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In recent years, the amount of data available from systems has drastically increased, motivating the use of direct data-driven control techniques that avoid the need of parametric modeling. The aim of this paper is to analyze closed-loop aspects of these approaches in the presence of noise. To analyze this, a unified formulation of several approaches, including Data-enabled Predictive Control (DeePC) and Subspace Predictive Control (SPC) is obtained and the influence of noise on closed-loop predictors is analyzed. The analysis reveals potential closed-loop correlation problems, which are closely related to well-known results in closed-loop system identification, and consequent control issues. A case study reveals the hazards of noise in data-driven control.

We present HiGlass, an open source visualization tool built on web technologies that provides a rich interface for rapid, multiplex, and multiscale navigation of 2D genomic maps alongside 1D genomic tracks, allowing users to combine various data types, synchronize multiple visualization modalities, and share fully customizable views with others. We demonstrate its utility in exploring different experimental conditions, comparing the results of analyses, and creating interactive snapshots to share with collaborators and the broader public. HiGlass is accessible online at http://higlass.ioand is also available as a containerized application that can be run on any platform.

The G protein–coupled receptor (GPCR) US28 encoded by the human cytomegalovirus (HCMV) is associated with accelerated progression of glioblastomas, aggressive brain tumors with a generally poor prognosis. Here, we showed that US28 increased the malignancy of U251 glioblastoma cells by enhancing signaling mediated by sphingosine-1-phosphate (S1P), a bioactive lipid that stimulates oncogenic pathways in glioblastoma. US28 expression increased the abundance of the key components of the S1P signaling axis, including an enzyme that generates S1P [sphingosine kinase 1 (SK1)], an S1P receptor [S1P receptor 1 (S1P1)], and S1P itself. Enhanced S1P signaling promoted glioblastoma cell proliferation and survival by activating the kinases AKT and CHK1 and the transcriptional regulators cMYC and STAT3 and by increasing the abundance of cancerous inhibitor of PP2A (CIP2A), driving several feed-forward signaling loops. Inhibition of S1P signaling abrogated the proliferative and anti-apoptotic effects of US28. US28 also activated the S1P signaling axis in HCMV-infected cells. This study uncovers central roles for S1P and CIP2A in feed-forward signaling that contributes to the US28-mediated exacerbation of glioblastoma.

Reduced erythrocyte survival and deformability may contribute to the so-called anemia of inflammation observed in septic patients. Erythrocyte structure and function are affected by both the membrane lipid composition and the organization. We therefore aimed to determine whether these parameters are affected during systemic inflammation.

Self-tolerance and immune homeostasis are orchestrated by FOXP3+ regulatory T cells (Tregs). Recent data have revealed that upon stimulation, Tregs may exhibit plasticity toward a proinflammatory phenotype, producing interleukin 17 (IL-17) and/or interferon γ (IFN-γ). Such deregulation of Tregs may contribute to the perpetuation of inflammatory processes, including graft-versus-host disease. Thus, it is important to identify immunomodulatory factors influencing Treg stability. Platelet-derived microparticles (PMPs) are involved in hemostasis and vascular health and have recently been shown to be intimately involved in (pathogenic) immune responses. Therefore, we investigated whether PMPs have the ability to affect Treg plasticity. PMPs were cocultured with healthy donor peripheral blood–derived Tregs that were stimulated with anti-CD3/CD28 monoclonal antibodies in the presence of IL-2, IL-15, and IL-1β. PMPs prevented the differentiation of peripheral blood–derived Tregs into IL-17– and IFN-γ–producing cells, even in the presence of the IL-17–driving proinflammatory cytokine IL-1β. The mechanism of action by which PMPs prevent Treg plasticity consisted of rapid and selective P-selectin–dependent binding of PMPs to a CCR6+HLA-DR+ memory-like Treg subset and their ability to inhibit Treg proliferation, in part through CXCR3 engagement. The findings that ∼8% of Tregs in the circulation of healthy individuals are CD41+P-selectin+ and that distinct binding of patient plasma PMPs to Tregs was observed support in vivo relevance. These findings open the exciting possibility that PMPs actively regulate the immune response at sites of (vascular) inflammation, where they are known to accumulate and interact with leukocytes, consolidating the (vascular) healing process.

The determination of intracellular protein concentrations is a prerequisite for understanding protein interaction networks in systems biology. Today, protein quantification is based either on mass spectrometry, which requires large cell numbers and sophisticated measurement protocols, or on quantitative Western blotting, which requires the expression and purification of a recombinant protein as a reference. Here, we present a method that uses a transiently expressed fluorescent fusion protein of the protein-of-interest as an easily accessible reference in small volumes of crude cell lysates. The concentration of the fusion protein is determined by fluorescence correlation spectroscopy, and this concentration is used to calibrate the intensity of bands on a Western blot. We applied this method to address cellular protein homeostasis by determining the concentrations of the plasma membrane-located transmembrane scaffolding protein LAT and soluble signaling proteins in naïve T cells and transformed T-cell lymphoma (Jurkat) cells (with the latter having nine times the volume of the former). Strikingly, the protein numbers of soluble proteins scaled with the cell volume, whereas that of the transmembrane protein LAT scaled with the membrane surface. This leads to significantly different stoichiometries of signaling proteins in transformed and naïve cells in concentration ranges that may translate directly into differences in complex formation.

Bioleaching test work was performed in continuously operated multi-stage reactor systems at 70°C using a thermophilic culture treating an Aguablanca Ni-Cu concentrate from Spain and a blend of Cu concentrates from Bor, Serbia. The copper in both these concentrates occurs as chalcopyrite and therefore the use of thermophiles was applied, which resulted in copper recoveries of over 95%. Qualitative assessment of the microbial community in the bioreactors was performed by terminal restriction enzyme fragment length polymorphism (T-RFLP) and clone library analysis of the 16S rRNA genes amplified by PCR. T-RFLP analysis revealed that only archaea were present, and that the communities in both the Aguablanca and Bor systems consisted of two different microorganisms. A 16S rRNA gene clone library using DNA from the Aguablanca system was constructed and screened. Again, two archaea were detected in similar relative abundance in the population as found by T-RFLP analyses. The sequences of these two cloned genes revealed that the dominant archaeon (up to 98% of the total archaea detected) was Acidianus brierleyi, and the other was Metallosphaera sedula. Quantitative assessment of the microbial community was performed by Q-PCR and confirmed the dominance of archaea in the system with Acidianus being the dominant strain (98-99% of the total population) and a minor part of the population (1-2%) consisted of Metallosphaera. Additionally, very small amounts of Sulfolobus spp. were detected. This study, along with other recent studies on the diversity of thermoacidophiles involved in the solubilization of copper from chalcopyrite concentrates, revealed that a wider variety of thermoacidophiles are involved in bioprocessing of metal sulfides, and showed that A. brierleyi should be considered an important biomining acidophile.

Several letters to the editor are presented in response to online articles alongwith the editor's response published in previous issues on topics including bitcoins as legal fees, basics on traffic stop rights and a video interview with Judge Randy Koschnick on electronic filing of court documents.

Neglect can cause problems in navigation in the environment, for instance because patients tend to bump into objects such as doorposts. The aim of this study was to analyse the extent to which neglect affected navigation skills. Nine stroke patients with adequate walking abilities, of whom five had visual neglect, were observed while they walked through an aperture. The width of the passage was varied, and in some trials a coloured strip was attached to either the left or the right side of the aperture in order to increase the salience of that side. Patients with neglect bumped into the sides of the aperture much more often than the patients without neglect or the controls (N = 18). The coloured cue had no effect on the number of collisions. The number of collisions correlated highly with paper and pencil tests of neglect. The results showed that there are differential patterns of performance. Three patients with mild neglect bumped into the left side, and two others with more severe neglect bumped predominantly into the right side. An important indicator of the coupling between perception and action is rotation of the shoulders while passing a narrow aperture. Although the patients were able to do so, they often failed to rotate their shoulders when this was required for a smooth passage, thus indicating an impairment at the level of perception-action coupling. This is even more interesting because patients were very well able to estimate the width of the aperture at the verbal level. The main findings are discussed in terms of contralateral attentional deficit and an ipsilateral release of “intentional” processes. Implications for future research are discussed.

Objective To investigate whether changes in peritoneal membrane characteristics and inflammatory mediators in dialysate precede the onset of overt infection during continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis.Design CAPD patients with a high peritonitis incidence stored every night bag at 4°C. Routinely, each bag was thrown away after two days. Only if patients developed peritonitis, all bags were delivered for study. Thus, two night bags immediately prior to the first peritonitis bag were available for analysis. A control study was done 14 days after recovery. Dialysate samples were measured for TNFα, IL-6, PGE2, 6-keto-PGF lα’ TxB2, and serum proteins. The clearance of β2-microglobulin was used as an indicator of the effective peritoneal surface area. The intrinsic peritoneal permeability was characterized by the restriction coefficient.Results Eight episodes occurred in 5 patients. The night dwells available prior to the first peritonitis effluent were drained maximally nine dwells and minimally one dwell before the first peritonitis bag. Dialysate leukocyte counts exceeded 100 × 106/L only on the day of manifest infection. However, bacterial cultures were already positive at least one day before overt infection in four episodes and in three of these cases two days before. No changes were observed prior to peritonitis for the clearance of β2-microglobulin or the restriction coefficient. In contrast to these permeability characteristics, the cytokines, TNFα and, though less significant, also IL-6, were increased in dialysate one day prior to overt infection, when compared to the values obtained at the control investigation. This was especially evident in effluents drained no longer than two dwells before the first peritonitis bag. Prostaglandin concentrations in dialysate were not different before the onset of manifest peritonitis from the values measured after recovery.Conclusion In this study, the increased effective peritoneal surface area and intrinsic peritoneal permeability during acute infection appeared to be preceded by elevations in the cytokines TNFα and, to a lesser extent, IL-6. These increments occurred only very shortly before the onset of clinical symptoms.

Summary A native from Surinam (South America), known to have a chronic gonarthritis for 20 years, died from an acute disseminated histoplasmosis. His gonarthritis was retrospectively shown to have been due to histoplasmosis. Although histoplasmosis rarely presents as a monarthritis, unacquaintance with this entity may result in fatal acute dissemination of the histoplasmosis.

Cytokine responses of chronic Q fever patients to the intracellular bacterium Coxiella burnetiihave mostly been studied using ex vivostimulation of immune cells with heat-killed C. burnetiidue to the extensive measures needed to work with viable biosafety level 3 agents. Whether research with heat-killed C. burnetiican be translated to immune responses to viable C. burnetiiis imperative for the interpretation of previous and future studies with heat-killed C. burnetii.

More than 150 years from the initial description of inflammation in atherosclerotic plaques, randomized clinical trials to test anti-inflammatory therapies in atherosclerosis have recently been initiated. Lymphocytes and macrophages are main participants in the inflammatory response in atherosclerosis. T lymphocytes operate mainly by exerting strong influences on the function of many cells in the immune system and beyond, and co-ordinating their interactions. Importantly, T lymphocytes are not a homogenous population, but include several subsets with specialized functions that can either promote or suppress inflammation. The interactions between these T-lymphocyte subsets have critical consequences on the course and outcome of inflammation. The complexity of the inflammatory response in atherosclerosis poses significant challenges on translating experimental findings into clinical therapies and makes the journey from bench to bedside an arduous one. Here, we summarize recent advances on the role of CD4+ T cells in the inflammatory process in atherosclerosis and discuss potential therapies to modulate these lymphocytes that may provide future breakthroughs in the treatment of atherosclerosis.

The article focuses on the role of Fair Flowers Fair Plants (FFP) to the flower and plant industry. FFP is a non-profit organization of producers, trade unions, and non-governmental organizations (NGOs) which is responsible on the production of flowers and plants throughout the world. It adds that flowers and plants with a clearly visible FFP sticker would give consumers an assurance that the product they would buy is an environment friendly and not being exploited or underpaying employees.

The article presents a comparative study of history, scope and significance of the judicial selection process such as merit selection and judicial elections in the State of Kansas and Iowa.

No relevant conflicts of interest to declare.

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