0000002449 00000 n Hooper, L. V., Stappenbeck, T. S., Hong, C. V. & Gordon, J. I. Angiogenins: a new class of microbicidal proteins involved in innate immunity. An interactive presentation, the viewer can click on one of five areas of the body that are hghlighted and can get an overview of the microbiome in that area. Gao X, Cao Q, Cheng Y, Zhao D, Wang Z, Yang H, Wu Q, You L, Wang Y, Lin Y, Li X, Wang Y, Bian JS, Sun D, Kong L, Birnbaumer L, Yang Y. This has implications for identifying individuals who are at risk of being malnourished or obese and treating them on the basis of a more personalized view of nutrition that considers their microbial ecology. Harvest of otherwise inaccessible nutrients and/or sources of energy from the diet, and synthesis of vitamins. UniFrac11,31,32 and other phylogenetic techniques address this problem for 16S rRNA gene data sets and could be extended to the assessment of metagenomic data. Subjects were sampled at one to three visits, for a total of over 11,000 samples. community assembly and composition Gao B, Bian X, Mahbub R, Lu K. 2017. In particular, heterogeneous rates of evolution in different protein families pose substantial problems for search-based methods: considerable similarities at the primary-structure level might not persist over time, and the secondary and tertiary structures of the proteins are usually unknown, thus preventing the use of structure-based alignment techniques. & Rosenzweig, M. L. The productivity diversity relationship: Tilman's pattern reflected in rodent communities. It is also unclear at what temporal and spatial scales this sampling should occur. The .gov means its official. BMC Bioinformatics 7, 371 (2006). (B) Metagenome means all genomes of the microorganisms, while 16S rDNA only covers a segment of the genomes. An ongoing project to sequence the genomes of 100 cultured representatives of the phylogenetic diversity in the human gut microbiota23 illustrates how reference genomes will help to interpret metagenomic studies. Describe the factors and processes that influence The HMP is not a single project. Microbiol. Environmental genome shotgun sequencing of the Sargasso Sea. Antimicrobials A study found a profound effect from triclosan, a common ingredient in antimicrobial products, on the gut microbiome in mice. Proc. Microbiota only means the microorganisms. Dia-Eldin A. Elnaiem Ph.D., University of Maryland Eastern Shore Specifically, the ob/ob mouse microbiome was enriched for genes involved in importing and metabolizing otherwise indigestible dietary polysaccharides to short-chain fatty acids, which are absorbed by the host and stored as more complex lipids in adipose tissue. Together, the genomes of these microbial. Importance of Human microbiome Did u try to use external powers for studying? ADS Nature Immunol. The observations about diversity in the human gut microbiota might fit with predictions of the neutral theory of community assembly, which states that most species share the same general niche (an ecological term that, in the case of microorganisms, refers to 'profession'), or the biggest niche, and therefore are likely to be functionally redundant18. 0000010337 00000 n Is altered production of neurologically active compounds (either directly, by the microbiota, or indirectly, by microbiota-mediated modulation of the expression of host genes that encode products normally involved in the biosynthesis and/or metabolism of these compounds) associated with any neurodevelopmental and/or psychiatric disorders? Infectious Diseases. 1), and how does this diversity affect adaptation by the microorganisms and the host to markedly different lifestyles and to various physiological or pathophysiological states? We've updated our privacy policy. 0000130331 00000 n Questions about the human microbiome are new only in terms of the system to which they apply. the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in An obesity-associated gut microbiome with increased capacity for energy harvest. Comparative metagenomics has uncovered functional attributes of the microbiome. Science 313, 11261130 (2006). Hyman, R. W. et al. Lozupone, C., Hamady, M. & Knight, R. UniFrac an online tool for comparing microbial community diversity in a phylogenetic context. Several issues need to be considered when designing ways to generate an initial set of reference microbiomes from healthy individuals. By whitelisting SlideShare on your ad-blocker, you are supporting our community of content creators. Human microbes are believed to play a broad role in cancer diagnosis, pathogenesis, and treatment by interacting with the host immune system [2]. 115(13):E2960-E2969. We've encountered a problem, please try again. 0000009837 00000 n The Effects of an Environmentally Relevant Level of Arsenic on the Gut Microbiome and Its Functional Metagenome. Broad sampling would enable the general principles that control community structure and function to be uncovered. PRIDE Group Coordinator Wu, L. et al. Bian X, L Chi, B Gao, P Tu, H Ru and K Lu. Pull, S. L., Doherty, J. M., Mills, J. C., Gordon, J. I. Natl Acad. Second, it will be necessary to find better, faster and more scalable heuristics for generating huge phylogenetic trees that contain millions of sequences. Presented By- 0000055541 00000 n What are the ethical, legal and logistical barriers that need to be overcome to obtain, without exploitation, samples and metadata (that is, 'relevant' environmental and host parameters) from people with diverse cultural and socio-economic backgrounds? Major microbial players in each body area also are provided with an overview of key information about each organisms, which often contains a link to further information.Contributing Team of Educators: Harold Chittum Ph.D., University of Pikeville Click here to review the details. To understand the range of human genetic and physiological diversity, the microbiome and the factors that influence the distribution and evolution of the constituent microorganisms must be characterized. Habitat can be defined over a range of scales, from the entire body to a specific surface area, such as the gut or a region within the gut. Enter HMP1 Characterization of microbiome and human host from three cohorts of microbiome-associated conditions, using multiple 'omics technologies. Science 308, 16351638 (2005). Is it feasible to identify novel biomarkers by mining public proteomics data? Ambient Ultrafine Particle Ingestion Alters Gut Microbiota in Association with Increased Atherogenic Lipid Metabolites. Well also hear how better understanding these complex interactions can help scientists develop interventions to slow, or even stop, progression of the disease. #\iE|)="6 ^8t+X7IL,8Pi 0, raTs&3 -&&SSqdHSd 2:\Z% W.lU[%$JNp!P8^4 5QSkP:vh,yw8^^Mr HMP1 was an interdisciplinary effort comprising four sequencing centers (the Broad Institute, Baylor College of Medicine, Washington University School of Medicine, and the J. Craig Venter Institute), a Data Analysis and Coordination Center (DACC), and several independent investigators involved in demonstration projects looking more closely at the associations between the microbiome and human health and disease, tool and technology development, and identification of ethical implications. 0000013333 00000 n Tap here to review the details. Microarray application in microbial ecology research. %PDF-1.4 % Characterization of microbiome and human host from three cohorts of microbiome-associated conditions, using multiple 'omics technologies. Nature Methods 4, 6372 (2007). We've updated our privacy policy. Explore the Human Microbiome Environ. 0000014830 00000 n Braun-Fahrlander, C. et al. The Theory of Island Biogeography (Princeton Univ. TETRA: a web-service and stand-alone program for the analysis and comparison of tetranucleotide usage patterns in DNA sequences. 71, 82288235 (2005). Venter, J. C. et al. Non-HMP investment in microbiome research at the NIH has increased over forty-fold since the inception of the HMP and spans over 20 of the NIH Institutes and Centers. 2018. NIEHS offers a broad range of job opportunities, career enhancement programs, and research training grants and programs in environmental health sciences and administration. Hinxton, Cambridge, UK. Lori West Ph.D., Lee University. Gao B, Tu P, Bian X, Chi L, Ru H, Lu K. 2017. 347, 869877 (2002). Miss Mugdha Pramod Padhye . Tringe, S. G. et al. You can read the details below. 2015. Grant, S. et al. Although microbes are so small that they require a microscope to see them, they contribute in big ways to human health and wellness. It is expected that the HMP will uncover whether the principles of ecology, gleaned from studies of the macroscopic world, apply to the microscopic world that humans harbour (see page 811). Ascribing metabolic phenotypes (also known as metabotypes) to the microbiota should extend our repertoire of personalized biomarkers of health and of disease susceptibility. For example, in the mouse gut microbiota, the effects of maternal transmission (kinship) are apparent over several generations in animals of the same inbred strain5. Accurate phylogenetic classification of variable-length DNA fragments. Now customize the name of a clipboard to store your clips. Appl. Proteomic tools, including Elucidator (http://www.rosettabio.com/products/elucidator) and SEQUEST (http://fields.scripps.edu/sequest), are also available for analysing complex samples. Sci. NPJ Biofilms Microbiomes; doi:10.1038/npjbiofilms.2016.3 [Online 4 May 2016]. They will also enable the variation that is typical of a healthy state to be defined, making it possible to search for deviations that are associated with disease. b, Hierarchical clustering based on the relative abundance of KEGG pathways. The Human Microbiome Project. The importance of Microorganisms in the human body, the importance and novel roe of the microorganisms on a human body is very effective and helpful. In addition, research in a mouse model of Alzheimers disease demonstrated thatexposure to cadmium altered an important communication pathway between the gut microbiome and the central nervous system called the gut-brain axis. just looking for general information about environmental health research or the institute, this page will help. The human microbiome Definition The term 'human microbiome refers to the complete set of genes contained in the entire collection of microorganisms that live in the human body. We have about 10 times as many microbial cells as human cells. Traditional microbiology has historically focused on the study of individual species as isolated units. Science 308, 19151920 (2005). Yet big questions remain and are the focus of continuing research supported by NIEHS. Nucleic Acids Res. The Human Microbiome 14:58 Taught By Rob Knight Professor Dr. Jessica L. Metcalf Senior Research Associate Dr. Katherine R. Amato Postdoctoral Research Associate Try the Course for Free Explore our Catalog Microbiome epidemiology and association studies in human health, Environment dominates over host genetics in shaping human gut microbiota, Current understanding of the human microbiome, Environmental factors shaping the gut microbiome in a Dutch population, Challenges and future directions for studying effects of host genetics on the gut microbiome, Health and disease markers correlate with gut microbiome composition across thousands of people, http://www.rosettabio.com/products/elucidator, http://www.ncbi.nlm.nih.gov/sites/entrez?db=proteinclusters, http://www.genome.gov/Pages/Research/Sequencing/SeqProposals/HGMISeq.pdf, The Association of Oral Microbiome Dysbiosis with Gastrointestinal Cancers and Its Diagnostic Efficacy, Therapeutic intervention based on gene sequencing analysis of microbial 16S ribosomal RNA of the intrauterine microbiome improves pregnancy outcomes in IVF patients: a prospective cohort study, Systematic comparison of transcriptomes of Caco-2 cells cultured under different cellular and physiological conditions, AGAMEMNON: an Accurate metaGenomics And MEtatranscriptoMics quaNtificatiON analysis suite, The colors of life: an interdisciplinary artist-in-residence project to research fungal pigments as a gateway to empathy and understanding of microbial life. 0000002335 00000 n Identification of eukaryotic open reading frames in metagenomic cDNA libraries made from environmental samples. You are using a browser version with limited support for CSS. Also, the modification of bile acids by microorganisms affects lipid metabolism in the host44. At present, there are 6.7 billion humans on Earth. NIEHS has a goal to ensure job opportunities and career enhancements programs for both our work force and our community. Heavy metalsArsenic exposure in mice changed the gut microbiome and altered molecular pathways in bacteria that are important to biological functions like DNA repair. Bian X, L Chi, B Gao, P Tu, H Ru and K Lu. & Stappenbeck, T. S. Activated macrophages are an adaptive element of the colonic epithelial progenitor niche necessary for regenerative responses to injury. From the Common Fund website: The Human Microbiome Project has transitioned from Common Fund support. Activate your 30 day free trialto continue reading. Mazmanian, S. K., Liu, C. H., Tzianabos, A. O. 0000012113 00000 n Ambramsky, Z. There are also links to other parts of the work including: Objectives, microbial profiling, data analysis, and more. 71, 41214126 (2005). The artificial sweetener acesulfame potassium affects the gut microbiome and body weight gain in CD-1 mice. 0000103482 00000 n The gut microbiota as an environmental factor that regulates fat storage. Germ-free animals, both wild-type and genetically engineered, that have been colonized at various stages of their lives with simplified microbial communities composed of a few sequenced members, or with more complex consortia, should be useful because they provide the opportunity to constrain several variables, including host genotype, microbial diversity and environmental factors such as diet. Mol. Madan JC, Hoen AG, Lundgren SN, Farzan SF, Cottingham KL, Morrison HG, Sogin ML, Li H, Moore JH, Karagas MR. 2016. NIEHS provides many opportunities for funding to individual researchers, organizations, and businesses. For example, they produce certain vitamins that we do not have the genes to make, break down our food to extract nutrients we need to survive, teach our immune systems how to recognize dangerous invaders and even produce helpful anti-inflammatory compounds that fight off other disease-causing microbes. 0000131014 00000 n There are no webcasts currently scheduled. Bioinformatics 20, 32463248 (2004). Large variation in bacterial lineages between people. [Online 17 Feb 2017], Enfermedades Provocadas por el Ambiente de A a Z, NIEHS Campus Tours & Information Sessions, About the Extramural Research and Training Division, Centers, Interagency Collaborations, and Consortia, Time-Sensitive Research Opportunities in Environmental Health, Translational Science, Outreach, and Education, Initiatives in Environmental Health Science, Explore Initiatives in Environmental Health Science, Coronavirus Research and Information From NIEHS, Diversity, Equity, Inclusion and Accessibility (DEIA), Environmental Health Disparities & Environmental Justice (EHD-EJ) Faculty, Environmental Health Language Collaborative, Environmental Influences on Child Health Outcomes (ECHO), Faculty for Advancing Neuroscience (FAN) Cross-divisional Group, Electron Paramagnetic Resonance/Electron Spin Resonance (EPR/ESR), International Myositis Assessment & Clinical Studies Group (IMACS), Data Management and Sharing Plan Development, NIEHS Medical Student Research Fellowships, Postdoctoral Training Opportunities in Translational Toxicology, National Toxicology Program Update Newsletter, Partnerships for Environmental Public Health, Superfund Research Program Science Digest, Environmental Health Disparities and Environmental Justice, Environmental Science Cyberinfrastructure, Scientific Coordination, Planning and Evaluation (SCOPE), Theme One: Advancing Environmental Health Sciences, Theme Two: Promoting Translation Data to Knowledge to Action, Theme Three: Enhancing EHS Through Stewardship and Support, Informatics and Information Technology Strategic Roadmap, Environmental Health Sciences Review Committee, National Advisory Environmental Health Sciences Council, Environmental Management System Frequently Asked Questions, as many microbes as there are human cells, increase the likelihood of developing conditions, Sucralose, an artificial sweetener, changes the gut microbiome, Chronic stress disturbs the gut microbiome, highfat diet affected the gut microbiome, type of microbes in the gut microbiome of infants, Precision Nutrition Improves Health at Individual Level, Expert Says, Connections Between Metabolism and Autism Explored in Webinar, Scientists Explore Exposures, Microbiome, and Nervous System, Autism Awareness Month Spotlights the Next Generation of Researchers, Microbiome Workshop Dives Deep Into Expanding Field, Enzyme May Play Key Role in Obesity-related Leaky Gut, Gut Bacteria and Human Cells Collaborate, Make Enzyme Needed for Life, Parkinsons Disease, Pesticides, and the Gut Microbiome (2021). Microbiol. The composition of thevaginal microbiome at birth can have lasting effects on offspring metabolism, immunity, and the brain. For samples taken from the colon, the differences between individuals are greater than the differences between different sampling sites in one individual15. Also, given the rapid development of new and more massively parallel sequencing technologies, systematic testing will be required to identify ways to maximize sequencing coverage affordably, while maintaining the ability to analyse and assemble genome fragments. Roadmap Analysis of microbial gene transcripts in environmental samples. It appears that you have an ad-blocker running. NIEHS intramural scientists have defined descriptive terms of particular relevance to their own research, and have ranked those terms accordingly. Pei, Z. et al. The construction and sequencing of complementary DNA libraries form an alternative approach, and these have already been used to examine microbial and eukaryotic mRNA from environmental samples36,37. Juan A. Vizcano juan@ebi.ac.uk Human Microbiome Project 11 December 2015 Access statistics: PRIDE Archive via the file repository Data download figures: 153.5 TB downloaded so far in 2015 by FTP 22.6 TB so far in 2015 by Aspera So far, 176 TB in 2015 (by mid November) 156 TB in 2014 FTP access for 2015, split per month. Article How stable and resilient is an individual's microbiota throughout one day and during his or her lifespan? Advances in DNA sequencing technologies in the mid 2000s contributed to the creation of a new field of research, called metagenomics, allowing for comprehensive examination of microbial communities without the need for cultivation. 10. The sequencing of more reference genomes, including genomes from multiple isolates of selected species-level phylotypes, should also help to answer questions about genetic variation within and between the major phylogenetic lineages in a given habitat, such as the gut. The Merck Manuals are a comprehensive medical and veterinary information source covering thousands of topics . The HMP is a logical conceptual and experimental extension of the Human Genome Project. The microbiome is the collection of all microbes, such as bacteria, fungi, viruses, and their genes, that naturally live on our bodies and inside us. 32, 13631371 (2004). Diet Dominates Host Genotype in Shaping the Murine Gut Microbiota. Click here to review the details. Federal government websites often end in .gov or .mil. Genome Biology; https://doi.org/10.1186/s13059-018-1389-1. The artificial sweetener acesulfame potassium affects the gut microbiome and body weight gain in CD-1 mice. NIEHS studies the microbiome to gain a better understanding of its complex relationships with the environment, and how these interactions may contribute to human wellbeing or disease. CAS *aP- 2\C&Y ac&Yuq/k+@. 112, 552559 (1982). 300 healthy adults between the ages of 18 and 40 were sampled at five major body sites (oral cavity, nasal cavity, skin, gastrointestinal tract and urogenital tract) with a total of 15 or 18 specific body sites. Furthermore, the incidence of asthma is correlated with exposure to bacteria during childhood52 and treatment with broad-spectrum antibiotics in early childhood53. Some progress has been made towards generating 'functional gene arrays', to determine the relative abundance of specific genes or transcripts in microbiomes33,34,35. Characterization of the microbiomes of healthy human subjects at five major body sites, using 16S and metagenomic shotgun sequencing. The Human Microbiome Project Description: Title: The Human Microbiome Project Author: ATUS Labs Last modified by: Jeff Young Created Date: 2/26/2010 6:04:31 PM Document presentation format - PowerPoint PPT presentation Number of Views: 161 Avg rating:3.0/5.0 Slides: 39 Provided by: ATUS6 Learn more at: https://fire.biol.wwu.edu Category: Science 308, 554557 (2005). By whitelisting SlideShare on your ad-blocker, you are supporting our community of content creators. In this article, we discuss the conceptual and experimental challenges that the HMP faces, as well as the rewards it might hold. Importance Trillions of symbiotic microbial organisms live in and on the surface of the human body. We've updated our privacy policy. A teacher's tools website with resources for use in biology classes learning about microbes. Press, Princeton, 1967). & Hattori, M. The KEGG resource for deciphering the genome. Proc. Schloss, P. D. & Handelsman, J. DOTUR, a computer program for defining operational taxonomic units and estimating species richness. What is meant by Human Microbiome Looks like youve clipped this slide to already. Cash, H. L., Whitham, C. V., Behrendt, C. L. & Hooper, L. V. Symbiotic bacteria direct expression of an intestinal bactericidal lectin. The Human Microbiome Project expands the toolbox for studying host and microbiome interactions Interagency Strategy Plan for Microbiome Research Released Read Report Expanding Our View of the Human Microbiome Dramatic Fluctuations of the Gut Microbiome in Individuals with Inflammatory Bowel Disease Because of their small size, however, microorganisms make up only about 1 to 3 percent of our body mass (that's 2 to 6 pounds of bacteria in a 200-pound adult). Because of various constraints, the human microbiome(s) will need to be characterized by comparing limited data types collected from a limited set of individuals. Biol. Activate your 30 day free trialto continue reading. Extending our view of self: the Human Gut Microbiome Initiative (HGMI). To obtain reference-genome sequences, it will be crucial to develop new methods for retrieving microorganisms that cannot be cultured at present. A strategy to understand the microbial components of the human genetic and metabolic landscape and how they contribute to normal physiology and predisposition to disease. Welcome to the Biology Department | College of Science & Engineering We focus on the gut when providing examples, because this habitat harbours the largest collection of microorganisms. Activate your 30 day free trialto unlock unlimited reading. Nature 444, 10221023 (2006). You can read the details below. Natl Acad. 210 0 obj <> endobj xref 210 42 0000000016 00000 n Introduction about PRIDE and PRIDE resources tailored for metaproteomics. Clipping is a handy way to collect important slides you want to go back to later. Danny L. Franke Ph.D., Alderson-Broaddus College This is one of the main goals of the Human Microbiome Project (HMP). For example, a comparison of members of the Firmicutes and Bacteroidetes should provide insight into the extent of genetic redundancy and/or specialization between these two divisions. 2018 Chronic stress promotes colitis by disturbing the gut microbiota and triggering immune system response. Initial 16S & mWGS metagenomic studies to generate an estimate of the complexity of the microbial community at each body site, providing initial answers to the questions of whether there is a core microbiome at each site. The first reported application of metagenomic techniques to a human microbiome involved two unrelated, healthy adults. Because the microbiome is a key interface between the body and the environment, these microbes can affect health in many ways and can even affect how we respond to certain environmental substances. It requires individuals from the clinical, biological and physical-engineering sciences to participate, including those with expertise in disciplines ranging from mathematics to statistics, computer science, computational biology, microbiology, ecology, evolutionary biology, comparative genomics and genetics, environmental and chemical engineering, chemistry and biochemistry, human systems physiology, anthropology, sociology, ethics and law. Deeper sequencing of more human gut microbiomes will be required to determine whether these features are common traits of the human microbiome. Appl. The results were visualized by using Java Treeview41. Use the Previous and Next buttons to navigate the slides or the slide controller buttons at the end to navigate through each slide. The human microbiome is the collection of all the microorganisms, which are non-negligible components of the human body, residing on or within human tissues and biofluids, such as the skin, oral mucosa, lung, and gastrointestinal tract [1]. In addition, susceptibility to colonization by enteropathogens is affected by the capacity of the microbiota to alter the expression of host genes encoding antimicrobial compounds48,51. The HMP produced 14 terabytes of genetic information about the microbes that naturally colonize our bodies. Cancer Res. The Human Microbiome is the collection of all the microorganisms living in association with the human body. Proc. 2015. Read more about 16S & metagenomic sampling and sequencing efforts, including metadata access. USA 104, 979984 (2007). USA 99, 1568115686 (2002). Sci. Microbes on the human vaginal epithelium. The gut microbiome in health and in disease. The HMP was supported by the Common Fund from 2007 to 2016. Proc. Bioinformatics 20, 14531454 (2004). Chi L, Bian X, Gao B, Tu P, Ru H, Lu K. 2017. NIEHS research uses state-of-the-art science and technology to investigate the interplay between environmental exposures, human biology, genetics, and common diseases to help prevent disease and improve human health. Research has yielded tremendous insight into the links between the microbiome, environmental exposures, and human health. Diversity of the human intestinal microbial flora. Environ. 0000004365 00000 n For example, in individuals with inflammatory bowel diseases, the immune response to the gut microbial community seems to be dysregulated: genome-wide association studies of patients with Crohn's disease have identified several human genes involved in both innate and adaptive immune responses50. The importance of the initial inoculating microbial community on the community composition at later stages is evident from animal studies. More than 90% of all phylogenetic types (phylotypes) of colonic bacteria belong to just 2 of the 70 known divisions (phyla) in the domain Bacteria: the Firmicutes and the Bacteroidetes. The NIH Human Microbiome Project - Title: PowerPoint Presentation Author: proctorlm Last modified by: Brian Foy Created Date: 2/7/2012 4:49:41 PM Document . Effects of Cesarean delivery and formula supplementation with the intestinal microbiome of 6-week-old infants. The NHMPAG adopted the FTAC-MM definition of a microbiome as "a multi-species population or community of microbes in a specific host or environment" where the term "microbes" included bacteria, fungi, archaea, eukaryotic viruses, and bacteriophage [ 26 ]. Gentry, T. J. et al. And it is one element of a worldwide effort to document, understand and respond to the consequences of human activities not only as they relate to human health but also as they relate to the sustainability of the biosphere. Nucleic Acids Res. Instant access to millions of ebooks, audiobooks, magazines, podcasts and more. Hubbell, S. P. Neutral theory and the evolution of ecological equivalence. 0000117740 00000 n McHardy, A. C. et al. Launched in 2007, the first phase (HMP1) focused on identifying and characterizing human microbiota. Ecol. Science Cabaret by Dr. Rodney Dietert "How to train your super organism..via No public clipboards found for this slide, Enjoy access to millions of presentations, documents, ebooks, audiobooks, magazines, and more. Human Microbiome Project, part 2. 0000006483 00000 n 0000008096 00000 n )2l"vH Pk'wty\'7h-e6"1@0^~"3CxY+OD!p..%S3"M{L8Cr0IiRN" $RwAT9A?sGXG^c*&o@GC~4qHWeQ9I`&@RR In particular, the following questions might be answered by the HMP. 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