipid handling and adipose dysfunction in biopsy-proven NASH.DESIGN: 14 patients were randomised to 1.8mg liraglutide or placebo for 12-weeks of the mechanistic component of a double-blind, randomized, placebo-controlled trial (ClinicalTrials.gov-NCT01237119). Patients underwent paired hyperinsulinaemic euglycaemic clamps, stable isotope tracers, adipose microdialysis and serum adipocytokine/metabolic profiling. In vitro isotope experiments on lipid flux were performed on primary human hepatocytes.RESULTS: Liraglutide reduced BMI (-1.9 vs. +0.04 kg/m2;p&lt;0.001), HbA1c (-0.3 vs. +0.3%;p&lt;0.01), cholesterol-LDL (-0.7 vs. +0.05 mmol/L;p&lt;0.01), ALT (-54 vs -4.0 IU/L;p&lt;0.01) and serum leptin, adiponectin, and CCL-2 (all p&lt;0.05). Liraglutide increased hepatic insulin sensitivity (-9.36 vs. -2.54% suppression of hepatic endogenous glucose production with low-dose insulin;p&lt;0.05). Liraglutide increased adipose tissue insulin sensitivity enhancing the ability of insulin to suppress lipolysis both globally (-24.9 vs. +54.8 pmol/L insulin required to ½ maximally suppress serum NEFA; p&lt;0.05), and specifically within subcutaneous adipose tissue (p&lt;0.05). In addition, liraglutide decreased hepatic DNL in-vivo (-1.26 vs. +1.30%; p&lt;0.05); a finding endorsed by the effect of GLP-1 receptor agonist on primary human hepatocytes (24.6% decrease in lipogenesis vs. untreated controls; p&lt;0.01).CONCLUSIONS: Liraglutide reduces metabolic dysfunction, insulin resistance and lipotoxicity in the key metabolic organs in the pathogenesis of NASH. Liraglutide may offer the potential for a disease-modifying intervention in NASH.</p