Neural network surrogates of Bayesian diagnostic models for fast inference of plasma parameters.

We present a framework for training artificial neural networks (ANNs) as surrogate Bayesian models for the inference of plasma parameters from diagnostic data collected at nuclear fusion experiments, with the purpose of providing a fast approximation of conventional Bayesian inference. Because of the complexity of the models involved, conventional Bayesian inference can require tens of minutes for analyzing one single measurement, while hundreds of thousands can be collected during a single plasma discharge. The ANN surrogates can reduce the analysis time down to tens/hundreds of microseconds per single measurement. The core idea is to generate the training data by sampling them from the joint probability distribution of the parameters and observations of the original Bayesian model. The network can be trained to learn the reconstruction of plasma parameters from observations and the model joint probability distribution from plasma parameters and observations. Previous work has validated the application of such a framework to the former case at the Wendelstein 7-X and Joint European Torus experiments. Here, we first give a description of the general methodological principles allowing us to generate the training data, and then we show an example application of the reconstruction of the joint probability distribution of an effective ion charge Zeff-bremsstrahlung model from data collected at the latest W7-X experimental campaign. One key feature of such an approach is that the network is trained exclusively on data generated with the Bayesian model, requiring no experimental data. This allows us to replicate the training scheme and generate fast, surrogate ANNs for any validated Bayesian diagnostic model.

Identification of internal poly(A) tracts (IPATs) of variable lengths in a novel tobacco rattle virus RNA2 in potatoes.

The nucleotide (nt) sequences of two closely related isolates (CeWF-2 and CeWGH-2) of a novel tobacco rattle virus (TRV) RNA2 were determined. The sequences of their RNA2-specific regions were almost identical and contained four open reading frames (ORFs) in an arrangement similar to that found in the previously described TRV TpO1 RNA2. Their predicted ORF 1 gene products shared 97 % amino acid sequence identity with the TpO1 coat protein, but the ORF 2 and ORF 3 gene products shared only 82 % sequence identity, and no appreciable sequence similarity was found between the CeWF-2/CeWGH-2 and TpO1 ORF 4 gene products. In the CeWGH-2 sequence, the RNA2-specific and RNA1-related regions were separated by seven adenine (A) residues. In CeWF-2, however, an internal poly(A) tract (IPAT) of variable size consisting of ca. 20 to 30 (A) residues was found. This is the first report of an IPAT occurring in a tobravirus RNA2.

Molecular characterization of a new tobacco rattle virus (TRV) RNA2 and identification of different TRV RNA1/RNA2 pairings in various potato-growing areas in Germany.

The almost complete nucleotide sequences lacking only the short primer-derived 5' and 3' ends were determined for two closely related isolates of a new tobacco rattle virus (TRV) RNA2, i.e., ByKT (Bav)-2 and ByKT (LS)-2. These isolates originated from corky-ringspot-affected potato-growing areas in southern Germany (Bavaria) and northern central Germany (Lower Saxony), respectively, where they were associated with distinct supporting TRV RNA1s. In potatoes in other parts of Germany, TRV RNA2s closely related to TRV TpO1 RNA2 were identified. They, too, were associated with distinct TRV RNA1s in different parts of the country.

[Anterior skull base defects - algorithm for reconstruction]. / Rhinobasisdefekt - was tun? Fallserie und Algorithmus.

BACKGROUND: After tumor surgery or traumatic defects the anterior skull base needs sufficient closure in order to prevent rhinoliquorrhea, ascending infection and brain tissue prolaps. Small defects are sufficiently closed by non-vital tissue, e. g. mucosa, muscle, fat, fascia, bone, allogenic, xenogenic or alloplastic material. Larger defects of the skull base often require more extensive surgery, including transfer of local or distal vascularized flaps. The current article presents a stepwise tutorial for reconstruction of the skull base and by a large case series focuses on the interdisciplinary therapy of complex (size, recurrence, after radiotherapy) skull base defects. MATERIAL AND METHOD: Complex defects with small diameter, which can occur after extended sinus surgery, were permanently closed by local mucosa flaps of the lower turbinate or of the septum (n=31). Larger defects, e. g. after combined transcranial and endonasal tumor surgery, were closed by a 'sandwich technique' containing a galea periost flap and a calvarian split transfer (n=10). Reconstruction of the dura with fascia lata and local transfer of the temporal muscle were efficient for frontobasal defects with a more lateral location (n=4). Transfer of a distal desepithelialised vascularized forearm flap represents the ultimate procedure for reconstruction of large skull base defects, which was performed in 4 of our patients. CONCLUSION: Successive escalation of the therapy and integra-tion of the entire repertoire of plastic-reconstructive surgery allows for durable closure of complex skull base defects. In every case, close cooperation between ENT- and neurosurgeons is necessary for planning and performance of a successful surgical procedure.

Thoracic outlet syndrome in 3T MR neurography-fibrous bands causing discernible lesions of the lower brachial plexus.

OBJECTIVES: To investigate whether targeted magnetic resonance neurography (MRN) of the brachial plexus can visualise fibrous bands compressing the brachial plexus and directly detect injury in plexus nerve fascicles. METHODS: High-resolution MRN was employed in 30 patients with clinical suspicion of either true neurogenic thoracic outlet syndrome (TOS) or non-specific TOS. The protocol for the brachial plexus included a SPACE (3D turbo spin echo with variable flip angle) STIR (short tau inversion recovery), a sagittal-oblique T2-weighted (T2W) SPAIR (spectral adiabatic inversion recovery) and a 3D PDW (proton density weighted) SPACE. Images were evaluated for anatomical anomalies compressing the brachial plexus and for abnormal T2W signal within plexus elements. Patients with abnormal MR imaging findings underwent surgical exploration. RESULTS: Seven out of 30 patients were identified with unambiguous morphological correlates of TOS. These were verified by surgical exploration. Correlates included fibrous bands (n = 5) and pseudarthrosis or synostosis of ribs (n = 2). Increased T2W signal was detected within compressed plexus portion (C8 spinal nerve, inferior trunk, or medial cord) and confirmed the diagnosis. CONCLUSIONS: The clinical suspicion of TOS can be diagnostically confirmed by MRN. Entrapment of plexus structures by subtle anatomical anomalies such as fibrous bands can be visualised and relevant compression can be confirmed by increased T2W signal of compromised plexus elements. KEY POINTS: • MR neurography (MRN) can aid the diagnosis of thoracic outlet syndrome (TOS). • Identifiable causes of TOS in MRN include fibrous bands and bony anomalies. • Increased T2W signal within brachial plexus elements indicate relevant nerve compression. • High positive predictive value allows confident and targeted indication for surgery.

Severe forms of Baraitser-Winter syndrome are caused by ACTB mutations rather than ACTG1 mutations.

ACTB and ACTG1 mutations have recently been reported to cause Baraitser-Winter syndrome (BRWS) - a rare condition characterized by ptosis, colobomata, neuronal migration disorder, distinct facial anomalies and intellectual disability. One of the patients carrying an ACTB mutation was previously diagnosed with Fryns-Aftimos syndrome (FAS), which is a rare and severe, multiple congenital anomaly (MCA) syndrome whose symptoms partially overlap with that of BRWS. However, several patients with Fryns-Aftimos were considered not to fit into the ACTB and ACTG1 spectrum because of their severe impairment and additional malformations. We report on three patients who had been diagnosed with FAS. All three patients carry a mutation in the ACTB gene. On the basis of the ACTB mutations and analysis of the clinical findings, we reclassify the diagnosis of these patients as severe BRWS. We suggest that mutations in ACTB cause a distinctly more severe phenotype than ACTG1 mutations, despite the structural similarity of beta- and gamma-actins and their overlapping expression pattern. We expand the spectrum of BRWS and confirm that FAS is not a separate entity but an early and severe manifestation of BRWS.

Tobacco rattle virus genome alterations in the Hosta hybrid 'Green Fountain' and other plants: reassortments, recombinations and deletions.

Tobacco rattle virus from a Hosta hybrid contained one RNA1 (Ho-1) and two RNA2 species (Ho-2a, Ho-2b). Whereas Ho-1 resembles TRV Al RNA1 from Alstroemerias, Ho-2a and Ho-2b resemble TRV TpO1 RNA2 from a potato field. Ho-2a has a complete RNA2-specific sequence, whereas that of Ho2-b carries a large deletion. The short RNA1-related 3' end of Ho-2a is distinct from that of Ho-1, whereas the longer one of Ho-2b is identical to that of Ho-1. TRV RNA2 molecules may apparently become associated with different TRV RNA1 molecules, from which they can acquire 3'ends of various lengths while often losing large portions of their RNA2-specific sequences.

Two novel WTX mutations underscore the unpredictability of male survival in osteopathia striata with cranial sclerosis.

Osteopathia striata with cranial sclerosis (OMIM ##300373) is an X-linked dominant sclerosing bone dysplasia that presents in females with macrocephaly, cleft palate, mild learning disabilities, sclerosis of the long bones and skull, and longitudinal striations visible on radiographs of the long bones, pelvis, and scapulae. In males this entity is usually associated with foetal or neonatal lethality, because of severe heart defects and/or gastrointestinal malformations, and is often accompanied by bilateral fibula aplasia. Recently, the disease-causing gene was identified as the WTX gene (FAM123B). Initially it was suggested that the mutations in the 5' region of the WTX gene are associated with male lethality. Mutation analysis in individuals of two families diagnosed with OSCS revealed two novel WTX mutations. In one family, the affected male is still alive in his teens. These mutations underline the unpredictability of male survival and suggest that WTX mutations should be considered in cases of male cranial sclerosis, even if striations are not present. An overview of all known mutations and their associated characteristics provide a valuable resource for the molecular analysis of OSCS.

Deletions and recombinations with the RNA1 3' ends of different tobraviruses have created a multitude of tobacco rattle virus TCM-related RNA2 species in Alstroemeria and tulip.

In vegetatively propagated Alstroemeria plants that showed pronounced stunting and necrotic leaf spots, a tobravirus infection was diagnosed in which one tobacco rattle virus (TRV, strain AL) RNA1 species was associated with seven different RNA2 species. The latter differed considerably in size and in the types of their 3' RNA1-related sequences. The 5' RNA2-specific part of all these RNA2 molecules showed almost 100% sequence identity with that of RNA2 of the TRV isolate TCM from tulip, but in some of these RNA2 molecules it was shorter than in the TCM isolate, whereas in others it was longer. One of the TRV AL RNA2 molecules, i.e. TC3'PE-a, contained the full set of three full-length RNA2-specific ORFs (ORF2a, -2b and -2c), whereas the previously analysed TCM sequence contained only ORF2a and -2b. In four of these TRV AL RNA2 molecules, i.e. those that had a relatively short RNA2-specific part, the 3' end was identical to that of the cognate TRV AL RNA1, but in the other three, which had a long RNA2-specific part, it was closely related to that of pea early browning virus (PEBV) RNA1, which was not detected in the infected plants. A comparison with previously described TRV/PEBV RNA2 recombinants suggested that the various TRV AL RNA2 molecules may represent various steps and side steps in an evolutionary process, which is apt to open the wide host range of TRV also to PEBV-derived RNA2 species.

Design criteria of the bolometer diagnostic for steady-state operation of the W7-X stellarator.

A bolometric diagnostic system with features necessary for steady-state operation in the superconducting stellarator W7-X was designed. During a pulse length of 1800 s with an ECRH (electron cyclotron resonance heating) power of 10 MW, the components suffer not only from a large thermal load but also from stray radiation of the nonabsorbed isotropic microwaves. This paper gives an overview of the technical problems encountered during the design work and the solutions to individual problems to meet the special requirements in W7-X, e.g., component thermal protection, detector offset thermal drift suppression, as well as a microwave shielding technique.

A single U/C nucleotide substitution changing alanine to valine in the beet necrotic yellow vein virus P25 protein promotes increased virus accumulation in roots of mechanically inoculated, partially resistant sugar beet seedlings.

Beet necrotic yellow vein virus (BNYVV) A type isolates E12 and S8, originating from areas where resistance-breaking had or had not been observed, respectively, served as starting material for studying the influence of sequence variations in BNYVV RNA 3 on virus accumulation in partially resistant sugar beet varieties. Sub-isolates containing only RNAs 1 and 2 were obtained by serial local lesion passages; biologically active cDNA clones were prepared for RNAs 3 which differed in their coding sequences for P25 aa 67, 68 and 129. Sugar beet seedlings were mechanically inoculated with RNA 1+2/RNA 3 pseudorecombinants. The origin of RNAs 1+2 had little influence on virus accumulation in rootlets. E12 RNA 3 coding for V(67)C(68)Y(129) P25, however, enabled a much higher virus accumulation than S8 RNA 3 coding for A(67)H(68)H(129) P25. Mutants revealed that this was due only to the V(67) 'GUU' codon as opposed to the A(67) 'GCU' codon.

Iranian beet necrotic yellow vein virus (BNYVV): pronounced diversity of the p25 coding region in A-type BNYVV and identification of P-type BNYVV lacking a fifth RNA species.

Beet necrotic yellow vein virus (BNYVV) was detected in 288 of the 392 samples collected in Iran. A-type BNYVV was detected most frequently. The p25 coding region on BNYVV RNA-3 was amplified by RT-PCR and sequenced. Nine different variants of the highly variable amino acid tetrad at positions 67-70 of p25 were identified, i.e. ACHG, AHHG, AYHG, ALHG, AFHR, AFHG, AHYG, VLHG and VHHG. These are more different tetrad variants than have been reported from any other country. The first three variants were found most commonly. In 23 out of the 288 BNYVV-positive samples, we detected P-type BNYVV that had previously been identified only in France, Kazakhstan and recently in the UK. Surprisingly, none of these samples contained the fifth RNA species usually associated with P-type BNYVV in other countries. As in other BNYVV P-type sources, the p25 amino acid tetrad in positions 67-70 of the Iranian P-type consists of SYHG.

Distribution of various types and P25 subtypes of Beet necrotic yellow vein virus in Germany and other European countries.

The distribution of various Beet necrotic yellow vein virus (BNYVV) genotypes was studied using beet samples received from Germany and neighbouring countries. Almost exclusively B type BNYVV was detected in Germany, whereas in neighbouring countries BNYVV A types with different compositions of the amino acid tetrad in positions 67-70 of the RNA-3-encoded P25 are widely distributed. Neither A types nor the P type have been able to become established in Germany in the past decades, although there must have been many opportunities for their introduction from neighbouring countries. In one field, however, an RNA-5-containing BNYVV genotype closely resembling the Chinese isolate Har4 was found.

Molecular and serological characterization of an Iranian isolate of Beet black scorch virus.

An isolate of Beet black scorch virus (BBSV) was obtained from Iranian sugar beet roots. Its genome organization closely resembles that of the previously described Chinese and North American isolates, but the nucleotide sequences of the three isolates differ considerably. Most of the nucleotide exchanges, however, are silent, and the Iranian and the Chinese isolates were serologically indistinguishable. Beets infected by the Iranian BBSV did not show black scorch symptoms, but severe root beardedness. This might have been caused by BBSV or the simultaneously present beet necrotic yellow vein virus, or both together.

Occurrence of two different types of RNA-5-containing beet necrotic yellow vein virus in the UK.

Two types of RNA-5-containing beet necrotic yellow vein virus (BNYVV) have been detected in the UK at different sites in Norfolk. On the basis of nucleotide (nt) sequence comparisons, one virus source (UK-MH) was clearly identified as P type BNYVV, a virus type that had previously only been detected in two widely separated parts of the world, France and Kazakhstan. The other virus source (UK-FF) has a complex genome composition. The analysed portions of its RNAs 2 and 4 are closely related to the corresponding portions in the RNAs of the East Asian A type isolate S, whereas those of its RNAs 1 and 3 resemble P type RNA 1 from Kazakhstan and European A type RNA 3, respectively. Interestingly, the P25 encoded on its RNA 3 has an unique TYHG tetrad in the highly variable amino acid positions 67-70. RNA 5 of the UK-FF BNYVV source shares properties with P type RNA 5, but also with East Asian types of RNA 5. The possible origin and epidemiology of BNYVV types is discussed.

Zygocactus virus X-based expression vectors and formation of rod-shaped virus-like particles in plants by the expressed coat proteins of Beet necrotic yellow vein virus and Soil-borne cereal mosaic virus.

Expression vectors were constructed from 35S promoter-containing full-length cDNA clones of Zygocactus virus X (ZVX). The expression of foreign genes was driven by the ZVX coat protein (cp) subgenomic promoter. It was successful only when the variable region downstream of the conserved putative promoter region GSTTAAGTT(X(12-13))GAA was retained. Most of the ZVX cp gene, except for a short 3' part, was replaced by the corresponding sequence of the related Schlumbergera virus X (SVX) and its cp subgenomic promoter to enable encapsidation of the transcribed RNA by an SVX/ZVX hybrid cp. Vector-expressed cp of Beet necrotic yellow vein virus (BNYVV) assembled in Chenopodium quinoa, Tetragonia expansa and Beta vulgaris leaves into particles resembling true BNYVV particles. The virus produced from these constructs retained its ability to express BNYVV cp in local infections during successive passages on C. quinoa. This ability was lost, however, in the rarely occurring systemic infections.

Molecular characterization of isolates of anagyris vein yellowing virus, plantago mottle virus and scrophularia mottle virus -- comparison of various approaches for tymovirus classification.

The complete nucleotide sequences were determined for the genomic RNAs of three tymoviruses, i.e. isolates of anagyris vein yellowing virus (AVYV), plantago mottle virus (PlMoV) and scrophularia mottle virus (SrMV) which are all serologically closely related to ononis yellow mosaic virus (ibid) and to Nemesia ring necrosis virus (NeRNV), a recently described recombinant virus which is widely spread in commercially grown ornamental plant species belonging to the Scrophulariaceae. Total nucleotide and coat protein amino acid sequence identities revealed similar groupings in the genus tymovirus as serological studies did. The latter, however, tended to suggest much closer relationships than the molecular data and may fail to recognise the distinctiveness of new tymovirus species. The usefulness of various species demarcation criteria for the classification of tymoviruses is discussed.

Nemesia ring necrosis virus: a new tymovirus with a genomic RNA having a histidylatable tobamovirus-like 3' end.

The complete nucleotide sequence of the genomic RNA of the new virus Nemesia ring necrosis virus (NeRNV), which is widespread in various ornamental plant species belonging to the Scrophulariaceae and Verbenaceae, has been determined. Based on its gene content, the folding properties of its 5'-untranslated region and in vitro translation experiments, NeRNV RNA is a typical tymovirus RNA. Its 3' end, however, differs greatly from those of the valine-specific tymoviral RNAs that have been analysed previously. It can be folded into an upstream pseudoknot domain and a histidine-specific tRNA-like structure, a combination that, so far, has been found only in tobamoviral RNAs. The identity elements found in NeRNV RNA for recognition by yeast histidyl-tRNA synthetase are more similar to those of yeast tRNAHis than the ones found in tobacco mosaic virus RNA. As a result NeRNV RNA can be charged with histidine even more efficiently than tobacco mosaic virus RNA.

Evaluation of various species demarcation criteria in attempts to classify ten new tombusvirus isolates.

The usefulness of various suggested species demarcation criteria was compared in attempts to determine the taxonomic status of ten new tombusvirus isolates. Five of them (Lim 1, 2, 3, 5 and 6) were obtained from different sources of commercially grown statice (Limonium sinuatum), two (Gyp 1 and 2) from different sources of commercially grown Gypsophila paniculata and three from water samples, i.e. from a small river (Schunter) in Northern Germany, from a brook (near Dossenheim) in Southern Germany and from the groundwater in a Limonium production glasshouse in the Netherlands (Lim 4). The immunoelectron microscopical decoration test allowed a quick preliminary assignment of various isolates to several known tombusviruses. A more precise analysis of the relationships was achieved by comparing the deduced amino acid sequences of the coat proteins. Sequence as well as serological data suggested that eight of the isolates should be classified as strains or variants of either Carnation Italian ringspot virus, Grapevine Algerian latent virus, Petunia asteroid mosaic virus or Sikte waterborne virus, respectively, whereas the 9th isolate (Lim 2) appears to represent a distinct new tombusvirus species. The case of the 10th isolate (Lim 5) illustrates the classification problems experienced when the properties of a virus place it close to the more or less arbitrary man-made borderline between virus species and virus strains. The coat protein gene sequences were also determined for some viruses for which these data had not yet been available, i.e. Neckar river virus, Sikte waterborne virus and Eggplant mottled crinkle virus. The sequences of the coat protein gene and also of ORF 1 of the latter virus proved to be almost identical to the corresponding genome regions of the recently described Pear latent virus, which for priority reasons should be renamed. Criteria which have been suggested in addition to serology and sequence comparisons for tombusvirus species demarcation, i.e. differences in natural and in experimental host ranges, in cytopathological features and in coat protein size, appear to be of little value for the classification of new tombusviruses.

Fusion of MRI and CT with subdural grid electrodes.

In patients with drug-resistant focal epilepsies subdural grid electrodes may be implanted to determine the seizure onset zone and eloquent cortex areas. Since the spatial relationship of the grid to the underlying brain is poorly visualized on MRI, we co-registered MRI before and CT after implantation of subdural grid electrodes. In this study we sought an appropriate algorithm to combine both imaging modalities. We compared six different co-registration algorithms including surface-oriented, mutual information-based and landmark-based methods. The resulting overlay matrices were analyzed by calculating rotational and translational shifts and by judging co-registered MRI and CT scans visually. A brain surface oriented method had the lowest rotational (axial 0.7 +/- 0.6 degrees; coronal 1.7 +/- 1.1 degrees; sagittal 1.9 +/- 1.8 degrees) and translational shifts (3.7 +/- 1.3 mm). It was judged visually to be the best, had a low intra- and inter-observer variability, and lasted approximately 15 minutes. This algorithm is recommended when co-registering MRI before and CT after implantation of subdural grid electrodes. Skin-, voxel-, and landmark-based algorithms are less accurate, which is most likely due to postsurgical deformation of extra- and intracranial soft tissue.