The Intermolecular Pauson-Khand Reaction: Applications,Challenges, and Opportunities

The rapid assembly of complex organic molecules from simple and structurally diverse building blocks is a prevalent challenge in organic synthesis. The Pauson-Khand reaction (PKR) is a method of choice for the construction of five membered rings that has historically been popularized as a late-stage intramolecular cyclization method. The intermolecular version of the PKR, on the other hand, constitutes a powerful approach for the rapid assembly of densely functionalized cyclopentanic cores at early stages of a synthetic sequence. Despite its potential, the intermolecular PKR is much less prevalent in the organic synthesis literature due to several historical limitations, most importantly a reduced scope with respect to the alkene component of the reaction. The last decade has witnessed important developments in the area including a) experimental and theoretical studies that provide a good mechanistic understanding of the reaction and its selectivity, b) methodological developments that have broadened the scope of potential alkene partners, and c) the development of catalytic enantioselective versions that provide useful levels of enantioselectivity. In parallel, remarkable synthetic applications of the intermolecular PKR have emerged, including (enantioselective) total syntheses of complex natural products (polycyclic terpenes, alkaloids, prostanes) as well as examples of industrial relevance. A fundamental limitation of the PKR that needs to be addressed in the future is the current lack of a ligand-accelerated version of the reaction, which would be a promising advance towards developing more efficient and general catalytic (enantioselective) reactions.     

The Role of Matrix Metalloproteinase in Inflammation with a Focus on Infectious Diseases

Matrix metalloproteinases (MMPs) are involved in extracellular matrix remodeling through the degradation of extracellular matrix components and are also involved in the inflammatory response by regulating the pro-inflammatory cytokines TNF-α and IL-1β. Dysregulation in the inflammatory response and changes in the extracellular matrix by MMPs are related to the development of various diseases including lung and cardiovascular diseases. Therefore, numerous studies have been conducted to understand the role of MMPs in disease pathogenesis. MMPs are involved in the pathogenesis of infectious diseases through a dysregulation of the activity and expression of MMPs. In this review, we discuss the role of MMPs in infectious diseases and inflammatory responses. Furthermore, we present the potential of MMPs as therapeutic targets in infectious diseases.     

Metal-modulated epitaxy of Mg-doped Al0.80In0.20N-based layer for application as the electron blocking layer in deep ultraviolet light-emitting diodes

This work reports the growth and characterization of p-AlInN layers doped with Mg by plasma-assisted molecular beam epitaxy (PAMBE). AlInN was grown with an Al molar fraction of 0.80 by metal-modulated epitaxy (MME) with a thickness of 180 nm on Si(111) substrates using AlN as buffer layers. Low substrate temperatures were used to enhance the incorporation of indium atoms into the alloy without clustering, as confirmed by X-ray diffraction (XRD). Cathodoluminescence measurements revealed ultraviolet (UV) range emissions. Meanwhile, Hall effect measurements indicated a maximum hole mobility of 146 cm²/(V∙s), corresponding to a free hole concentration of 1.23 × 10¹⁹ cm⁻³. The samples were analyzed by X-ray photoelectron spectroscopy (XPS) estimating the alloy composition and extracting the Fermi level by valence band analysis. Mg-doped AlInN layers were studied for use as the electron-blocking layer (EBL) in LED structures. We varied the Al composition in the EBL from 0.84 to 0.96 molar fraction to assess its theoretical effects on electroluminescence, carrier concentration, and electric field, using SILVACO Atlas. The results from this study highlight the importance and capability of producing high-quality Mg-doped p-AlInN layers through PAMBE. Our simulations suggest that an Al content of 0.86 is optimal for achieving desired outcomes in electroluminescence, carrier concentration, and electric field.     

A further note on "Prognostic scales in schizophrenia".

Replies to commentary by A. Farina (see record 2005-10655-011) on the original article by S. L. Garfield and D. M. Sundland (see record 1966-04456-001) regarding prognostic scales in schizophrenia. Marital status and premorbid personality are discussed as prognostic indicators of improvement in schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nitric oxide production by peritoneal macrophages of cirrhotic rats: a host response against bacterial peritonitis

BACKGROUND & AIMS: Patients and rats with cirrhosis and ascites are prone to develop peritonitis. The aim of this study was to assess whether peritoneal macrophages of cirrhotic rats without peritoneal infection produce nitric oxide and express inducible NO synthase (iNOS). METHODS: NO2- accumulation produced by macrophages from control rats and cirrhotic rats with ascites was determined. iNOS messenger RNA and protein expression were analyzed by Northern and Western blot and immunocytochemical analysis. The in vivo effects of inhibiting iNOS were investigated by giving the specific iNOS inhibitor L-N-(1-iminoethyl)-lysine (L-NIL) or sterile saline to 9 and 7 cirrhotic rats with ascites, respectively. RESULTS: Cirrhotic macrophages produced NO2- that was around fourfold greater than that of control macrophages after 30 hours in culture. Northern and Western blot and immunocytochemical analysis showed the presence of iNOS messenger RNA and protein in macrophages of cirrhotic rats. Ascites cultures were positive in all rats administered L-NIL and negative in those administered saline. CONCLUSIONS: Macrophages of cirrhotic rats produce NO and express iNOS messenger RNA and protein, and these changes are not a consequence of overt bacterial infection. Because iNOS inhibition results in peritoneal infection, these results suggest that iNOS induction in macrophages of cirrhotic rats is a host defense response to prevent bacterial peritonitis.     

Attitudes toward training in diagnostic testing: A survey of directors of internship training.

Reports responses to a questionnaire secured from 80 approved internship centers on various aspects of training in diagnostic testing. While there was some variation from center to center, a majority believed that university training was inadequate, and a number of them perceived the university as instilling an overly critical attitude toward diagnostic testing in their students. The techniques emphasized in internship training are presented, and the implications of the differences in emphases between academic and field settings are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evaluating outcome in psychotherapy: A hardy perennial.

Discusses issues raised by D. Fiske (see pa, vol. 47:issue 5) and by L. Luborsky (see pa, vol. 47:issue 5) with reference to outcome research in psychotherapy generally, and to a previous paper by the authors (see pa, vol. 47:issue 5 ) in particular. While attention in the past has tended to focus on general criteria of improvement, it is believed that in the future more consideration must be given to the specific changes sought by means of therapy with multiple measures devised for appraising such change. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

"High-load" polyethylene glycol-polystyrene (PEG-PS) graft supports for solid-phase synthesis

In the rat dorsal hippocampus and dorsal raphe nucleus, the microiontophoretic application of ergotamine and 5-HT suppressed the firing activity of CA3 pyramidal neurons and 5-HT neurons, an effect antagonized by selective 5-HT1A receptor antagonists. Co-application of ergotamine prevented the inhibitory action of 5-HT on the firing activity of CA3 pyramidal neurons but not of 5-HT neurons, indicating that ergotamine acted as a partial 5-HT1A receptor agonist in the dorsal hippocampus and as a full agonist at 5-HT1A autoreceptors. Ergotamine decreased, in a concentration-dependent manner, the electrically evoked release of [3H]5-HT in preloaded rat and guinea pig hypothalamus slices; this effect was prevented by the nonselective 5-HT receptor antagonist methiothepin but not by the selective 5-HT1B/1D receptor antagonist GR 127935 or the alpha 2-adrenoceptor antagonist idazoxan. Although body temperature in humans remained unchanged following inhaled ergotamine, in the rat, subcutaneously injected ergotamine produced a hypothermia that was prevented by a pretreatment with the 5-HT1A/1B receptor/beta-adrenoceptor antagonist pindolol. Finally in humans, ergotamine did not alter prolactin or adrenocorticotropic hormone levels, but increased growth hormone level, which was prevented by pindolol. Cortisol level was increased in humans by ergotamine, but this enhancement was unaltered by pindolol. In conclusion, the present results suggest that ergotamine acted in the rat brain as a 5-HT1A receptor agonist and as an agonist of terminal 5-HT autoreceptor of a yet undefined subtype. In humans, ergotamine also displayed some 5-HT1A receptor activity but, probably because of lack of receptor selectivity, it did not present the same profile as other 5-HT1A receptor agonists.