From analysis to synthesis: new ligand binding sites on the lactate dehydrogenase framework. Part II

In Part I of this article (published in the March issue of TIBS1), substrate-binding and catalysis in lactate dehydrogenase were examined by genetic modification of the protein structure and analysis of the functional consequences. In Part II, the conclusions are used in the design and synthesis of two modified forms of the enzyme; one in which the substrate specificity is shifted to produce a more effective malate dehydrogenase than that isolated from the host organism and one which no longer requires its allosteric activator (fructose 1,6-bisphosphate).     

Pre-existing fairness concerns restrict the cultural evolution and generalization of inequitable norms in children

Many social exchanges produce benefits that would not exist otherwise, but anticipating conflicts about how to distribute these benefits can derail exchange and destroy the gains. Coordination norms can solve this problem by providing a shared understanding of how to distribute benefits, but such norms can also perpetuate group-level inequality. To examine how inequitable norms evolve culturally and whether they generalize from one setting to another, we conducted an incentivized lab-in-the-field experiment among kindergarten (5–6) and second-grade (8–9) children living in Switzerland (4′228 decisions collected from 326 children). In Part 1, we created two arbitrarily marked groups, triangles and circles. We randomly and repeatedly formed pairs with one triangle and one circle, and players in a pair played a simple bargaining game in which failure to agree destroyed the gains from social exchange. At the beginning of Part 1 we suggested a specific way to play the game. In symmetric treatments, this suggestion did not imply inequality between the groups, while in asymmetric treatments it did. Part 2 of the experiment addressed the generalization of norms. Retaining their group affiliations from Part 1, each child had to distribute resources between an in-group member and an out-group member. Children of both age groups in symmetric treatments used our suggestions about how to play the game to coordinate in Part 1. In asymmetric treatments, children followed our suggestions less consistently, which reduced coordination but moderated inequality. In Part 2, older children did not generalize privilege from Part 1. Rather, they compensated the underprivileged. Younger children neither generalized privilege nor compensated the underprivileged.     

Scale-up engineering in animal cell technology: Part II

In the first part of this article we defined what is meant by scale-up. We also introduced the idea that engineers, in seeking to scale up bioprocesses, look at parameters that limit that process. If the parameters are independent of scale or reactor configuration they may enable the calculation of engineering data to predict behavior at large scales. In this exercise, dimensional analysis is one of the engineer's most important tools.In Part II, we will examine the application of the approach outlined in Part I to the analysis of scale-up in situations where shear or mass transfer may be limiting factors, situations which are particularly likely to arise in animal cell culture.     

The theory and practice of psychological medicine in the Ayurvedic tradition

In this paper I attempt to elucidate and render intelligible to a non-Western reader the internal logic and the consistency in both theory and practice of Ayurvedic psychological medicine. In Part 1, I deal with the classical metaphysical base (Sämkya philosophy) on which the Ayurvedic concept of mind rests. I also deal with the theory of psychological medicine as stated in ancient Sanskrit texts. In Part II, I deal with the manner in which the classic theory is implemented in contemporary practice in Sri Lanka, while Part III deals with case studies of two patients taking Ayurvedic therapy.     

Accessory respiration in the climbing perch anabas scandens

Eleven species of blackfly larvae were collected in a survey of Upper Teesdale streams, Northern England. Their distribution in these streams is given. In one stream, Moss Burn, which was studied in detail, a zonation of species occurred along its length and changes in species composition are described for one part of the stream in three summers.Part of the work included in this paper was undertaken while the author was a member of the Department of Zoology, University of Newcastle upon TynePart of the work included in this paper was undertaken while the author was a member of the Department of Zoology, University of Newcastle upon Tyne     

Thermal expansion measurements of cryoprotective agents. Part II: measurements of DP6 and VS55, and comparison with DMSO

As part of an ongoing effort to characterize the mechanical behavior of biological tissues in the cryogenic temperature range, the current study focuses on thermal expansion measurements of cryoprotective agents. Utilizing the experimental apparatus described in the previous report (Part I), the current report (Part II) includes thermal expansion measurements of the cryoprotectant mixtures DP6 and VS55, and comparison with available data from the literature on DMSO. In the temperature range in which the cryoprotectant mixture behaves like low viscosity liquid, results of this study show that the thermal expansion coefficient of VS55 and DP6 is 22% and 40% lower than that of 3M DMSO, respectively, where 3M DMSO is only one component of each cryoprotectant mixture. This significant difference is attributed to the presence of 3M formamide in VS55.     

Destabilization and stabilization of proteins

In Part I the history of progress in the stabilization and destabilization of protein conformations by means of cosolvents is outlined in terms of distinct conceptual steps. In Part II it is shown that a straightforward application of the Kirkwood-Buff theory of solutions leads to formulas for the preferential interaction and the free energy of unfolding, which confirm and generalize the results of Part I.     

Growth and Development of the Banana Plant: 3. A. The Origin of the Inflorescence and the Development of the Flowers: B. The Structure and Development of the Fruit

In this paper, which is presented in two parts, the growth anddevelopment of the banana plant have been examined from thestandpoint of the origin of the inflorescence and the developmentof the flowers (Part A) and the structure and development ofthe fruit (Part B). First the main centres of growth in thesestructures are located and the manner of their development ispresented. Thereafter, attention is focused upon the salientevents which determine the alternative courses of developmentwith a view to designating the chemical and physiological stimulithat may be required.     

A new catheter for tumor-targeting with radioactive microspheres in representative hepatic artery systems--part II: solid tumor-targeting in a patient-inspired hepatic artery system

In this second part, the methodology for optimal tumor-targeting is further explored, employing a patient-inspired hepatic artery system which differs significantly from the idealized configuration discussed in Part I. Furthermore, the fluid dynamics of a microsphere supply apparatus is also analyzed. The best radial catheter positions and particle-release intervals for tumor targeting were determined for both the idealized and patient-inspired configurations. This was accomplished by numerically analyzing generated particle release maps (PRMs) for ten equally spaced intervals throughout the pulse. As in Part I, the effects of introducing a catheter were also investigated. In addition to the determination of micro-catheter positioning and, hence, optimal microsphere release, a microsphere-supply apparatus (MSA) was analyzed, which transports the particles to the catheter-nozzle, considering different axial particle injection functions, i.e., step, ramp, and S-curve. A refined targeting methodology was developed which demonstrates how the optimal injection region and interval can be determined with the presence of a catheter for any geometric configuration. Additionally, the less abrupt injection functions (i.e., ramp and S-curve) were shown to provide a more compact particle stream, making them better choices for targeting. The results of this study aid in designing the smart micro-catheter (SMC) in conjunction with the MSA, bringing this innovative treatment procedure one step closer to implementation in clinical practice.     

THE TOPICAL AND SYSTEMIC USE OF CORTISONE IN DERMATOLOGY

Part I of this report deals with the topical use of cortisone in a variety of skin diseases. Fifteen patients with chronic discoid lupus erythematosus, four patients with necrobiosis lipoidica diabeticorum, four with psoriasis, one with lichen planus and one with granuloma annulare were treated with cortisone ointment. All the patients with chronic discoid lupus erythematosus had some degree of improvement. In two patients with chronic lupus erythematosus, complete clearing of the eruption occurred. In four patients with necrobiosis lipoidica diabeticorum remarkable involution resulted. Patients with psoriasis, lichen planus and granuloma annulare were not benefited.Part II deals with the systemic use of cortisone. Eight patients with severe serum sickness-like penicillin reaction responded dramatically to parenterally administered cortisone. In two cases of pemphigus vulgaris and one case of Sulzberger-Garbe disease, the disease was kept in remission with cortisone administered intramuscularly as well as orally. Partial improvement resulted in a case of localized myxedema associated with malignant exophthalmus. Two patients with exfoliative dermatitis due to therapy with heavy metals responded dramatically to cortisone. No beneficial effects were noted in patients with chronic urticaria and atopic dermatitis.The systemic use of ACTH and cortisone in dermatology at present should be confined to patients with known fatal or hopelessly incapacitating diseases and to patients with extreme hypersensitivity reactions which may be protracted or life-endangering, and which can be controlled or cured with a relatively small total dosage of the agents in a short time.     

The allotetraploidization of maize

Summary Allotetraploidization is the creation of artificial allotetraploids. Allotetraploidization of maize can be accomplished by concentrating differential pairing affinity (DPA) factors into lines by a recurrent selection breeding system. Selection will be based on changes in genetic ratios which are the result of changes in the relative frequencies of various pairing configurations caused by DPA. Part 1 of this series gave extensive data on gene segregation in trisomic and tetraploid heterozygotes. Some of these tetraploids behaved like segmental allotetraploids. Part 2 presented a model for gene segregation in segmental allotetraploids. This paper presents an analogous model for gene segregation in trisomic heterozygotes. The pairing configurations of trisomes are analyzed by considering pairing in single arms which then are combined to obtain pairing configurations for whole chromosomes. The chromosome disjunction patterns of the various pairing configurations are hypothesized and expected genetic ratios are given that result from different levels of DPA expressed in several hypothetical trisomes. The model analyzes the effect of random pairing in one arm and non-random pairing in the other arms. Also, the effect of crossing over is taken into account. Because crossing over rates are affected by the environment, part of the variability in the data (Part 1) is explained. In addition, an hypothesis is advanced to explain the frequent enhancement of pairing affinity following x-irradiation.Contribution from Agricultural Research/Science and Education Administration, US Department of Agriculture, University of Missouri, Columbia, Missouri, Missouri Agric. Exp. Sta. Jounal Series No. 8 670     

Student-oriented learning: an inquiry-based developmental biology lecture course

In this junior-level undergraduate course, developmental life cycles exhibited by various organisms are reviewed, with special attention--where relevant--to the human embryo. Morphological features and processes are described and recent insights into the molecular biology of gene expression are discussed. Ways are studied in which model systems, including marine invertebrates, amphibia, fruit flies and other laboratory species are employed to elucidate general principles which apply to fertilization, cleavage, gastrulation and organogenesis. Special attention is given to insights into those topics which will soon be researched with data from the Human Genome Project. The learning experience is divided into three parts: Part I is a in which the Socratic (inquiry) method is employed by the instructor (GMM) to organize a review of classical developmental phenomena; Part II represents an in which students study the details related to the surveys included in Part I as they have been reported in research journals; Part III focuses on a class project--the preparation of a spiral bound on a topic of relevance to human developmental biology (e.g.,Textbook of Embryonal Stem Cells). Student response to the use of the Socratic method increases as the course progresses and represents the most successful aspect of the course.     

Human behavioral ecology: II

Human behavioral ecology is an interdisciplinary field of study applying theory from evolutionary ecology to a variety of anthropological questions. In Part I of this essay,¹ which appeared in an earlier issue, I surveyed key theoretical and methodological elements of the field, and summarized representative studies and issues in the topical area of subsistence strategies. In Part II, I turn to studies of reproductive strategies, and those analyzing patterns of cooperation and competition in an ecological and adaptive framework. I conclude with a brief look at possible future developments in the field.     

Gating mechanisms of mechanosensitive channels of large conductance, II: systematic study of conformational transitions

Part II of this study is based on the continuum mechanics-based molecular dynamics-decorated finite element method (MDeFEM) framework established in Part I. In Part II, the gating pathways of Escherichia coli-MscL channels under various basic deformation modes are simulated. Upon equibiaxial tension (which is verified to be the most effective mode for gating), the MDeFEM results agree well with both experiments and all-atom simulations in literature, as well as the analytical continuum models and elastic network models developed in Part I. Different levels of model sophistication and effects of structural motifs are explored in detail, where the importance of mechanical roles of transmembrane helices, cytoplasmic helices, and loops are discussed. The conformation transitions under complex membrane deformations are predicted, including bending, torsion, cooperativity, patch clamp, and indentation. Compared to atom-based molecular dynamics simulations and elastic network models, the MDeFEM framework is unusually well-suited for simulating complex deformations at large length scales. The versatile hierarchical framework can be further applied to simulate the gating transition of other mechanosensitive channels and other biological processes where mechanical perturbation is important.     

Life Cycle Assessment of Water Production Technologies - Part 2: Reverse Osmosis Desalination versus the Ebro River Water Transfer (9 pp)

- Preamble. This series of two papers analyses and compares the environmental loads of different water production technologies in order to establish, in a global, rigorous and objective way, the less aggressive technology for the environment with the present state of the art of technology. Further, an estimation of the potential environmental loads that the considered technologies could provoke in future is also presented, taking into account the most suitable evolution of the technology. - Part 1 presents the assessment of most commercial desalination technologies which are spread worldwide: Reverse Osmosis, Multi Effect Desalination and Multi Stage Flash. Part 2 presents the comparative LCA analysis of a big hydraulic infrastructure, as is to be found in the Ebro River Water Transfer project, with respect to desalination. - Intention, Goal and Background. In this paper some relevant results of a research work are presented, the main aim of which consists of performing the environmental assessment of different water production technologies in order to establish, in a global, rigorous and objective way, the less aggressive technology for the environment for supplying potable water to the end users. The scope of this paper is mostly oriented to the comparative Life Cycle Assessment of different water production technologies instead of presenting new advancements in the LCA methodology. Based on the results obtained in Part 1 (LCA of most widespread commercial desalination technologies), the particular case of a big hydraulic project, which is the Ebro River Water Transfer (ERWT) considered in the Spanish National Hydrologic Plan, versus the production by desalination of the same amount of water to be diverted, is compared in Part 2. The assessment technique is the Life Cycle Analysis (LCA), which includes the entire life cycle of each technology, encompassing: extraction and processing raw materials, manufacturing, transportation and distribution, operation and final waste disposal. Methods and Main Features. The software SimaPro 5.0, developed by Dutch PRé Consultants, has been used as the analysis tool, because it is a well known, internationally accepted and validated tool. Different evaluation methods have been applied in the LCA evaluation: CML 2 baseline 2000, Eco-Points 97 and Eco-Indicator 99. Data used in the inventory analysis of this Part 2 come from: a) desalination: data obtained for existing plants in operation; b) ERWT: Project approved in the Spanish National Hydrologic Plan and its Environmental Impact Evaluation and; c) data bases implemented in the SimaPro software – BUWAL 250, ETH-ESU 96, IDEMAT 2001. Different scenarios have been analyzed in both parts in order to estimate not only the potential of reduction of the provoked environmental loads with the present state of the art of technology, but also the most likely future trend of technological evolution. In Part 1, different energy production models and the integration of desalination with other productive processes are studied, while the effect of the most likely technological evolution in the midterm, and the estimation of the environmental loads to the water transfer during drought periods are considered in Part 2. Results and Discussion As proven in Part 1, RO is a less aggressive desalination technology for the environment. Its aggression is one order of magnitude lower than that of the thermal processes, MSF and MED. The main contribution to the global environmental impact of RO comes from the operation, while the other phases, construction and disposal, are almost negligible when compared to it. In the case of the ERWT, the contribution of the operation phase is also the most important one, but the construction phase has an important contribution too. Its corresponding environmental load, with the present state of the art of technology, is slightly lower than that provoked by the RO desalination technology. However, the results obtained in the different scenarios analyzed show that the potential reduction of the environmental load in the case of the ERWT is significantly lower than that in the case of the RO. The effect of drought periods in the assessed environmental loads of the water transfer is not negligible, obtaining as a result an increasing environmental load per m3 of diverted water. Conclusion The environmental load associated with RO, with the present state of the art of technology, is slightly higher than that provoked by the ERWT. However, considering the actual trend of technological improvement of the RO and the present trend of energy production technology in the address of reducing the fossil fuels\ contribution in the electricity production, the environmental load associated with RO in the short mid-term would be likely to be lower than that corresponding to the ERWT. Recommendations and Outlook Although desalination technologies are energy intensive and provoke an important environmental load, as already explained in Part 1, they present a high potential of reducing it. In respect to ERWT, the results indicate, when the infrastructure of ERWT is completed (by 2010–2012), that the LCA of RO will be likely to be against the water transfer. With the present technological evolution of water production technologies and from the results obtained in this paper, it seems, from an environmental viewpoint, that big hydraulic projects should be considered the last option because they are rigid and long-term infrastructures (several decades and even centuries of operation) that provoke important environmental loads with only a small margin for reducing them.     

Fit for purpose: the importance of quality standards in the cultivation and use of live plant collections for conservation

The one activity that is common to all botanic gardens is the cultivation of plants. Many also have education, science, conservation, events and exhibitions programmes but cultivating plants is at the core of every botanic garden and plants are used to support all these activities. With existing and potential threats to plants and habitats it is essential that botanic gardens contribute to both the science and practice of plant conservation. This is because they have the staff skills and some of the resources required to make a significant contribution. However, if the live plant collections are to play a part in this work, and they must, then they must be guided by a Collection Policy and achieve the highest standards of sampling, record keeping and cultivation to make sure that the plants in question are fit for purpose. After describing the Collection Policy for the Royal Botanic Garden Edinburgh (RBGE) in Part 1, the paper covers the importance of wild origin material, targets, review and audits in driving up standards in Part 2. In Part 3, the inadequacy of some conservation collections are described. The approach taken by three different conservation programmes at RBGE which have embraced the need for rigorous standards in conservation collections are then described. These are the International Conifer Conservation Programme, the Scottish Plants Programme and RBGE’s Target 8 (of the Global Strategy for Plant Conservation) Project. Examples from RBGE’s Living Collection and Collection Policy are used throughout to illustrate the points being made.     

Life Cycle Assessment of Water Production Technologies - Part 1: Life Cycle Assessment of Different Commercial Desalination Technologies (MSF,MED, RO) (9 pp)

- Preamble. This series of two papers analyses and compares the environmental loads of different water production technologies in order to establish, in a global, rigorous and objective way, the less aggressive technology for the environment with the present state of the art of the technology. Further, it is also presented an estimation of the potential environmental loads that the considered technologies could provoke in future, taking into account the most suitable evolution of the technology. - Part 1 presents the assessment of most commercial desalination technologies which are spread worldwide: Reverse Osmosis, Multi Effect Desalination and Multi Stage Flash. Part 2 presents the comparative LCA analysis of a big hydraulic infrastructure, as is to be found in the Ebro River Water Transfer project, with respect to desalination. - DOI: http://dx.doi.org/10.1065/lca2004.09.179.1 - Intention, Goal and Background. In this paper, some relevant results of a research work are presented, the main aim of which consists of performing the environmental assessment of different water production technologies in order to establish, in a global, rigorous and objective way, the less aggressive technology for the environment of potable water supply to the end users. That is, the scope of this paper is mostly oriented to the comparative Life Cycle Assessment of different water production technologies instead of presenting new advancements in the LCA methodology. In Part 1, the environmental loads associated with the most widespread and important commercial desalination technologies all over the world - Reverse Osmosis (RO), Multi Effect Desalination (MED) and Multi Stage Flash (MSF) – are compared. The assessment technique is the Life Cycle Analysis (LCA), which includes the entire life cycle of each technology, encompassing: extraction and processing raw materials, manufacturing, transportation and distribution, operation and final waste disposal.- Methods and Main Features. The software SimaPro 5.0, developed by Dutch PRé Consultants, has been used as the analysis tool, because it is a well known, internationally accepted and validated tool. Different evaluation methods have been applied in the LCA evaluation: CML 2 baseline 2000, Eco-Points 97 and Eco-Indicator 99. Data used in the inventory analysis of this Part 1 come from: a) existing plants in operation; b) data bases implemented in the SimaPro 5.0 software -BUWAL 250, ETH-ESU 96, IDEMAT 2001. Different scenarios have been analyzed in both parts in order to estimate, not only the potential of reduction of the provoked environmental loads with the present state of the art of technology, but also the most likely future trend of technological evolution. In Part 1, different energy production models and the integration of desalination with other productive processes are studied, while the effect of the most likely technological evolution in the midterm, and the estimation of the environmental loads to the water transfer during drought periods are considered in Part 2. Results and Discussion The main contribution to the global environmental impact of desalination technologies comes from the operation, while the other phases, construction and disposal, are almost negligible when compared to it. Energy is very important in desalination, for this reason the environmental loads change a lot depending on the technology used for providing the energy used in the desalination process. Among the different analyzed technologies, RO is the least aggressive desalination technology (one order of magnitude lower than the thermal processes, MSF and MED) for the environment. When integrating thermal desalination with other productive processes taking advantage of the residual heat, the environmental loads of thermal desalination technologies is highly reduced, obtaining similar loads to that of RO. The environmental loads of desalination technologies are significantly reduced when an energy model based on renewable energies is used. Taking into account the technological evolution, which is experiencing the RO, a reduction of its environmental load by about 40% is to be expected in the mid-term. Conclusion The main conclusion of Part 1 is that, with the present state of the art of the technology, RO is clearly the desalination technology with a reduced environmental load (one order of magnitude lower than the thermal processes, MSF and MED). In the case of thermal desalination technologies, their environmental load can be highly reduced (about 1,000 times less) when integrated with other industrial processes. In the case of RO, the scores and the airborne emissions obtained from an electricity production model based on renewable energies are about 65-70 times lower than those obtained when the electricity production model is mainly based on fossil fuels. Recommendations and Outlook Although desalination technologies are energy intensive and provoke an important environmental load, they present a high potential in being reduced since: a) in the mid-term, it is to be expected that the different technologies could improve their efficiency significantly, b) the environmental loads would be highly reduced if the energy production models were not mainly based on fossil fuels and c) the energy consumption, particularly in the case of thermal desalination, can be drastically reduced when integrating desalination with other productive processes. The results presented in this paper indicate that a very interesting and promising field of research is available in order to reduce the environmental load of these vigorous and increasing desalination technologies.     

Comparison of the organization and fine structure of a chicken and a Xenopus laevis vitellogenin gene

The structural organization and the coding nucleotide sequence of the Xenopus laevis A2 and the chicken major vitellogenin genes have been compared. Both genes show the same exon-intron organization. However, the degree of homology between the nucleotide and derived amino acid sequences varies extensively along the genes. Several of the 35 exons are quite similar, and a unique cysteine motif in the lipovitellin II domain is conserved between the two genes. In contrast, one internal region is quite divergent. Part of this region encodes phosvitin, which appears to have evolved rapidly by both point mutations and duplications of serines or short other amino acid stretches. On the basis of these observations, we discuss the possible mechanism of evolution of phosvitin in vertebrates.     

Cannabidiol: an overview of some chemical and pharmacological aspects. Part I: chemical aspects

Over the last few years considerable attention has focused on cannabidiol (CBD), a major non-psychotropic constituent of Cannabis. In Part I of this review we present a condensed survey of the chemistry of CBD; in Part II, to be published later, we shall discuss the anti-convulsive, anti-anxiety, anti-psychotic, anti-nausea and anti-rheumatoid arthritic properties of CBD. CBD does not bind to the known cannabinoid receptors and its mechanism of action is yet unknown. In Part II we shall also present evidence that it is conceivable that, in part at least, its effects are due to its recently discovered inhibition of anandamide uptake and hydrolysis and to its anti-oxidative effect.     

Haptic control of a pneumatic muscle actuator to provide resistance for simulated isokinetic exercise: Part I – dynamic test station and human quadriceps dynamic simulator

Pneumatic muscle actuators (PMAs) have a high power to weight ratio and possess unique characteristics which make them ideal actuators for applications involving human interaction. PMAs are difficult to control due to nonlinear dynamics, presenting challenges in system implementation. Despite these challenges, PMAs have great potential as a source of resistance for strength training and rehabilitation. The objective of this work was to control a PMA for use in isokinetic exercise, potentially benefiting anyone in need of optimal strength training through a joint's range of motion. A human quadriceps dynamic simulator (HQDS) was developed so that control effectiveness and accommodation could be tested prior to human implementation. The experimental set-up and HQDS are discussed in Part I of this work. The development of a PMA haptic controller and its interaction with the HQDS are discussed in Part II.