Gaussian versus Non-Gaussian Filtering of Phase-Insensitive Nonclassicality.

Measures of quantum properties are essential to understanding the fundamental differences between quantum and classical systems as well as quantifying resources for quantum technologies. Here, two broad classes of bosonic phase-space functions, which are filtered versions of the Glauber-Sudarshan P function, are compared with regard to their ability to uncover nonclassical effects of light through their negativities. Gaussian filtering of the P function yields the family of s-parametrized quasiprobabilities, while more powerful regularized nonclassicality quasiprobabilities are obtained by non-Gaussian filtering. A method is proposed to directly sample such phase-space functions for the restricted case of phase-independent quantum states from balanced homodyne measurements. This overcomes difficulties of previous approaches that manually append uniformly distributed optical phases to the measured quadrature data. We experimentally demonstrate this technique for heralded single- and two-photon states using balanced homodyne detection with varying efficiency. The s-parametrized quasiprobabilities, which can be directly sampled, are non-negative for detection efficiencies below 0.5. By contrast, we show that significant negativities of non-Gaussian filtered quasiprobabilities uncover nonclassical effects for arbitrarily low efficiencies.

['How harmful is your mania to you or others?' Sharing decisions about antidepressant treatment in bipolar depression]. / 'Hoe schadelijk is uw manie voor u en uw naasten?' Gedeelde besluitvorming over antidepressiva bij bipolaire depressie.

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Transcriptome analysis reveals a classical interferon signature induced by IFNλ4 in human primary cells.

The IFNL4 gene is negatively associated with spontaneous and treatment-induced clearance of hepatitis C virus infection. The activity of IFNλ4 has an important causal role in the pathogenesis, but the molecular details are not fully understood. One possible reason for the detrimental effect of IFNλ4 could be a tissue-specific regulation of an unknown subset of genes. To address both tissue and subtype specificity in the interferon response, we treated primary human hepatocytes and airway epithelial cells with IFNα, IFNλ3 or IFNλ4 and assessed interferon mediated gene regulation using transcriptome sequencing. Our data show a surprisingly similar response to all three subtypes of interferon. We also addressed the tissue specificity of the response, and identified a subset of tissue-specific genes. However, the interferon response is robust in both tissues with the majority of the identified genes being regulated in hepatocytes as well as airway epithelial cells. Thus we provide an in-depth analysis of the liver interferon response seen over an array of interferon subtypes and compare it to the response in the lung epithelium.

ISG56/IFIT1 is primarily responsible for interferon-induced changes to patterns of parainfluenza virus type 5 transcription and protein synthesis.

Interferon (IFN) induces an antiviral state in cells that results in alterations of the patterns and levels of parainfluenza virus type 5 (PIV5) transcripts and proteins. This study reports that IFN-stimulated gene 56/IFN-induced protein with tetratricopeptide repeats 1 (ISG56/IFIT1) is primarily responsible for these effects of IFN. It was shown that treating cells with IFN after infection resulted in an increase in virus transcription but an overall decrease in virus protein synthesis. As there was no obvious decrease in the overall levels of cellular protein synthesis in infected cells treated with IFN, these results suggested that ISG56/IFIT1 selectively inhibits the translation of viral mRNAs. This conclusion was supported by in vitro translation studies. Previous work has shown that ISG56/IFIT1 can restrict the replication of viruses lacking a 2'-O-methyltransferase activity, an enzyme that methylates the 2'-hydroxyl group of ribose sugars in the 5'-cap structures of mRNA. However, the data in the current study strongly suggested that PIV5 mRNAs are methylated at the 2'-hydroxyl group and thus that ISG56/IFIT1 selectively inhibits the translation of PIV5 mRNA by some as yet unrecognized mechanism. It was also shown that ISG56/IFIT1 is primarily responsible for the IFN-induced inhibition of PIV5.

Pulse oximetry during intraaortic balloon pump application.

BACKGROUND: Pulse oximeters are multiple used devices in anaesthesiology and intensive care medicine and must provide reliable data during various conditions of signal interference, including light, motion and reduced perfusion. The aim of this study was to evaluate the reliability of different new-generation pulse oximeters during intraaortic balloon pump (IABP) therapy. METHODS: In the experimental setting, the validity of three pulse oximetry technologies (Masimo Radical 7, Nellcor N-600 and Datex Ohmeda TruSat) was evaluated in patients with IABP treatment. Arterial blood gas analysis (BGA-SaO2) data were compared with the pulse oximetric values (SpO2) during 1:1, 1:2 and 1:3 support ratio. RESULTS: The mean differences (bias) during 1:1, 1:2 and 1:3 IABP support between BGA-SaO2 and Datex-SpO2 were 3.38% [95% confidence intervals (CI):±1.39%], 1.41% (95% CI 1.14%) and 2.10% (95% CI:±0.94%), respectively. Between BGA-SaO2 and Nellcor-SpO2, a bias of 0.77% (95% CI:±0.46%), 0.85% (95% CI:±0.40%) and 0.59% (95% CI:±0.38%) was found. In the comparison of BGA-SaO2 and Masimo-SpO2, a bias of 0.58% (95% CI:±0.56%), 0.19% (95% CI:±0.40%) and -0.01% (95% CI:±0.43%) was found, respectively. CONCLUSIONS: In patients with IABP support, the pulse oximetric values of the Masimo Radical 7 are accurate in 1:2 and 1:3 support ratio compared with blood gas analysis. In these support ratios, the Masimo Radical 7 is superior to the Nellcor N-600. The Datex Ohmeda TruSat showed a significant difference between the measured pulse oximetric values and blood gas analysis in all support ratios.

Tracing the fate of steroids through a hypersaline microbial mat (Kiritimati, Kiribati/Central Pacific).

Eukaryotic steranes are typically absent or occur in very low concentrations in Precambrian sedimentary rocks. However, it is as yet unclear whether this may reflect low source inputs or a preservational bias. For instance, it has been proposed that eukaryotic lipids were profoundly degraded in benthic microbial mats that were ubiquitous prior to the advent of vertical bioturbation in the Cambrian ("mat-seal effect"). It is therefore important to test the microbial turnover and degradation of eukaryotic steroids in real-world microbial mats. Here we assessed steroid inventories in different layers of a microbial mat from a hypersaline lake on Kiritimati (Central Pacific). Various eukaryote-derived C27 -C30 steroids were detected in all mat layers. These compounds most likely entered the mat system as unsaturated sterols from the water column or the topmost mat, and were progressively altered during burial in the deeper, anoxic mat layers over c. 103  years. This is reflected by increasing proportions of saturated sterols and sterenes, as well as the presence of thiosteranes in certain horizons. Sterol alteration can partly be assigned to microbial transformation but is also due to chemical reactions promoted by the reducing environment in the deeper mat layers. Notably, however, compounds with a sterane skeleton were similarly abundant in all mat layers and their absolute concentrations did not show any systematic decrease. The observed decrease of steroid/hopanoid ratios with depth may thus rather indicate a progressive "dilution" by lipids derived from heterotrophic bacteria. Further, pyrolysis revealed that steroids, in contrast to hopanoids, were not sequestered into non-extractable organic matter. This may lead to a preservational bias against steroids during later stages of burial. Taken together, steroid preservation in the microbial mat is not only controlled by heterotrophic degradation, but rather reflects a complex interplay of taphonomic processes.

The taphonomic fate of isorenieratene in Lower Jurassic shales-controlled by iron?

Fossil derivatives of isorenieratene, an accessory pigment in brown-colored green sulfur bacteria, are often used as tracers for photic zone anoxia through Earth's history, but their diagenetic behavior is still incompletely understood. Here, we assess the preservation of isorenieratene derivatives in organic-rich shales (1.5-8.4 wt.% TOC) from two Lower Jurassic anoxic systems (Bächental oil shale, Tyrol, Austria; Posidonia Shale, Baden-Württemberg, Germany). Bitumens and kerogens were investigated using catalytic hydropyrolysis (HyPy), closed-system hydrous pyrolysis (in gold capsules), gas chromatography-mass spectrometry (GC-MS) and gas chromatography combustion isotope ratio-mass spectrometry (GC-C-IRMS). Petrography and biomarkers indicate a syngenetic relationship between bitumens and kerogens. All bitumens contain abundant isorenieratane, diverse complex aromatized isorenieratene derivatives, and a pseudohomologous series of 2,3,6-trimethyl aryl isoprenoids. In contrast, HyPy and mild closed-system hydrous pyrolysis of the kerogens yielded only minor amounts of these compounds. Given the overall low maturity of the organic matter (below oil window), it appears that isorenieratene and its abundant derivatives from the bitumen had not been incorporated into the kerogens. Accordingly, sulfur cross-linking, the key mechanism for sequestration of functionalized lipids into kerogens in anoxic systems, was not effective in the Jurassic environments studied. We explain this by (i) early cyclization/aromatization and (ii) hydrogenation reactions that have prevented effective sulfurization. In addition, (iii) sulfide was locally removed via anoxygenic photosynthesis and efficiently trapped by the reaction with sedimentary iron, as further indicated by elevated iron contents (4.0-8.7 wt.%) and the presence of abundant pyrite aggregates in the rock matrix. Although the combined processes have hampered the kerogen incorporation of isorenieratene and its derivatives, they may have promoted the long-term preservation of these biomarkers in the bitumen fraction via early defunctionalization. This particular taphonomy of aromatic carotenoids has to be considered in studies of anoxic iron-rich environments (e.g., the Proterozoic ocean).

Heterodimerization of AML1/ETO with CBFß is required for leukemogenesis but not for myeloproliferation.

The AML1/Runx1 transcription factor and its heterodimerization partner CBFß are essential regulators of myeloid differentiation. The chromosomal translocation t(8;21), fusing the DNA binding domain of AML1 to the corepressor eight-twenty-one (ETO), is frequently associated with acute myeloid leukemia and generates the AML1/ETO (AE) fusion protein. AE represses target genes usually activated by AML1 and also affects the endogenous repressive function of ETO at Notch target genes. In order to analyze the contribution of CBFß in AE-mediated leukemogenesis and deregulation of Notch target genes, we introduced two point mutations in a leukemia-initiating version of AE in mice, called AE9a, that disrupt the AML1/CBFß interaction (AE9aNT). We report that the AE9a/CBFß interaction is not required for the AE9a-mediated aberrant expression of AML1 target genes, while upregulation/derepression of Notch target genes does require the interaction with CBFß. Using retroviral transduction to express AE9a in murine adult bone marrow-derived hematopoietic progenitors, we observed that both AE9a and AE9aNT lead to increased myeloproliferation in vivo. However, both development of leukemia and long-term replating capacity are only observed with AE9a but not with AE9aNT. Thus, deregulation of both AML1 and Notch target genes is required for the development of AE9a-driven leukemia.

Reverse genetics of coronaviruses using vaccinia virus vectors.

In this article, we describe the reverse genetic system that is based on the use of vaccinia virus cloning vectors. This system represents a generic approach to coronavirus reverse genetics and was first described for the generation of recombinant human coronavirus 229E representing a group I coronavirus. Subsequently, the same approach has been used to generate recombinant avian infectious bronchitis coronavirus and, recently, recombinant mouse hepatitis virus, representing group III and group II coronaviruses, respectively. We describe how vaccinia virus-mediated homologous recombination can be used to introduce specific mutations into the coronavirus genomic cDNA during its propagation in vaccinia virus and how recombinant coronaviruses can be isolated. Finally, we describe how the coronavirus reverse genetic system has now been extended to the generation of coronavirus replicon RNAs.

Interaction of SARS and MERS Coronaviruses with the Antiviral Interferon Response.

Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) are the most severe coronavirus (CoV)-associated diseases in humans. The causative agents, SARS-CoV and MERS-CoV, are of zoonotic origin but may be transmitted to humans, causing severe and often fatal respiratory disease in their new host. The two coronaviruses are thought to encode an unusually large number of factors that allow them to thrive and replicate in the presence of efficient host defense mechanisms, especially the antiviral interferon system. Here, we review the recent progress in our understanding of the strategies that highly pathogenic coronaviruses employ to escape, dampen, or block the antiviral interferon response in human cells.

Microbe-like inclusions in tree resins and implications for the fossil record of protists in amber.

During the past two decades, a plethora of fossil micro-organisms have been described from various Triassic to Miocene ambers. However, in addition to entrapped microbes, ambers commonly contain microscopic inclusions that sometimes resemble amoebae, ciliates, microfungi, and unicellular algae in size and shape, but do not provide further diagnostic features thereof. For a better assessment of the actual fossil record of unicellular eukaryotes in amber, we studied equivalent inclusions in modern resin of the Araucariaceae; this conifer family comprises important amber-producers in Earth history. Using time-of-flight secondary ion mass spectrometry (ToF-SIMS), we investigated the chemical nature of the inclusion matter and the resin matrix. Whereas the matrix, as expected, showed a more hydrocarbon/aromatic-dominated composition, the inclusions contain abundant salt ions and polar organics. However, the absence of signals characteristic for cellular biomass, namely distinctive proteinaceous amino acids and lipid moieties, indicates that the inclusions do not contain microbial cellular matter but salts and hydrophilic organic substances that probably derived from the plant itself. Rather than representing protists or their remains, these microbe-like inclusions, for which we propose the term 'pseudoinclusions', consist of compounds that are immiscible with the terpenoid resin matrix and were probably secreted in small amounts together with the actual resin by the plant tissue. Consequently, reports of protists from amber that are only based on the similarity of the overall shape and size to extant taxa, but do not provide relevant features at light-microscopical and ultrastructural level, cannot be accepted as unambiguous fossil evidence for these particular groups.

Nitric oxide and blood-brain barrier integrity.

The blood-brain barrier (BBB) is comprised of the endothelial cells that line the capillaries of the brain. The unique characteristics of this barrier include tight intercellular junctions, a complex glycocalyx, a paucity of pinocytic vesicles, and an absence of fenestra. These properties allow for the selective exchange of substances between the systemic circulation and the extracellular fluid compartment of the brain. It is well established that there are many conditions, including those mediated by nitric oxide (NO), that can lead to an opening of the BBB, eventually leading to vasogenic edema and secondary brain damage. The precise molecular mechanisms mediating NO-induced tissue injury and the breakdown of the BBB are complex and not completely understood. NO is a soluble, easily diffusible gas that is generated by NO synthase. Two of the isoforms of NO synthase are constitutive, calcium-dependent enzymes that modulate many physiological functions, including the regulation of smooth muscle contraction and blood flow. The third isoform is calcium-independent and inducible and can be stimulated by stress, inflammation, and infection. Under these conditions, NO can be generated in large quantities and has detrimental effects on the CNS. NO has been shown to increase permeability of the BBB, allowing substances to enter into the brain passively. This review considers the role of NO and BBB integrity.

Replication and transcription of HCV 229E replicons. p6.

Replicons based upon the human coronavirus 229E (HCV 229E) genome were transfected into HCV 229E infected cells. We demonstrate that a synthetic RNA comprised of 646 nucloetides from the 5' end and 1465 nucloetides from the 3' end of the HCV 229E genome is replication competent. We conclude that the cis-acting elements necessary for replication are located in these 5' and 3' genomic regions. Furthermore, we inserted the intergenic region of the HCV 229E nucleocapsid protein gene into this basic construct and were able to demonstrate the transcription of "subgenomic" RNAs.

Characterization of a papain-like cysteine-proteinase encoded by gene 1 of the human coronavirus HCV 229E.

Expression of the coronaviral gene 1 polyproteins, pp 1a and pp 1ab, involves a series of proteolytic events that are mediated by virus-encoded proteinases similar to cellular papain-like cysteine-proteinases and the 3C-like proteinases of picornaviruses. In this study, we have characterized, in vitro, the human coronavirus HCV 229E papain-like cysteine-proteinase PCP 1. We show that PCP 1 is able to mediate cleavage of an aminoterminal polypeptide, p9, from in vitro translation products representing the aminoproximal region of pp 1a/pp 1ab. Mutagenesis studies support the prediction of Cys1054 and His1278 as the catalytic amino acids of the HCV 229E PCP 1, since mutation of these residues abolishes the proteolytic activity of the enzyme.

A strategy for the generation of infectious RNAs and autonomously replicating RNAs based on the HCV 229E genome.

A strategy to generate in vitro transcripts representing infectious RNAs and autonomously replicating RNAs based on the HCV 229E genome is presented. PCR-DNAs were ligated in vitro, resulting in 27 kbp and 22 kbp ligation products. These DNAs can now be transcribed in vitro and the RNAs tested for infectivity and their ability to replicate.

Long distance RT-PCRs of human coronavirus 229E RNA.

The generation and cloning of cDNA fragments longer than 10 kb is often a difficult and time consuming task. In this study, we have analysed the conditions necessary of produce reverse transcripts longer than 10 kb that can be amplified by polymerase chain reaction. Thus, we isolated poly(A)-RNA from human coronavirus 229E infected MRC-5 cells and did reverse transcription using a sequence-specific primer. Subsequently, we amplified PCR products of varying length upstream of the primer position. Optimisation of the poly(A)-RNA preparation, the reverse transcription protocol and the polymerase chain reaction cycle conditions enabled us to successfully amplify regions of the human coronavirus 229E genome between 11.5 and 20.3 kb in length.

[Evidence-based nursing--the missing link between research and practice]. / Evidence-based Nursing--missing link zwischen Forschung und Praxis.

UNLABELLED: Evidence-based nursing (EBN) is being introduced promising to professionalize and emancipate nursing. Three questions are discussed as to whether this can be accomplished. The analysis comes to the following conclusions: Evidence-based nursing (EBN) as a problem solving process will become part of the German health care service by means of social legislation. The concept joins clinical experience and best evidence under the principle of patient adapted intervention. This complies with the demand for rationally justified, transparent, and economically comparable performance. One specific trait of research in nursing is the importance of qualitative methods that make the dimension of subjective meaning comprehensible. Only under a normative paradigm can the concept of evidence-based intervention be applied immediately. This leads to problems of adaptation that have to be solved when introducing EBN. Evidence-based nursing practice fits into modern concepts of professional nursing as well as into current visions regarding the reform of German nursing education. However, some peculiarities that characterize German nursing practice in particular must be taken into consideration. This includes the professional ideology of nursing staff as well as applied nursing science, which is still in its beginnings. CONCLUSION: With careful implementation the concept of evidence-based intervention can develop its potential to improve nursing practice. Further, EBN offers Germany an opportunity to catch up with international standards.

The isotopic biosignatures of photo- vs. thiotrophic bivalves: are they preserved in fossil shells?

Symbiont-bearing and non-symbiotic marine bivalves were used as model organisms to establish biosignatures for the detection of distinctive symbioses in ancient bivalves. For this purpose, the isotopic composition of lipids (δ13C) and bulk organic shell matrix (δ13C, δ34S, δ15N) from shells of several thiotrophic, phototrophic, or non-symbiotic bivalves were compared (phototrophic: Fragum fragum, Fragum unedo, Tridacna maxima; thiotrophic: Codakia tigerina, Fimbria fimbriata, Anodontia sp.; non-symbiotic: Tapes dorsatus, Vasticardium vertebratum, Scutarcopagia sp.). ∆13C values of bulk organic shell matrices, most likely representing mainly original shell protein/chitin biomass, were depleted in thio- and phototrophic bivalves compared to non-symbiotic bivalves. As the bulk organic shell matrix also showed a major depletion of δ15N (down to -2.2 ‰) for thiotrophic bivalves, combined δ13C and δ15N values are useful to differentiate between thio-, phototrophic, and non-symbiotic lifestyles. However, the use of these isotopic signatures for the study of ancient bivalves is limited by the preservation of the bulk organic shell matrix in fossils. Substantial alteration was clearly shown by detailed microscopic analyses of fossil (late Pleistocene) T. maxima and Trachycardium lacunosum shell, demonstrating a severe loss of quantity and quality of bulk organic shell matrix with time. Likewise, the composition and δ13C-values of lipids from empty shells indicated that a large part of these compounds derived from prokaryotic decomposers. The use of lipids from ancient shells for the reconstruction of the bivalve's life style therefore appears to be restricted.

[Observational study on outpatient sleeve gastrectomy]. / Chirurgie bariatrique en ambulatoire: étude observationnelle à propos de 68 sleeve gastrectomies.

UNLABELLED: The development of outpatient surgery is one of the major goals of the public health policy in 2010. The purpose of this observational study is to evaluate the feasibility of the laparoscopic sleeve gastrectomy (LSG) in ambulatory. METHODS: This prospective observational study was conducted from May 2011 to June 2013. The procedure was proposed for patients undergoing LSG who were predetermined inclusion criteria. Following preoxygenation, anaesthesia was induced with propofol and sufentanil. Tracheal intubation was facilitated with rocuronium. Anaesthesia was maintained with desflurane and remifentanil target-controlled infusion. Antiemetic prophylaxis was supplied with intravenous (IV) droperidol and dexamethasone; postoperative pain prophylaxis was IV paracetamol, nefopam, tramadol, and ropivacaine infiltration. The patients were extubated in the operating room and kept in the postoperative care unit. A water-soluble contrast examination was performed in the output of the postoperative care unit. Oral feeding was resumed immediately in the absence of fistula on this leak test in an ambulatory surgical unit. When the patient has satisfied the modified Post-Anaesthesia Discharge Scoring System (PADSS) criteria, he or she can then be discharged and sent home. RESULTS: Among 280 patients operated on for obesity by laparoscopic sleeve gastrectomy during the study period, 68 (24.2 %) underwent ambulatory procedure. Of the 68 obese patients, 94.1 % were female. Mean age was 34.4 years (22-55). Mean preoperative BMI was 42.6kg/m(2). Thirteen patients (19.1 %) had HTN; 7 (10.2 %) had dyslipidemia and 6 (8.8 %) had diabetes not requiring treatment. The mean operating time was 60minutes (range, 45-95) and there were no conversions to open surgery. No intra-operative anesthetic or surgical complications occurred. Mean time in the recovery room was 86.5minutes (35-240). The overall satisfaction rate was 92.6 % (n=63). No patients were admitted because of nausea or inadequate pain control. There were no re-admissions or hospitalizations were reported. We recorded five surgical complications including two case of gastric fistula, one case of gastric stenosis, one case of scar dehiscence and one case of splenic upper pole ischemia. Its complications have arisen from the fourth postoperative day. This does not undermine the ambulatory procedure. CONCLUSION: The laparoscopic sleeve gastrectomy in ambulatory is feasible with a dedicated anesthesiological concept in an expert surgical team. Appropriate patient selection is important in order to secure safety and quality of care within outpatient program. The risk versus benefit must be adequately evaluated on an individual basis.

Coupled reductive and oxidative sulfur cycling in the phototrophic plate of a meromictic lake.

Mahoney Lake represents an extreme meromictic model system and is a valuable site for examining the organisms and processes that sustain photic zone euxinia (PZE). A single population of purple sulfur bacteria (PSB) living in a dense phototrophic plate in the chemocline is responsible for most of the primary production in Mahoney Lake. Here, we present metagenomic data from this phototrophic plate--including the genome of the major PSB, as obtained from both a highly enriched culture and from the metagenomic data--as well as evidence for multiple other taxa that contribute to the oxidative sulfur cycle and to sulfate reduction. The planktonic PSB is a member of the Chromatiaceae, here renamed Thiohalocapsa sp. strain ML1. It produces the carotenoid okenone, yet its closest relatives are benthic PSB isolates, a finding that may complicate the use of okenone (okenane) as a biomarker for ancient PZE. Favorable thermodynamics for non-phototrophic sulfide oxidation and sulfate reduction reactions also occur in the plate, and a suite of organisms capable of oxidizing and reducing sulfur is apparent in the metagenome. Fluctuating supplies of both reduced carbon and reduced sulfur to the chemocline may partly account for the diversity of both autotrophic and heterotrophic species. Collectively, the data demonstrate the physiological potential for maintaining complex sulfur and carbon cycles in an anoxic water column, driven by the input of exogenous organic matter. This is consistent with suggestions that high levels of oxygenic primary production maintain episodes of PZE in Earth's history and that such communities should support a diversity of sulfur cycle reactions.