The 10 m prototype facility at the Albert-Einstein-institute (AEI) in Hanover, Germany, employs three large seismic attenuation systems to reduce mechanical motion. The AEI seismic-attenuation-system ...(AEI-SAS) uses mechanical anti-springs in order to achieve resonance frequencies below 0.5 Hz. This system provides passive isolation from ground motion by a factor of about 400 in the horizontal direction at 4 Hz and in the vertical direction at 9 Hz. The presented isolation performance is measured under vacuum conditions using a combination of commercial and custom-made inertial sensors. Detailed analysis of this performance led to the design and implementation of tuned dampers to mitigate the effect of the unavoidable higher order modes of the system. These dampers reduce RMS motion substantially in the frequency range between 10 and 100 Hz in 6 degrees of freedom. The results presented here demonstrate that the AEI-SAS provides substantial passive isolation at all the fundamental mirror-suspension resonances.
Recombinantly expressed fragments of the protein encoded by ORF149 (pORF149), a structural protein from the common- and koi-carp-infecting cyprinid herpesvirus-3 (CyHV-3) that was previously shown to ...be antigenic, were used to obtain evidence that its amino-terminal part contains immunodominant epitopes in fish populations that survived the infection. To obtain such evidence, nonspecific binding of carp serum tetrameric IgM had to be overcome by a novel ELISA protocol (rec2-ELISA). Rec2-ELISA involved pre-adsorption of carp sera with a heterologous recombinant fragment before incubation with pORF149 fragments and detection with anti-carp IgM monoclonal antibodies. Only in this way was it possible to distinguish between sera from uninfected and survivor carp populations. Although IgM from survivors recognised pORF149 fragments to a lesser degree than whole virus, specificity was confirmed by correlation of rec2- and CyHV-3-ELISAs, inhibition of rec2-ELISA by an excess of frgII
ORF149
, ELISA using IgM-capture, Western blotting, and reduction of reactivity in CyHV-3-ELISA by pre-adsorption of sera with frgII
ORF149
. The similarity of IgM-binding profiles between frgI
ORF149
(amino acid residues 42-629) and frgII
ORF149
(42-159) and their reactivities with previously described anti-CyHV-3 monoclonal antibodies confirmed that most pORF149 epitopes were localised in its amino-terminal part.
We present Gemini longslit optical spectroscopy and Very Large Array radio observations of the nuclear region of NGC 4178, a late-type bulgeless disk galaxy recently confirmed to host an active ...galactic nucleus (AGN) through infrared and X-ray observations. Our observations reveal that the dynamical center of the galaxy is coincident with the location of the Chandra X-ray point source discovered in a previous work, providing further support for the presence of an AGN. While the X-ray and IR observations provide robust evidence for an AGN, the optical spectrum shows no evidence for the AGN, underscoring the need for the penetrative power of mid-IR and X-ray observations in finding buried or weak AGNs in this class of galaxy. Finally, the upper limit to the radio flux, together with our previous X-ray and IR results, is consistent with the scenario in which NGC 4178 harbors a deeply buried AGN accreting at a high rate.
Koi herpesvirus (KHV) causes KHV disease (KHVD). The virus is highly contagious in carp or koi and can induce a high mortality. Latency and, in some cases, a lack of signs presents a challenge for ...virus detection. Appropriate immunological detection methods for anti‐KHV antibodies have not yet been fully validated for KHV. Therefore, it was developed and validated an enzyme‐linked immunosorbent assay (ELISA) to detect KHV antibodies. The assay was optimized with respect to plates, buffers, antigens and assay conditions. It demonstrated high diagnostic and analytical sensitivity and specificity and was particularly useful at the pond or farm levels. Considering the scale of the carp and koi industry worldwide, this assay represents an important practical tool for the indirect detection of KHV, also in the absence of clinical signs.
Here, we report on the outcome of the 2nd International Danube Symposium on advanced biomarker development that was held in Vienna, Austria, in early 2018. During the meeting, cross-speciality ...participants assessed critical aspects of non-invasive, quantitative biomarker development in view of the need to expand our understanding of disease mechanisms and the definition of appropriate strategies both for molecular diagnostics and personalised therapies. More specifically, panelists addressed the main topics, including the current status of disease characterisation by means of non-invasive imaging, histopathology and liquid biopsies as well as strategies of gaining new understanding of disease formation, modulation and plasticity to large-scale molecular imaging as well as integrative multi-platform approaches. Highlights of the 2018 meeting included dedicated sessions on non-invasive disease characterisation, development of disease and therapeutic tailored biomarkers, standardisation and quality measures in biospecimens, new therapeutic approaches and socio-economic challenges of biomarker developments. The scientific programme was accompanied by a roundtable discussion on identification and implementation of sustainable strategies to address the educational needs in the rapidly evolving field of molecular diagnostics. The central theme that emanated from the 2nd Donau Symposium was the importance of the conceptualisation and implementation of a convergent approach towards a disease characterisation beyond lesion-counting “lumpology” for a cost-effective and patient-centric diagnosis, therapy planning, guidance and monitoring. This involves a judicious choice of diagnostic means, the adoption of clinical decision support systems and, above all, a new way of communication involving all stakeholders across modalities and specialities. Moreover, complex diseases require a comprehensive diagnosis by converging parameters from different disciplines, which will finally yield to a precise therapeutic guidance and outcome prediction. While it is attractive to focus on technical advances alone, it is important to develop a patient-centric approach, thus asking “What can we do with our expertise to help patients?”
Koi herpesvirus (KHV) causes a highly infectious disease afflicting common carp and koi, Cyprinus carpio L. Various molecular and antibody‐based detection methods have been used to elucidate the ...rapid attachment and dissemination of the virus throughout carp tissues, facilitating ongoing development of effective diagnostic approaches. In situ hybridization (ISH) was used here to determine the target tissues of KHV during very early infection, after infecting carp with a highly virulent KHV isolate. Analysis of paraffin‐embedded tissues (i.e. gills, skin, spleen, kidney, gut, liver and brain) during the first 8 h and following 10 days post‐infection (hpi; dpi) revealed positive signals in skin mucus, gills and gut sections after only 1 hpi. Respiratory epithelial cells were positive as early as 2 hpi. Viral DNA was also detected within blood vessels of various tissues early in the infection. Notable increases in signal abundance were observed in the gills and kidney between 5 and 10 dpi, and viral DNA was detected in all tissues except brain. This study suggests that the gills and gut play an important role in the early pathogenesis of this Alloherpesvirus, in addition to skin, and demonstrates ISH as a useful diagnostic tool for confirmation of acutely infected carp.
The development and evaluation of a protocol based on polymerase chain reaction (PCR) and nucleic acid hybridization techniques for the specific detection of lymphocystis disease virus (LCDV) in ...several marine fish species. The pair of primers for PCR, OBL3 and OBL4, was designed based on published nucleotide sequence (LCDV-1) and amplifies a fragment within the major capsid protein. The sensitivity was evaluated using DNA from purified viral particles, as well as from cells inoculated with several viral concentrations. The PCR combined with slot blot was the most sensitive methodology, detecting 2·5 ng of viral DNA. Using this methodology LCDV was detected at 5 days postinoculation from SAF-1 cells initially inoculated with 10⁻⁵ TCID₅₀ ml⁻¹. The combination of PCR with membrane hybridization has also been proved to be adequate to detect LCDV from apparently healthy carriers by means of caudal fin sample analysis. This asymptomatic infection was also demonstrated by classical virological methods (cell culture and immunoblot). The protocol described in this study allows the specific detection of LCDV, both in cell cultures and in fin homogenates from asymptomatic fish. The detection of asymptomatic carriers by a rapid molecular method using caudal fin sampling, which does not imply animal killing, could be an important tool to control epizootics caused by LCDV, as fish could be analysed before their introduction and/or mobilization in farm facilities.
Cyprinid herpesvirus 2 is a pathogen of goldfish, inducing a disease referred to as herpesviral hematopoietic necrosis. The disease is described so far in Japan, North America, Taiwan, Australia, the ...United Kingdom, and recently also Italy. Here the authors describe histologic lesions in clinically affected fish in comparison with clinically normal but virus DNA–positive goldfish in Switzerland. While necrosis or enhanced single-cell necrosis in the hematopoietic tissue in the pronephros or mesonephros was evident in dead and sick animals, in clinically normal goldfish, only single-cell necrosis was observed. Virus DNA was demonstrated in dead as well as clinically affected and subclinically infected goldfish by polymerase chain reaction and in situ hybridization. This study identifies the presence of goldfish herpesvirus in Switzerland and highlights the fact that the virus might be more widespread than assumed, as clinically normal goldfish can also carry cyprinid herpesvirus 2, showing histologically similar lesions but of lesser extent and severity.
To assess the relationship between prior exposure to immune checkpoint inhibitors (ICIs) and the risk of postoperative complications in cancer patients.
Single-center retrospective cohort study.
The ...main exposure was treatment with an FDA-approved ICI within 6 months before surgery.
Exposure to ICIs and covariates was determined from the electronic health record. The primary outcome was a composite of postoperative complications, including prolonged pressor or oxygen dependence, kidney injury, or myocardial injury. Secondary outcomes included each subcomponent of the primary outcome. Of 7674 subjects with cancer admitted to the ICU after surgery, 247 were exposed to one or more ICIs in the 6 months before surgery. After propensity score matching, 197 ICI-exposed subjects were matched to 777 nonexposed. The composite outcome occurred in 70 of 197 (35.5%) ICI-exposed subjects and 251 of 777 (32.3%) nonexposed. There was no difference between exposed and nonexposed groups in the primary composite outcome (odds ratio OR, 1.12; 95% CI, 0.80-1.58) by conditional logistic regression. Risk of the secondary outcome of prolonged pressor dependence was significantly higher in ICI-exposed subjects (OR, 1.64; 95% CI, 1.01-2.67). Risks of oxygen dependence (OR, 1.13; 95% CI, 0.75-1.73), kidney injury (OR, 1.15; 95% CI, 0.77-1.71), and myocardial injury (OR, 1.76; 95% CI, 1.00-3.10) were not significantly different. There was no difference between groups in the time to hospital discharge alive (
= 0.62).
Exposure to ICIs within 6 months before high-risk surgery was not associated with the composite outcome of cardiopulmonary instability or organ injury in patients with cancer. The potential for an association with the secondary outcomes of cardiac instability and injury is worthy of future study.
Collares FM, Leitune VCB, Rostirolla FV, Trommer RM, Bergmann CP, Samuel SMW. Nanostructured hydroxyapatite as filler for methacrylate‐based root canal sealers. International Endodontic Journal, 45, ...63–67, 2012.
Aim To evaluate the effect of different concentrations of nanostructured hydroxyapatite on the radiopacity, flow and film thickness of an experimental root canal sealer.
Methodology An experimental dual‐cured root canal sealer was produced with a methacrylate‐based comonomer blend. Nanostructured hydroxyapatite/calcium tungstate solutions (ratios 10 : 90, 20 : 80, 30 : 70 and 40 : 60) were added to produce the sealer. Radiopacity was evaluated using a digital system and an aluminium step wedge (n = 5). Flow and thickness tests were conducted in accordance with ISO 6876 (n = 3). The data were analysed using one‐way anova and Tukey’s test (α = 0.05).
Results All groups had levels of radiopacity in accordance with ISO 6876. The flow of the experimental sealers was not significantly different (P = 0.204). All groups had a film thickness in accordance with ISO 6876 and with no statistical difference (P = 0.654).
Conclusion The addition of up to 40% HAnano to root canal sealers did not alter their radiopacity and film thickness.
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