Hit to Leads with Cytotoxic Effect in Leukemic Cells: Total Synthesis Intermediates as a Molecule Treasure Chest

A previously designed and developed 12-step total synthesis that includes [1,1′-biphenyl]-2-amine and carbazole intermediates and that ultimately produces the carbazole alkaloid carbazomycin G was exploited as a screening compound library with the goal of identifying potential lead compound(s) with cytotoxic effect. These compounds were investigated by using in-vitro tests involving the two human cell lines HL-60 and MOLM-13, which both model acute myeloid leukaemia (AML). The in-vitro biological test results were used together with the molecular structures of the various intermediates in a concise SAR analysis. Several of the intermediates revealed cytotoxicity (IC₅₀<10⁻⁴ M), although the final natural product carbazomycin G did not reveal cytotoxicity versus the two said human cell lines.     

Predicting patient change from therapist competence and patient-therapist complementarity in short-term anxiety-provoking psychotherapy: A pilot study.

Examined therapist competence and patient–therapist complementarity, measured by the Structural Analysis of Social Behavior system (L. S. Benjamin, 1974), as to their interrelation and their unique, collective, and interactive contributions to patient change in 20 sessions of short-term anxiety-provoking psychotherapy (STAPP; P. E. Sifneos, 1979). Patients were 15 highly educated outpatients (mean age 30 yrs) with mainly anxiety diagnoses. Therapists were in postgraduate manual-guided STAPP training. Results show that competence in an early session did not relate to patient change. In contrast, patient–therapist complementarity ratings predicted patient change both alone and over and above competence. Predictions were strongest for changes in general distress and dysfunctional attitudes and for shorter term change rather than for longer term change. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Physical Context of Creativity

Creative processes are complex and consist of sub‐processes, e.g. value creation, scaffolding, imagination and materialization. Creativity takes place in a physical context, i.e. in a confined space. Such space restricts and enables the free flow of sensory experiences and proximity of other people. The confinements may make certain sensory experiences available, e.g. vision of source material, sight and sound (including noise). This framing allows certain cognitive processes and restricts others. This may induce emotions that, in turn, facilitate or reduce the enhancement of creativity. Physical space affects the well‐being of people, the channels of information, the availability of knowledge tools and sets the stage for coherence and continuity, which may contribute to competitive advantages.     

Influence of the Workpiece Stiffness on the Electromagnetic Sheet Metal Forming Process into Dies

Electromagnetic sheet metal forming is a high speed forming process using pulsed magnetic fields to form metals with high electrical conductivity such as aluminum. Thereby, workpiece velocities of more than 300 m/s are achievable, which can cause difficulties when forming into a die. The kinetic energy, which is related to the workpiece velocity, must be dissipated in a short time slot when the workpiece hits the die; otherwise undesired effects, for example rebound can occur. One possibility to handle this shortcoming is to locally increase the stiffness of the workpiece. A modal analysis is carried out in order to determine the stiffness of specific regions of the workpiece so that an estimation concerning the feasibility of the desired geometry is possible in advance without doing cost and time consuming experiments. Thereby, the desired geometry of the workpiece will be fractionized in significant sectors. This approach has to define the internal force variables acting on the cutting edge, which are required to constrain the numerical model. Finally, a method will be developed with the objective of calculating the stiffness of each sector. The numerical results will be verified by experiments. This article was presented at Materials Science & Technology 2006, Innovations in Metal Forming symposium held in Cincinnati, OH, October 15-19, 2006.     

Data reconciliation and optimal operation of a catalytic naphtha reformer

The naphtha reforming process converts low-octane gasoline blending components to high-octane components for use in high-performance gasoline fuels. The reformer also has an important function as the producer of hydrogen to the refinery hydrotreaters. A process model based on a unit model structure, is used for estimation of the process condition using data reconciliation. Measurements are classified as redundant or non-redundant and the model variables are classified as observable, barely observable or unobservable. The computed uncertainty of the measured and unmeasured variables shows that even if a variable is observable it may have a very large uncertainty and may thereby be practically unobservable. The process condition at 21 data points, sampled from two years of operation, was reconciled and used to optimize the process operation. There are large seasonal variations in the reformer product price and two operational cases are studied. In case 1, the product price is high and throughput is maximized with respect to process and product quality constraints. In case 2, the product price is low and the throughput is minimized with respect to a low constraint on the hydrogen production. Based on the characteristics of the optimal operation, a “self optimizing” control structure is suggested for each of the two operational cases.     

Will musculoskeletal and visual stress change when Visual Display Unit (VDU) operators move from small offices to an ergonomically optimized office landscape?

This study investigated the effect of moving from small offices to a landscape environment for 19 Visual Display Unit (VDU) operators at Alcatel Denmark AS. The operators reported significantly improved lighting condition and glare situation. Further, visual discomfort was also significantly reduced on a Visual Analogue Scale (VAS). There was no significant correlation between lighting condition and visual discomfort neither in the small offices nor in the office landscape. However, visual discomfort correlated significantly with glare in small offices i.e. more glare is related to more visual discomfort. This correlation disappeared after the lighting system in the office landscape had been improved. There was also a significant correlation between glare and itching of the eyes as well as blurred vision in the small offices, i.e. more glare more visual symptoms. Experience of pain was found to reduce the subjective assessment of work capacity during VDU tasks. There was a significant correlation between visual discomfort and reduced work capacity in small offices and in the office landscape. When moving from the small offices to the office landscape, there was a significant reduction in headache as well as back pain. No significant changes in pain intensity in the neck, shoulder, forearm, and wrist/hand were observed.The pain levels in different body areas were significantly correlated with subjective assessment of reduced work capacity in small offices and in the office landscape.By careful design and construction of an office landscape with regard to lighting and visual conditions, transfer from small offices may be acceptable from a visual-ergonomic point of view.     

Science and technology in the region: The output of regional science and technology, its strengths and its leading institutions

Summary We operationalize scientific output in a region by means of the number of articles (as in the SciSearch database) per year and technology output by means of the number of patent applications (as in the database of the European Patent Office) per priority year. All informetric analyses were done using the DIALOG online-system. The main research questions are the following: Which scientific and technological fields or topics are most influent within a region and which institutions or companies are mainly publishing articles or holding patents? Do the distributions of regional science and technology fields and of publishing institutions follow the well-known informetric function? Are there - as it is expected - only few fields and few institutions which dominate the region? Is there a connection between the economic power of a region and the regional publication and patent output? Examples studied in detail are seven German regions: Aachen, D&uuml;sseldorf, Hamburg, K&ouml;ln (Cologne), Leipzig - Halle - Dessau, M&uuml;nchen (Munich), and Stuttgart. Three different indicators were used, science and technology attraction of a region (number of scientific articles and patents), science and technology intensity (articles and patents per 1,000 inhabitants), and science and technology density (articles and patents per 1 billion EURO gross value added). Top region concerning both attraction and intensity is Munich, concerning density it is Aachen.     

Extreme discordant sib pairs for mapping quantitative trait loci in humans

Analysis of differences between siblings (sib pair analysis) is a standard method of genetic linkage analysis for mapping quantitative trait loci, such as those contributing to hypertension and obesity, in humans. In traditional designs, pairs are selected at random or with one sib having an extreme trait value. The majority of such pairs provide little power to detect linkage; only pairs that are concordant for high values, low values, or extremely discordant pairs (for example, one in the top 10 percent and the other in the bottom 10 percent of the distribution) provide substantial power. Focus on discordant pairs can reduce the amount of genotyping necessary over conventional designs by 10- to 40-fold.