Phosphoinositides play a major role in cellular signaling and membrane organization. During the last three decades we have learned that enzymes turning over phosphoinositides control vital physiological processes and are involved in the initiation and progression of cancer, inflammation, neurodegenerative, cardiovascular, metabolic disease and more. In two volumes, this book elucidates the crucial mechanisms that control the dynamics of phosphoinositide conversion. Starting out from phosphatidylinositol, a chain of lipid kinases collaborates to generate the oncogenic lipid phosphatidylinositol(3,4,5)-trisphosphate. For every phosphate group added, there are specific lipid kinases - and phosphatases to remove it. Additionally, phospholipases can cleave off the inositol head group and generate poly-phosphoinositols, which act as soluble signals in the cytosol. Volume II extends into the role of phosphoinositides in membrane organization and vesicular traffic. Endocytosis and exocytosis are modulated by phosphoinositides, which determine the fate and activity of integral membrane proteins. Phosphatidylinositol(4,5)-bisphosphate is a prominent flag in the plasma membrane, while phosphatidylinositol-3-phosphate decorates early endosomes. The Golgi apparatus is rich in phosphatidylinositol-4-phosphate, stressed cells increase phosphatidylinositol(3,5)-bisphosphate, and the nucleus has a phosphoinositide metabolism of its own. Phosphoinositide-dependent signaling cascades and the spatial organization of distinct phosphoinositide species are required in organelle function, fission and fusion, membrane channel regulation, cytoskeletal rearrangements, adhesion processes, and thus orchestrate complex cellular responses including growth, proliferation, differentiation, cell motility, and cell polarization.

Abl Family Kinases in Development and Disease provides an overview of the functions of Abl family kinases in Development and Disease. This new title discusses the biochemical, genetic, and cell biological data that elucidate the cellular roles for these kinases in these processes.

Humans are exposed to foreign compounds such as drugs, household products and environmental chemicals by swallowing or breathing. Also, food is considered a foreign compound. Such foreign compounds can be non-essential and non-functional to life, and commonly are referred to as xenobiotics. Some xenobiotics are not toxic; however, many of them are potentially toxic or become toxic after conversion to metabolic intermediates. A considerable number of foreign compounds belong to non-polar, lipophilic substances. Lipophilic compounds are not soluble in water. Metabolic conversion of lipophilic foreign compounds to facilitate their removal from the body is essentially carried out by biochemical reactions catalyzed by two classes of metabolizing enzymes, namely, activation enzymes and detoxification enzymes. Activation enzyme-catalyzed functionalization reaction introduces a functional group to a lipophilic compound. Functionalization modifies many foreign compounds to form reactive intermediates capable of interacting with cellular components (proteins, DNA and lipids), leading to a variety of conditions for diseases. Functionalized compounds are further metabolized through detoxification enzyme-catalyzed reactions, which result in an increase in the solubility of parent compounds and an inactivation of metabolic intermediates, thus facilitating their excretion from the body. To minimize the exposure of potentially toxic metabolic intermediates, it is essential to keep them at a minimum level. Extensive investigations have revealed that foreign compound-metabolizing enzymes exhibit genetic polymorphisms. Variations in their activities can produce different results as to the susceptibility to potential toxic effects. Moreover, the expressions of activation enzymes and detoxification enzymes are inducible. A number of chemical compounds are capable of acting as modulators for these two classes of enzymes. These findings have lead to the proposal of modulating metabolizing enzymes as a useful approach for human health benefits. Importantly, many of these chemical compounds are present in human daily diets. There are many advances that have been made in the past decades towards the understanding of functions and implications of activation enzymes and detoxification enzymes. An organized, concise overview is needed for the readers who are initially exposed to this important subject, particularly for students and researchers in the areas of biomedical sciences, biochemistry, nutrition, pharmacology and chemistry. This book is intended to serve this purpose as an introduction to the subject. Furthermore, major topics in the book, excluding catalytic reactions and structural properties, may have interest to other readers who have knowledge of basic sciences and understanding enzyme related information. The book discusses subjects associated with foreign compound metabolizing enzymes with emphasis on biochemical aspects, including lipophilic foreign compounds, catalytic properties, reactive intermediates, biomedical and biochemical effects, genetic polymorphisms, enzyme inducibility, enzyme modulation for health benefits, dietary related enzyme modulators, and structural characteristics of enzyme inducers.

The last systematic description of heme peroxidases was published in 1999 by Brian Dunford, from the University of Alberta in Canada. The book Heme per- idases covers discussion on three-dimensional structure, reaction mechanism, kinetics, and spectral properties of representative enzymes from bacterial, plant, fungal, and animal origin. Since 1999, vast information on basic but also applied aspects of heme peroxidases has been generated. We believe fusion of these two aspects will bene?t research of those dedicated to development of biocatalytic process. The aim of this book is to present recent advances on basic aspects such as evolution, structure-function relation, and catalytic mechanism, as well as applied aspects, such as bioreactor and protein engineering, in order to provide the tools for rational design of enhanced biocatalysts and biocatalytic processes. The book does not include an exhaustive listing of references but rather a selected collection to enrich discussion and to allow envisioning future directions for research. This book is organized in three parts. In Part I, current knowledge of structure and mechanism of peroxidases is covered. From the molecular phylogeny, going through the in?uence of structural factors over oxidative ability to the molecular mechanism of catalysis, the authors intend to provide an understanding of per- idases at the molecular level. The understanding of the fundamental behavior of peroxidases will allow further adequation, design, and/or optimization of pero- dase-based catalysis to a particular process. In Part II, research on potential applications of peroxidases in several ?elds is presented and discussed.

The inflammasome was first described in 2002 as a molecular complex activating proinflammatory caspases and therefore regulating the maturation and biological activities of cytokines such as IL-1 and IL-18. This finding was substantiated by the identification of several mutations in the cias1 gene, encoding the human NLRP3 protein, responsible for several autoinflammatory disorders such as the Muckle Wells syndrome. Since, the interest for this complex has constantly increased and several inflammasome complexes with different specificities have been described. These inflammasomes sense a wide variety of pathogens and danger signals and are key players in the inflammatory response. With the contributions of leading international experts in the field, this book provides an extensive overview of the current knowledge of inflammasome biology and their role in health and disease.

This 1994 book provides a fascinating account of the fast-moving field of lipase research. The contributions, written by active research workers, summarise developments in the field and give access to recent literature. It covers both the lipases proper (triglyceride lipases and the phospholipases. It gives a comprehensive picture of the state of knowledge of these enzymes, with a strong bias towards the fields that are attracting the greatest attention: their detailed molecular structure, their mechanism of action, their position in the evolution of enzymes, and their application both in the laboratory and industry. The book will continue to be of interest to those working in universities, in research institutes and in companies specialising in biotechnology. The book will also be a useful reference book for postgraduate students entering this field of research.

This book brings together lmportant work on the structure and function of the dehydrogenases requiring nicotinamide coenzymes. The structure and function of lactate dehydrogen- ase, alcohol dehydrogenase, and glyceraldehyde 3-phosphate dehydrogenase are compared. These are the relatively simple oligomeric dehydrogenases for which very extensive structural and mechanistic information is available. Kinetic studies are dealt with in general terms, with selected examples. Genetic and structural relationships revealed by primary structure are discussed. General features of the specificity of dehydrogen- ase reactions are described. The pyridine nucleotide - disulphide oxidoreductases exemplify a type of multicomponent enzyme complex. Lipoamide dehydrogenase, glutathione reductase, and thioredoxin reduct- ase are described and compared. The fatty acid synthesizing systems of some organ- isms are nonaggregated, whereas in other organisms they are multienzyme complexes containing, in animal tissues for example, two closely related multifunctional polypeptide chains. The dehydrogenase activities of the fatty acid syn- thesizing systems afford many points of interest, which are described and discussed. Hydroxymethylglutaryl-CoA reductase occupies a key position in the synthesis of isoprenoid compounds, including cholesterol. It probably occurs in all forms of life; in animal cells it is a microsomal enzyme. Its properties are reviewed.

This volume is concerned with the enzymes of the nervous system. Cerebral enzymes form the basis of the functional brain. They are needed for the control of the energetics of the nervous system, whether it be their release or their direction; for the elaboration of transmitters and for their destruction; for the synthesis, transport, and breakdown of all metabolites of the nervous system. They are indispensable for the control of the multitude of factors that govern our thinking and our behavior. They make it possible for us to comprehend what is taking place around us and perhaps to understand what may be in store for us. Enzymes are the stuff of life, and no living cell can be without them. They are the results of many millions of years of evolution, from the time when biological membranes first came into being and were folded to produce the first cells within which the earliest enzymes were wrought. Countless changes have taken place within them, so that, now, only those enzymes exist that play specific roles in the functions of the living cells of today. Those in the nervous system possess a mUltiple role: in the creation, maintenance, and ultimate breakdown of the component cells and in enabling consciousness, perception, memory, and thought to become possible. But though life may go on forever, the enzymes that make life possible will undergo the many changes involved in the evolutionary process.

Phosphoinositides play a major role in cellular signaling and membrane organization. During the last three decades we have learned that enzymes turning over phosphoinositides control vital physiological processes and are involved in the initiation and progression of cancer, inflammation, neurodegenerative, cardiovascular, metabolic disease and more. In two volumes, this book elucidates the crucial mechanisms that control the dynamics of phosphoinositide conversion. Starting out from phosphatidylinositol, a chain of lipid kinases collaborates to generate the oncogenic lipid phosphatidylinositol(3,4,5)-trisphosphate. For every phosphate group added, there are specific lipid kinases - and phosphatases to remove it. Additionally, phospholipases can cleave off the inositol head group and generate poly-phosphoinositols, which act as soluble signals in the cytosol. Volume I untangles the web of these enzymes and their products, and relates them to function in health and disease. Phosphoinositide 3-kinases and 3-phosphatases have received a special focus in volume I, and recent therapeutic developments in human disease are presented along with a historical perspective illustrating the impressive progress in the field.

The Springer Handbook of Enzymes provides concise data on some 5,000 enzymes sufficiently well characterized - and here is the second, updated edition. Their application in analytical, synthetic and biotechnology processes as well as in food industry, and for medicinal treatments is added. Data sheets are arranged in their EC-Number sequence. The new edition reflects considerable progress in enzymology: the total material has more than doubled, and the complete 2nd edition consists of 39 volumes plus Synonym Index. Starting in 2009, all newly classified enzymes are treated in Supplement Volumes.

Major advances have been made in recent years in clarifying the molecular properties of the cytochrome P-450 system. These advances stem, in practical terms, from the generally recognized importance of cytochrome P-450 in the metabolism of drugs and in the bioactivation of xenobiotics to toxic products. The fascinating multiplicity and differential regulation of cytochrome P-450 isozymes, and their ability to catalyze extraordinarily difficult chemical transformations, have independently drawn many chemists and biochemists into the P-450 circle. Progress in the field, from a technical point of view, has been propelled by the de velopment of reliable procedures for the purification of membrane-bound enzymes, by the growing repertoire of molecular biological techniques, and by the development of chemical models that mimic the catalytic action of P-450. As a result, our understanding of the P-450 system is moving from the descriptive, pharmacological level into the tangible realm of atomic detail. The rapid progress and multidisciplinary character of the cytochrome P-450 field, which cuts across the lines that traditionally divide disciplines as diverse as inorganic chemistry and genetics, have created a need for an up-to-date evaluation of the advances that have been made. It is hoped that this book, with its molecular focus on the cytochrome P-450 system, will alleviate this need. The authors of the individual chapters have strived to emphasize recent results without sacrificing the background required to make their chapters comprehensible to informed nonspecialists.

Ribonucleases are a ubiquitous and functionally diverse group of enzymes that have a common ability to cleave RNA. Either through scission of internal phosphodiesters, or removal of nucleotides from RNA 5' or 3' ends, ribonucleases perform essential roles in gene expression and regulation, genome replication and maintenance, host defense, stress response, and viral strategies of infection. Ribonucleases have also served as highly informative models to understand virtually every aspect of biomolecular structure and function. The fifteen chapters in this volume are written by recognized researchers in the field, and provide in-depth analyses of the major ribonuclease families. Particular focus is given to the relation of ribonuclease structure and mechanism to biological function, as well as ribonuclease dysfunction in certain disease states. Other topics include the evolutionary genetics and functional diversification of ribonucleases, engineered ribonucleases as anti-cancer agents, the mechanisms of action of artificial ribonucleases, and ribonucleases as models to understand protein folding and stability. This volume should serve as an essential reference for a broad range of researchers and educators with interests in RNA metabolism, enzymology, and gene regulation.

For a long time, enzymes have been studied by measuring their activity, which has led to the advancement of "enzyme kinetics." In recent years, the mechanism of enzyme reaction has been explained in detail on the basis of the 3D structure. Genetic engineering and the 3D structural analysis of enzymes contribute to these advancements in enzymology. This book starts with an introduction to various enzymes to show how interesting enzymes are, which is followed by historical kinetic studies on enzymes and the overall and rapid-reaction kinetics. The subsequent topics describe the basics of protein structure, the control of enzyme activity, and the purification of enzymes. A case on the kinetic and structural studies of l-phenylalanine oxidase is also presented. There are many good books on enzyme kinetics, but few describe their kinetic and structural aspects. This book deals with both and contains many references that can be good sources for further reading. It is handy and is especially helpful for beginners. A number of figures, including some with stereo expression, facilitate observing the 3D structure of enzymes.

The study of a single well-chosen substance, here aspartate transcarb amylase, can provide an excellent basis for a laboratory course. The student is introduced to a variety of scientific ideas and to many experi mental and interpretive techniques. This enzyme is readily available, is relatively stable, has an extensive literature, and its behavior has many facets: substrate inhibition, a large change in structure upon homo tropic activation by substrates, allosteric stimulation by ATP, allosteric inhibition by CTP synergistic with VTP, positive cooperativity for sub strates, negative cooperativity for CTP binding, and dissociation and reassembly of subunits Cand R2 from the holoenzyme CI\5. In addition 3 6 to the known biochemical aspects of these properties, the results ob tained here can be interpreted in the light of the high-resolution X-ray diffraction structures of the T and R forms, the low-angle X-ray scattering results, and the large number of mutants now available by recombinant DNA methods. Future development of this course could also involve part of these methods, as well as the carefully chosen experiments described here. This approach resembles research more than the approaches one usually finds in biochemical laboratory courses. A consistent develop ment of ideas about a single enzyme, which shows so many facets in its behavior, is sure to hold the interest of the student. Moreover, one explores a depth, and reasons to move forward, that are an essential part of research."

In September 1998 experts from 19 countries came together for an interdisciplinary discussion of the function of animal peroxidases, a family of enzymes embracing myeloperoxidase, eosinophil peroxidase, thyroid peroxidase and lactoperoxidase. Their papers have been updated for publication, yielding a wide-ranging overview of the state of the art. The chapters cover a wide range of topics, including three-dimensional structure of representative family members, their biosynthesis and intracellular transport, mechanism of action as well as applications to clinical medicine. They are of clinical relevance in, for example, arteriosclerosis, multiple sclerosis, infections, tumorigenesis, rheumatic diseases and hypothyroidism. This book forms an excellent introduction for anyone interested in the peroxidase family of enzymes.

Obesity is a risk factor for breast cancer in older women. A number of adipose-derived and obesity-related factors have been shown to affect tumour cell growth. These include adipokines, insulin, IGF-1 and oestrogens. The majority of obesity-related postmenopausal breast cancers are oestrogen-dependent. Since the ovaries no longer produce oestrogens after menopause, and that circulating levels are negligible, it is evident that it is the oestrogens produced locally within the breast adipose that are responsible for the increased growth of breast cancer cells. Aromatase is the enzyme that converts androgens into oestrogens and its regulation is dependent on the activity of a number of tissue-specific promoters. Targeting oestrogen biosynthesis in obesity may be useful for the prevention of breast cancer. Aromatase inhibitors are efficacious at treating postmenopausal breast cancer and recent studies suggest that they may also be useful in the prevention setting. However, these compounds inhibit the catalytic activity of aromatase and as a consequence lead to a number of undesirable side-effects, including arthralgia and possible cognitive defects due to inhibition of aromatase in the bone and brain, respectively. Novel therapies, such as those employed to treat obesity-associated disease, including anti-diabetics, may prove successful at inhibiting aromatase specifically within the breast. This SpringerBrief will explore all of these issues in depth and the authors are in a unique position to write about this topic, having extensive experience in the field of aromatase research.

Prior to the start of the eighth meeting, I had the good sense to ask Professor Rosa Angela Canuto of Turin, Italy if she would help me organize the ninth meeting. She quickly suggested that both she and Dr. Guiliana Muzio, also of Turin, help plan the meet ing. Each of our previous eight meetings was a unique experience for the participants. The science was always outstanding and the presentations and discussions were excellent. By moving each meeting to a different part of the world we were able to experience exciting foods and cultural aspects of the world in addition to the science. The ninth meeting was no exception. We met from June 18 to 22 in the small mountain city of Varallo, Italy, the birth place of Dr. Canuto. Holding the scientific sessions in a several-hundred-year-old converted mansion and having an afternoon trip to either Lago Maggiore or Monte Rosa made some aspects of this meeting extremely memorable. An additional unique aspect of the social portion of the meeting was our ability to invite the townspeople to share with us a concert performed in an old church. Though the social and cultural aspects of the meeting were outstanding, the pur pose of the meeting was to exchange scientific information about the status of the three enzyme systems.

This volume represents a collection of lectures delivered by outstanding specialists in the fields of biophysics and of related scientific disciplines th during the 7 International Summer School on Biophysics held in Rovinj, Croatia from 14 to 25 September 2000 under the title "Super molecular Structure and Function ." This scientific-educational event was organized by the Ruder Boskovic Institute ofZagreb, Croatia with substantial material and intellectual support of a number of national and international institutions including the Croatian Biophysical Society (CBS), the International Union of Pure and Applied Biophysics (IUPAB), the International Centre for Genetic Engineering and Biotechnology (ICGEB) and the UNESCO Venice Office - Regional Office for Science and Technology for Europe (UVO-ROSTE). The seventh edition of the series of International Summer Schools on Biophysics, which was started in 198I, attracted more than 120 young researchers and post-graduate students coming from 27 countries of Europe, Asia, Africa and Latin America. Twenty-five outstanding experts in pure and applied biophysics presented the most advanced knowledge ofthis very interdisciplinary area of science during their lectures and round tables. It was commonly acknowledge that the Summer School achieved great success and fully reached its objectives. The success of the Rovinj Summer School was also due to the constantly growing attention being paid by scientific communities to younger generations of scientists, thanks also to the major outcomes of the World Conference on Science "Science for the Twenty-first Century: A New Commitment" held by UNESCO and ICSU in Budapest, Hungary in June 1999.

Ch. P. Kubicek, Vienna: "The Cellulase Proteins of Trichoderma reesei: Structure, Multiplicity, Mode of Action and Regulation of Formation" Dr.A. Singh, Dr. P.K.R. Kumar, Dr. K. Sch}gerl, Hannover: "Bioconversion of Cellulosic Materials to Ethanol by Filamentous Fungi" Dr. T. Coolbear, Palmerston North, New Zealand, Dr. R.M. Da- niel, Dr. H.W. Morgan, Hamilton, New Zealand: "The Enzymes from Extreme Thermophiles: Bacterial Sources, Thermostabilities and Industrial Relevance" Dr. N. Weber, M}nster, Dr. D. C. Taylor, Dr. E. W. Under- hill, Saskatoon (Canada): "Biosynthesis of Storage Lipids in Plant Cell and Embryo Cultures"

Presently, intensive and global attention is being devoted to "biotechnology"--the technology utilizing marvelous capacities of living things for human welfare. Each country is strongly promo ting its development. In particular, enzyme engineering, whose pur pose is to utilize efficiently enzymes, microorganisms, and cultured plant as well as animal cells as organic catalysts, is one of the main themes in the field of biotechnology. Under these circumstances, the Sixth Enzyme Engineering Confe rence was held at Kashikojima, Mie Prefecture, Japan from September 20 to 25, 1981, under the joint auspices of the Engineering Foun dation of New York and the Japanese Society of Enzyme Engineering. This series of international conferences has been held biannually since 1971. The first three and the fifth conferences were held in the United States and the fourth one was in the Federal Republic of Germany. This sixth conference was the first to be held in Asia; and it was significant that a number of participantGBP could visit Japany, which has produced successful achievements in the field of biotechnology.

Soil enzymes are one of the vital key mediators involved in nutrient recycling and the decomposition of organic matter and thereby in maintaining soil quality and fertility. This Soil Biology volume covers the various facets of soil enzymes, such as their functions, biochemical and microbiological properties and the factors affecting their activities. Enzymes in the rhizosphere, in forest soils, and in volcanic ash-derived soils are described. Soil enzymes covered include phosphohydrolases, lignocellulose-degrading enzymes, phenol oxidases, fungal oxidoreductases, keratinases, pectinases, xylanases, lipases and pectinases. Several chapters treat the soil enzymatic activities in the bioremediation of soils contaminated with pesticides and pollutants such as oil, chlorinated compounds, synthetic dyes and aromatic hydrocarbons. The role of soil enzymes as bioindicators is a further important topic addressed.

The invention of the polymerase chain reaction (PCR) won the Nobel Prize in Chemistry in 1994 and remains one of the most important scientific discoveries of the twentieth century. More than 50,000 researchers in the United States use PCR replication technology, and yet a book has not been published on the subject in more than ten years. In this book, Dr. Stephen A. Bustin, a world-renowned PCR expert, examines in detail the latest innovations and the overall impact of PCR on many areas of molecular research. The book contains personal reflections, opinions, and comments by leading authorities on the many applications of the PCR and how this technology has revolutionized their respective areas of interest. This book conveys the ways in which PCR has overcome many obstacles in life science and clinical research and also charts the PCR s development from time-consuming, low throughput, non-quantitative procedure to today s rapid, high throughput, quantitative super method.

Enzyme kinetics has undergone very rapid growth and development during the past fifteen years and has been well received by the biochemical community. A cursory glance at the current biochem ical literature reveals the increasing popularity of enzyme ki netics1 yet, there are very few books available to guide the enzymologist who wishes to conduct kinetic experiments. This monograph was undertaken to provide the fledgling kineticist with an outline of contemporary initial rate enzyme kinetics. A large portion of the material contained in this book is presented in a second-year, graduate-level course in biochemistry at Iowa State University. I have found that the presentation in this course has enabled students without a strong background in math ematics to undertake initial rate studies at the research bench. The monograph obviously is more comprehensive than any course could be, and should permit similar accomplishment. As the title implies, the major emphasis of this monograph is on initial rate enzyme kinetics. I considered at length the advis ability of including chapters on integrated rate equations and on the theory and application of rapid reaction kinetics, such as rapid-mixing stopped-flow, and temperature-jump kinetics. These, however, are topics that would require a good deal of space to develop if they were to be helpful to the beginner."

Key Building Blocks via Enzyme-Mediated Synthesis, by Thomas Fischer and Jorg Pietruszka
*
Engineered Biosynthesis of Plant Polyketides: Structure-Based and Precursor-Directed Approach, by Ikuro Abe
*
Enzymatic and Chemo-Enzymatic Approaches Towards Natural and Non-Natural Alkaloids: Indoles, Isoquinolines, and Others, by Joachim Stockigt, Zhong Chen, and Martin Ruppert
*
Chemoenzymatic and Bioenzymatic Synthesis of Carbohydrate Containing Natural Products, by Bohdan Ostash, Xiaohui Yan, Victor Fedorenko, and Andreas Bechthold
*
Total (Bio)Synthesis: Strategies of Nature and of Chemists, by Alexandra A. Roberts, Katherine S. Ryan, Bradley S. Moore, and Tobias A.M. Gulder"

The development of agents capable of cleaving RNA and DNA has attracted considerable attention from researchers in the last few years, because of the immediate and very important applications they can find in the emerging fields of biotechnology and pharmacology. There are essentially two classes of these agents - nucleases that occur naturally inside cells and synthetically produced artificial nucleases. The first class includes protein enzyme nucle ases and catalytic RNA structured ribozymes that perform cleavage of the phosphodiester bonds in nucleic acids according to a hydrolytic pathway in the course of different biochemical processes in the cell. A different pathway is used by some antibiotics which cleave DNA via redox-based mechanisms resulting in oxidative damage of nucleotide units and breakage of the DNA backbone. The above molecules are indispensable tools for manipulating nucleic acids and processing RNA; DNA-cleaving antibiotics and cytotoxic ribonucleases have demonstrated utility as chemotherapeutic agents. The second class, artificial nucleases, are rationally designed to imitate the active centers of natural enzymes by simple structures possessing minimal sets of the most important characteristics that are essential for catalysis. A dif ferent approach, in vitro selection, was also used to create artificial RNA and DNA enzymes capable of cleaving RNA. Being less efficient and specific as compared to the natural enzymes, the primitive mimics are smaller and robust and can function in a broad range of conditions."