All-trans-retinoic acid 4-hydroxylation in human liver microsomes: in vitro modulation by therapeutic retinoids

All-trans retinoic acid (ATRA) induces remission in patients with acute promyelocytic leukaemia. Other retinoids, including 9-cis- and 13-cis-retinoic acid (9-cis- and 13-cis-RA), are now being evaluated for their therapeutic potential. The elimination of ATRA is partially dependent on cytochrome P450 (P450)-mediated 4-hydroxylation, but the interaction of other retinoids with P450 has not yet been assessed. In the present study 9-cis- and 13-cis-RAs, as well as all-trans-retinol and three isomeric retinals were found to inhibit ATRA 4-hydroxylation in human hepatic microsomes, but the arotinoids acitretin and etretinate were not inhibitors 9-cis- and 13-cis-RA were competitive inhibitors of ATRA 4-hydroxylation (Ki:Km ratios 3.5 +/- 0.8 and 6.3 +/- 0.5, respectively) suggesting that these retinoids are alternate, but inferior, substrates for the P450 enzyme(s) that mediate the activity. The biotransformation of therapeutic retinoids containing the beta-ionone ring system is likely to involve the microsomal ATRA 4-hydroxylase P450.     

Amines compounds as inhibitors of PCDD/Fs de novo formation on sintering process fly ash

The polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) are highly toxic compounds produced by some natural processes and different human activities. Waste incineration as well as steel and iron industries, in particular, the sintering process, are among the principal sources of these pollutants. In this paper, two inhibitors, triethanolamine (TEA) and monoethanolamine (MEA) are tested relating to their abilityto prevent the de novo formation of PCDD/Fs on sinter plant fly ash. The amounts of both PCDDs and PCDFs, formed by thermal treatment of the fly ash, decrease when inhibitors are added. The best results, up to 90% reduction of the PCDD/ Fs formation, are obtained when MEA is mixed with the fly ash at the highest concentration tested (2 wt %). The addition of inhibitors modifies the PCDFs/PCDDs ratios and, under some experimental conditions, the PCDD/Fs homologue distributions, suggesting that more than one pathway for the de novo formation of PCDD/Fs exist. On the other hand, no modification in the PCDD/Fs isomer distributions is observed as a result of the addition of inhibitors, in accordance with the possible thermodynamic control of these distributions. The temperature tested, 325 and 400 degrees C, does not affect the inhibition activity; however, longer reaction times (4 h instead of 2 h) give better percentages of PCDD/Fs reduction. The results suggest that the two inhibitors and especially MEA can reduce the PCDD/Fs formation on sinter plant fly ash under various conditions of temperature and reaction time, making them suitable for use in the real process. Tests performed in parallel at a real sinter plant are in good agreement with the laboratory experiments and confirm that the use of inhibitors is an appropriate technique for the prevention of PCDD/Fs emissions from sintering processes.     

Characterization of a Female-Produced Courtship Pheromone in the Parasitoid Nasonia vitripennis

Males of the parasitoid Nasonia vitripennis (Walker) (Hymenoptera: Pteromalidae) show a characteristic courtship behavior. We demonstrate that male arrestment and key behavioral elements of the courtship sequence are mediated by a female-derived contact sex pheromone. Males were arrested on paper disks treated with female extracts but not on those treated with male extracts. Male responsiveness was influenced by the surface to which female extracts were applied. Extracts applied to an extracted beetle elytron arrested males more strongly than those applied to filter paper of comparable size. However, more complex behavioral elements, such as head nodding and copulation attempts, were shown only when extracts were applied to extracted male cadavers, suggesting that tactile or visual cues synergize the male response. The chemicals involved are stable, of low volatility, and nonpolar. Dead females arrested males and elicited courtship behavior for at least 8 d. Males showed no sign of attraction to live females at a distance of 3 cm in an olfactometer. Fractionation of female extracts demonstrated that the activity was exclusively located in the nonpolar fraction. Analysis of the active fraction by gas chromatography–mass spectrometry revealed that cuticular hydrocarbons with chain lengths between 25 and 37 carbon units were present. Comparison of hydrocarbon profiles from males and females showed qualitative and quantitative differences. These results suggest that sex-specific cuticular hydrocarbons are the key signals mediating the male courtship behavior in N. vitripennis.     

Effects of Rationally Designed Physico-Chemical Variants of the Peptide PuroA on Biocidal Activity towards Bacterial and Mammalian Cells

Antimicrobial peptides (AMPs) often exhibit wide-spectrum activities and are considered ideal candidates for effectively controlling persistent and multidrug-resistant wound infections. PuroA, a synthetic peptide based on the tryptophan (Trp)-rich domain of the wheat protein puroindoline A, displays strong antimicrobial activities. In this work, a number of peptides were designed based on PuroA, varying in physico-chemical parameters of length, number of Trp residues, net charge, hydrophobicity or amphipathicity, D-versus L-isomers of amino acids, cyclization or dimerization, and were tested for antimicrobial potency and salt and protease tolerance. Selected peptides were assessed for effects on biofilms of methicillin-resistant Staphylococcus aureus (MRSA) and selected mammalian cells. Peptide P1, with the highest amphipathicity, six Trp and a net charge of +7, showed strong antimicrobial activity and salt stability. Peptides W7, W8 and WW (seven to eight residues) were generally more active than PuroA and all diastereomers were protease-resistant. PuroA and certain variants significantly inhibited initial biomass attachment and eradicated preformed biofilms of MRSA. Further, P1 and dimeric PuroA were cytotoxic to HeLa cells. The work has led to peptides with biocidal effects on common human pathogens and/or anticancer potential, also offering great insights into the relationship between physico-chemical parameters and bioactivities, accelerating progress towards rational design of AMPs for therapeutics.     

Flexible distillation test rig on a laboratory scale for characterization of additively manufactured packings

Additive manufacturing is increasingly being used to develop innovative packings for absorption and desorption columns. Since distillation has not been in focus so far, this article aims to fill this gap. The objective is to obtain a miniaturized three dimensional (3D) printed packed column with optimized properties in terms of scalability and reproducibility, which increases process development efficiency. For this purpose, a flexible laboratory scale test rig is presented combining standard laboratory equipment with 3D printed components such as innovative multifunctional trays or the column wall with packing. The test rig offers a particularly wide operating range for column diameters between and . First results regarding the time to reach steady-state, operational stability, and separation efficiency measurements are presented using a 3D printable version of the Rombopak 9M. Currently, further developed and newly designed packing structures are being characterized, which should exhibit optimized properties especially with respect to scalability and separation efficiency.     

Comparison of the Generalized Species Transfer Model with a Two-Field Approach for Interfacial Mass Transfer

Two different approaches can be applied to calculate the mass transfer in a two-phase system using computational fluid dynamics and the volume-of-fluid method, single-field and two-field approaches. The used method affects the stability of the calculation as well as the accuracy of the result. Two volume-of-fluid-based approaches, namely, the generalized continuous species transfer model, a single-field approach, and a two-field approach are compared. The models are implemented in the OpenFOAM® framework and validated in a 1D test case. Although both approaches show great agreement with the analytical solution for large time steps, numerical instabilities of the two-field model are revealed with a reduced time step size, which leads to false results.     

Analyzing motoric and physiological data in describing upper extremity movement in the aged

Cognitive functions, motoric expression, and changes in physiology are often studied separately, with little attention to the relationships or correlations among them. The study presented in this paper implements an integrated approach by combining motion capture (action) and EMG (physiological) parameters as synchronized data streams resulting from the action and associated physiological data. The reported experiments were designed to measure the preparatory movement capabilities of the upper extremities. In particular, measurement of changes in preparatory activity during the aging process is of interest in this context, as the attempt is to develop means to compensate for loss of adaptive capabilities that aging entails. To achieve this goal, it is necessary to quantify preparation phases (timing and intensity). Motion capture and EMG parameters were measured when subjects raised their arms without constraint (condition one) and raised their arms while holding a ball (second condition). Furthermore, on comparing aging and young participants, it was confirmed that with aging the temporal relationships between actual movement and the preceding EMG signal change.     

Antecapere ergo sum: what price knowledge?

In the age of ubiquitous technology, humans are reshaped through each transaction they are involved in. AI-driven networks, online games, and multisensory interactive environments make up alternate realities. Within such alternate worlds, users are reshaped as deterministic agents. Technology’s focus on reducing complexity leads to a human being dependent on prediction-driven machines and behaving like them. Meaning and information are disconnected. Existence is reduced to energy processes. The immense gain in efficiency translates as prosperity. Citizens of advanced economies, hurrying in the rhythm of machine-driven interactions, feel entitled to it. Successful at the price of self-awareness, they no longer know what this means. Happiness and prosperity are not consubstantial. Lack of happiness leads to aggression. This is the image of the world as we see it, no longer looking at each other, eye to eye, but screen to screen. The questions eliminated in the process of transferring responsibility from the individual to machines will inevitably become society’s new focus. When the goal is to get everyone to behave like a machine, the Singularity hypothesis becomes self-fulfilling prophecy. If, in addition to having exhausted natural resources, society does not want to end up making the human mind superfluous, it has to seek a better understanding of what makes anticipation possible. As a definitory characteristic of the living, corresponding to its complexity, anticipation can no longer be taken for granted, while every effort is made to reduce complexity for efficiency’s sake. Awareness of the processes conducive to its expression in successful human action will position human beings as masters of their destiny, not slaves of their own making. Antecapere ergo sum might be the counterclaim to Descartes’ Dubito ergo sum. To resist being perfected into oblivion, that is, unsustainable prosperity, means to reclaim the knowledge corresponding to higher levels of complexity.     

Participation in job redesign: An evaluation of the use of a sociotechnical tool and its impact

In this article we describe the use of a sociotechnical tool within a company manufacturing photographic products. The tool was used by shop‐floor operators and managers to redesign a group of jobs and tasks prior to the introduction of new technology. The tool involved two stages: (a) generating alternative scenarios of ways to reconfigure existing and new jobs and tasks within the plant; and (b) using a set of decision criteria (e.g., control, skill variety, and opportunity for social contact) to evaluate these scenarios, drawing on established sociotechnical and job design principles. The tool proved to be successful in generating new job designs, reinforcing the value of such design techniques, and highlighting the value of shop‐floor involvement in the design process. However, participation in the design process was not without its problems. We discuss these further in terms of the critical role of the workshop facilitator and the important role played by factors such as selection of participants and their background knowledge. © 2001 John Wiley & Sons, Inc.