All-optical switching in ferromagnetic superlattices.

The unexpected observation of ultrafast demagnetization (UDM) and subsequent time-resolved studies of laser-induced magnetization switching opened a new door to both fundamental physics and technological applications of magnetic materials. All-optical switching (AOS) can be initiated faster than the precession limit, hinting to its potential in increasing the writing speed and data storage density. However, notwithstanding considerable research interest, the mechanism of AOS in ferromagnetic materials remained unclear. Ferromagnetic superlattices were deposited on glass substrates with e-beam evaporation and sputtering. Magnetization curves were measured in magneto-optical and vibrating sample magnetometer experiments. A femtosecond Ti:S laser was utilized in a writing setup to induce AOS in Co/Pd ferromagnetic superlattices at different fluences and beam polarizations. Magnetic force and polarizing microscopy were applied to image the magnetic structure and identify optimal AOS parameters. High-repetition rate pulses of the Ti:S laser resulted in heat accumulation in the samples. For a better understanding of the relation between temperature and domain wall motion, we solved the heat diffusion equation numerically. The solution for our sample displayed a tilted thermal wave front, consistent with the tilted magnetic domains observed. This supports our model of AOS, in which thermal forces acting on domain walls leads to their expansion and magnetization switching (chapter 3). Polarizing microscopy images also revealed a complementary pattern of magnetic domains after laser writing, suggesting that demagnetizing fields are not negligible. Furthermore, comparison of pump-probe UDM measurements with AOS writing measurements pointed to a demagnetized state before AOS emergence. This motivated us to apply micromagnetic simulations to investigate the time evolution of a demagnetized state and in particular the role of demagnetizing fields in the development of different final states. We show using this method that demagnetizing fields can nucleate and, together with thermally-induced forces, develop a switched state (chapter 4). Using the pump-probe setup, we measured the frequency dependence of laser-induced temperature modulations in Co/Au, Co/Ag and Co/Pd superlattices on glass substrates. Green\u27s function solutions of the heat diffusion equation show that a glass layer with properties distinct from the glass substrate is present near the metallic superlattices (chapter 5)

G-protein-coupled receptors for free fatty acids: nutritional and therapeutic targets

It is becoming evident that nutrients and metabolic intermediates derived from such nutrients regulate cellular function by activating a number of cell-surface G-protein coupled receptors (GPCRs). Until now, members of the GPCR family have largely been considered as the molecular targets that communicate cellular signals initiated by hormones and neurotransmitters. Recently, based on tissue expression patterns of these receptors and the concept that they may elicit the production of a range of appetite- and hunger-regulating peptides, such nutrient sensing GPCRs are attracting considerable attention due to their potential to modulate satiety, improve glucose homeostasis and supress the production of various pro-inflammatory mediators. Despite the developing interests in these nutrients sensing GPCR both as sensors of nutritional status, and targets for limiting the development of metabolic diseases, major challenges remain to exploit their potential for therapeutic purposes. Mostly, this is due to limited characterisation and validation of these receptors because of paucity of selective and high-potency/affinity pharmacological agents to define the detailed function and regulation of these receptors. However, ongoing clinical trials of agonists of free fatty acid receptor 1 suggest that this receptor and other receptors for free fatty acids may provide a successful strategy for controlling hyperglycaemia and providing novel approaches to treat diabetes. Receptors responsive to free fatty acid have been of particular interest, and some aspects of these are considered herein

Catalyst-Controlled Stereoselective Olefin Metathesis as a Principal Strategy in Multistep Synthesis Design: A Concise Route to (+)-Neopeltolide

Molybdenum-, tungsten-, and ruthenium-based complexes that control the stereochemical outcome of olefin metathesis reactions have been recently introduced. However, the complementary nature of these systems through their combined use in multistep complex molecule synthesis has not been illustrated. A concise diastereo- and enantioselective route that furnishes the anti-proliferative natural product neopeltolide is now disclosed. Catalytic transformations are employed to address every stereochemical issue. Among the featured processes are an enantioselective ring-opening/cross-metathesis promoted by a Mo monoaryloxide pyrrolide (MAP) complex and a macrocyclic ring-closing metathesis that affords a trisubstituted alkene and is catalyzed by a Mo bis(aryloxide) species. Furthermore, Z-selective cross-metathesis reactions, facilitated by Mo and Ru complexes, have been employed in the stereoselective synthesis of the acyclic dienyl moiety of the target molecule.National Institutes of Health (U.S.) (NIH grant GM-59426)National Institutes of Health (U.S.) (NIH grant GM-57212)AstraZeneca (Firm) (Graduate Fellowship)National Science Foundation (U.S.) (NSF award CHE-1362763

Preparation of Macrocyclic

The first examples of catalyst-controlled stereoselective macrocyclic ring-closing metathesis reactions that generate Z-enoates as well as (E,Z)- or (Z,E)-dienoates are disclosed. Reactions promoted by 3.0–10 mol % of a Mo-based monoaryloxide pyrrolide complex proceed to completion within 2–6 h at room temperature. The desired macrocycles are formed in 79:21 to >98:2 Z/E selectivity; stereoisomerically pure products can be obtained in 43–75% yield after chromatography. Utility is demonstrated by application to a concise formal synthesis of the natural product (+)-aspicilin.United States. National Institutes of Health (GM-59426

Direct synthesis of Z-alkenyl halides through catalytic cross-metathesis

Olefin metathesis has had a large impact on modern organic chemistry, but important shortcomings remain: for example, the lack of efficient processes that can be used to generate acyclic alkenyl halides. Halo-substituted ruthenium carbene complexes decompose rapidly or deliver low activity and/or minimal stereoselectivity, and our understanding of the corresponding high-oxidation-state systems is limited. Here we show that previously unknown halo-substituted molybdenum alkylidene species are exceptionally reactive and are able to participate in high-yielding olefin metathesis reactions that afford acyclic 1,2-disubstituted Z-alkenyl halides. Transformations are promoted by small amounts of a catalyst that is generated in situ and used with unpurified, commercially available and easy-to-handle liquid 1,2-dihaloethene reagents, and proceed to high conversion at ambient temperature within four hours. We obtain many alkenyl chlorides, bromides and fluorides in up to 91 per cent yield and complete Z selectivity. This method can be used to synthesize biologically active compounds readily and to perform site- and stereoselective fluorination of complex organic molecules.National Institute of General Medical Sciences (U.S.) (GM-59426 and GM-57212

A systematic review and meta-analysis: probiotics in the treatment of irritable bowel syndrome

<p>Abstract</p> <p>Background</p> <p>Irritable Bowel Syndrome (IBS) is a common chronic gastrointestinal disorder and the evidence for efficacy of most drug therapies in the treatment of IBS is weak. A popular alternative is probiotics, which have been used in several conditions. including IBS. Probiotics are live microbial food supplements.</p> <p>The aim of this systematic review and meta-analysis of randomized trials study was to evaluate the efficacy of probiotics in alleviating symptoms in patients with irritable bowel syndrome. We searched Ovid versions of MEDLINE (1950–2007), EMBASE (1980–2007), CINAHL (1982–2007), AMED (1985–2007), the Cochrane library and hand searched retrieved papers.</p> <p>Results</p> <p>We identified 14 randomized placebo controlled trials. Combined data suggested a modest improvement in overall symptoms after several weeks of treatment: for dichotomous data from seven trials the overall Odds Ratio (OR) was 1.6 (95% CI, 1.2 to 2.2); for continuous data from six trials the standardised mean difference (SMD) was 0.23 (95% CI, 0.07 to 0.38).</p> <p>For individual symptoms the results differed between the pooled dichotomous and pooled continuous data. Trials varied in relation to the length of treatment (4–26 weeks), dose, organisms and strengths of probiotics used.</p> <p>Conclusion</p> <p>Probiotics may have a role in alleviating some of the symptoms of IBS, a condition for which currently evidence of efficacy of drug therapies is weak. However, as IBS is a condition that is chronic and usually intermittent longer term trials are recommended. Such research should focus on the type, optimal dose of probiotics and the subgroups of patients who are likely to benefit the most.</p

Solvent effects on Grubbs’ pre-catalyst initiation rates

Initiation rates for Grubbs and Grubbs-Hoveyda second generation pre-catalysts have been measured accurately in a range of solvents. Solvatochromic fitting reveals different dependencies on key solvent parameters for the two pre-catalysts, consistent with different mechanisms by which the Grubbs and Grubbs-Hoveyda pre-catalysts initiate

Synthesis of Molybdenum and Tungsten Alkylidene Complexes That Contain Sterically Demanding Arenethiolate Ligands

Imido alkylidene complexes of Mo and W and oxo alkylidene complexes of W that contain thiophenoxide ligands of the type S-2,3,5,6-Ph[subscript 4]C[subscript 6]H (STPP) and S-2,6-(mesityl)[subscript 2]C[subscript 6]H[subscript 3] (SHMT = S-hexamethylterphenyl) have been prepared in order to compare their metathesis activity with that of the analogous phenoxide complexes. All thiolate complexes were significantly slower (up to ∼10× slower) for the metathesis homocoupling of 1-octene or polymerization of 2,3-dicarbomethoxynorbornene, and none of them was Z-selective. The slower rates could be attributed to the greater σ-donating ability of a thiophenoxide versus the analogous phenoxide and consequently a higher electron density at the metal in the thiophenoxide complexes.National Institutes of Health (U.S.) (Grant GM-59426