Local Velocity and Concentration of the Single Components in Water/Oil Mixtures Monitored by Means of MRI Flow Experiments in Steady Tube Flow

In this paper the spatially resolved determination of velocities in two‐phase systems consisting of water and oil by means of nuclear magnetic resonance (NMR) imaging (MRI) techniques is described and applied to steady tube flows with regard to the total flow rate. As MRI offers the possibility to study the flow of multiphase materials spatially resolved with various forms of contrast, even optically opaque water/oil mixtures can be studied in the interior of the material. Besides snapshot images of the actual flow pattern also local velocity and concentration fields of both phases can be obtained separately. The insight into the inner micro flow processes and microstructure allows to characterize fluid mixtures or emulsions. Flow rate and preparation/mixing method were varied in order to realize changes of the flow pattern and the structure of the mixture during flow. Physical models of the flow behavior and physical stability of these complex systems can be based upon this information.     

Hot isostatic pressing of nanostructured γ-TiAI powders

A study of the hot isostatic pressing (HIP’ing) of γ-TiAl powders produced by mechanical alloying, has demonstrated that full density can be achieved 400°C or more below the temperature required for conventional powder; that is 725°C or below. Nanostructured grains (≤ 100 nm) are observed after HIP’ing up to 850°C.     

Designing honest experiments.

Challenges A. G. Miller's (see record 1973-03488-001) notion that role playing and deception are the only research strategies available to experimental social psychologists and presents 4 alternative strategies that do not involve deception. Given the available range of possibilities, those involving deception are recommended only after consideration of the alternatives. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Robotic And Automated Systems In The Pharmaceutical QC

Since the beginning of this decade the use of automated or robotic-systems for analytical purposes has decreased rapidely. Starting from the analysis of agriculturing products or medical samples, these instruments are now more and more common in the pharmaceutical industry.The systems are used for R&D purposes mainly in the area of combinatorial chemistry to analyze the huge amount of synthesis products in the biomedical labs and in chemical-physical laboratories of Quality Contol Units. Extensive stability studies, which have to be perfomed for new drug applications, and the release testing of medicinal products with a very high manufacturing batch-rate per year need highly effective analytical methods. Thus, Byk Gulden has introduced two automated systems based on Zymark products (TPWII and MultiDose), for the stability tests of an enteric-coated tablet. The number of batches, pack types and storage conditions (total number of samples: appr. 40 for the 3- and 6-months timepoints), for this stability study was required automation of the most time consuming test methods for purity, assay and dissolution of the tablets, because of the tight schedule for timepoints in the first year of storage (in general: two weeks). In order to have these automated systems in place for routine testing in a very short time, the method transfer from the manual procedure as well as the optimization and validation work (MTOV), were done completely by the supplier, Zymark. The other system, which is a customer designed robotic system built also by Zymark, is used for the release testing of an xray contrast medium with a very high batch-rate per year (approxmimately four batches per day that have to be analyzed). This enormous testing frequency is hardly to be realized by manual methods. Experiences with an already existent robotic systems has shown that the laboratory flow-through times are 30 to 50% decreased compared to manual testing.     

Interplay of the proto-oncogene proteins CrkL and CrkII in insulin-like growth factor-I receptor-mediated signal transduction

The closely related proto-oncogene proteins CrkII and CrkL consist of one SH2 and two SH3 domains and share 60% overall homology with the highest identity within their functional domains. In this study we show that CrkL and CrkII may play overlapping but different roles in insulin-like growth factor (IGF)-I receptor-mediated signal transduction. While both proteins are substrates involved in IGF-I receptor signaling, they apparently demonstrate important different properties and different biological responses. Evidence supporting this hypothesis includes (a) the oncogenic potential of CrkL versus the absence of this potential in CrkII overexpressing cell lines, (b) the inhibition of IGF-I-dependent cell cycle progression by overexpression of CrkII, and (c) the differential regulation of the phosphorylation status of selective proteins in CrkII and CrkL overexpressing cell lines. In addition we demonstrate the specific association of CrkL and CrkII with the newly characterized IRS-4 protein, again in a differential manner. Whereas CrkL strongly interacts with IRS-4 via its SH2 and N-terminal SH3 domains, CrkII interacts only via its SH2 domain, possibly explaining the unstable nature of IRS-4-CrkII association. The results obtained allow us to propose a unique mechanism of CrkL and CrkII tyrosine phosphorylation in response to IGF-I stimulation. Thus these highly homologous proteins apparently possess structural features that allow for the differential association of each protein with different effector molecules, thereby activating different signaling pathways and resulting in unique biological roles of these proteins.     

Structure‐Based Design of a Monosaccharide Ligand Targeting Galectin‐8

Galectin‐8 is a β‐galactoside‐recognising protein that has a role in the regulation of bone remodelling and is an emerging new target for tackling diseases with associated bone loss. We have designed and synthesised methyl 3‐O‐[1‐carboxyethyl]‐β‐d ‐galactopyranoside (compound 6 ) as a ligand to target the N‐terminal domain of galectin‐8 (galectin‐8N). Our design involved molecular dynamics (MD) simulations that predicted 6 to mimic the interactions made by the galactose ring as well as the carboxylic acid group of 3′‐O‐sialylated lactose (3′‐SiaLac), with galectin‐8N. Isothermal titration calorimetry (ITC) determined that the binding affinity of galectin‐8N for 6 was 32.8 μm , whereas no significant affinity was detected for the C‐terminal domain of galectin‐8 (galectin‐8C). The crystal structure of the galectin‐8N– 6 complex validated the predicted binding conformation and revealed the exact protein–ligand interactions that involve evolutionarily conserved amino acids of galectin and also those unique to galectin‐8N for recognition. Overall, we have initiated and demonstrated a rational ligand design campaign to develop a monosaccharide‐based scaffold as a binder of galectin‐8.     

Periparturient dairy cows do not exhibit hepatic insulin resistance,yet adipose-specific insulin resistance occurs in cows prone to high weight loss

The periparturient period in dairy cows is associated with alterations in insulin action in peripheral tissues; however, the molecular mechanism underlying this process is not completely understood. The objective was to examine the response to a glucose tolerance test (GTT) and to analyze insulin signaling in liver and adipose tissues in pre- and postpartum dairy cows. Liver and adipose tissue biopsies were taken before and after GTT, at 17 d prepartum and again at 3 to 5 d postpartum from 8 high-yielding Israeli Holstein dairy cows. Glucose clearance rate after GTT was similar pre- and postpartum. Basal insulin concentrations and the insulin response to GTT were approximately 4-fold higher prepartum than postpartum. In accordance, phosphorylation of the hepatic insulin receptor after GTT was higher prepartum than postpartum. Across periods, a positive correlation was observed between the basal and peak plasma insulin and phosphorylated insulin receptor after GTT in the liver. Hepatic phosphorylation of protein kinase B after GTT was elevated pre- and postpartum. Conversely, in adipose tissue, phosphorylation of protein kinase B after GTT pre- and postpartum was increased only in 4 out of 8 cows that lost less body weight postpartum. Our results demonstrate that hepatic insulin signaling is regulated by plasma insulin concentrations as part of the homeorhetic adjustments toward calving, and do not support a model of hepatic insulin resistance in periparturient cows. Nevertheless, we suggest that specific insulin resistance in adipose tissue occurs pre- and postpartum only in cows prone to high weight loss. The different responses among these cows imply that genetic background may affect insulin responsiveness in adipose tissue pre- and postpartum.     

Deceiving ourselves about deception: Comment on Smith and Richardson's "Amelioration of deception and harm in psychological research."

Comments on the conclusions of S. S. Smith and D. Richardson (see record 1984-00117-001) that research Ss who had been deceived evaluated their participation more favorably than Ss who had not been deceived and that effective debriefing eliminated negative effects perceived by Ss who felt they had been harmed. It is suggested that the data they present do not support these conclusions. Although the effect of deceptive studies needs to be researched, the case presented by Smith and Richardson is weak. (3 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Determination of Oxygen Tension by Measurement of Net Charge Transport

Conventional electrodes that are used to measure oxygen tension in the biological environment have been plagued by one or more of three major problems: 1) flow sensitivity, 2) instability, and 3) inadequate response time. Pulsatile operation of the electrode has the potential of eliminating these problems. A new technique of measurement using integration of output current has been developed. This new method of measurement enhances the pulsatile operation in the Po2 electrode. The technique effectively determines the difference in charge transport that occurs during the polarization potential. Using this technique, it has been possible to measure net charge transport, which is proportional to the oxygen tension level of whole blood as early as 1 ms after application of the polarization pulse. Also, the subtraction of the discharging current component appears to stabilize electrode drift. The short polarization time required allows for the elimination of flow sensitivity by reducing the extension of the oxygen diffusion gradient to less than 8 ?m from the electrode face. The short duration of active measurement will tend to decrease poisoning by allowing use of an operating duty cycle of minimal duration.