Current Open Questions Research Articles

3–4D soil model as challenge for future soil research: Quantitative soil modeling based on the solid phase

AbstractA 3–4D soil model represents a logical step forward from one‐dimensional soil columns (1D), two‐dimensional soil maps (2D), and three‐dimensional soil volumes (3D) toward dynamic soil models (4D), with time as the fourth dimension. The challenge is to develop modeling tools that account for the states of soil properties, including the spatial structure of solids and pores, as well as their dynamics, including soil mass and solute transfers in landscapes. Our envisioned 3–4D soil model approach aims at improving the capability to predict fundamental soil functions (e.g., plant growth, storage, matter fluxes) that provide ecosystem services in the socioeconomic context.This study provides a structured overview on current soil models, challenges, open questions, and urgent research needs for developing a 3–4D soil model. A 3–4D soil model should provide an inventory of spatially distributed and temporally variable soil properties. As basis for this, we propose a mass balance model for the solid phase, which needs to be supplemented by a model describing its structure. This should eventually provide adequate 3D parameter sets for the numerical modeling of soil functions (e.g., flow and transport). The target resolution is decameters in the horizontal plane and centimeters to decimeters in the vertical direction to represent characteristic soil properties and soil horizons. The actual state of soils and their properties can be estimated from spatial data that represent the soil forming factors, with the use of machine learning tools. Improved modeling of the dynamics of soil bulk density, biological processes, and the pore structure are required to relate the solid mass balance to matter fluxes.A 3–4D soil model can be built from several types of modeling approaches. We distinguish between (1) process models that simulate mass balances, fluxes and soil structure dynamics, (2) statistical pedometric models using machine learning and geostatistics to estimate the soil inventory within landscapes, and (3) pedotransfer functions to link observable attributes to specific model parameters required to simulate soil functions including water and matter fluxes. This should provide the prerequisites to predict the spatial distribution of soil functions and their changes in response to external forcing.This endeavor can draw upon many already established models and techniques, yet combining them into a newly created 3–4D soil model is a truly an ambitious, but promising task. The core of such a model is the bookkeeping of the solid mass together with soil structure, while accounting for biogeochemical and mechanical processes. The presented concepts are ambitious in context for research avenues toward the improvement of soil modeling by conjoining methods from a wide range of disciplines, including geological, geophysical, pedological, and remote sensing and visualization applications. The paper reviews and outlines research tools and needs for the 3‐D, spatially continuous representation of relevant soil properties and the modeling to represent the dynamics of soil properties and soil functions.

A Review of Diopatra Ecology: Current Knowledge, Open Questions, and Future Threats for an Ecosystem Engineering Polychaete.

Simple SummaryMost of the world is ocean, and most of the ocean bottom is mud or sand. Understanding the ecology of sedimentary habitats is therefore important for understanding marine ecosystems writ large. Marine sediments are typically occupied by burrowing and tube-building animals that physically structure the habitat. In coastal sediments, an especially widespread example is the annelid worm Diopatra, which builds large tubes up to 2 m deep and 1 cm in diameter. These tubes have extensive physical effects on other organisms in the habitat, including commercially important fish and crustaceans. Diopatra are currently being impacted by climate change, species invasions, and (in some areas) the bait-digging industry. In this article, I review what we know about Diopatra ecology with an eye to identifying major open questions and future threats facing this important architect of coastal marine systems.A well-known example of marine ecosystem engineering is the annelid genus Diopatra, which builds large tubes in coastal sediments worldwide. Early studies of Diopatra were among the first to recognize the importance of facilitation in ecology, and Diopatra has become a key marine soft-sediment application of the ecosystem engineering concept. Here, I review our current knowledge of Diopatra ecology, including its natural history, ecosystem engineering effects, and trophic relationships. I particularly explore how human activities are influencing Diopatra in terms of climate change, bait fishing, and species invasions. Most of what we know about Diopatra ecology comes from focal studies of a few species in a few well-known regions. Further evaluating how our current understanding applies to other species and/or other regions will help to refine and deepen our understanding of structure and function in marine systems.

Behandlung von Staphylococcus-aureus-Blutstrominfektionen

Staphylococcus aureus bloodstream infections (SAB) represent a distinct clinical entity. Due to the frequency and the associated high morbidity and mortality, special requirements apply to the clinical management. Thus, in contrast to coagulase-negative staphylococci, even the detection of S. aureus in a single blood culture bottle is considered to be an infection requiring treatment. A classification into complicated versus uncomplicated bloodstream infections is carried out, with implications for the recommended duration of treatment (2 vs. 4–6 weeks). The use of transesophageal echocardiography to exclude endocarditis is indicated in the vast majority of cases. Because of frequent clinically silent septic metastases, positron emission tomography with computed tomography (PET-CT) is a useful tool for detection of nidi. For methicillin-sensitive S. aureus (MSSA), flucloxacillin and cefazolin are applied as basic treatment and for methicillin-resistant S. aureus (MRSA), vancomycin or daptomycin are used depending on the focus and comorbidity. If foreign material is present, a combination of basic treatment with rifampicin or fosfomycin should be considered. Source control by abscess drainage or removal of infected intravascular catheters, intracardiac devices or if necessary artificial joints is important. Studies show that infectious disease consultations improve the quality of care and mortality in SAB. Current open questions address the identification of subpopulations that benefit from combination treatment, the effectiveness and timing of stepdown oral antibiotic treatment, and a possible reduction in the overall duration of treatment. This review article summarizes the current standards for diagnostics and treatment of patients with SAB and presents recent relevant studies on this condition.

Genetics of Transformed Follicular Lymphoma

Histological transformation (HT) to a more aggressive disease–mostly diffuse large B-cell lymphoma–is considered one of the most dismal events in the clinical course of follicular lymphoma (FL). Current knowledge has not found a single biological event specific for HT, although different studies have highlighted common genetic alterations, such as TP53 and CDKN2A/B loss, and MYC translocations, among others. Together, they increase genomic complexity and mutational burden at HT. A better knowledge of HT pathogenesis would presumably help to find diagnostic biomarkers allowing the identification of patients at high-risk of transformation, as well as the discrimination from patients with FL recurrence, and those who remain in remission. This would also help to identify new drug targets and the design of clinical trials for the treatment of transformation. In the present review we provide a comprehensive overview of the genetic events frequently identified in transformed FL contributing to the switch towards aggressive behaviour, and we will discuss current open questions in the field of HT.

Intensive care management of cancer patients

Cancer patients compromise about 15-20 % of all patients on the intensive Care Unit (ICU). Moreover, recent therapeutic developments in hematology oncology as chimeric T-cells (CAR T-cells) regularly require critical care and therefore the amount of cancer patients in the ICU is expected to grow in the coming years. Although their prognosis has dramatically improved over the past decades, the mortality on cancer patients on the ICU is still high compared to non-cancer patients. Therefore, the interdisciplinary management of these patients is crucial in order to accurately identify patients who benefit from transfer to the ICU and to optimize treatment of these vulnerable and often complex patients. Consequently, large cohort studies have shown a positive impact of daily interdisciplinary patient visits including hematology-oncology and critical care medicine on survival of cancer patients on the ICU. This short review summarizes current knowledge and open questions in the critical care management of cancer patients.

Influence of Culture Conditions on Ex Vivo Expansion of T Lymphocytes and Their Function for Therapy: Current Insights and Open Questions.

Ex vivo expansion of T lymphocytes is a central process in the generation of cellular therapies targeted at tumors and other disease-relevant structures, which currently cannot be reached by established pharmaceuticals. The influence of culture conditions on T cell functions is, however, incompletely understood. In clinical applications of ex vivo expanded T cells, so far, a relatively classical standard cell culture methodology has been established. The expanded cells have been characterized in both preclinical models and clinical studies mainly using a therapeutic endpoint, for example antitumor response and cytotoxic function against cellular targets, whereas the influence of manipulations of T cells ex vivo including transduction and culture expansion has been studied to a much lesser detail, or in many contexts remains unknown. This includes the circulation behavior of expanded T cells after intravenous application, their intracellular metabolism and signal transduction, and their cytoskeletal (re)organization or their adhesion, migration, and subsequent intra-tissue differentiation. This review aims to provide an overview of established T cell expansion methodologies and address unanswered questions relating in vivo interaction of ex vivo expanded T cells for cellular therapy.

Ethical assurance: a practical approach to the responsible design, development, and deployment of data-driven technologies

This article offers several contributions to the interdisciplinary project of responsible research and innovation in data science and AI. First, it provides a critical analysis of current efforts to establish practical mechanisms for algorithmic auditing and assessment to identify limitations and gaps with these approaches. Second, it provides a brief introduction to the methodology of argument-based assurance and explores how it is currently being applied in the development of safety cases for autonomous and intelligent systems. Third, it generalises this method to incorporate wider ethical, social, and legal considerations, in turn establishing a novel version of argument-based assurance that we call ‘ethical assurance.’ Ethical assurance is presented as a structured method for unifying the myriad practical mechanisms that have been proposed. It is built on a process-based form of project governance that enlists reflective innovation practices to operationalise normative principles, such as sustainability, accountability, transparency, fairness, and explainability. As a set of interlocutory governance mechanisms that span across the data science and AI lifecycle, ethical assurance supports inclusive and participatory ethical deliberation while also remaining grounded in social and technical realities. Finally, this article sets an agenda for ethical assurance, by detailing current challenges, open questions, and next steps, which serve as a springboard to build an active (and interdisciplinary) research programme as well as contribute to ongoing discussions in policy and governance.

ASTRI Mini-Array core science at the Observatorio del Teide

The ASTRI (Astrofisica con Specchi a Tecnologia Replicante Italiana) Project led by the Italian National Institute for Astrophysics (INAF) is developing and will deploy at the Observatorio del Teide a mini-array (ASTRI Mini-Array) composed of nine telescopes similar to the small-size dual-mirror Schwarzschild-Couder telescope (ASTRI-Horn) currently operating on the slopes of Mt. Etna in Sicily. The ASTRI Mini-Array will surpass the current Cherenkov telescope array differential sensitivity above a few tera-electronvolt (TeV), extending the energy band well above hundreds of TeV. This will allow us to explore a new window of the electromagnetic spectrum, by convolving the sensitivity performance with excellent angular and energy resolution figures. In this paper we describe the Core Science that we will address during the first four years of operation, providing examples of the breakthrough results that we will obtain when dealing with current open questions, such as the acceleration of cosmic rays, cosmology and fundamental physics and the new window, for the TeV energy band, of the time-domain astrophysics.

DNA binding by polycomb-group proteins: searching for the link to CpG islands.

Polycomb group proteins predominantly exist in polycomb repressive complexes (PRCs) that cooperate to maintain the repressed state of thousands of cell-type-specific genes. Targeting PRCs to the correct sites in chromatin is essential for their function. However, the mechanisms by which PRCs are recruited to their target genes in mammals are multifactorial and complex. Here we review DNA binding by polycomb group proteins. There is strong evidence that the DNA-binding subunits of PRCs and their DNA-binding activities are required for chromatin binding and CpG targeting in cells. In vitro, CpG-specific binding was observed for truncated proteins externally to the context of their PRCs. Yet, the mere DNA sequence cannot fully explain the subset of CpG islands that are targeted by PRCs in any given cell type. At this time we find very little structural and biophysical evidence to support a model where sequence-specific DNA-binding activity is required or sufficient for the targeting of CpG-dinucleotide sequences by polycomb group proteins while they are within the context of their respective PRCs, either PRC1 or PRC2. We discuss the current knowledge and open questions on how the DNA-binding activities of polycomb group proteins facilitate the targeting of PRCs to chromatin.

Linking interindividual variability in brain structure to behaviour.

What are the brain structural correlates of interindividual differences in behaviour? More than a decade ago, advances in structural MRI opened promising new avenues to address this question. The initial wave of research then progressively led to substantial conceptual and methodological shifts, and a replication crisis unveiled the limitations of traditional approaches, which involved searching for associations between local measurements of neuroanatomy and behavioural variables in small samples of healthy individuals. Given these methodological issues and growing scepticism regarding the idea of one-to-one mapping of psychological constructs to brain regions, new perspectives emerged. These not only embrace the multivariate nature of brain structure-behaviour relationships and promote generalizability but also embrace the representation of the relationships between brain structure and behavioural data by latent dimensions of interindividual variability. Here, we examine the past and present of the study of brain structure-behaviour associations in healthy populations and address current challenges and open questions for future investigations.

Access Control Metamodels: Review, Critical Analysis, and Research Issues

The new generation of networking environments such as the internet of things (IoT), cloud computing, etc. is emerging and releases new prospects to traditional information systems by merging new technologies and services for seamless access to information sources at anytime and anywhere. Concurrently, this emergence opens new threats to information security and new challenges to controlling access to resources. To ensure security, several techniques have been employed, and access control (AC) is one of the essential security requirements especially for recent networking environments. Various authentication and AC methods are proposed to enforce AC policy and to prevent any unauthorized access to logical/physical assets. The continuous technology upgrades and the diversity of AC models force the need to find AC metamodels with a higher level of abstraction that serves as a unifying framework for specifying any AC policy. AC metamodels are proposed to encompass AC features and are used to derive various instances of AC models and methods. In this paper we review the proposed AC metamodels and their implementation scenarios, we analyze them, their objectives, their limitations, and present current research issues and open questions that still need to be addressed.

Ultrafast Spectroscopy of Fe(II) Complexes Designed for Solar-Energy Conversion: Current Status and Open Questions.

One major challenge of future sustainable photochemistry is to replace precious and rare transition metals in applications such as energy conversion or electroluminescence by earth-abundant, cheap, and recyclable materials. This involves using coordination complexes of first row transition metals such as Cu, Cr, or Mn. In the case of iron, which is attractive due to its natural abundance, fundamental limitations imposed by the small ligand field splitting energy have recently been overcome. In this review article, we briefly summarize the present knowledge and understanding of the structure-property relationships of Fe(II) and Fe(III) complexes with excited state lifetimes in the nanosecond range. However, our main focus is to examine to which extent the ultrafast spectroscopy methods used so far provided insight into the excited state structure and the photo-induced dynamics of these complexes. Driven by the main question of how to spectroscopically, i. e. in energy and concentration, differentiate the population of ligand- vs. metal-centered states, the hitherto less exploited ultrafast vibrational spectroscopy is suggested to provide valuable complementary insights.

Survey on Deep Learning-Based Point Cloud Compression

Point clouds are becoming essential in key applications with advances in capture technologies leading to large volumes of data. Compression is thus essential for storage and transmission. In this work, the state of the art for geometry and attribute compression methods with a focus on deep learning based approaches is reviewed. The challenges faced when compressing geometry and attributes are considered, with an analysis of the current approaches to address them, their limitations and the relations between deep learning and traditional ones. Current open questions in point cloud compression, existing solutions and perspectives are identified and discussed. Finally, the link between existing point cloud compression research and research problems to relevant areas of adjacent fields, such as rendering in computer graphics, mesh compression and point cloud quality assessment, is highlighted.

Mediterranean cyclones: current knowledge and open questions on dynamics, prediction, climatology and impacts

Abstract. A large number of intense cyclones occur every year in the Mediterranean basin, one of the climate change hotspots. Producing a broad range of severe socio-economic and environmental impacts in such a densely populated region, Mediterranean cyclones call for coordinated and interdisciplinary research efforts. This article aims at supporting these efforts by reviewing the status of knowledge in the broad field of Mediterranean cyclones. First, we focus on the climatology of Mediterranean cyclone tracks, their relationship to large-scale atmospheric circulation and their future trends. Second, we discuss the dynamics and atmospheric processes that govern the genesis and development of Mediterranean cyclones. Then, we present the different subtypes of Mediterranean cyclones, devoting special attention to medicanes, i.e. cyclones with tropical characteristics and subjects of numerous recent studies. In a subsequent section, we review the state of the art in forecasting cyclones and relevant high-impact weather, and we discuss in detail the challenges and recent efforts to increase their forecast skill. Finally, we discuss the main impacts produced by cyclones, namely heavy precipitation, windstorms, dust transport, storm surges and sea wave extremes. In the last section of this review article, we thoroughly outline the future directions of research that would advance the broader field of Mediterranean cyclones.

Roles of the Circadian Clock Mechanism in the Regulation of Daily Rhythms of Body Temperature

Body temperature of thermostatic animals does not stay constant but displays a regular circadian fluctuation, which has a role in maintaining homeostasis of sleep and metabolism as well as entraining the peripheral circadian clocks in the body. Following the discovery of clock genes that generate the circadian rhythm and the master clock structure in the brain and recent advances in infrared temperature imaging, there is a greater opportunity to investigate the mechanism underlying body temperature regulation, which currently remains unclear. In this review, we summarize our recent findings on a mechanism of body temperature regulation through a non-coding cis-element of the core clock gene Per2. The body temperature during siesta is controlled by the calcitonin receptors, which exhibit restricted expression in the suprachiasmatic nucleus, the locus of the central circadian clock in the brain. This review also refers to a recent machine learning-assisted thermography recording procedure, a technique that enables real-time simultaneous monitoring of circadian fluctuations in body temperature, locomotor activity, feeding, and drinking behaviors of animals. We will discuss the current challenges and open questions in understanding the molecular and circuit level mechanisms that give rise to circadian rhythms in body temperature.

Wave Dark Matter

We review the physics and phenomenology of wave dark matter: a bosonic dark matter candidate lighter than about 30 eV. Such particles have a de Broglie wavelength exceeding the average interparticle separation in a galaxy like the Milky Way and are, thus, well described as a set of classical waves. We outline the particle physics motivations for such particles, including the quantum chromodynamics axion as well as ultralight axion-like particles such as fuzzy dark matter. The wave nature of the dark matter implies a rich phenomenology: ▪ Wave interference gives rise to order unity density fluctuations on de Broglie scale in halos. One manifestation is vortices where the density vanishes and around which the velocity circulates. There is one vortex ring per de Broglie volume on average. ▪ For sufficiently low masses, soliton condensation occurs at centers of halos. The soliton oscillates and undergoes random walks, which is another manifestation of wave interference. The halo and subhalo abundance is expected to be suppressed at small masses, but the precise prediction from numerical wave simulations remains to be determined. ▪ For ultralight ∼10−22eV dark matter, the wave interference substructures can be probed by tidal streams or gravitational lensing. The signal can be distinguished from that due to subhalos by the dependence on stream orbital radius or image separation. ▪ Axion detection experiments are sensitive to interference substructures for wave dark matter that is moderately light. The stochastic nature of the waves affects the interpretation of experimental constraints and motivates the measurement of correlation functions.Current constraints and open questions, covering detection experiments and cosmological, galactic, and black hole observations, are discussed.

Introduction: Causation, inferences, and solution types in configurational comparative methods

This special issue addresses questions of causality and validity of different solution types in configurational comparative methods (CCMs). First, what main parameters characterize the debate about correct causal interpretation of solution types? Second, to what extent has this debate been linked to a theory of causation? The special issue contribution by Mahoney and Acosta bases qualitative comparative analysis (QCA) within a regularity theory of causation integrating type-level inferences and counterfactual cases. Swiatczak clarifies how the different algorithms underlying QCA and Coincidence Analysis (CNA) produce non-identical models. Baumgartner defines and benchmarks QCA solution types against the search target of minimal robust sufficiency. Alamos-Concha et al. identify the conservative solution as most appropriate for a multimethod design combining a counterfactual causal understanding at the cross-case level with an in-depth mechanistic explanation at the within-case level. Finally, Mahoney and Owen develop a general set-theoretic framework for the study of necessity and sufficiency in quantitative research using a counterfactual understanding of causality. Our introduction reviews the state of the art, identifies current limitations and open questions regarding the theoretical basis for causal interpretation of QCA solutions.

Current Landscape and Open Questions on Adjuvant Therapies in Melanoma.

Melanoma is a form of skin cancer that is frequently diagnosed at early stages. In most cases, surgical resection is curative. In case of thicker melanomas (> pT1b) without clinical or instrumental evidence of metastasis, a sentinel lymph node biopsy is recommended for staging purposes. If the lymph nodes are the only site of disease (macroscopic or microscopic> 1mm), configuring stage III, the international guidelines recommend the use of adjuvant therapy with checkpoint inhibitors (nivolumab or pembrolizumab) or targeted therapies (dabrafenib plus trametinib). These drugs have shown a significant increase in recurrence-free survival, although some doubts and open questions remain. Specifically, none of the available treatments has shown a clear benefit in the overall survival rates, the advantages they give in stage IIIA are not well known, and finally there are still no prospective clinical studies identifying the best approach to continue the therapeutic process in case of relapse. Furthermore, there are new opportunities opening up with the upcoming results of the neoadjuvant trials that could revolutionize the treatment of clinically evident stage III melanoma.

Reading and surviving the harsh conditions in desert biological soil crust: the cyanobacterial viewpoint.

Biological soil crusts (BSCs) are found in drylands, cover ∼12% of the Earth's surface in arid and semi-arid lands and their destruction is considered an important promoter of desertification. These crusts are formed by the adhesion of soil particles to polysaccharides excreted mostly by filamentous cyanobacteria, which are the pioneers and main primary producers in BSCs. Desert BSCs survive in one of the harshest environments on Earth, and are exposed to daily fluctuations of extreme conditions. The cyanobacteria inhabiting these habitats must precisely read the changing conditions and predict, for example, the forthcoming desiccation. Moreover, they evolved a comprehensive regulation of multiple adaptation strategies to enhance their stress tolerance. Here, we focus on what distinguishes cyanobacteria able to revive after dehydration from those that cannot. While important progress has been made in our understanding of physiological, biochemical and omics aspects, clarification of the sensing, signal transduction and responses enabling desiccation tolerance are just emerging. We plot the trajectory of current research and open questions ranging from general strategies and regulatory adaptations in the hydration/desiccation cycle, to recent advances in our understanding of photosynthetic adaptation. The acquired knowledge provides new insights to mitigate desertification and improve plant productivity under drought conditions.

The gate to metastasis: key players in cancer cell intravasation.

Metastasis is a leading cause of cancer‐related death and consists of a sequence of events including tumor expansion, intravasation of cancer cells into the circulation, survival in the bloodstream, extravasation at distant sites, and subsequent organ colonization. Particularly, intravasation is a process whereby cancer cells transverse the endothelium and leave the primary tumor site, pioneering the metastatic cascade. The identification of those mechanisms that trigger the entry of cancer cells into the bloodstream may reveal fundamentally novel ways to block metastasis at its start. Multiple factors have been implicated in cancer progression, yet, signals that unequivocally provoke the detachment of cancer cells from the primary tumor are still under investigation. Here, we discuss the role of intrinsic properties of cancer cells, tumor microenvironment, and mechanical cues in the intravasation process, outlining studies that suggest the involvement of various factors and highlighting current understanding and open questions in the field.