Synthesis of Novel Alkaline Earth Metal Acetylides

Acetylide complexes of the heavy alkaline-earth metals were first introduced by our group. With our group being interested in how the ligand and donor affect the structural chemistry of the resulting complexes, my project was focused on the detailed analysis of past work and the extension towards new ligand and donor sets. The work required the analysis and development of synthetic procedures towards these highly reactive species. Past synthetic work in our group had established several synthetic routes towards the target compounds including transamination and toluene elimination. Using toluene elimination, I was able to reproduce the synthesis of M(C≡CSiPh3)2(18-crown-6) (M = Sr, Ba), a group of compounds previously only prepared by transamination. I was also able to reproduce the calcium compound using the original transamination route. Extension of toluene elimination to Ca(C≡CSiPh3)2(18-crown-6) compound has so far proven elusive due to the difficult preparation of the dibenzyl Ca(CH2Ph)2 starting material. Acetylene ligand systems employed in my work included the commercially available compounds HC≡CR with R = SiPh3, SiMe3, 4-tBuC6H4, and t-Bu. Donor studies focused mainly on crown ethers, specifically 18-crown-6, which had been shown to bind favorably to calcium, strontium, and barium. Studies also included donors of lower hapticity including the monodentate tetrahydrofuran (THF) and the bidentate N,N,N\u27,N\u27-tetramethylethylenediamine (TMEDA). To compare the chemistry of the highly reactive calcium, strontium, and barium acetylides with the more stable, lighter magnesium, a series of magnesium acetylides was also prepared: Mg(C≡CtBu)2(TMEDA)2, Mg(C≡CC6H4tBu)2(TMEDA)2, Mg(C≡CC6H4tBu)2(15-crown-5), Mg(C≡CSiMe3)2(TMEDA)2, and Mg(C≡CSiPh3)2(THF)4. Overall, the molecular geometries of the magnesium compounds adhered to the predicted octahedral geometry for the 6-coordinate compounds and pentagonal bipyramidal geometry for the 7-coordinate compound. The Mg-C bond length was found to be slightly longer for the more sterically demanding ligands. However, this metal-ligand bond was not affected by coordination number or donor choice. The general trend in the alkaline earth metal acetylides, including magnesium compounds, shows a decrease in the C-M-C and C≡C-M angles as one descends group 2, as explained by the decreased covalent metal-ligand bond character

From usable to useful assessment knowledge and evaluation

In this article contrasts are made between usable and useful knowledge. Usable knowledge represents knowledge that someone finds pertinent. Useful knowledge has a function and can lead to specific action. The applications to educational assessment and evaluation are clear in that much assessment knowledge is developed at a level that is nominally usable, but provides no real guidance in the improvement of learning. Knowledge management through the measurement of social and organizational capital is suggested as a strategy to augment accountability policies based exclusively on test scores. This approach would work as a way to set targets and monitor the development of schools as an institution, responsible for performance by adults and students that extend beyond measured performance

Transient but not genetic loss of miR-451 attenuates the development of pulmonary arterial hypertension

<b>Rationale:</b> MicroRNAs are small non-coding RNAs involved in the regulation of gene expression and have recently been implicated in the development of pulmonary arterial hypertension (PAH). Previous work established that miR-451 is up-regulated in rodent models of PAH.<p></p> <b>Objectives:</b> The role of miR-451 in the pulmonary circulation is unknown. We therefore sought to assess the involvement of miR-451 in the development of pulmonary arterial hypertension.<p></p> <b>Methods:</b> Silencing of miR-451 was performed in vivo using miR-451 knockout mice and an antimiR targeting mature miR-451 in rats. Coupled with exposure to hypoxia, indices of pulmonary arterial hypertension were assessed. The effect of modulating miR-451 on human pulmonary artery smooth muscle cell proliferation and migration was analysed.<p></p> <b>Measurements and Main Results:</b> We observed a reduction in systolic right ventricular pressure in hypoxic rats pre-treated with antimiR-451 compared to hypoxia alone (47.7 ± 1.36mmHg and 56.0 ± 2.03mmHg respectively, p<0.01). In miR-451 knockout mice following exposure to chronic hypoxia, no significant differences were observed compared to wild type hypoxic mice. In vitro analysis demonstrated that over-expression of miR-451 in human pulmonary artery smooth muscle cells promoted migration under serum-free conditions. No effect on cellular proliferation was observed.<p></p> <b>Conclusions:</b> Transient inhibition of miR-451 attenuated the development of pulmonary arterial hypertension in hypoxia exposed rats. Genetic deletion of miR-451 had no beneficial effect on indices of pulmonary arterial hypertension, potentially due to pathway redundancy compensating for the loss of miR-451.<p></p&gt

8. Issues in Intelligent Computer-Assisted Instruction: Eval uation and Measurement

In this chapter we plan to explore two issues in the field of intelligent computer assisted instruction (ICAI) that we feel offer opportunities to advance the state of the art. These issues are evaluation of ICAI systems and the use of the underlying technology in ICAI systems to develop tests. For each issue we will provide a theoretical context, discuss key constructs, provide a brief window to the appropriate literature, suggest methodological solutions and conclude with a concrete example of the feasibility of the solution from our own research. INTELLIGENT COMPUTER-ASSISTED INSTRUCTION (ICAI) ICAI is the application of artificial intelligence to computer-assisted instruction. Artificial intelligence, a branch of computer science, is making computers smart in order to (a) make them more useful and (b) understand intelligence (Winston, 1977). Topic areas in artificial intelligence have included natural language processing (Schank, 1980), vision (Winston, 1975), knowledge representation (Woods, 1983), spoken language (Lea, 1980), planning (Hayes-Roth, 1980), and expert systems (Buchanan, 1981). The field of Artificial Intelligence (AI) has matured in both hardware and software. The most commonly used language in the field is LISP (List Processing). A major development in the hardware area is that personal LISP machines are now available at a relatively low cost (20-50K) with the power of prior mainframes. In the software area two advances stand out: (a) programming support environments such as LOOPS (Bobrow & Stefik, 1983) and (b) expert system tools. These latter tools are now running on powerful micros. The application of expert systems technology to a host of real-world problems has demonstrated the utility of artificial intelligence techniques in a very dramatic style. Expert system technology is the branch of artificial intelligence at this point most relevant to ICAI. Expert Systems Knowledge-based systems or expert systems are a collection of problem-solving computer programs containing both factual and experiential knowledge and data in a particular domain. When the knowledge embodied in the program is a result of a human expert elicitation, these systems are called expert systems. A typical expert system consists of a knowledge base, a reasoning mechanism popularly called an inference engine and a friendly user interface. The knowledge base consists of facts, concepts, and numerical data (declarative knowledge), procedures based on experience or rules of thumb (heuristics), and causal or conditional relationships (procedural knowledge). The inference engine searches or reasons with or about the knowledge base to arrive at intermediate conclusions or final results during the course of problem solving. It effectively decides when and what knowledge should be applied, applies the knowledge and determines when an acceptable solution has been found. The inference engine employs several problem-solving strategies in arriving at conclusions. Two of the popular schemes involve starting with a good description or desired solution and working backwards to the known facts or current situation (backward chaining), and starting with the current situation or known facts and working toward a goal or desired solution (forward chaining). The user interface may give the user choices (typically menu-driven) or allow the user to participate in the control of the process (mixed initiative). The interface allows the user: to describe a problem, input knowledge or data, browse through the knowledge base, pose question, review the reasoning process of the system, intervene as necessary, and control overall system operation. Successful expert systems have been developed in fields as diverse as mineral exploration (Duda & Gaschnig, 1981) and medical diagnosis (Clancy, 1981). ICAI Systems ICAI systems use approaches artificial intelligence and cognitive science to teach a range of subject matters. Representative types of subjects include: (a) collection of facts, for example, South American geography in SCHOLAR (Carbonell & Collins, 1973); (b) complete system models, for example, a ship propulsion system in STEAMER (Stevens & Steinberg, 1981) and a power supply in SOPHIE (Brown, Burton, & de Kleer, 1982); (c) completely described procedural rules, for example, strategy learning, WEST (Brown, Burton, & de Kleer, 1982), or arithmetic in BUGGY (Brown & Burton, 1978); (d) partly described procedural rules, for example, computer programming in PROUST (Johnson & Soloway, 1983); LISP Tutor (Anderson, Boyle, & Reiser, 1985); rules in ALGEBRA (McArthur, Stasz, & Hotta, 1987); diagnosis of infectious diseases in GUIDON (Clancey, 1979); and an imperfectly understood complex domain, causes of rainfall in WHY (Stevens, Collins, & Goldin, 1978). Excellent reviews by Barr and Feigenbaum (1982) and Wenger (1987) document many of these ICAI systems. Representative research in ICAI is described by O\u27Neil, Anderson, and Freeman (1986) and Wenger (1987). Although suggestive evidence has been provided by Anderson et al. (1985), few of these ICAI projects have been evaluated in any rigorous fashion. In a sense they have all been toy systems for research and demonstration. Yet, they have raised a good deal of excitement and enthusiasm about their likelihood of being effective instructional environments. With respect to cognitive science, progress has been made in the following areas: identification and analysis of misconceptions or bugs (Clement, Lockhead, & Soloway, 1980), the use of learning strategies (O\u27Neil & Spielberger, 1979; Weinstein & Mayer, 1986), expert versus novice distinction (Chi, Glaser, & Rees, 1982), the role of mental models in learning (Kieras & Bovair, 1983), and the role of self-explanations in problem solving (Chi, Bassok, Lewis, Reimann, & Glaser, 1987). The key components of an ICAI system consist of a knowledge base: that is, (a) what the student is to learn; (b) a student model, either where the student is now with respect to subject matter or how student characteristics interact with subject matters, and (c) a tutor, that is, instructional techniques for teaching the declarative or procedural knowledge. These components are described in more detail by Fletcher (1985)

Analytical solution of the geodesic equation in Kerr-(anti) de Sitter space-times

The complete analytical solutions of the geodesic equations in Kerr-de Sitter and Kerr-anti-de Sitter space-times are presented. They are expressed in terms of Weierstrass elliptic p, zeta, and sigma functions as well as hyperelliptic Kleinian sigma functions restricted to the one-dimensional theta-divisor. We analyze the dependency of timelike geodesics on the parameters of the space-time metric and the test-particle and compare the results with the situation in Kerr space-time with vanishing cosmological constant. Furthermore, we systematically can find all last stable spherical and circular orbits and derive the expressions of the deflection angle of flyby orbits, the orbital frequencies of bound orbits, the periastron shift, and the Lense-Thirring effect.Comment: 18 pages, 11 figure

Development of a transgenic Plasmodium berghei line (Pb pfpkg) expressing the P. falciparum cGMP-dependent protein kinase, a novel antimalarial drug target.

With the inevitable selection of resistance to antimalarial drugs in treated populations, there is a need for new medicines to enter the clinic and new targets to progress through the drug discovery pipeline. In this study we set out to develop a transgenic rodent model for testing inhibitors of the Plasmodium falciparum cyclic GMP-dependent kinase in vivo. A model was needed that would allow us to investigate whether differences in amino acid sequence of this enzyme between species influences in vivo efficacy. Here we report the successful development of a transgenic P. berghei line in which the cyclic GMP-dependent protein kinase (PKG) was replaced by the P. falciparum orthologue. We demonstrate that the P. falciparum orthologue was able to functionally complement the endogenous P. berghei pkg gene throughout blood stage development and early sexual development. However, subsequent development in the mosquito was severely compromised. We show that this is due to a defect in the female lineage of the transgenic by using genetic crosses with both male and female deficient P. berghei lines. This defect could be due to expression of a female-specific target in the mosquito stages of P. berghei that cannot be phosphorylated by the P. falciparum kinase. Using a previously reported anti-coccidial inhibitor of the cyclic GMP-dependent protein kinase, we show no difference in in vivo efficacy between the transgenic and control P. berghei lines. This in vivo model will be useful for screening future generations of cyclic GMP-dependent protein kinase inhibitors and allowing us to overcome any species-specific differences in the enzyme primary sequence that would influence in vivo efficacy in the rodent model. The approach will also be applicable to in vivo testing of other antimalarial compounds where the target is known

Opportunities and challenges for using automatic human affect analysis in consumer research

The ability to automatically assess emotional responses via contact-free video recording taps into a rapidly growing market aimed at predicting consumer choices. If consumer attention and engagement are measurable in a reliable and accessible manner, relevant marketing decisions could be informed by objective data. Although significant advances have been made in automatic affect recognition, several practical and theoretical issues remain largely unresolved. These concern the lack of cross-system validation, a historical emphasis of posed over spontaneous expressions, as well as more fundamental issues regarding the weak association between subjective experience and facial expressions. To address these limitations, the present paper argues that extant commercial and free facial expression classifiers should be rigorously validated in cross-system research. Furthermore, academics and practitioners must better leverage fine-grained emotional response dynamics, with stronger emphasis on understanding naturally occurring spontaneous expressions, and in naturalistic choice settings. We posit that applied consumer research might be better situated to examine facial behavior in socio-emotional contexts rather than decontextualized, laboratory studies, and highlight how AHAA can be successfully employed in this context. Also, facial activity should be considered less as a single outcome variable, and more as a starting point for further analyses. Implications of this approach and potential obstacles that need to be overcome are discussed within the context of consumer research

Levels of Pesticides and Their Metabolites in Wistar Rat Amniotic Fluids and Maternal Urine upon Gestational Exposure.

Concentrations of pesticides and selected metabolites in rat urine and amniotic fluid were determined as biomarker upon oral administration of Wistar rats to two pesticide mixtures consisting of three to five pesticides (bitertanol, propiconazole, cypermethrin, malathion, and terbuthylazine). The pesticides and their metabolites were found in rat amniotic fluid and urine, generally in dose-response concentrations in relation to dosage. The measurement of the substances in the amniotic fluid indicated that the fetus was exposed to the pesticides as well as their metabolites. Moreover, the pesticides detected in urine demonstrated the exposure as well as the ability of the rat to excrete these compounds

DC-2005 en Madrid: España más cerca del mundo de los metadatos

El instituto universitario Agustín Millares de Documentación y Gestión de la Información, junto al Departamento de Biblioteconomía y Documentación de la Universidad Carlos III de Madrid, serán anfitriones este año de la International Conference on Dublin Core and Metadata Applications (DC- 2005) que se celebrará en el campus de Leganés, del 12 al 15 de septiembre

Deep-water chemosynthetic ecosystem research during the Census of Marine Life Decade and Beyond: A Proposed Deep-Ocean Road Map

The ChEss project of the Census of Marine Life (2002–2010) helped foster internationally-coordinated studies worldwide focusing on exploration for, and characterization of new deep-sea chemosynthetic ecosystem sites. This work has advanced our understanding of the nature and factors controlling the biogeography and biodiversity of these ecosystems in four geographic locations: the Atlantic Equatorial Belt (AEB), the New Zealand region, the Arctic and Antarctic and the SE Pacific off Chile. In the AEB, major discoveries include hydrothermal seeps on the Costa Rica margin, deepest vents found on the Mid-Cayman Rise and the hottest vents found on the Southern Mid-Atlantic Ridge. It was also shown that the major fracture zones on the MAR do not create barriers for the dispersal but may act as trans-Atlantic conduits for larvae. In New Zealand, investigations of a newly found large cold-seep area suggest that this region may be a new biogeographic province. In the Arctic, the newly discovered sites on the Mohns Ridge (71°N) showed extensive mats of sulfur-oxidisng bacteria, but only one gastropod potentially bears chemosynthetic symbionts, while cold seeps on the Haakon Mossby Mud Volcano (72°N) are dominated by siboglinid worms. In the Antarctic region, the first hydrothermal vents south of the Polar Front were located and biological results indicate that they may represent a new biogeographic province. The recent exploration of the South Pacific region has provided evidence for a sediment hosted hydrothermal source near a methane-rich cold-seep area. Based on our 8 years of investigations of deep-water chemosynthetic ecosystems worldwide, we suggest highest priorities for future research: (i) continued exploration of the deep-ocean ridge-crest; (ii) increased focus on anthropogenic impacts; (iii) concerted effort to coordinate a major investigation of the deep South Pacific Ocean – the largest contiguous habitat for life within Earth's biosphere, but also the world's least investigated deep-ocean basin