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Nutrition has long been considered more the domain of medicine and agriculture than of the biological sciences, yet it touches and shapes all aspects of the natural world. The need for nutrients determines whether wild animals thrive, how populations evolve and decline, and how ecological communities are structured.The Nature of Nutritionis the first book to address nutrition's enormously complex role in biology, both at the level of individual organisms and in their broader ecological interactions. Stephen Simpson and David Raubenheimer provide a comprehensive theoretical approach to the analysis of nutrition--the Geometric Framework. They show how it can help us to understand the links between nutrition and the biology of individual animals, including the physiological mechanisms that determine the nutritional interactions of the animal with its environment, and the consequences of these interactions in terms of health, immune responses, and lifespan. Simpson and Raubenheimer explain how these effects translate into the collective behavior of groups and societies, and in turn influence food webs and the structure of ecosystems. Then they demonstrate how the Geometric Framework can be used to tackle issues in applied nutrition, such as the problem of optimizing diets for livestock and endangered species, and how it can also help to address the epidemic of human obesity and metabolic disease Drawing on a wealth of examples from slime molds to humans,The Nature of Nutritionhas important applications in ecology, evolution, and physiology, and offers promising solutions for human health, conservation, and agriculture.

Dietary Reference Intakes for Water, Potassium, Sodium, Chloride, and Sulfate The Dietary Reference Intakes (DRIs) are quantitative estimates of nutrient intakes to be used for planning and assessing diets for healthy people. This new report, the sixth in a series of reports presenting dietary reference values for the intakes of nutrients by Americans and Canadians, establishes nutrient recommendations on water, potassium, and salt for health maintenance and the reduction of chronic disease risk. Dietary Reference Intakes for Water, Potassium, Sodium, Chloride, and Sulfate discusses in detail the role of water, potassium, salt, chloride, and sulfate in human physiology and health. The major findings in this book include the establishment of Adequate Intakes for total water (drinking water, beverages, and food), potassium, sodium, and chloride and the establishment of Tolerable Upper Intake levels for sodium and chloride. The book makes research recommendations for information needed to advance the understanding of human requirements for water and electrolytes, as well as adverse effects associated with the intake of excessive amounts of water, sodium, chloride, potassium, and sulfate. This book will be an invaluable reference for nutritionists, nutrition researchers, and food manufacturers.

Research has repeatedly shown that high-quality requirements are essential for the success of development projects. While the term “quality” is pervasive in the field of requirements engineering and while the body of research on requirements quality is large, there is no meta-study of the field that overviews and compares the concrete quality attributes addressed by the community. To fill this knowledge gap, we conducted a systematic mapping study of the scientific literature. We retrieved 6905 articles from six academic databases, which we filtered down to 105 relevant primary studies. The primary studies use empirical research to explicitly define, improve, or evaluate requirements quality. We found that empirical research on requirements quality focuses on improvement techniques, with very few primary studies addressing evidence-based definitions and evaluations of quality attributes. Among the 12 quality attributes identified, the most prominent in the field are ambiguity, completeness, consistency, and correctness. We identified 111 sub-types of quality attributes such as “template conformance” for consistency or “passive voice” for ambiguity. Ambiguity has the largest share of these sub-types. The artefacts being studied are mostly referred to in the broadest sense as “requirements”, while little research targets quality attributes in specific types of requirements such as use cases or user stories. Our findings highlight the need to conduct more empirically grounded research defining requirements quality, using more varied research methods, and addressing a more diverse set of requirements types.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and a phenotypically similar recessive condition (CARASIL) have emerged as important genetic model diseases for studying the molecular pathomechanisms of cerebral small vessel disease (SVD). CADASIL, the most frequent and intensely explored monogenic SVD, is characterized by a severe pathology in the cerebral vasculature including the mutation-induced aggregation of the Notch3 extracellular domain (Notch3ECD) and the formation of protein deposits of insufficiently determined composition in vessel walls. To identify key molecules and pathways involved in this process, we quantitatively determined the brain vessel proteome from CADASIL patient and control autopsy samples (n = 6 for each group), obtaining 95 proteins with significantly increased abundance. Intriguingly, high-temperature requirement protein A1 (HTRA1), the extracellular protease mutated in CARASIL, was found to be strongly enriched (4.9-fold, p = 1.6 × 10−3) and to colocalize with Notch3ECD deposits in patient vessels suggesting a sequestration process. Furthermore, the presence of increased levels of several HTRA1 substrates in the CADASIL proteome was compatible with their reduced degradation as consequence of a loss of HTRA1 activity. Indeed, a comparison with the brain vessel proteome of HTRA1 knockout mice (n = 5) revealed a highly significant overlap of 18 enriched proteins (p = 2.2 × 10−16), primarily representing secreted and extracellular matrix factors. Several of them were shown to be processed by HTRA1 in an in vitro proteolysis assay identifying them as novel substrates. Our study provides evidence for a loss of HTRA1 function as a critical step in the development of CADASIL pathology linking the molecular mechanisms of two distinct SVD forms.

Requirements specification is a core activity in the requirements engineering phase of a software development project. Researchers have contributed extensively to the field of requirements specification, but the extent to which their proposals have been adopted in practice remains unclear. We gathered evidence about the state of practice in requirements specification by focussing on the artefacts used in this activity, the application of templates or guidelines, how requirements are structured in the specification document, what tools practitioners use to specify requirements, and what challenges they face. We conducted an interview-based survey study involving 24 practitioners from 12 different Swedish IT companies. We recorded the interviews and analysed these recordings, primarily by using qualitative methods. Natural language constitutes the main specification artefact but is usually accompanied by some other type of instrument. Most requirements specifications use templates or guidelines, although they seldom follow any fixed standard. Requirements are always structured in the document according to the main functionalities of the system or to project areas or system parts. Different types of tools, including MS Office tools, are used, either individually or combined, in the compilation of requirements specifications. We also note that challenges related to the use of natural language (dealing with ambiguity, inconsistency, and incompleteness) are the most frequent challenges that practitioners face in the compilation of requirements specifications. These findings are contextualized in terms of demographic factors related to the individual interviewees, the organization they are affiliated with, and the project they selected to discuss during our interviews. A number of our findings have been previously reported in related studies. These findings show that, in spite of the large number of notations, models and tools proposed from academia for improving requirements specification, practitioners still mainly rely on plain natural language and general-purpose tool support. We expect more empirical studies in this area in order to better understand the reason of this low adoption of research results.

The amount of nutrients required by an individual is determined by a number of physiological processes, including absorption, metabolism, stability, and bio-activation. These processes determine nutrient needs and provide variations in requirements in the population. All have modifiers and sensitizers, such as sex, genetics, pregnancy, age, pharmaceuticals, toxins, food matrix, and epigenetics. Disease can also be a major modifier of these processes. In April 2018, the National Academies of Science, Engineering and Medicine convened a workshop in order to explore the evidence for special nutritional requirements in disease states and the medical conditions that cannot be met with a normal diet. Participants explored the impact a disease state can have on nutrient metabolism and nutritional status, and attempted to close informational gaps. This publication summarizes the presentations and discussions from the workshop.

Human nutrition.

Organisations are becoming concerned with effectively dealing with privacy-related requirements. Existing Requirements Engineering methods based on structured natural language suffer from several limitations both in eliciting and specifying privacy requirements. In our previous study, we proposed a structured natural-language approach called the “Privacy Criteria Method” (PCM), which demonstrates potential advantages over user stories. Our goal is to present a PCM evaluation that focused on the opinions of software practitioners from different companies on PCM’s ability to support the specification of privacy requirements and the quality of the privacy requirements specifications produced by these software practitioners. We conducted a multiple case study to evaluate PCM in four different industrial contexts. We gathered and analysed the opinions of 21 practitioners on PCM usage regarding Coverage, Applicability, Usefulness, and Scalability. Moreover, we assessed the syntactic and semantic quality of the PCM artifacts produced by these practitioners. PCM can aid developers in elaborating requirements specifications focused on privacy with good quality. The practitioners found PCM to be useful for their companies’ development processes. PCM is considered a promising method for specifying privacy requirements. Some slight extensions of PCM may be required to tailor the method to the characteristics of the company.

Low power wide area network (LPWAN) is a promising solution for long range and low power Internet of Things (IoT) and machine to machine (M2M) communication applications. This paper focuses on defining a systematic and powerful approach of identifying the key characteristics of such applications, translating them into explicit requirements, and then deriving the associated design considerations. LPWANs are resource-constrained networks and are primarily characterized by long battery life operation, extended coverage, high capacity, and low device and deployment costs. These characteristics translate into a key set of requirements including M2M traffic management, massive capacity, energy efficiency, low power operations, extended coverage, security, and interworking. The set of corresponding design considerations is identified in terms of two categories, desired or expected ones and enhanced ones, which reflect the wide range of characteristics associated with LPWAN-based applications. Prominent design constructs include admission and user traffic management, interference management, energy saving modes of operation, lightweight media access control (MAC) protocols, accurate location identification, security coverage techniques, and flexible software re-configurability. Topological and architectural options for interconnecting LPWAN entities are discussed. The major proprietary and standards-based LPWAN technology solutions available in the marketplace are presented. These include Sigfox, LoRaWAN, Narrowband IoT (NB-IoT), and long term evolution (LTE)-M, among others. The relevance of upcoming cellular 5G technology and its complementary relationship with LPWAN technology are also discussed.

The human high-temperature requirement A2 (HtrA2) mitochondrial protease is critical for cellular proteostasis, with mutations in this enzyme closely associated with the onset of neurodegenerative disorders. HtrA2 forms a homotrimeric structure, with each subunit composed of protease and PDZ (PSD-95, DLG, ZO-1) domains. Although we had previously shown that successive ligand binding occurs with increasing affinity, and it has been suggested that allostery plays a role in regulating catalysis, the molecular details of how this occurs have not been established. Here,we use cysteine-based chemistry to generate subunits in different conformational states along with a protomer mixing strategy, biochemical assays, and methyl-transverse relaxation optimized spectroscopy–based NMR studies to understand the role of interprotomer allostery in regulating HtrA2 function. We show that substrate binding to a PDZ domain of one protomer increases millisecond-to-microsecond timescale dynamics in neighboring subunits that prime them for binding substrate molecules. Only when all three PDZ-binding sites are substrate bound can the enzyme transition into an active conformation that involves significant structural rearrangements of the protease domains. Our results thus explain why when one (or more) of the protomers is fixed in a ligand-binding–incompetent conformation or contains the inactivating S276C mutation that is causative for a neurodegenerative phenotype in mouse models of Parkinson’s disease, transition to an active state cannot be formed. In this manner, wild-type HtrA2 is only active when substrate concentrations are high and therefore toxic and unregulated proteolysis of nonsubstrate proteins can be suppressed.