Nessa Carey, a leading epigenetics researcher, connects the field’s arguments to such diverse phenomena as how ants and queen bees control their colonies; why tortoiseshell cats are always female; why some plants need cold weather before they can flower; and how our bodies age and develop disease. Reaching beyond biology, epigenetics now informs work on drug addiction, the long-term effects of famine, and the physical and psychological consequences of childhood trauma. Carey concludes with a discussion of the future directions for this research and its ability to improve human health and well-being.
We all have a rage circuit we can’t fully control once it is engaged as R. Douglas Fields, PhD, reveals in this essential book for our time. The daily headlines are filled with examples of otherwise rational people with no history of violence or mental illness suddenly snapping in a domestic dispute, an altercation with police, or road rage attack. We all wish to believe that we are in control of our actions, but the fact is, in certain circumstances we are not. The sad truth is that the right trigger in the right circumstance can unleash a fit of rage in almost anyone.
But there is a twist: Essentially the same pathway in the brain that can result in a violent outburst can also enable us to act heroically and altruistically before our conscious brain knows what we are doing. Think of the stranger who dives into a frigid winter lake to save a drowning child.
Dr. Fields is an internationally recognized neurobiologist and authority on the brain and the cellular mechanisms of memory. He has spent years trying to understand the biological basis of rage and anomalous violence, and he has concluded that our culture’s understanding of the problem is based on an erroneous assumption: that rage attacks are the product of morally or mentally defective individuals, rather than a capacity that we all possess.
Fields shows that violent behavior is the result of the clash between our evolutionary hardwiring and triggers in our contemporary world. Our personal space is more crowded than ever, we get less sleep, and we just aren't as fit as our ancestors. We need to understand how the hardwiring works and how to recognize the nine triggers. With a totally new perspective, engaging narrative, and practical advice, Why We Snap uncovers the biological roots of the rage response and how we can protect ourselves—and others.
From the Hardcover edition.
Stem Cell Research For Dummies offers a balanced, plain-English look at this politically charged topic, cutting away the hype and presenting the facts clearly for you, free from debate. It explains what stem cells are and what they do, the legalities of harvesting them and using them in research, the latest research findings from the U.S. and abroad, and the prospects for medical stem cell therapies in the short and long term.Explains the differences between adult stem cells and embryonic/umbilical cord stem cells Provides both sides of the political debate and the pros and cons of each side's opinions Includes medical success stories using stem cell therapy and its promise for the future
Comprehensive and unbiased, Stem Cell Research For Dummies is the only guide you need to understand this volatile issue.
Includes New and Updated Material
Now in its second edition, this work is the culmination of research and discussions with technical experts, as well as USP and FDA representatives on various topics of interest to the pharmaceutical microbiologist and those responsible for the microbial quality of products, materials, equipment, and manufacturing facilities. New in this edition is an entire chapter dedicated to the topic of biofilms and their impact on pharmaceutical and biopharmaceutical operations. The subject of rapid methods in microbiology has been expanded and includes a discussion on the validation of alternative microbiological methods and a case study on microbial identification in support of a product contamination investigation.
Substantially updated and revised, this book assists readers in understanding the fundamental issues associated with pharmaceutical microbiology and provides them with tools to create effective microbial contamination control and microbial testing programs for the areas under their responsibility.
It is now evident that the "illegal biologicals" he referred to included the pathogenic agents which have led to the AIDS epidemic and other world health crisis.
In The Extremely Unfortunate Skull Valley Incident the authors trace history of the secret war against and the terrible experiments performed upon their own citizens as well as the Third World populations. But Skull Valley does more than that. In their research the father-son team discovered the links between AIDS and many other diseases now increasing dramatically worldwide. Chief among these is myalgic encephalomyelitis/fibromyalgia dismissively labelled " chronic fatigue syndrome" by the government researchers.
In addition to AIDS and ME/FM the Scotts also demonstrate the etiological links to other neurosystemic degenerative diseases such as Alzheimer's, multiple sclerosis, Parkinson's, diabetes, schizophrenia, Crohn's-colitis, etc. All are said to be "of no known cause and having no known cure". Researchers Donald and William Scott have discovered that there is a "known cause" and there may well be a cure.
The cause is a little known organism called the "mycoplasma" which has the capacity to access genetically pre-disposed cells and to destroy them by up-taking pre-formed sterols. This process is the "degeneration" which characterizes all of the diseases under study. When the cells of the endocrine system are destroyed by a sufficient concentration of mycoplasmas, the balance of the physiological balance is altered and the immune system loses its ability to defend the infected victim, and co-factors such as the human immune-deficiency virus (HIV), and those with cause pneumonia, are free to have their way, leading to full-blown AIDS.
Science is on the cusp of a revolutionary breakthrough. We now understand more about aging—and how to prevent and reverse it—than ever before.
In recent years, our understanding of the nature of aging has grown exponentially, and dramatic life extension—even age reversal—has moved from science fiction to real possibility.
Dr. Michael Fossel has been in the forefront of aging research for decades and is the author of the definitive textbook on human aging. In The Telomerase Revolution, he takes us on a detailed but highly accessible scientific journey, providing startling insights into the nature of human aging.
Twenty years ago, there was still considerable debate of the nature of human aging, with a variety of competing theories in play. But scientific consensus is forming around the telomere theory of aging. The essence of this theory is that human aging is the result of cellular aging. Every time a cell reproduces, its telomeres (the tips of the chromosomes) shorten. With every shortening of the telomeres, the cell’s ability to repair its molecules decreases. It ages. Human aging is the result of the aging of the body’s trillions of cells.
But some of our cells don’t age. Sex cells and stem cells can reproduce indefinitely, without aging, because they create telomerase. Telomerase re-lengthens the telomeres, keeping these cells young.
The Telomerase Revolution describes how telomerase will soon be used as a powerful therapeutic tool, with the potential to dramatically extend life spans and even reverse human aging. Telomerase-based treatments are already available, and have shown early promise, but much more potent treatments will become available over the next decade.
The Telomerase Revolution is the definitive work on the latest science on human aging, covering both the theory and the clinical implications. It takes the reader to the forefront of the upcoming revolution in human medicine.
In Cracking the Aging Code, theoretical biologist Josh Mitteldorf and award-winning writer and ecological philosopher Dorion Sagan reveal that evolution and aging are even more complex and breathtaking than we originally thought. Using meticulous multidisciplinary science, as well as reviewing the history of our understanding about evolution, this book makes the case that aging is not something that “just happens,” nor is it the result of wear and tear or a genetic inevitability. Rather, aging has a fascinating evolutionary purpose: to stabilize populations and ecosystems, which are ever-threatened by cyclic swings that can lead to extinction.
When a population grows too fast it can put itself at risk of a wholesale wipeout. Aging has evolved to help us adjust our growth in a sustainable fashion as well as prevent an ecological crisis from starvation, predation, pollution, or infection.
This dynamic new understanding of aging is provocative, entertaining, and pioneering, and will challenge the way we understand aging, death, and just what makes us human.
This book can be used as a text for a year long graduate course in statistics, computer science, or mathematics, for self-study, and as an invaluable research reference on probabiliity and its applications. Particularly worth mentioning are the treatments of distribution theory, asymptotics, simulation and Markov Chain Monte Carlo, Markov chains and martingales, Gaussian processes, VC theory, probability metrics, large deviations, bootstrap, the EM algorithm, confidence intervals, maximum likelihood and Bayes estimates, exponential families, kernels, and Hilbert spaces, and a self contained complete review of univariate probability.
The book begins with a general coverage of the characteristics of swine and the swine industry with emphasis on the gastrointestinal tract. It then describes the various classes of nutrients and how these nutrients are metabolized by swine and the factors affecting their utilization. The next section covers the practical aspects of swine nutrition from birth through gestation and lactation in sows and to the feeding of adult boars. The nutritional aspects of the various feedstuffs commonly fed to swine are covered in the following section. The final chapters of the book are devoted to coverage of various techniques used in swine nutrition research.
Signal transduction third edition further elaborates on diverse signaling cascades within particular contexts such as muscle contraction, innate and adaptive immunity, glucose metabolism, regulation of appetite, oncogenic transformation and cell fate decision during development or in stem cell niches. The subjects have been enriched with descriptions of the relevant anatomical, histological, physiological or pathological condition.In-depth insight into a subject central to cell biology and fundamental to biomedicine, including the search for novel therapeutic interventionsEssential signaling events embedded in rich physiological and pathological contextsExtensive conceptual colour artwork to assist with comprehension of key topicsSpecial emphasis on how molecular structure determines protein function and subcellular localizationEmployment of unambiguous protein names (symbols) in agreement with leading protein- and gene databases, allowing the learner to extend his/her exploration on the web
This volume provides formulas and procedures for determination of sample size required not only for testing equality, but also for testing non-inferiority/superiority, and equivalence (similarity) based on both untransformed (raw) data and log-transformed data under a parallel-group design or a crossover design with equal or unequal ratio of treatment allocations. It contains a comprehensive and unified presentation of statistical procedures for sample size calculation that are commonly employed at various phases of clinical development. Each chapter includes, whenever possible, real examples of clinical studies from therapeutic areas such as cardiovascular, central nervous system, anti-infective, oncology, and women's health to demonstrate the clinical and statistical concepts, interpretations, and their relationships and interactions.
The book highlights statistical procedures for sample size calculation and justification that are commonly employed in clinical research and development. It provides clear, illustrated explanations of how the derived formulas and/or statistical procedures can be used.
Rapid advances in DNA sequencing technology have led to a major change in the way that prokaryotes are classified. Sequence analysis of highly conserved regions of the bacterial genome, such as the small subunit rRNA gene, now provide us with a universal method of estimating the evolutionary relationships among all organisms. Such gene-based phylogenetic classifications have led to many new discoveries about prokaryotes that were not reflected in the classification used in the first edition of the Manual. We now know that the prokaryotes fall into two broad domains: the Archaea and the Bacteria. Whereas the Archaea were once thought of as the more primitive of the prokaryotic lineages, we now realize that they are more closely related to the eukaryotes than to the Bacteria by this measure. We have come to realize that many taxa based on shared phenotypic features may be quite distinct from one another based on phylogenetic evidence. The Chromatium, a genus of anoxygenic photosynthetic bacteria are more closely related to E. coli than to some other lineages of anoxygenic photosynthetic bacteria; Mycoplasma and other cell-wall deficient species are members of the Gram-positive clade; the medically important Chlamydia are aligned with the Planctomyces; and the Clostridium, which form a phenotypically coherent group, fall into more than a dozen phylogenetically disparate groups of Gram-positive bacteria. We have also come to realize that prokaryotes represent one of the major sources of biodiversity in nature and play a major role in the functioning of all ecosystems.
In addition to such fundamental revelations, the widespread application of new methods of classifying prokaryotes has led to an explosive growth in the number of validly published species and higher taxa. Since completion of the first edition of the Manual, the number of published species has more than tripled and has been accompanied by numerous taxonomic realignments that take into consideration newly published findings.
Phylogenetic classification is now broadly accepted as the preferred method of representing taxonomic relationships among prokaryotes and eukaryotes alike. While the evolutionary history of the prokaryotes is far from complete, there is already sufficient data to provide a reasonable view of the major lines of descent of the cultivable species. Although the second edition of the Manual retains it’s unique and highly structured style of presentation of information along genus and species lines, the arrangement of content is along the phylogenetic lines of the small subunit rRNA gene, so that the reader is presented with the information in a more natural, biological perspective. The second edition of the Manual also contains more in-depth ecological information about individual taxa and many new introductory essays.
In the preface to the first edition of Bergey’s Manual of Determinative Bacteriology, published in 1923, one of the stated goals of that work was to "stimulate efforts to perfect the classification of bacteria..." The editors of the first edition regarded the Manual as "a progress report leading to a more satisfactory classification in the future" rather than a definitive classification. Bergey’s Manual Trust continues in this tradition and recognizes that, for the Manual to remain scientifically meaningful and useful to the scientific community, it is time for the new edition.
Overview of the second edition of the Manual
As before, the Manual is subdivided into multiple volumes and each genus occurs as a separate chapter with introductory text provided at higher taxonomic levels. The second edition differs from the first in that clinically relevant species are not grouped together into two volumes. Rather, these taxa appear in their proper phylogenetic place. The text is arranged to follow the lineages defined by the large-scale phylogenetic trees maintained by the Ribosomal Database Project and the ARB Project to which a formalized, hierarchical taxonomy and nomenclature have been applied. As volume 2 goes to press, the taxonomy encompasses 6466 species that are assigned to 26 phyla, 41 classes, 88 orders, 240 families and 1194 genera. Each volume contains a collection of introductory essays on the history and use of the Manual; a detailed discussion of the prokaryotic domains; overviews of the classification, identification, and naming of prokaryotes; prokaryotic ecology and phylogeny; the role of culture collections in microbiology; and intellectual property of prokaryotes. Each volume also includes taxon specific essays and a detailed road map that presents the reader with a broad view of how the entire edition will be arranged, a mapping of phylogenetic groups to the phenotypic groups used in the first edition (Volume 1), or an update of newly published taxa and combinations appearing in print since the preceding volume (Volumes 2-5). The details of each volume in print (Volume 1), in press (Volume 2) or in preparation (Volumes 3-5) follow.
Volume 1 "The Archaea and the Deeply Branching and Phototrophic Bacteria" (2001) David R. Boone and Richard W. Castenholz (Volume Editors), George M. Garrity (Editor-in-Chief) with contributions from 105 colleagues. 742 pages with 320 figures and 95 tables. The volume provides descriptions of 413 species in 165 genera that are assigned to the phyla Crenarchaeota, Euryarchaeota, Aquificae, Thermatogae, Thermodesulfobacteria, "Deinococcus-Thermus", Chrysiogenetes, Chloroflexi, Thermomicrobia, Nitrospira, Deferribacteres, Cyanobacteria, and Chlorobi. In addition, the volume contains an introductory chapter to nonoxygenic, phototropic species of Bacteria belonging to the Proteobacteria and Firmicutes, which will be repeated in more detail in subsequent volumes.
Volume 2 "The Proteobacteria." (2004) Don J. Brenner, Noel R. Krieg, James T. Staley (Volume Editors), and George M. Garrity (Editor-in-Chief) with contributions from 339 colleagues. The volume provides descriptions of more than 2000 species in 538 genera that are assigned to the phylum Proteobacteria. This volume is subdivided into three parts. Part A, The Introductory Essays (332 pgs, 76 figures, 37 tables); Part B, The Gammaproteobacteria (1203 pages, 222 figures, and 300 tables); and Part C The Alpha-, Beta-, Delta-, and Epsilonproteobacteria (1256 pages, 512 figures, and 371 tables).
Volume 3 "The Firmicutes". (2005 anticipated). Paul De Vos, Dorothy Jones, Fred A. Rainey, Karl-Heinz Schleifer, Joseph Tully, (Volume Editors) and George M. Garrity (Editor-in-Chief), with contributions from 120 colleagues. This volume will provide descriptions of more than 1346 species in 235 genera belonging to the phylum Firmicutes. Anticipated length 2100 pages.
Volume 4 "The Actinobacteria". (2006 anticipated) 1141 species in 106 genera. Estimated page length: 878 with 192 tables and 321 figures. Michael Goodfellow, Peter Kaempfer, Peter H.A. Sneath, Stanley T. Williams (Volume Editors) and George M. Garrity (Editor-in-Chief) with contributions from 60 colleagues. This volume will provide descriptions of over 1534 species in 174 genera belonging to the phylum Firmicutes. Anticipated length 2454 pages.
Volume 5 "The Planctomycetes, Chlamydiae, Spirochetes, Fibrobacters, Bacteroidetes, Fusobacteria, Acidobacteria, Verrucomicrobia, Dictyoglomi, and Gemmatomonadetes " more than 405 species assigned to 114 genera in 10 phyla. Anticipated length: 648 pages Editors and authors under discussion.
With research gleaned from the National Institutes of Health, T.S. Wiley and Bent Formby deliver staggering findings: Americans really are sick from being tired. Diabetes, heart disease, cancer, and depression are rising in our population. We’re literally dying for a good night’s sleep.
Our lifestyle wasn’t always this way. It began with the invention of the lightbulb.
When we don’t get enough sleep in sync with seasonal light exposure, we fundamentally alter a balance of nature that has been programmed into our physiology since day one. This delicate biological rhythm rules the hormones and neurotransmitters that determine appetite, fertility, and mental and physical health. When we rely on artificial light to extend our day until 11 p.m., midnight, and beyond, we fool our bodies into living in a perpetual state of summer. Anticipating the scarce food supply and forced inactivity of winter, our bodies begin storing fat and slowing metabolism to sustain us through the months of hibernation and hunger that never arrive. Our own survival instinct, honed over millennia, is now killing us.
Wiley and Formby also reveal:
-That studies from our own government research prove the role of sleeplessness in diabetes, heart disease, cancer, infertility, mental illness, and premature aging
-Why the carbohydrate-rich diets recommended by many health professionals are not only ridiculously ineffective but deadly
-Why the lifesaving information that can turn things around is one of the best-kept secrets of our day.
Lights Out is one wake-up call none of us can afford to miss.
* Provides complete coverage of basic biology of adenoviruses, as well as the construction, propagation and purification of adenoviral vectors
* Introduces common strategies for the development of adenoviral vectors along with cutting-edge methods for their improvement
* Demonstrates noninvasive imaging of adenovirus-mediated gene transfer
* Discusses utility of adenoviral vectors in animal disease models
* Considers Federal Drug Administration regulations for human clinical trials
Topics covered in Long Acting Injections and Implants include the historical development of the field, drugs, diseases and clinical applications for long acting injections and implants, anatomy and physiology for these systems, specific injectable technologies (including lipophilic solutions, aqueous suspensions, microspheres, liposomes, in situ forming depots and self-assembling lipid formulations), specific implantable technologies (including osmotic implants, drug eluting stents and microfabricated systems), peptide, protein and vaccine delivery, sterilization, drug release testing and regulatory aspects of long acting injections and implants.
This volume provides essential information for experienced development professionals but was also written to be useful for scientists just beginning work in the field and for others who need an understanding of long acting injections and implants. This book will also be ideal as a graduate textbook.
The recent International Conference on Harmonisation (ICH) revisions of regulatory requirements for quality, nonclinical, and clinical pharmaceutical product registration are the focus of this timely update.
This cutting-edge resource includes the major headings in the modular structure of the Common Technical Document (CTD), which is now the agreed format for product information submission. The format, specification, and technical requirements of the e-CTD, the electronic version of CTD, are also thoroughly discussed.
The book is organized into six highly practical segments:Part I: CTD, eCTD, Module 1, and Environmental Risk Assessment Part II: CTD Summaries Part III: Quality Topics Part IV: Nonclinical Topics Part V: Clinical Topics Part VI: Other Topics (including drug-device combination products)
This text is a must-have for those in the pharmaceutical industry determining regulatory requirements for the major world markets in Europe, the US, Canada, and Japan.
New to this Edition:Updated and increased coverage of real time PCR and the mathematics used to measure gene expressionMore sample problems in every chapter for readers to practice concepts
A comprehensive reference, the book includes definitive information on every aspect of the anatomy, pathophysiology, and differential diagnosis of infectious diseases affecting reptiles. Beginning with a thorough review of the biology, anatomy, and histology of reptiles, the introductory chapters cover all major systems and provide the most complete single source for color images of reptile histology. It addresses the mechanism of reptile immunology and the response to pathogens, and explains how immunological response is key to differential diagnosis. Given the difficulty in isolating certain pathogens for identification, the book provides an overview of electron microscopy, complete with electron micrographs of reptile pathogens, and introduces the necessity of molecular methods for diagnosis. The text outlines serodiagnostics and the development and use of immunological reagents specifically designed for reptiles in tests such as indirect enzyme linked immunosorbent assays (ELISA). Finally, the book devotes several chapters to the viral, bacterial, fungal, and parasitic diseases known to reptiles and methods for isolating these pathogens.
With up-to-the-minute data, a never-before-seen collection of images, and a stellar panel of contributors, Infectious Diseases and Pathology of Reptiles is the definitive resource forveterinarians, biologists, and researchers involved in the study of pathogens infecting reptiles.
Synchrony is a science in its infancy, and Strogatz is a pioneer in this new frontier in which mathematicians and physicists attempt to pinpoint just how spontaneous order emerges from chaos. From underground caves in Texas where a French scientist spent six months alone tracking his sleep-wake cycle, to the home of a Dutch physicist who in 1665 discovered two of his pendulum clocks swinging in perfect time, this fascinating book spans disciplines, continents, and centuries. Engagingly written for readers of books such as Chaos and The Elegant Universe, Sync is a tour-de-force of nonfiction writing.
It is not yet possible to give a complete account of the relations between the organelles of two compartments and of the mechanisms by which some degree of order is maintained in the cell as a whole. However, a new breed of scientists, known as molecular cell biologists, have already contributed in some measure to our understanding of several biological phenomena notably interorganelle communication. Take, for example, intracellular membrane transport: it can now be expressed in terms of the sorting, targeting, and transport of protein from the endoplasmic reticulum to another compartment.
This volume contains the first ten chapters on the subject of organelles. The remaining four are in Volume 3, to which sections on organelle disorders and the extracellular matrix have been added.
*A one-stop source for proven methods and protocols for synthesizing bioconjugates in the lab
*Step-by-step presentation makes the book an ideal source for researchers who are less familiar with the synthesis of bioconjugates
*More than 600 figures that visually describe the complex reactions associated with the synthesis of bioconjugates
*Includes entirely new chapters on the latest areas in the field of bioconjugation as follows:
Microparticles and nanoparticles
Silane coupling agents
Dendrimers and dendrons
Discrete PEG compounds
Buckyballs,fullerenes, and carbon nanotubes
Mass tags and isotope tags
Bioconjugation in the study of protein interactions
This comprehensive collection of reviews written by leaders in the field of epigenetics provides a broad view of this important and evolving topic. From molecular mechanisms and epigenetic technology to discoveries in human disease and clinical epigenetics, the nature and applications of the science will be presented for those with interests ranging from the fundamental basis of epigenetics to therapeutic interventions for epigenetic-based disorders.Contributions by leading international investigators involved in molecular research and clinical and therapeutic applicationsIntegrates methods and biological topics with basic and clinical discoveriesIncludes coverage of new topics in epigenetics such as prions, regulation of long-term memory by epigenetics, metabolic aspects of epigenetics, and epigenetics of neuronal disorders
Developed at MIT in collaboration with award-winning high school teachers, BioBuilder teaches the foundational ideas of the emerging synthetic biology field, as well as key aspects of biological engineering that researchers are exploring in labs throughout the world. These lessons will empower teachers and students to explore and be part of solving persistent real-world challenges.Learn the fundamentals of biodesign and DNA engineeringExplore important ethical issues raised by examples of synthetic biologyInvestigate the BioBuilder labs that probe the design-build-test cycleTest synthetic living systems designed and built by engineersMeasure several variants of an enzyme-generating genetic circuitModel "bacterial photography" that changes a strain’s light sensitivityBuild living systems to produce purple or green pigmentOptimize baker’s yeast to produce ?-carotene
* Thoroughly revised and expanded by over 30% with 3400 new entries
* Expanded coverage of areas greatly impacted by genomics
* Includes new terms that relate to the recent elucidation of underlying mechanisms of cell cycle regulation, apoptosis, relationship between mitochondria and disease, metabolic control, and stem cell biology
* Consistently provides the most complete short definitions of technical terminology for anyone working in life sciences today
* Extensively cross-referenced
* Provides multiple definitions, notes on word origins, and other useful features
Now in its third edition, Primate Anatomy discusses species that are new to science since the last edition with details concerning anatomical features among primates that were re-discovered. New research in molecular primatology is also included due to recent relevant findings in molecular biology in accordance with new technology. The basics of biological taxonomy are introduced, along with photographs of all major groups. Important new and controversal issues make this edition key for every primatologists, anthropologist, and anatomist.Offers up-to-date reviews of molecular primatology and primate genomicsConcentrates on living primates and their overall biologyDiscusses the genetic connection of function where knownIntroduces primate genomics for the first time in a textbookProvides instructive and comprehensive review tablesIncludes many unique, novel and easily understandable illustrations
This book provides a comprehensive guide to the methodology involved in the development of cell lines and the cell engineering approach that can be employed to enhance productivity, improve cell function, glycosylation and secretion and control apoptosis. It presents an overall picture of the current topics central to expression engineering including such topics as epigenetics and the use of technologies to overcome positional dependent inactivation, the use of promoter and enhancer sequences for expression of various transgenes, site directed engineering of defined chromosomal sites, and examination of the role of eukaryotic nucleus as the controller of expression of genes that are introduced for production of a desired product. It includes a review of selection methods for high producers and an application developed by a major biopharmaceutical industry to expedite the cell line development process. The potential of cell engineering approch to enhance cell lines through the manipulation of single genes that play important roles in key metabolic and regulatory pathways is also explored throughout.