Direct Current Auditory Evoked Potentials During Wakefulness, Anesthesia, and Emergence from Anesthesia

Direct current auditory evoked potentials (DC-AEPs) are a sensitive indicator of depth of anesthesia in ani-mals. However, they have never been investigated in humans. To assess the potential usefulness of DC-AEPs as an indicator of anesthesia in humans, we performed an explorative study in which DC-AEPs were recorded during propofol and methohexital anesthesia in hu-mans. DC-AEPs were recorded via 22 scalp electrodes in 19 volunteers randomly assigned to receive either propofol or methohexital. DC-AEPs were evoked by binaurally presented 2-s, 60-dB, 800-Hz tones; meas-urements were taken during awake baseline, anesthesia, and emergence. Statistical analysis included analy-sis of variance and discriminant analysis of data acquired during these three conditions. About 500 ms after stimulus presentation, DC-AEPs could be ob-served. These potentials were present only during base-line and emergence—not during anesthesia. Statistically significant differences were found between baseline and anesthesia and between anesthesia and emergence. In conclusion, similar effects, as reported in animal studies of anesthetics on the DC-AEPs, could be observed in anesthetized humans. These results dem-onstrate that DC-AEPs are potentially useful in the assessment of cortical function during anesthesia and might qualify the method for monitoring anesthesia in humans

Geospatial Technologies for Investigating Roman Settlement Structures in the Noric-Pannonian Borderland – Selected Aspects of a New Research Project

A new research project, currently in the application stage, wants to contribute to the research into settlement structure(s) of the Roman empire in the territories of Flavia Solva, Celeia, Poetovio, Salla and Savaria.In a preview of the project, we will present new methods to combine state of the art spatial analysis and remote sensing on the one hand, and archaeological evaluation of find-spots on the other hand, integrating geospatial and archaeological data from diverse sources and qualities ranging from 19th century find reports up to modern, GIS-based excavation documentation or ALS data, into a sustainable and accessible standard taking into account requirements of both geotechnological applications and data warehousing principles of the historical disciplines such as the CIDOC CRM.Based on this data model descriptive statistical methods will be employed to characterize the status quo in a designated test area in Southeastern Noricum, and to implement geographical concepts by GIS-analytic methods to gain new insights from the combination of thematically related layers. The result of this first attempt is the establishment of a sound geospatial and geostatistical workflow in a multidisciplinary approach of the involved researchers for the project, which can be used as a basis for further analysis with special focus on the spatial aspect

Schmallenberg virus pathogenesis, tropism and interaction with the innate immune system of the host

Schmallenberg virus (SBV) is an emerging orthobunyavirus of ruminants associated with outbreaks of congenital malformations in aborted and stillborn animals. Since its discovery in November 2011, SBV has spread very rapidly to many European countries. Here, we developed molecular and serological tools, and an experimental in vivo model as a platform to study SBV pathogenesis, tropism and virus-host cell interactions. Using a synthetic biology approach, we developed a reverse genetics system for the rapid rescue and genetic manipulation of SBV. We showed that SBV has a wide tropism in cell culture and “synthetic” SBV replicates in vitro as efficiently as wild type virus. We developed an experimental mouse model to study SBV infection and showed that this virus replicates abundantly in neurons where it causes cerebral malacia and vacuolation of the cerebral cortex. These virus-induced acute lesions are useful in understanding the progression from vacuolation to porencephaly and extensive tissue destruction, often observed in aborted lambs and calves in naturally occurring Schmallenberg cases. Indeed, we detected high levels of SBV antigens in the neurons of the gray matter of brain and spinal cord of naturally affected lambs and calves, suggesting that muscular hypoplasia observed in SBV-infected lambs is mostly secondary to central nervous system damage. Finally, we investigated the molecular determinants of SBV virulence. Interestingly, we found a biological SBV clone that after passage in cell culture displays increased virulence in mice. We also found that a SBV deletion mutant of the non-structural NSs protein (SBVΔNSs) is less virulent in mice than wild type SBV. Attenuation of SBV virulence depends on the inability of SBVΔNSs to block IFN synthesis in virus infected cells. In conclusion, this work provides a useful experimental framework to study the biology and pathogenesis of SBV

Deep Learning Improves Macromolecule Identification in 3D Cellular Cryo-Electron Tomograms

International audienceCryogenic electron tomography (cryo-ET) visualizes the 3D spatial distribution of macromolecules at nanometer resolution inside native cells. However, automated identification of macromolecules inside cellular tomograms is challenged by noise and reconstruction artifacts, as well as the presence of many molecular species in the crowded volumes. Here, we present DeepFinder, a computational procedure that uses artificial neural networks to simultaneously localize multiple classes of macromolecules. Once trained, the inference stage of DeepFinder is faster than template matching and performs better than other competitive deep learning methods at identifying macromolecules of various sizes in both synthetic and experimental datasets. On cellular cryo-ET data, DeepFinder localized membrane-bound and cytosolic ribosomes (~3.2 MDa), Rubisco (~560 kDa soluble complex), and photosystem II (~550 kDa membrane complex) with an accuracy comparable to expert-supervised ground truth annotations. DeepFinder is therefore a promising algorithm for the semi-automated analysis of a wide range of molecular targets in cellular tomograms

Extracerebral metastases determine the outcome of patients with brain metastases from renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>In the era of cytokines, patients with brain metastases (BM) from renal cell carcinoma had a significantly shorter survival than patients without. Targeted agents (TA) have improved the outcome of patients with metastatic renal cell carcinoma (mRCC) however, their impact on patients with BM is less clear. The aim of this analysis was to compare the outcome of patients with and without BM in the era of targeted agents.</p> <p>Methods</p> <p>Data from 114 consecutive patients who had access to targeted agent were analyzed for response rates (ORR), progression free survival (PFS) and overall survival (OS). All patients diagnosed with BM underwent local, BM-specific treatment before initiation of medical treatment.</p> <p>Results</p> <p>Data of 114 consecutive patients who had access to at least one type of targeted agents were analyzed. Twelve out of 114 renal cell carcinoma (RCC) patients (10.5%) were diagnosed with BM. Systemic treatment consisted of sunitinib, sorafenib, temsirolimus or bevacizumab. The median PFS was 8.7 months (95% CI 5.1 - 12.3) and 11.4 months (95% CI 8.7 - 14.1) for BM-patients and non-BM-patients, respectively (p = 0.232). The median overall survival for patients with and without BM was 13.4 (95% CI 1- 43.9) and 33.3 months (95% CI 18.6 - 47.0) (p = 0.358), respectively. No patient died from cerebral disease progression. ECOG Performance status and the time from primary tumor to metastases (TDM) were independent risk factors for short survival (HR 2.74, p = 0.001; HR: 0.552, p = 0.034).</p> <p>Conclusions</p> <p>Although extracerebral metastases determine the outcome of patients with BM, the benefit from targeted agents still appears to be limited when compared to patients without BM.</p

Kant on the role of the imagination (and images) in the transition from intuition to experience

In this chapter I will argue against both of these interpretations and will begin to develop an alternate account of imagination in experience. Against those who minimize imagination’s role, I will highlight the distinctive contribution of the imagination to experience. In particular, I will foreground the specific role that the imagination plays in making possible the distinct mental act, intermediate between intuition and experience, that Kant calls “perception [Wahrnehmung]” as the “empirical consciousness [Bewußtsein]” of appearances (cf. B207). Because perception involves images essentially (cf. A120), and because Kant understands experience itself to be a “synthesis of perceptions” (cf. B218), this strongly suggests (against minimalists) that experience, too, will incorporate images into the manner in which it allows us to cognize physical objects. By highlighting the contribution of imagination prior to experience, my own account, therefore, overlaps in part with the readings that seek instead to maximize the role of imagination. Against maximalists, however, I will argue that imagination contributes only in (and after) the transition from intuition to perception, rather than already being at work in the stage of intuition itself. More specifically, I will argue that Kant takes the activity of imagination to make perception possible by acting on already-formed intuitions in order to bring about the consciousness of them, rather than to bring the intuitions about in the first place. I will also argue that this synthesis of intuitions should be kept distinct from the activity of understanding

A promoter toolbox for tissue-specific expression supporting translational research in cassava (Manihot esculenta)

There is an urgent need to stimulate agricultural output in many tropical and subtropical countries of the world to combat hunger and malnutrition. The starchy crop cassava (Manihot esculenta), growing even under sub-optimal conditions, is a key staple food in these regions, providing millions of people with food. Cassava biotechnology is an important technique benefiting agricultural progress, but successful implementation of many biotechnological concepts depends on the availability of the right spatiotemporal expression tools. Yet, well-characterized cassava promoters are scarce in the public domain. In this study, we investigate the promoter activity and tissue specificity of 24 different promoter elements in stably transformed cassava plants. We show that many of the investigated promoters, especially from other species, have surprisingly low activity and/or tissue specificity, but feature several promoter sequences that can drive tissue-specific expression in either autotrophic-, transport- or storage tissues. We especially highlight pAtCAB1, pMePsbR, and pSlRBCS2 as strong and specific source promoters, pAtSUC2, pMeSWEET1-like, and pMeSUS1 as valuable tools for phloem and phloem parenchyma expression, and pStB33, pMeGPT, pStGBSS1, as well as pStPatatin Class I, as strong and specific promoters for heterotrophic storage tissues. We hope that the provided information and sequences prove valuable to the cassava community by contributing to the successful implementation of biotechnological concepts aimed at the improvement of cassava nutritional value and productivity.ISSN:1664-462