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To improve the identification and management of viral respiratory infections, we established a clinical and virologic surveillance program for pediatric patients fulfilling pre-defined case criteria of influenza-like illness and viral respiratory infections. The program resulted in a cohort comprising 6,073 patients (56% male, median age 1.6 years, range 0–18.8 years), where every patient was assessed with a validated disease severity score at the point-of-care using the ViVI ScoreApp. We used machine learning and agnostic feature selection to identify characteristic clinical patterns. We tested all patients for human adenoviruses, 571 (9%) were positive. Adenovirus infections were particularly common and mild in children ≥1 month of age but rare and potentially severe in neonates: with lower airway involvement, disseminated disease, and a 50% mortality rate (n = 2/4). In one fatal case, we discovered a novel virus: HAdV-80. Standardized surveillance leveraging digital technology helps to identify characteristic clinical patterns, risk factors, and emerging pathogens.

Plant–microbe–arthropod (PMA) three-way interactions have important implications for plant health. However, our poor understanding of the underlying regulatory mechanisms hampers their biotechnological applications. To this end, we searched for potential common patterns in plant responses regarding taxonomic groups or lifestyles. We found that most signaling modules regulating two-way interactions also operate in three-way interactions. Furthermore, the relative contribution of signaling modules to the final plant response cannot be directly inferred from two-way interactions. Moreover, our analyses show that three-way interactions often result in the activation of additional pathways, as well as in changes in the speed or intensity of defense activation. Thus, detailed, basic knowledge of plant–microbe–arthropod regulation will be essential for the design of environmentally friendly crop management strategies., This paper was inspired by scientific discussions among members of the COST Action FA1405. We thank the COST Action members that contributed to identify relevant publications. We thank Júlia Lidoy and Víctor Lidoy for drawing Figure 1. This work was financially supported by COST Action FA1405 and the Slovenian Research Agency’s research core funding No Z4-706, the Spanish Ministry of Science, Innovation and Universities (grants AGL2016-75819-C2-1-R and RTI2018-094350-B-C31), General Secreterial of Research and Technology, Greece co-financed with EU (T1- RCE-05301), and the Onassis Foundation (RZJ-003-2). A.M.M. Acknowledges funding from the program for attracting talent to Salamanca from the Fundación Salamanca Ciudad de Cultura y Saberes and Ayuntamiento de Salamanca

SARS-CoV-2 utilizes the ACE2 transmembrane peptidase as essential cellular entry receptor. Several studies have suggested abundant ACE2 expression in the human lung, inferring strong permissiveness to SARS-CoV-2 infection with resultant alveolar damage and lung injury. Against this expectation, we provide evidence that ACE2 expression must be considered scarce, thereby limiting SARS-CoV-2 propagation in the human alveolus. Instead, spectral imaging of ex vivo infected human lungs and COVID-19 autopsy samples depicted that alveolar macrophages were frequently positive for SARS-CoV-2, indicating viral phagocytosis. Single-cell transcriptomics of SARS-CoV-2 infected human lung tissue further revealed strong inflammatory and anti-viral activation responses in macrophages and monocytes, comparable to those induced by MERS-CoV, but with virus-specific gene expression profiles. Collectively, our findings indicate that severe lung injury in COVID-19 likely results from an overwhelming immune activation rather than direct viral damage of the alveolar compartment. Funding: ACH, LES, SH were supported by Berlin University Alliance GC2 Global Health (Corona Virus Pre-Exploration Project). ACH, SH, TW and CD were supported by BMBF (RAPID) and ACH, SH by BMBF (alvBarriereCOVID-19). KH, LB, SL, SH, CD, TW, ACH were funded by BMBF (NFN-COVID 19, Organo-Strat). KH, NS, LES, MW, SH, ADG, CD, TW and ACH were supported by DFG (SFB-TR 84). ACH was supported by BIH, Charite 3R, and Charite-Zeiss MultiDim. KH was supported by BMBF (Camo-COVID-19). MW, NS and SH was supported by BMBF (PROVID). MW and NS was supported by BIH and BMBF (SYMPATH, CAPSyS, NAPKON). BO and DB were funded through the BIH Clinical Single Cell Bioinformatics Pipeline. LB was supported by the BMBF (CoIMMUNE), the DFG (KFO 342) and the IZKF of the Medical Faculty of the WWU. Conflict of Interest: The authors declare no competing interests. Ethical Approval: The study was approved by the ethics committee at the Charite clinic (projects EA2/079/13) and Arztekammer Westfalen-Lippe and of the Westfalischen Wilhelms-Universitat (AZ: 2016-265-f-S). Written informed consent was obtained from all patients.

Interactions with soil microbes can strongly affect plant growth and defense against aboveground herbivores. Plant species often accumulate specific soil pathogens in their rhizosphere, leading to reduced growth of plants in soils originating from stands of conspecific plants compared to soils from heterospecific plants. However, whereas effects of such conspecific vs. heterospecific soil biota on plant growth have been well documented, their effects on plant resistance and tolerance to aboveground insect herbivores have not. We compared growth and defense of Triadica sebifera plants from populations where the species is native (China), when grown in sterilized soils, or in soils harbouring belowground biota from conspecific (native Triadica) or heterospecific (native grass) soils. In each of these soils, plants were exposed to a 15-day period of foliar herbivory by a specialist weevil (Heterapoderopsis bicallosicollis), a specialist caterpillar (Gadirtha inexacta), or no herbivory (cage), followed by a 60-day recovery period. Soil biota from conspecific and hetetospecific soils differed in their effects on plant growth and defense. First, in the absence of herbivory, soil biota from heterospecific soils slightly enhanced plant growth, whereas those from conspecific soils strongly reduced plant growth. Second, soil biota from conspecific soils strongly affected plant resistance and tolerance to foliar herbivory, whereas soil biota from heterospecific plants did not. The effects of soil biota on plant defense were herbivore-specific. In particular, conspecific soil biota reduced resistance to caterpillar but not to weevil feeding, whereas they enhanced tolerance to weevil but not to caterpillar feeding. Conspecific soil biota also mitigated induction of root flavonoids by herbivores and led to reduced root phenolics in response to herbivory. Conversely, caterpillar feeding increased AMF colonization, but under these conditions, AMF colonization was negatively associated with plant biomass. In addition to testing effects on native plants, we also tested effects of native soil biota on growth and resistance of plants from the introduced range (North America). Plants from the introduced range had higher shoot production, shoot-to-root ratio, and leaf phenolic and flavonoid production than plants from the native range, but their interactions with soil biota showed only minor differences compared to plants from the native range. Our results suggest that incorporating the effects of soil biota in interactions between plants and foliar herbivores is critical for understanding variations in growth, defense, and performance among plant populations at local and broader geographic scales.

We prepared UV-polymerized phospholipid and copolymer nanomembranes at the air-water-interface by Langmuir-Blodgett (LB) technology. The freestanding as well as substrate-supported 2D nanomembranes were investigated in vacuum by helium-ion-microscopy (HIM) and under ambient condition with atomic force microscopy (AFM). We found intact and robust 2D nanomembranes by UV-polymerization of 1-palmitoyl-2-(10,12-tricosadiynoyl)-sn-glycero-3-phosphoethanolamine (PTPE) and by diblock copolymer polybutadiene(1,2)-b-polyethylene oxide (PB-b-PEO) formation that were able to form freestanding membranes with at least 8 µm in size. Further investigation of the UV-polymerized PTPE nanomembranes with attenuated total reflection infrared (ATR-IR) spectroscopy allowed us to monitor the polymerization process, where a shift in frequency of C=O absorption was observed together with the rise of other characteristic signals of the UV light-induced conversion.

Boolean satisfiability (SAT) solving is one of the most competitive research areas of theoretical computer science. The performance of state-of-the-art SAT solvers has been continuously improving in the last decades and has reached a level where SAT solvers can be employed to solve real world problems in fields such as hardware and software verification, automated planning and many others. One of the important driving forces of this progress are the yearly organized (since 2002) SAT competitions. In this paper we describe the 2015 SAT Race that featured the traditional sequential and parallel tracks (with 64 core computers) and introduced the Incremental Library Track, which is particularly interesting for developers of SAT based applications. We describe the 2015 SAT Race and provide a detailed analysis of its results.

Background: Dilated cardiomyopathy (DCM) could be caused by mutations in more than 40 different genes. However, the pathogenic impact of specific mutations is in most cases unknown complicating the genetic counseling of affected families. Therefore, functional studies could contribute to distinguish pathogenic mutations and benign variants. Here, we present a novel heterozygous DES missense variant (c.407C > T; p.L136P) identified by next generation sequencing in a DCM patient. DES encodes the cardiac intermediate filament protein desmin, which has important functions in mechanical stabilization and linkage of the cell structures in cardiomyocytes. Methods and results: Cell transfection experiments and assembly assays of recombinant desmin in combination with atomic force microscopy were used to investigate the impact of this novel DES variant on filament formation. Desmin-p.L136P forms cytoplasmic aggregates indicating a severe intrinsic filament assembly defect of this mutant. Co-transfection experiments of wild-type and mutant desmin conjugated to different fluorescence proteins revealed a dominant affect of this mutant on filament assembly. These experiments were complemented by apertureless scanning near-field optical microscopy. Conclusion: In vitro analysis demonstrated that desmin-p.L136P is unable to form regular filaments and accumulate instead within the cytoplasm. Therefore, we classified DES-p.L136P as a likely pathogenic mutation. In conclusion, the functional characterization of DES-p.L136P might have relevance for the genetic counseling of affected families with similar DES mutations and could contribute to distinguish pathogenic mutations from benign rare variants. (C) 2016 Elsevier Ltd. All rights reserved.

The publisher regrets that the co-authors in the “European region influenza surveillance network” were not tagged correctly. The full and complete list of authors and their affiliations for this article is given above. The publisher would like to apologise for any inconvenience caused.

Defensive chemicals produced by plants can travel up the food chain by being sequestered by herbivores, and then in turn being sequestered by their parasitoids. Insect species with wide host ranges are predicted to perform poorly in the face of specific chemical defence. However, a species at a high trophic level is expected to have a wide host range. This creates a conflict for hyperparasitoids, many of which depend on specialized hosts. We studied the performance of two hyperparasitoids, Lysibia nana and Gelis agilis, both of which have wide host ranges, on two host species, one chemically defended and the other not. We predicted that both hyperparasitoids would perform better using the undefended host Cotesia glomerata than the defended host C. melitaearum, which sequesters terpenoid allelochemicals (iridoid glycosides). Furthermore, we expected that the progeny of G. agilis collected from an area where hosts defended by iridoid glycosides are absent (the Netherlands) would perform poorly using C. melitaearum in comparison with G. agilis collected from an area where C. melitaearum is a common host (angstrom land, Finland). In a series of laboratory experiments we found that, contrary to prediction, both hyperparasitoids performed well on both hosts, reaching a larger size on C. glomerata, but having a higher conversion efficiency and developing more quickly on the chemically defended C. melitaearum. Lysibia nana metabolized the plant derived iridoid glycosides, which are chemicals that it does not normally encounter. Cells agilis retained some of the iridoid glycosides. But whereas Finnish G. agilis retained both aucubin and catalpol, Dutch G. agilis mainly retained aucubin, illustrating that though generalists, local populations still cope differently with toxic allelochemicals.

Background In respiratory infections, human adenoviruses (hAdV) of species B1 and C are frequently detected, but severe or even fatal disease outbreaks are predominantly caused by only few serotypes. The molecular typing of hAdV hexon sequences can help to speed up the discrimination of serotypes, thus improving on-time epidemiological examinations and patient care. Objectives We aimed to develop a molecular method for the rapid species B1 and C serotype identification in respiratory samples based on sequence generation of the hexon hypervariable region (HVR). Study design We developed two PCR-based genotyping systems for a generic HVR amplification and sequence determination of species B1 and C viruses. The assays were applied to hAdV prototypes and 106 samples. Results The primer sets proved to be capable of amplifying all B1 and C serotypes. The viruses detected in clinical samples belong to serotypes 1, 2, 3, 5 and 6. The obtained sequences of serotypes 2, 3 and 5 form 2–3 phylogenetic clusters that are based on the characteristic amino acid changes within the variable HVR sites. Conclusions Our assay can significantly speed up the time-span needed for serotype identification and will improve epidemiological surveillance and patient care. The obtained hexon sequences of field viruses vary significantly and form multiple genetic lineages. The variability is focussed on the HVR sites and can be interpreted as the ongoing evolutionary process. Further research is needed on the hexon sequence variability of other (respiratory) hAdV serotypes.

Given a quantified boolean formula (QBF) in prenex conjunctive normal form (PCNF), we consider the problem of identifying variable dependencies. In related work, a formal definition of dependencies has been suggested based on quantifier prefix reordering: two variables are independent if swapping them in the prefix does not change satisfiability of the formula. Instead of the general case, we focus on the sets of depending existential variables for all universal variables. This is relevant particularly for expansion-based QBF solvers. We present an approach for efficiently computing existential dependency sets by means of a directed connection relation over variables and demonstrate how this relation can be compactly represented as a tree using a union-find data structure. Experimental results show the effectiveness of our approach.

Human adenoviruses (hAdV) have been recognized as a highly prevalent virus family causing severe disease in immunocompromised patients. In xenotransplantation the xenograft therefore will be exposed to these viruses, which in case of its infection might contribute to posttransplant complications. To evaluate the susceptibility of porcine cells for hAdV, we infected the porcine cell line POEK with seven serotypes representing all six hAdV species. Additionally, a second porcine cell line (ST) was infected with two serotypes. Viral replication of serotypes varied: porcine cells were fully permissive for serotypes 1, 4 and 17, semi-permissive for 11 and 21, and non-permissive for 31 and 40. Furthermore, we demonstrated the interaction of serotype 1 with the porcine homologue of the coxsackie-adenovirus receptor, the receptor used by many hAdV serotypes for cell attachment. Thus, various adenovirus types of different hAdV species may be capable of infecting different porcine tissue types.

Symbolic model checking is PSPACE complete. Since QBF is the standard PSPACE complete problem, it is most natural to encode symbolic model checking problems as QBF formulas and then use QBF decision procedures to solve them. We discuss alternative encodings for unbounded and bounded safety checking into SAT and QBF. One contribution is a linear encoding of simple path constraints, which usually are necessary to make k-induction complete. Our experimental results show that indeed a large reduction in the size of the generated formulas can be obtained. However, current QBF solvers seem not to be able to take advantage of these compact formulations. Despite these mostly negative results the availability of these benchmarks will help improve the state of the art of QBF solvers and make QBF based symbolic model checking a viable alternative.

In this short note we give an overview on past and ongoing projects in the context of formal methods for industrial critical systems of the Formal Methods Group of the Computer Systems Institute at ETH Zurich.

Temporal logic is widely used for specifying hardware and software systems. Typically two types of properties are distinguished, safety and liveness properties. While safety can easily be checked by reachability analysis, and many efficient checkers for safety properties exist, more sophisticated algorithms have always been considered to be necessary for checking liveness. In this paper we describe an efficient translation of liveness checking problems into safety checking problems. A counter example is detected by saving a previously visited state in an additional state recording component and checking a loop closing condition. The approach handles fairness and thus extends to full LTL.

This research compares and contrasts the college and career experiences of graduates of the Agribusiness and Agricultural Economics undergraduate degree programs at Kansas State University. Using survey data, salary models were estimated for both majors. Starting salaries were not statistically different across majors, whereas current salaries were significantly higher for Agricultural Economics graduates. Alumni of both majors were found to be mobile and enjoy a high degree of satisfaction with their college and career experiences. Agribusiness majors were more likely to supervise employees and be more satisfied with working conditions than Agricultural Economics graduates.

Parkinson's disease (PD) is a neurodegenerative disorder that is pathologically characterized by the presence of intracytoplasmic Lewy bodies. Recently, two point mutations in alpha-synuclein were found to be associated with familial PD, but as of yet no mutations have been described in the homologous genes beta- and gamma-synuclein. alpha-Synuclein forms the major fibrillar component of Lewy bodies, but these do not stain for beta- or gamma-synuclein. This result is very surprising, given the extent of sequence conservation and the high similarity in expression and subcellular localization, in particular between alpha- and beta-synuclein. Here we compare in vitro fibrillogenesis of all three purified synucleins. We show that fresh solutions of alpha-, beta-, and gamma- synuclein show the same natively unfolded structure. While over time alpha-synuclein forms the previously described fibrils, no fibrils could be detected for beta- and gamma-synuclein under the same conditions. Most importantly, beta- and gamma-synuclein could not be cross-seeded with alpha-synuclein fibrils. However, under conditions that drastically accelerate aggregation, gamma-synuclein can form fibrils with a lag phase roughly three times longer than alpha-synuclein. These results indicate that beta- and gamma-synuclein are intrinsically less fibrillogenic than alpha-synuclein and cannot form mixed fibrils with alpha-synuclein, which may explain why they do not appear in the pathological hallmarks of PD, although they are closely related to alpha-synuclein and are also abundant in brain.

Parkinson's disease (PD) is a neurodegenerative disorder that is pathologically characterized by the presence of intracytoplasmic Lewy bodies, the major components of which are filaments consisting of α-synuclein. Two recently identified point mutations in α-synuclein are the only known genetic causes of PD. α-Synuclein fibrils similar to the Lewy body filaments can be formedin vitro, and we have shown recently that both PD-linked mutations accelerate their formation. This study addresses the mechanism of α-synuclein aggregation: we show that (i) it is a nucleation-dependent process that can be seeded by aggregated α-synuclein functioning as nuclei, (ii) this fibril growth follows first-order kinetics with respect to α-synuclein concentration, and (iii) mutant α-synuclein can seed the aggregation of wild type α-synuclein, which leads us to predict that the Lewy bodies of familial PD patients with α-synuclein mutations will contain both, the mutant and the wild type protein. Finally (iv), we show that wild type and mutant forms of α-synuclein do not differ in their critical concentrations. These results suggest that differences in aggregation kinetics of α-synucleins cannot be explained by differences in solubility but are due to different nucleation rates. Consequently, α-synuclein nucleation may be the rate-limiting step for the formation of Lewy body α-synuclein fibrils in Parkinson's disease.

This paper reports the analysis of two groups of wheat producers: American White Wheat Producers Association members who produce white wheat under contract with the cooperative and those who have chosen not to do so. The results show the diversity of producers' attitudes, preferences, knowledge and decision making. Nonmembers tend to rely more on short-term profitability and are less willing to risk innovation for unproven profits. Nonmembers also are less supportive of contract production and less inclined to use a young cooperative in that situation. This study demonstrates that the development of a new coordination mechanism entails much education of participants and that producer involvement also depends on learning on the part of everyone in the supply chain.