Ben-Gurion University of the Negev

Abstract Whereas much of organic chemistry has classically dealt with the preparation and study of the properties of individual molecules, an increasingly significant portion of the activity in chemical research involves understanding and utilizing the nature of the interactions between molecules. Two representative areas of this evolution are supramolecular chemistry and molecular recognition. The interactions between molecules are governed by intermolecular forces whose energetic and geometric properties are much less well understood than those of classical chemical bonds between atoms. Among the strongest of these interactions, however, are hydrogen bonds, whose directional properties are better understood on the local level (that is, for a single hydrogen bond) than many other types of non‐bonded interactions. Nevertheless, the means by which to characterize, understand, and predict the consequences of many hydrogen bonds among molecules, and the resulting formation of molecular aggregates (on the microscopic scale) or crystals (on the macroscopic scale) has remained largely enigmatic. One of the most promising systematic approaches to resolving this enigma was initially developed by the late M. C. Etter, who applied graph theory to recognize, and then utilize, patterns of hydrogen bonding for the understanding and design of molecular crystals. In working with Etter's original ideas the power and potential utility of this approach on one hand, and on the other, the need to develop and extend the initial Etter formalism was generally recognized. It with that latter purpose that we originally undertook the present review.

In this paper we report the set-up and results of the Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) organized in conjunction with the MICCAI 2012 and 2013 conferences. Twenty state-of-the-art tumor segmentation algorithms were applied to a set of 65 multi-contrast MR scans of low- and high-grade glioma patients-manually annotated by up to four raters-and to 65 comparable scans generated using tumor image simulation software. Quantitative evaluations revealed considerable disagreement between the human raters in segmenting various tumor sub-regions (Dice scores in the range 74%-85%), illustrating the difficulty of this task. We found that different algorithms worked best for different sub-regions (reaching performance comparable to human inter-rater variability), but that no single algorithm ranked in the top for all sub-regions simultaneously. Fusing several good algorithms using a hierarchical majority vote yielded segmentations that consistently ranked above all individual algorithms, indicating remaining opportunities for further methodological improvements. The BRATS image data and manual annotations continue to be publicly available through an online evaluation system as an ongoing benchmarking resource.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is thatthere is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the completeprocess including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increasedautophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in manycases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as forreviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multipleassays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagyrelated protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

A crucial part of statistical analysis is evaluating a model's quality and fit, or performance. During analysis, especially with regression models, investigating the fit of models to data also often involves selecting the best fitting model amongst many competing models. Upon investigation, fit indices should also be reported both visually and numerically to bring readers in on the investigative effort.

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.

Abstract The International Mineralogical Association's approved amphibole nomenclature has been revised in order to simplify it, make it more consistent with divisions generally at 50%, define prefixes and modifiers more precisely and include new amphibole species discovered and named since 1978, when the previous scheme was approved. The same reference axes form the basis of the new scheme and most names are little changed but compound species names like tremolitic hornblende (now magnesiohornblende) are abolished and also crossite (now glaucophane or ferroglaucophane or magnesioriebeckite or riebeckite), tirodite (now manganocummingtonite) and dannemorite (now manganogrunerite). The 50% rule has been broken only to retain tremolite and actinolite as in the 1978 scheme so the sodic calcic amphibole range has therefore been expanded. Alkali amphiboles are now sodic amphiboles. The use of hyphens is defined. New amphibole names approved since 1978 include nyböite, leakeite, kornite, ungarettiite, sadanagaite and cannilloite. All abandoned names are listed. The formulae and source of the amphibole end member names are listed and procedures outlined to calculate Fe 3+ and Fe 2+ when not determined by analysis.

With data from 33 nations, we illustrate the differences between cultures that are tight (have many strong norms and a low tolerance of deviant behavior) versus loose (have weak social norms and a high tolerance of deviant behavior). Tightness-looseness is part of a complex, loosely integrated multilevel system that comprises distal ecological and historical threats (e.g., high population density, resource scarcity, a history of territorial conflict, and disease and environmental threats), broad versus narrow socialization in societal institutions (e.g., autocracy, media regulations), the strength of everyday recurring situations, and micro-level psychological affordances (e.g., prevention self-guides, high regulatory strength, need for structure). This research advances knowledge that can foster cross-cultural understanding in a world of increasing global interdependence and has implications for modeling cultural change.

The synthesis of a control algorithm that stirs a nonlinear system to a given manifold and keeps it within this constraint is considered. Usually, what is called sliding mode is employed in such synthesis. This sliding mode is characterized, in practice, by a high-frequency switching of the control. It turns out that the deviation of the system from its prescribed constraints (sliding accuracy) is proportional to the switching time delay. A new class of sliding modes and algorithms is presented and the concept of sliding mode order is introduced. These algorithms feature a bounded control continuously depending on time, with discontinuities only in the control derivative. It is also shown that the sliding accuracy is proportional to the square of the switching time delay.

Ensemble methods are considered the state‐of‐the art solution for many machine learning challenges. Such methods improve the predictive performance of a single model by training multiple models and combining their predictions. This paper introduce the concept of ensemble learning, reviews traditional, novel and state‐of‐the‐art ensemble methods and discusses current challenges and trends in the field. This article is categorized under: Algorithmic Development > Ensemble Methods Technologies > Machine Learning Technologies > Classification

Movement of individual organisms is fundamental to life, quilting our planet in a rich tapestry of phenomena with diverse implications for ecosystems and humans. Movement research is both plentiful and insightful, and recent methodological advances facilitate obtaining a detailed view of individual movement. Yet, we lack a general unifying paradigm, derived from first principles, which can place movement studies within a common context and advance the development of a mature scientific discipline. This introductory article to the Movement Ecology Special Feature proposes a paradigm that integrates conceptual, theoretical, methodological, and empirical frameworks for studying movement of all organisms, from microbes to trees to elephants. We introduce a conceptual framework depicting the interplay among four basic mechanistic components of organismal movement: the internal state (why move?), motion (how to move?), and navigation (when and where to move?) capacities of the individual and the external factors affecting movement. We demonstrate how the proposed framework aids the study of various taxa and movement types; promotes the formulation of hypotheses about movement; and complements existing biomechanical, cognitive, random, and optimality paradigms of movement. The proposed framework integrates eclectic research on movement into a structured paradigm and aims at providing a basis for hypothesis generation and a vehicle facilitating the understanding of the causes, mechanisms, and spatiotemporal patterns of movement and their role in various ecological and evolutionary processes. "Now we must consider in general the common reason for moving with any movement whatever." (Aristotle, De Motu Animalium, 4th century B.C.).

Over the last decade, 'user experience' (UX) became a buzzword in the field of human - computer interaction (HCI) and interaction design. As technology matured, interactive products became not only more useful and usable, but also fashionable, fascinating things to desire. Driven by the impression that a narrow focus on interactive products as tools does not capture the variety and emerging aspects of technology use, practitioners and researchers alike, seem to readily embrace the notion of UX as a viable alternative to traditional HCI. And, indeed, the term promises change and a fresh look, without being too specific about its definite meaning. The present introduction to the special issue on 'Empirical studies of the user experience' attempts to give a provisional answer to the question of what is meant by 'the user experience'. It provides a cursory sketch of UX and how we think UX research will look like in the future. It is not so much meant as a forecast of the future, but as a proposal - a stimulus for further UX research.

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

This paper provides a critical look at the challenges facing the field of health promotion. Pointing to the persistence of the disease orientation and the limits of risk factor approaches for conceptualizing and conducting research on health, the salutogenic orientation is presented as a more viable paradigm for health promotion research and practice. The Sense of Coherence framework is offered as a useful theory for taking a salutogenic approach to health research.

Long‐term measurements by the AERONET program of spectral aerosol optical depth, precipitable water, and derived Angstrom exponent were analyzed and compiled into an aerosol optical properties climatology. Quality assured monthly means are presented and described for 9 primary sites and 21 additional multiyear sites with distinct aerosol regimes representing tropical biomass burning, boreal forests, midlatitude humid climates, midlatitude dry climates, oceanic sites, desert sites, and background sites. Seasonal trends for each of these nine sites are discussed and climatic averages presented.

Physical ecosystem engineers are organisms that directly or indirectly control the availability of resources to other organisms by causing physical state changes in biotic or abiotic materials. Physical ecosystem engineering by organisms is the physical modification, maintenance, or creation of habitats. Ecological effects of engineers on many other species occur in virtually all ecosystems because the physical state changes directly create nonfood resources such as living space, directly control abiotic resources, and indirectly modulate abiotic forces that, in turn, affect resource use by other organisms. Trophic interactions and resource competition do not constitute engineering. Engineering can have significant or trivial effects on other species, may involve the physical structure of an organism (like a tree) or structures made by an organism (like a beaver dam), and can, but does not invariably, have feedback effects on the engineer. We argue that engineering has both negative and positive effects on species richness and abundances at small scales, but the net effects are probably positive at larger scales encompassing engineered and nonengineered environments in ecological and evolutionary space and time. Models of the population dynamics of engineers suggest that the engineer/habitat equilibrium is often, but not always, locally stable and may show long-term cycles, with potential ramifications for community and ecosystem stability. As yet, data adequate to parameterize such a model do not exist for any engineer species. Because engineers control flows of energy and materials but do not have to participate in these flows, energy, mass, and stoichiometry do not appear to be useful in predicting which engineers will have big effects. Empirical observations suggest some potential generalizations about which species will be important engineers in which ecosystems. We point out some of the obvious, and not so obvious, ways in which engineering and trophic relations interact, and we call for greater research on physical ecosystem engineers, their impacts, and their interface with trophic relations.

This review of major depressive disorder is a comprehensive account of the genetic, biochemical, and neurophysiological changes that have been implicated in the disorder. No single mechanism can account for all the clinical variations in this condition. The monoamine oxidase theory can explain many of the actions of antidepressants, but genetic factors, stress, and psychosocial factors also play a part in depression.

BACKGROUND: Trials comparing the effectiveness and safety of weight-loss diets are frequently limited by short follow-up times and high dropout rates. METHODS: In this 2-year trial, we randomly assigned 322 moderately obese subjects (mean age, 52 years; mean body-mass index [the weight in kilograms divided by the square of the height in meters], 31; male sex, 86%) to one of three diets: low-fat, restricted-calorie; Mediterranean, restricted-calorie; or low-carbohydrate, non-restricted-calorie. RESULTS: The rate of adherence to a study diet was 95.4% at 1 year and 84.6% at 2 years. The Mediterranean-diet group consumed the largest amounts of dietary fiber and had the highest ratio of monounsaturated to saturated fat (P<0.05 for all comparisons among treatment groups). The low-carbohydrate group consumed the smallest amount of carbohydrates and the largest amounts of fat, protein, and cholesterol and had the highest percentage of participants with detectable urinary ketones (P<0.05 for all comparisons among treatment groups). The mean weight loss was 2.9 kg for the low-fat group, 4.4 kg for the Mediterranean-diet group, and 4.7 kg for the low-carbohydrate group (P<0.001 for the interaction between diet group and time); among the 272 participants who completed the intervention, the mean weight losses were 3.3 kg, 4.6 kg, and 5.5 kg, respectively. The relative reduction in the ratio of total cholesterol to high-density lipoprotein cholesterol was 20% in the low-carbohydrate group and 12% in the low-fat group (P=0.01). Among the 36 subjects with diabetes, changes in fasting plasma glucose and insulin levels were more favorable among those assigned to the Mediterranean diet than among those assigned to the low-fat diet (P<0.001 for the interaction among diabetes and Mediterranean diet and time with respect to fasting glucose levels). CONCLUSIONS: Mediterranean and low-carbohydrate diets may be effective alternatives to low-fat diets. The more favorable effects on lipids (with the low-carbohydrate diet) and on glycemic control (with the Mediterranean diet) suggest that personal preferences and metabolic considerations might inform individualized tailoring of dietary interventions. (ClinicalTrials.gov number, NCT00160108.)

This is an introductory book on solid state physics. It is a translation of a Hebrew version, written for the Open University in Israel. Aimed mainly for self-study, the book contains appendices with the necessary background, explains each calculation in detail and contains many solved problems. The bulk of the book discusses the basic concepts of periodic crystals, including lattice structures, radiation scattering off crystals, crystal bonding, vibrations of crystals, and electronic properties. On the other hand, the book also presents brief reviews of advanced topics, e.g. quasicrystals, soft condensed matter, mesoscopic physics and the quantum Hall effect. There are also many specific examples drawn from modern research topics, e.g. perovskite oxides relevant for high temperature superconductivity, graphene, electrons in low dimensions and more.

Despite decades of unequivocal evidence that waist circumference provides both independent and additive information to BMI for predicting morbidity and risk of death, this measurement is not routinely obtained in clinical practice. This Consensus Statement proposes that measurements of waist circumference afford practitioners with an important opportunity to improve the management and health of patients. We argue that BMI alone is not sufficient to properly assess or manage the cardiometabolic risk associated with increased adiposity in adults and provide a thorough review of the evidence that will empower health practitioners and professional societies to routinely include waist circumference in the evaluation and management of patients with overweight or obesity. We recommend that decreases in waist circumference are a critically important treatment target for reducing adverse health risks for both men and women. Moreover, we describe evidence that clinically relevant reductions in waist circumference can be achieved by routine, moderate-intensity exercise and/or dietary interventions. We identify gaps in the knowledge, including the refinement of waist circumference threshold values for a given BMI category, to optimize obesity risk stratification across age, sex and ethnicity. We recommend that health professionals are trained to properly perform this simple measurement and consider it as an important 'vital sign' in clinical practice.

Many have speculated that trust plays a critical role in stimulating consumer purchases over the Internet. Most of the speculations have rallied around U.S. consumers purchasing from U.S.–based online merchants. The global nature of the Internet raises questions about the robustness of trust effects across cultures. Culture may also affect the antecedents of consumer trust; that is, consumers in different cultures might have differing expectations of what makes a web merchant trustworthy. Here we report on a cross-cultural validation of an Internet consumer trust model. The model examined both antecedents and consequences of consumer trust in a Web merchant. The results provide tentative support for the generalizability of the model.