Complementarity and the selection of nature reserves: algorithms and the origins of conservation planning, 1980–1995

This paper reconstructs the history of the introduction and use of iterative algorithms in conservation biology in the 1980s and early 1990s in order to prioritize areas for protection as nature reserves. The importance of these algorithms was that they led to greater economy in spatial extent (“efficiency”) in the selection of areas to represent biological features adequately (that is, to a specified level) compared to older methods of scoring and ranking areas using criteria such as biotic “richness” (the number of features of interest). The development of these algorithms was critical to producing a research program for conservation biology that was distinct from ecology and eventually led to what came to be called systematic conservation planning. Very similar algorithmic approaches were introduced independently in the 1980–1990 period in Australia, South Africa, and (arguably) the United Kingdom. The key rules in these algorithms were the use of rarity and what came to be called complementarity (the number of new or under-represented features in an area relative to those that had already been selected). Because these algorithms were heuristic, they were not guaranteed to produce optimal (most “efficient”) solutions. However, complementarity came to be seen as a principle rather than a rule in an algorithm and its use was also advocated for the former reason. Optimal solutions could be produced by reformulating the reserve selection problem in a mathematical programming formalism and using exact algorithms developed in that context. A dispute over the relevance of full optimality arose and was never resolved. Moreover, exact algorithms could not easily incorporate criteria determining the spatial configuration of networks of selected areas, in contrast to heuristic algorithms. Meanwhile metaheuristic algorithms emerged in the 1990s and came to be seen as a credible more effective alternative to the heuristic algorithms. Ultimately what was important about these developments was that the reserve selection problem came to be viewed a complex optimal decision problem under uncertainty, resource, and other constraints. It was a type of problem that had no antecedent in traditional ecology.     

Developments in biotechnology

This issue of EXPERIENTIA on ‘Developments in Biotechnology’ is dedicated to Professor Armin Fiechter who celebrated his 65th birthday in October. He is one of the most eminent promoters of biotechnology in Switzerland and he was instrumental in establishing the Institute for Biotechnology at ETH in 1982 of which he is still director. By pioneering the combination of fundamental and applied aspects he has greatly influenced the advancement of biotechnology in teaching and research in Switzerland. Distinguished scientists from various countries were invited to contribute to this special issue of EXPERIENTIA to review aspects of yeast physiology, process optimization and control, analytics, and applications. We are well aware that the articles presented here are only a narrow selection of the current activities in biotechnology but since Professor Fiechter has devoted most of his scientific career to research on yeast physiology, process development and instrumentation it is appropriate to focus this issue on these aspects. We thank all the authors who have contributed to mark this special event. Professor Fiechter continues to actively stimulate progress in biotechnology with a still lively awareness of future developments. May he continue to persue his objectives and, together with Mrs. Fiechter, enjoy the time to come.     

Endothelium-derived nitric oxide and vascular physiology and pathology

In 1980, Furchgott and Zawadzki demonstrated that the relaxation of vascular smooth muscle cells in response to acetylcholine is dependent on the anatomical integrity of the endothelium. Endothelium-derived relaxing factor was identified 7 years later as the free radical gas nitric oxide (NO). In endothelium, the amino acid L-arginine is converted to L-citrulline and NO by one of the three NO synthases, the endothelial isoform (eNOS). Shear stress and cell proliferation appear to be, quantitatively, the two major regulatory factors of eNOS gene expression. However, eNOS seems to be mainly regulated by modulation of its activity. Stimulation of specific receptors to various agonists (e.g., bradykinin, serotonin, adenosine, ADP/ATP, histamine, thrombin) increases eNOS enzymatic activity at least in part through an increase in intracellular free Ca²⁺. However, the mechanical stimulus shear stress appears again to be the major stimulus of eNOS activity, although the precise mechanisms activating the enzyme remain to be elucidated. Phosphorylation and subcellular translocation (from plasmalemmal caveolae to the cytoskeleton or cytosol) are probably involved in these regulations. Although eNOS plays a major vasodilatory role in the control of vasomotion, it has not so far been demonstrated that a defect in endothelial NO production could be responsible for high blood pressure in humans. In contrast, a defect in endothelium-dependent vasodilation is known to be promoted by several risk factors (e.g., smoking, diabetes, hypercholesterolemia) and is also the consequence of atheroma (fatty streak infiltration of the neointima). Several mechanisms probably contribute to this decrease in NO bioavailability. Finally, a defect in NO generation contributes to the pathophysiology of pulmonary hypertension. Elucidation of the mechanisms of eNOS enzyme activity and NO bioavailability will contribute to our understanding the physiology of vasomotion and the pathophysiology of endothelial dysfunction, and could provide insights for new therapies, particularly in hypertension and atherosclerosis.     

The growth plate’s response to load is partially mediated by mechano-sensing via the chondrocytic primary cilium

Mechanical load plays a significant role in bone and growth-plate development. Chondrocytes sense and respond to mechanical stimulation; however, the mechanisms by which those signals exert their effects are not fully understood. The primary cilium has been identified as a mechano-sensor in several cell types, including renal epithelial cells and endothelium, and accumulating evidence connects it to mechano-transduction in chondrocytes. In the growth plate, the primary cilium is involved in several regulatory pathways, such as the non-canonical Wnt and Indian Hedgehog. Moreover, it mediates cell shape, orientation, growth, and differentiation in the growth plate. In this work, we show that mechanical load enhances ciliogenesis in the growth plate. This leads to alterations in the expression and localization of key members of the Ihh-PTHrP loop resulting in decreased proliferation and an abnormal switch from proliferation to differentiation, together with abnormal chondrocyte morphology and organization. Moreover, we use the chondrogenic cell line ATDC5, a model for growth-plate chondrocytes, to understand the mechanisms mediating the participation of the primary cilium, and in particular KIF3A, in the cell’s response to mechanical stimulation. We show that this key component of the cilium mediates gene expression in response to mechanical stimulation.     

Three-dimensional structure of motor molecules

Images, calculated from electron micrographs, show the three-dimensional structures of microtubules and tubulin sheets decorated stoichiometrically with motor protein molecules. Dimeric motor domains (heads) of kinesin and ncd, the kinesin-related protein that moves in the reverse direction, each appeared to bind to tubulin in the same way, by one of their two heads. The second heads show an interesting difference in position that seems to be related to the directions of movement of the two motors. X-ray crystallographic results showing the structures of kinesin and ncd to be very similar at atomic resolution, and homologous also to myosin, suggest that the two motor families may use mechanisms that have much in common. Nevertheless, myosins and kinesins differ kinetically. Also, whereas conformational changes in the myosin catalytic domain are amplified by a long lever arm that connects it to the stalk domain, kinesin and ncd do not appear to possess a structure with a similar function but may rely on biased diffusion in order to move along microtubules.     

Prediction in context: On the comparative epistemic merit of predictive success

The considerations set out in the paper are intended to suggest that in practical contexts predictive power does not play the outstanding roles sometimes accredited to it in an epistemic framework. Rather, predictive power is part of a network of other merits and achievements. Predictive power needs to be judged differently according to the specific conditions that apply. First, predictions need to be part of an explanatory framework if they are supposed to guide actions reliably. Second, in scientific expertise, the demand for accurate predictions is replaced with the objective of specifying a robust corridor of estimates. Finally, it is highly uncertain to predict the success of research projects. The overall purpose of the paper is to enlarge the debate about predictions by addressing specifically the roles of predictions in application-oriented research.     

The Newton letters (Vols. I and II)

The metaphysical commitment to the circle as the essential element in the analysis of celestial motion has long been recognized as the hallmark of classical astronomy. What has not always been clear, however, is that the circle continued to serve Kepler as a central element in his astronomy after the discovery of the elliptical orbit of Mars. Moreover, the circle also functioned for Kepler in geometry to select the basic polygons, in music to select the basic harmonies, and in astrology to select the basic aspects. His basic set of polygons consisted of those figures that could be constructed using only a compass and a rule; the set of fundamental harmonies consisted of the consonances of the just intonation; and the traditional set of astrological aspects were enlarged by Kepler to include three new aspects in order to make the astrological set consistent with geometry and music. And as the circle served to unify these three areas, so also did it serve to supply the fundamental answers to astronomical problems well after the discovery of his new astronomy—a topic to be discussed in Part II of this paper.     

2006～2010年革兰阴性菌对碳青霉烯类抗生素耐药性分析

目的调查分析我院20ff6～2010年临床分离的革兰阴性菌对碳青霉烯类抗生素的耐药性。方法采用纸片扩散法进行抗菌药物敏感实验,采用WHONET5．4软件及SPSS13．0软件进行数据分析。结果大肠埃希菌和肺炎克雷伯菌对亚胺培南和美罗培南的耐药率呈上升趋势,但最高不超过4．5％。铜绿假单胞菌对亚胺培南的耐药率2006年和2007年监测显示为21．3％和41％。2008年达到44．8％,在2009年下降为12．4％,但2010年爽迅速增加到30．1％。鲍曼不动杆菌对亚胺培南耐药率的逐年上升更为显著,从2006年9．1％上升到2010年的68％,差异具有统计学意义（P〈0．01）。嗜麦芽窄食单胞菌对碳青霉烯类抗生素天然耐药,2006年对亚胺培南耐药率为30％,但自2007年起就增加到80．8％,最高达100％。结论肠杆菌科细菌对碳青霉烯类敏感性高,近年耐药率有上升趋势。铜绿假单胞菌和鲍曼不动杆菌对碳青霉烯类耐药率高,尤其是鲍曼不动杆菌的分离率逐年增加,耐药形势严峻。临床应合理使用抗生素,减少多重耐药株的产生。     

Zinc,copper and selenium in reproduction

Of the nine biological trace elements, zinc, copper and selenium are important in reproduction in males and females. Zinc content is high in the adult testis, and the prostate has a higher concentration of zinc than any other organ of the body. Zinc deficiency first impairs angiotensin converting enzyme (ACE) activity, and this in turn leads to depletion of testosterone and inhibition of spermatogenesis. Defects in spermatozoa are frequently observed in the zinc-deficient rat. Zinc is thought to help to extend the functional life span of the ejaculated spermatozoa. Zinc deficiency in the female can lead to such problems as impaired synthesis/secretion-of (FSH) and (LH), abnormal ovarian development, disruption of the estrous cycle, frequent abortion, a prolonged gestation period, teratogenicity, still-births, difficulty in parturition, pre-eclampsia, toxemia and low birth weights of infants. The level of testosterone in the male has been suggested to play a role in the severity of copper deficiency. Copper-deficient female rats are protected against mortality due to copper deficiency, and the protection has been suggested to be provided by estrogens, since estrogens alter the subcellular distribution of copper in the liver and increase plasma copper levels by inducing ceruloplasmin synthesis. The selenium content of male gonads increases during pubertal maturation. Selenium is localized in the mitochondrial capsule protein (MCP) of the midpiece. Maximal incorporation in MCP occurs at steps 7 and 12 of spermatogenesis and uptake dereases by step 15. Selenium deficiency in females results in infertility, abortions and retention of the placenta. The newborns from a selenium-deficient mother suffer from muscular weakness, but the concentration of selenium during pregnancy does not have any effect on the weight of the baby or length of pregnancy. The selenium requirements of a pregnant and lactating mother are increased as a result of selenium transport to the fetus via the placenta and to the infant via breast milk.     

Subjective confidence in forecasts

Forecasts have little value to decision makers unless it is known how much confidence to place in them. Those expressions of confidence have, in turn, little value unless forecasters are able to assess the limits of their own knowledge accurately Previous research has shown very robust patterns in the judgements of individuals who have not received special training in confidence assessment: Knowledge generally increases as confidence increases. However, it increases too swiftly, with a doubling of confidence being associated with perhaps a 50 per cent increase in knowledge. With all but the easiest of tasks, people tend to be overconfident regarding how much they know These results have typically been derived from studies of judgements of general knowledge. The present study found that they also pertained to confidence in forecasts. Indeed, the confidence-knowledge curves observed here were strikingly similar to those observed previously. The only deviation was the discovery that a substantial minority of judges never expressed complete confidence in any of their forecasts. These individuals also proved to be better assessors of the extent of their own knowledge Apparently confidence in forecasts is determined by processes similar to those that determine confidence in general knowledge. Decision makers can use forecasters assessments in a relative sense, in order to predict when they are more and less likely to be correct. However, they should be hesitant to take confidence assessments literally. Someone is more likely to be right when he or she is ‘certain’than when he or she is ‘fairly confident’; but there is no guarantee that the certain forecast will come true.     

Heat shock proteins and infection: interactions of pathogen and host.

Invasive microorganisms encounter defensive attempts of the host to starve, destroy and eliminate the infection. In experimental model systems aiming to imitate defensive actions of the host, microorganisms respond by the rapid acceleration in the rate of expression of heat shock and other stress proteins. Heat shock proteins (hsp) of most if not all pathogens are major immune targets for both B- and T-cells. Host cells involved in the defensive action cannot avoid exposure to their own reactive compounds, such as oxygen radicals, resulting in premature cell death and tissue damage. Long-term consequences to the host may include cancer. In cells in tissue culture, induction of host-specific hsps occurs upon exposure to oxidants and in viral infections. Drugs that bind to members of the hsp70 family induce peroxisome proliferation and hepatocarcinoma, but may open the way for the development of novel drugs in support of antimetabolite treatment of infections and cancer.     

Molecular basis for differences between human joints

The molecular program of a cell determines responses including induction or inhibition of genes for function and activity, and this is true of the cells within articular cartilage, a major functional component of the joint. While our studies have previously focussed on differences in the molecular programs of the cells within the superficial and deep zones, we have recently begun to focus on relative differences between joints, such as the knee and ankle. In the human, these joints vary greatly in their susceptibility to joint diseases, such as osteoarthritis (OA). We have predicted that there would be a molecular basis for differences between joints that could lead to differences in susceptibility to OA, if inherent pathways locked into the resident cells induce differences in their response to their environment. We have been able to show that there are differences between the matrix components and water content; these properties correspond to a higher equilibrium modulus and dynamic stiffness but lower hydraulic permeability and serve to make the ankle cartilage stiffer, slowing movement of molecules through the cartilage. In addition to these biochemical differences in the cartilage matrix, we have also identified relative differences in the strength of the response to stimulation of chondrocytes from knee and ankle. The stronger response of the knee chondrocytes includes factors that increase damage to the cartilage matrix, such as a depression of matrix synthesis and increased enzyme activity. This response by the knee chondrocytes results in enzyme damage to the matrix that the cells may not be able to repair, while the weaker response of the ankle chondrocytes may allow the cells to repair their matrix damage.     

Objectivity in confirmation: Post hoc monsters and novel predictions

The aim of this paper is to put in place some cornerstones in the foundations for an objective theory of confirmation by considering lessons from the failures of predictivism. Discussion begins with a widely accepted challenge, to find out what is needed in addition to the right kind of inferential–semantical relations between hypothesis and evidence to have a complete account of confirmation, one that gives a definitive answer to the question whether hypotheses branded as “post hoc monsters” can be confirmed. The predictivist view is then presented as a way to meet this challenge. Particular attention is paid to Worrall’s version of predictivism, as it appears to be the most sophisticated of the lot. It is argued that, despite its faults, his view turns our heads in the right direction by attempting to remove contingent considerations from confirmational matters. The demand to remove such considerations becomes the first of four cornerstones. Each cornerstone is put in place with the aim to steer clear of the sort of failures that plague various kinds of predictivism. In the process, it becomes obvious that the original challenge is wrongheaded and in need of revision. The paper ends with just such a revision.     

Defective phosphoinositide metabolism in primary hypertension

An increase in free cytosolic calcium content has been reported in essential hypertension. Since within the membrane, the phosphoinositides participate in the control of cell calcium homeostasis, we investigated whether impaired phosphoinositide metabolism could account for the calcium handling abnormality observed in hypertensives. In erythrocyte membranes of hypertensives the activity of kinases involved in polyphosphoinositide formation appears to be impaired and could be related to the alteration in calcium handling binding capacity and ATP-dependent calcium transport. In platelets of hypertensives, the hyperactivity of phospholipase C (observed even in the absence of calcium in the external medium) is likely to be responsible for the hypersensitivity of cells to various agonists. These observations are consistent with the hypothesis that in cells from hypertensives, a membrane defect linked to phosphoinositide metabolism is involved in the overall calcium handling defect.     

For or against structural realism? A verdict from high energy physics

When it comes to supporting the main ontic structural realist thesis, that we are better off with a metaphysics purged of objects, its proponents have to meet several challenges, three of which are to ensure that objects can be recast in terms of structure alone at both the level of theory and the level of ontology, to justify on physical grounds that structure exists in the world in a way that affects the goings-on in it, and to show that the relation between objects and structure is non-reciprocal, so that structure is ontologically prior to objects but not the converse. Assuming—tacitly or explicitly—that the objects of physics can be thus recast using symmetry group structure, supporters of the thesis have, therefore, to meet the remaining challenges. The present paper discusses and contests two such attempts, which typify arguments in favor of ontic structural realism from high-energy physics.     

Eine neue morphologische Deutung des Vogelgehirns auf Grund neuer Forschungsergebnisse

Summary The embryological fact (Kallén) that hyperstriatum, neostriatum and archistriatum in birds are homologous to the neopallium, palaeostriatum primitivum and augmentatum to the basal ganglions of the mammals, is made probable by recent results in the fields of morphology, physiology and animal psychology.The differentiation and form of the neopallial parts of the birds brain is not produced by a surface development, as in mammals, but in a three dimensional structure of the hemisphere, by mass in birds.This differentiation is strongly pronounced in highly cerebralized forms, and the stratified arrangement of the elements is to be interpreted as a structure of integration.With regard to function and organization, the neopallium of birds is strictly comparable to that of mammals.     

The epistemological virtues of assumptions: towards a coming of age of Boltzmann and Meinong’s objections to ‘the prejudice in favour of the actual’?

Two complementary debates of the turn of the nineteenth and twentieth century are examined here: the debate on the legitimacy of hypotheses in the natural sciences and the debate on intentionality and ‘representations without object’ in philosophy. Both are shown to rest on two core issues: the attitude of the subject and the mode of presentation chosen to display a domain of phenomena. An orientation other than the one which contributed to shape twentieth-century philosophy of science is explored through the analysis of the role given to assumptions in Boltzmann’s research strategy, where assumptions are contrasted to hypotheses, axioms, and principles, and in Meinong’s criticism of the privileged status attributed to representations in mental activities. Boltzmann’s computational style in mathematics and Meinong’s criticism of the confusion between representation and judgment give prominence to an indirect mode of presentation, adopted in a state of suspended belief which is characteristic of assumptions and which enables one to grasp objects that cannot be reached through direct representation or even analogies. The discussion shows how assumptions and the movement to fiction can be essential steps in the quest for objectivity. The conclusion restates the issues of the two debates in a contemporary perspective and shows how recent developments in philosophy of science and philosophy of language and mind can be brought together by arguing for a twofold conception of reference.     

Protein intrinsic disorder as a flexible armor and a weapon of HIV-1

Many proteins and protein regions are disordered in their native, biologically active states. These proteins/regions are abundant in different organisms and carry out important biological functions that complement the functional repertoire of ordered proteins. Viruses, with their highly compact genomes, small proteomes, and high adaptability for fast change in their biological and physical environment utilize many of the advantages of intrinsic disorder. In fact, viral proteins are generally rich in intrinsic disorder, and intrinsically disordered regions are commonly used by viruses to invade the host organisms, to hijack various host systems, and to help viruses in accommodation to their hostile habitats and to manage their economic usage of genetic material. In this review, we focus on the structural peculiarities of HIV-1 proteins, on the abundance of intrinsic disorder in viral proteins, and on the role of intrinsic disorder in their functions.     

Water or ice?--the challenge for invertebrate cold survival

The ecophysiology of cold tolerance in many terrestrial invertebrate animals is based on water and its activity at low temperatures, affecting cell, tissue and whole organism functions. The normal body water content of invertebrates varies from 40 to 90% of their live weight, which is influenced by water in their immediate environment, especially in species with a water vapour permeable cuticle. Water gain from, or loss to, the surrounding atmosphere may affect animal survival, but under sub-zero conditions body water status becomes more critical for overwinter survival in many species. Water content influences the supercooling capacity of many insects and other arthropods. Trehalose is known to maintain membrane integrity during desiccation stress in several taxa. Dehydration affects potential ice nucleators by reducing or masking their activity and a desiccation protection strategy has been detected in some species. When water crystallises to ice in an animal it greatly influences the physiology of nearby cells, even if the cells remain unfrozen. A proportion of body water remains unfrozen in many cold hardened invertebrates when they are frozen, which allows basal metabolism to continue at a low level and aids recovery to normal function when thawing occurs. About 22% of total body water remains unfrozen from calculations using differential scanning calorimetry (compared with ca 19% in food materials). The ratio of unfrozen to frozen water components in insects is 1:4 (1:6 for foods). Such unfrozen water may aid recovery of freezing tolerant species after a freezing exposure. Rapid changes in cold hardiness of some arthropods may be brought about by subtle shifts in body water management. It is recognised that cold tolerance strategies of many invertebrates are related to desiccation resistance, and possibly to mechanisms inherent in insect diapause, but the role of water is fundamental to them all. Detailed experimental studies are needed to provide information which will allow a more complete and coherent understanding of the behaviour of water in biological systems and aid the cryopreservation of a wide range of biological material.