Taking enzyme kinetics out of control; putting control into regulation

The matrix formulation of metabolic control analysis, which states that multiplying the elasticity matrix for any system by the corresponding control matrix yields an identity matrix, can be transformed into a statement that multiplying a matrix expressing internal regulatory properties by a matrix expressing external regulatory properties also yields an identity matrix. This transformation supplies the formal basis for metabolic regulation analysis, and provides the key to determining the control structure of a system without the need to know the exact changes in enzyme activities that are made to measure control coefficients.     

Visualization and quantification of the mechanical deformation induced by an electrical field in poly(ethylene naphthalene 2,6‐dicarboxylate) (PEN) films

An optical nondestructive strain measurement technique was performed to analyze the mechanical deformation induced by an electrical field within the insulating materials. Poly(ethylene naphthalene 2,6‐dicarboxylate) (PEN) films were then subjected to constant electrical fields right up to their electrical breakdown. The experimental technique made it possible to follow the various stages of the mechanical behavior of PEN in real time. The final breakdown occurred in the observation zone and the related mechanical deformation was captured. A “margarita” structure was observed with a hole at the center. The experimental results indicated that the level of the induced‐mechanical deformations depended on the local environment. We defined two different zones representing the inside and the outside of the damaged area. The induced‐deformations were larger in the damaged zone. It was also observed that deformations increased when the sample had a lower degree of crystallinity. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Recognizing, assessing, and intervening with problems of professional competence.

Working collaboratively, psychologist educators and trainers at the doctoral, internship, and postdoctoral levels; credentialers; practitioners; and students offer 8 proposals for psychologists to consider in recognizing, assessing, and intervening with problems of professional competence in students and practicing professionals. In the proposals, the authors address the following topics: definitions and categories; preparing the system; self-assessment; remediation; diversity; communication across various levels of the system; confidentiality; and ethical, regulatory, and legal underpinnings. They also propose future directions for the assessment of problems in professional competence in both students and practicing psychologists. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The impact of CHP generation on CO2 emissions

The combined generation of heat and power (cogeneration) is praised by many as a technique for reducing the emissions of CO₂ in industrialized nations. This is generally true but not always. In this article we discuss the impact of some major variables on the CO₂ emission reduction capacity of cogeneration. Two sets of variables are predominant: the characteristics of the CHP process and the composition of the electricity generation sector. We highlight the interaction between the two sets of variables with the help of diagrams.     

Long-term stability of an Au/Al2O3 catalyst prepared by incipient wetness in continuous-flow glucose oxidation

A 0.3% Au/Al₂O₃ catalyst prepared by the incipient wetness (IW) method was investigated in the continuous-flow liquid-phase glucose oxidation. Therefore, a continuous stirred tank reactor (CSTR) system equipped with an ultrasonic separator was used. The continuous-flow glucose oxidation was carried out at 40 °C, pH 9 and 1 bar oxygen partial pressure. Residence time and glucose concentration were varied. The IW gold catalyst showed very high activity and selectivity to gluconic acid within its 110 days of operation and, thus, an excellent long-term stability. Even after severe microbial contaminations of the catalyst, its activity could be completely restored by in situ regeneration with 2-propanol.     

Synthesis and Pharmacological In Vitro Investigations of Novel Shikonin Derivatives with a Special Focus on Cyclopropane Bearing Derivatives

Melanoma is the deadliest form of skin cancer and accounts for about three quarters of all skin cancer deaths. Especially at an advanced stage, its treatment is challenging, and survival rates are very low. In previous studies, we showed that the constituents of the roots of Onosma paniculata as well as a synthetic derivative of the most active constituent showed promising results in metastatic melanoma cell lines. In the current study, we address the question whether we can generate further derivatives with optimized activity by synthesis. Therefore, we prepared 31, mainly novel shikonin derivatives and screened them in different melanoma cell lines (WM9, WM164, and MUG-Mel2 cells) using the XTT viability assay. We identified (R)-1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl 2-cyclopropyl-2-oxoacetate as a novel derivative with even higher activity. Furthermore, pharmacological investigations including the ApoToxGlo^TM Triplex assay, LDH assay, and cell cycle measurements revealed that this compound induced apoptosis and reduced cells in the G1 phase accompanied by an increase of cells in the G2/M phase. Moreover, it showed hardly any effects on the cell membrane integrity. However, it also exhibited cytotoxicity against non-tumorigenic cells. Nevertheless, in summary, we could show that shikonin derivatives might be promising drug leads in the treatment of melanoma.     

Functional Characterisation of Three Glycine N-Acyltransferase Variants and the Effect on Glycine Conjugation to Benzoyl–CoA

The glycine conjugation pathway in humans is involved in the metabolism of natural substrates and the detoxification of xenobiotics. The interactions between the various substrates in this pathway and their competition for the pathway enzymes are currently unknown. The pathway consists of a mitochondrial xenobiotic/medium-chain fatty acid: coenzyme A (CoA) ligase (ACSM2B) and glycine N-acyltransferase (GLYAT). The catalytic mechanism and substrate specificity of both of these enzymes have not been thoroughly characterised. In this study, the level of evolutionary conservation of GLYAT missense variants and haplotypes were analysed. From these data, haplotype variants were selected (156Asn > Ser, [17Ser > Thr,156Asn > Ser] and [156Asn > Ser,199Arg > Cys]) in order to characterise the kinetic mechanism of the enzyme over a wide range of substrate concentrations. The 156Asn > Ser haplotype has the highest frequency and the highest relative enzyme activity in all populations studied, and hence was used as the reference in this study. Cooperative substrate binding was observed, and the kinetic data were fitted to a two-substrate Hill equation. The coding region of the GLYAT gene was found to be highly conserved and the rare 156Asn > Ser,199Arg > Cys variant negatively affected the relative enzyme activity. Even though the 156Asn > Ser,199Arg > Cys variant had a higher affinity for benzoyl-CoA (s_0.5,benz = 61.2 µM), k_cat was reduced to 9.8% of the most abundant haplotype 156Asn > Ser (s_0.5,benz = 96.6 µM), while the activity of 17Ser > Thr,156Asn > Ser (s_0.5,benz = 118 µM) was 73% of 156Asn > Ser. The in vitro kinetic analyses of the effect of the 156Asn > Ser,199Arg > Cys variant on human GLYAT enzyme activity indicated that individuals with this haplotype might have a decreased ability to metabolise benzoate when compared to individuals with the 156Asn > Ser variant. Furthermore, the accumulation of acyl-CoA intermediates can inhibit ACSM2B leading to a reduction in mitochondrial energy production.     

Differently sized native milk fat globules separated by microfiltration: fatty acid composition of the milk fat globule membrane and triglyceride core

The aim of this study was to characterize the fatty acid composition of the core and membrane of differently sized milk fat globules separated by microfiltration, which can now be used to manufacture dairy products. Native milk fat globules of various mean diameters, ranging from d₄₃ = 2.3 µm to 8.0 µm, were obtained using microfiltration of raw whole milk. After milk fat globule washing, the milk fat globule membrane (MFGM) and the triglyceride core (TC) were separated by manual churning. After total lipid extraction from each fraction, their fatty acid composition was characterized using methyl ester analysis by gas chromatography. Regardless of season, no significant differences were observed in the fatty acid composition of the MFGM phospholipids. Conversely, significant differences were found in the fatty acid composition of TC; particularly, small fat globule TC contained more medium‐chain fatty acids and less stearic acid than large fat globule TC. These results show that the previously observed differences in total fatty acid composition among differently sized milk fat globules are due to their triglyceride composition and MFGM amount rather than to the composition of the MFGM.     

Measuring Cognitive Load Using Linguistic Features: Implications for Usability Evaluation and Adaptive Interaction Design

An intelligent adaptable system, aware of a user’s experienced cognitive load, may help improve performance in complex, time-critical situations by dynamically deploying more appropriate output strategies to reduce cognitive load. However, measuring a user’s cognitive load robustly, in real-time is not a trivial task. Many research studies have attempted to assess users’ cognitive load using different measurements, but these are often unsuitable for deployment in real-life applications due to high intrusiveness. Relatively novel linguistic behavioral features as potential indices of user’s cognitive load is proposed. These features may be collected implicitly and nonintrusively supporting real-time assessment of users’ cognitive load and accordingly allowing adaptive usability evaluation and interaction. Results from a laboratory experiment show significantly different linguistic patterns under different task complexities and cognitive load levels. Implications of the research for adaptive interaction are also discussed, that is, how the cognitive load measurement-based approach could be used for user interface evaluation and interaction design improvement.