The gas phase cyclization of deprotonated N-aryl-2-cyano-2-diazoacetamides

The document attached has been archived with permission from the publisher.1-Aryl-4-cyano-5-hydroxy-1,2,3-triazoles can be obtained in solution by base-catalysed cyclization of N-aryl-2-cyano-2-diazoacetamides. A similar reaction was shown to take place under conditions of negative ion chemical ionization in the ion source of a mass spectrometer. High resolution mass spectrometry, tandem mass spectrometry, charge reversal spectra, synthesis of the ions with known structures and quantum chemical calculations were used to prove the latter statement. The fact of the observed cyclization demonstrates once again the ability of mass spectrometry to study the gas phase chemical reactions that take place in solution.Vladislav V. Lobodin, Yuriy Yu. Morzherin, Tom Blumenthal, Daniel Bilusich, Vladimir V. Ovcharenko, John H. Bowie, and Albert T. Lebede

Sedation and regional anaesthesia in the adult patient

This review discusses sedation for regional anaesthesia in the adult population. The first section deals with general aspects of sedation and shows that the majority of patients receiving sedation for regional anaesthesia are satisfied and would choose it again. Methods of assessing the level of sedation are discussed with emphasis on clinical measures. The pharmacology of the drugs involved in sedation is discussed, with propofol and remifentanil appearing to be the combination of choice for sedation in regional anaesthesia. The techniques for administering sedation are discussed and replacement of the traditional repeated boluses or continuous infusion with pharmacokinetic and patient-controlled systems is supported. Patient satisfaction studies suggest that patient-controlled systems are preferre

Parallel quantized charge pumping

Two quantized charge pumps are operated in parallel. The total current generated is shown to be far more accurate than the current produced with just one pump operating at a higher frequency. With the application of a perpendicular magnetic field the accuracy of quantization is shown to be $<$20 ppm for a current of $108.9$pA. The scheme for parallel pumping presented in this work has applications in quantum information processing, the generation of single photons in pairs and bunches, neural networking and the development of a quantum standard for electrical current. All these applications will benefit greatly from the increase in output current without the characteristic decrease in accuracy as a result of high-frequency operation

The End-to-End Argument and Application Design: The Role of Trust

Symposium: Rough Consensus and Running Code: Integrating Engineering Principles into Internet Policy Debates, held at the University of Pennsylvania\u27s Center for Technology Innovation and Competition on May 6-7, 2010. Policy debates about the evolution of the Internet show varying degrees of understanding about the underlying technology. A fundamental principle of the design of the Internet, from the early 1980s, is the so-called end-to-end argument articulated in a seminal technical paper. Intended to provide guidance for what kind of capability is built into a network as opposed to the devices that use the network, the end-to-end argument has been invoked in discussions about freedom, neutrality, and other qualities that may be associated with the supply and use of the Internet and with related public policy. This Article builds on the technical discussions of end-to-end to address the design of applications that use the Internet. It explores the role of trust as a factor in decisions about the structure of applications and their interaction with the Internet as part of a larger system

The levonorgestrel-releasing intrauterine system: Safety, efficacy, and patient acceptability

The levonorgestrel-releasing intrauterine system (LNG-IUS) is a safe, effective and acceptable form of contraception used by over 150 million women worldwide. It also has a variety of noncontraceptive benefits including treatment for menorrhagia, endometriosis, and endometrial hyperplasia. The LNG-IUS has also been used in combination with estrogen for hormone replacement therapy and as an alternative to hysterectomy. Overall, the system is very well tolerated and patient satisfaction is quite high when proper education regarding possible side effects is provided. However, despite all of the obvious benefits of the LNG-IUS, utilization rates remain quite low in the developed countries, especially in the United States. This is thought to be largely secondary to the persistent negative impressions from the Dalkon Shield intrauterine experience in the 1970s. This history continues to negatively influence the opinions of both patients and health care providers with regards to intrauterine devices. Providers should resolve to educate themselves and their patients on the current indications and uses for this device, as it, and intrauterine contraception in general, remains a largely underutilized approach to a variety of women’s health issues

Potential of Peroxisome Proliferator-Activated Receptor Gamma Antagonist Compounds as Therapeutic Agents for a Wide Range of Cancer Types

PPARγ is a therapeutic target that has been exploited for treatment of type II diabetes mellitus (T2DM) with agonist drugs. Since PPARγ is expressed by many hematopoietic, mesodermal and epithelial cancers, agonist drugs were tested and shown to have both preclinical and clinical anticancer activities. While preclinical activity has been observed in many cancer types, clinical activity has been observed only in pilot and phase II trials in liposarcoma and prostate cancer. Most studies address agonist compounds, with substantially fewer reports on anticancer effects of PPARγ antagonists. In cancer model systems, some effects of PPARγ agonists were not inhibited by PPARγ antagonists, suggesting noncanonical or PPARγ-independent mechanisms. In addition, PPARγ antagonists, such as T0070907 and GW9662, have exhibited antiproliferative effects on a broad range of hematopoietic and epithelial cell lines, usually with greater potency than agonists. Also, additive antiproliferative effects of combinations of agonist plus antagonist drugs were observed. Finally, there are preclinical in vivo data showing that antagonist compounds can be administered safely, with favorable metabolic effects as well as antitumor effects. Since PPARγ antagonists represent a new drug class that holds promise as a broadly applicable therapeutic approach for cancer treatment, it is the subject of this review

Germination thresholds of species in the mixed-grass prairie as affected by global climate change: a FACE study

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