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.     

Directly Compressible Acetaminophen Compositions Prepared by Fluidized-Bed Granulation

Polyvinylpyrrolidone (PVP) in aqueous solution was used as a binding agent in a fluidized-bed system to agglomerate acetaminophen powder into directly compressible granules. It was found that a minimal amount of 5% w/w PVP in a concentration of 7.5% w/v or less was needed to produce granules with an acceptable flow and the corresponding tablets having enough hardness without capping. There was a strong correlation between the time for 80% dissolved (T₈₀) and the logarithm of granule volume-surface mean diameter. A directly compressible acetaminophen composition to manufacture tablets having a T₈₀ value less than 30 min can be prepared simply by adding an appropriate amount of disintegrant (crospovidone, sodium starch glycolate, or pregelatinized starch) to the agglomerated granules.     

Inhibiting effects of serotonin and serotonin antagonists on the migration of mononuclear leucocytes

The effect of serotonin and the serotonin antagonists ketanserin, methiotepine and ICS-205-930 on the migration of leucocytes was studied by using the sealed capillary migration technique. The migration of mononuclear leucocytes was inhibited by serotonin at 10(-4) and 10(-6)-10(-10)mol/l. An inhibition of the mononuclear leucocyte migration was also caused by ICS-205-930 at 10(-4)mol/l, ketanserin at 10(-4) and 10(-8)-10(-10)mol/l and methiotepine at 10(-4) and 10(-6)-10(-8)mol/l. No inhibiting effects of serotonin or the serotonin antagonists were found on the migration of polymorphonuclear leucocytes. Thus, both serotonin and serotonin antagonists may inhibit mononuclear leucocyte migration.     

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.     

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.     

An assessment of the ability of computational fluid dynamic models to predict reactive gas–solid flows in a fluidized bed

Fine grid, two dimensional simulations of reactive gas–solid flows occurring in a fluidized bed reactor were carried out using the Eulerian multi-fluid kinetic theory of granular flow (KTGF) approach in the commercial flow solver, ANSYS FLUENT 12.1. The fuel reactor of a pilot scale Chemical Looping Combustion rig, operated in the bubbling fluidization regime at the Vienna University of Technology, was simulated. Grid dependence studies were carried out as well as sensitivity studies to the fuel inlet condition and the inclusion of gas phase turbulence. Simulations could not accurately reproduce the experimental trend for the case when highly reactive nickel oxide was used as the oxygen carrier material, but in general satisfactory quantitative agreement was observed. The failure to correctly capture the experimental trend was primarily attributed to the fine length-scales at the feed gas inlets not being adequately resolved even at the finest grid investigated. The trend quickly worsened when coarser grids were used, indicating that the generality of the model is lost when grid dependence effects are present. A number of possible dimensional effects were also discussed. Subsequently, the model was used to successfully capture another experimental trend obtained with a much less reactive ilmenite oxygen carrier material. The model captured this trend correctly because the reaction was now limited by the reaction rate and not by species transfer to the large scale gas-emulsion interfaces. Results were therefore not as sensitive to the correct hydrodynamic modelling of the interface, especially near the gas inlets, and the model retained its generality over a wide range of operating conditions.     

Associations between driving under the influence of alcohol or drugs,speeding and seatbelt use among fatally injured car drivers in Norway

Since 2005, all fatal road traffic crashes in Norway have been analyzed in-depth by multidisciplinary investigation teams organized by the Norwegian Public Roads Administration (NPRA). During the period 2005–2010, 608 drivers of cars or vans were killed in road traffic crashes. Blood samples were collected from 372 (61%) of the drivers and analyzed for alcohol and a large number of psychoactive drugs at the Norwegian Institute of Public Health (NIPH). After coupling the analytical results with the NPRA crash database, 369 drivers with a fatal outcome were identified and included. Alcohol or drug concentrations in blood above the legal limits were found in 39.8% of the drivers who were investigated for alcohol or drug impairment; 33.9% had blood alcohol concentrations above 0.5 g/L or concentrations of drugs above the equivalent Norwegian legal impairment limits or concentrations of amphetamines above 200 μg/L. Among drivers with a fatal outcome who had been impaired by alcohol or drugs, 64.6% were unbelted and 71.7% were speeding when the crash occurred; whereas 24.2% and 33.2% of the sober drivers were unbelted or speeding, respectively. Statistically significant associations were found between impairment by alcohol or amphetamines and driving unbelted or speeding. Excessive speeding is one of the main reasons for road traffic crashes and together with being unbelted the main reasons for a fatal outcome. This behavior might in many cases be due to increased risk-taking or negligence of safety measures as a result of alcohol or drug use.