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Purpose: Computed tomography (CT) is used for initial diagnosis and therapy monitoring of patients with coronavirus disease 2019 (COVID-19). As patients of all ages are affected, radiation dose is a concern. While follow-up CT examinations lead to high cumulative radiation doses, the ALARA principle states that the applied dose should be as low as possible while maintaining adequate image quality. The aim of this study was to evaluate parameter settings for two commonly used CT scanners to ensure sufficient image quality/diagnostic confidence at a submillisievert dose., Materials and Methods: We retrospectively analyzed 36 proven COVID-19 cases examined on two different scanners. Image quality was evaluated objectively as signal-to-noise ratio (SNR)/contrast-to-noise ratio (CNR) measurement and subjectively by two experienced, independent readers using 3-point Likert scales. CT dose index volume (CTDIvol) and dose-length product (DLP) were extracted from dose reports, and effective dose was calculated., Results: With the tested parameter settings we achieved effective doses below 1 mSv (median 0.5 mSv, IQR: 0.2 mSv, range: 0.3-0.9 mSv) in all 36 patients. Thirty-four patients had typical COVID-19 findings. Both readers were confident regarding the typical COVID-19 CT-characteristics in all cases (3 ± 0). Objective image quality parameters were: SNR normal lung : 17.0 ± 5.9, CNR GGO/normal lung : 7.5 ± 5.0, and CNR consolidation/normal lung : 15.3 ± 6.1., Conclusion: With the tested parameters, we achieved applied doses in the submillisievert range, on two different CT scanners without sacrificing diagnostic confidence regarding COVID-19 findings., Competing Interests: The authors declare no conflict of interest., (© 2020 The Author(s).)

Biorefining of renewable feedstocks is one of the most promising routes to replace fossil-based products. Since many common fermentation hosts, such as Saccharomyces cerevisiae , are naturally unable to convert many component plant cell wall polysaccharides, the identification of organisms with broad catabolism capabilities represents an opportunity to expand the range of substrates used in fermentation biorefinery approaches. The red basidiomycete yeast Rhodosporidium toruloides is a promising and robust host for lipid- and terpene-derived chemicals. Previous studies demonstrated assimilation of a range of substrates, from C 5 /C 6 sugars to aromatic molecules similar to lignin monomers. In the current study, we analyzed the potential of R. toruloides to assimilate d-galacturonic acid, a major sugar in many pectin-rich agricultural waste streams, including sugar beet pulp and citrus peels. d-Galacturonic acid is not a preferred substrate for many fungi, but its metabolism was found to be on par with those of d-glucose and d-xylose in R. toruloides A genomewide analysis by combined transcriptome sequencing (RNA-seq) and RB-TDNA-seq revealed those genes with high relevance for fitness on d-galacturonic acid. While R. toruloides was found to utilize the nonphosphorylative catabolic pathway known from ascomycetes, the maximal velocities of several enzymes exceeded those previously reported. In addition, an efficient downstream glycerol catabolism and a novel transcription factor were found to be important for d-galacturonic acid utilization. These results set the basis for use of R. toruloides as a potential host for pectin-rich waste conversions and demonstrate its suitability as a model for metabolic studies with basidiomycetes. IMPORTANCE The switch from the traditional fossil-based industry to a green and sustainable bioeconomy demands the complete utilization of renewable feedstocks. Many currently used bioconversion hosts are unable to utilize major components of plant biomass, warranting the identification of microorganisms with broader catabolic capacity and characterization of their unique biochemical pathways. d-Galacturonic acid is a plant component of bioconversion interest and is the major backbone sugar of pectin, a plant cell wall polysaccharide abundant in soft and young plant tissues. The red basidiomycete and oleaginous yeast Rhodosporidium toruloides has been previously shown to utilize a range of sugars and aromatic molecules. Using state-of-the-art functional genomic methods and physiological and biochemical assays, we elucidated the molecular basis underlying the efficient metabolism of d-galacturonic acid. This study identified an efficient pathway for uronic acid conversion to guide future engineering efforts and represents the first detailed metabolic analysis of pectin metabolism in a basidiomycete fungus., (Copyright © 2019 Protzko et al.)

Fungal plant cell wall degradation processes are governed by complex regulatory mechanisms, allowing the organisms to adapt their metabolic program with high specificity to the available substrates. While the uptake of representative plant cell wall mono- and disaccharides is known to induce specific transcriptional and translational responses, the processes related to early signal reception and transduction remain largely unknown. A fast and reversible way of signal transmission are post-translational protein modifications, such as phosphorylations, which could initiate rapid adaptations of the fungal metabolism to a new condition. To elucidate how changes in the initial substrate recognition phase of Neurospora crassa affect the global phosphorylation pattern, phospho-proteomics was performed after a short (2 min) induction period with several plant cell wall-related mono- and disaccharides. The MS/MS-based peptide analysis revealed large-scale substrate-specific protein phosphorylation and de-phosphorylations. Using the proteins identified by MS/MS, a protein-protein-interaction (PPI) network was constructed. The variance in phosphorylation of a large number of kinases, phosphatases and transcription factors indicate the participation of many known signaling pathways, including circadian responses, two-component regulatory systems, MAP kinases as well as the cAMP-dependent and heterotrimeric G-protein pathways. Adenylate cyclase, a key component of the cAMP pathway, was identified as a potential hub for carbon source-specific differential protein interactions. In addition, four phosphorylated F-Box proteins were identified, two of which, Fbx-19 and Fbx-22, were found to be involved in carbon catabolite repression responses. Overall, these results provide unprecedented and detailed insights into a so far less well known stage of the fungal response to environmental cues and allow to better elucidate the molecular mechanisms of sensory perception and signal transduction during plant cell wall degradation., (Copyright © 2019 Horta, Thieme, Gao, Burnum-Johnson, Nicora, Gritsenko, Lipton, Mohanraj, de Assis, Lin, Tian, Braus, Borkovich, Schmoll, Larrondo, Samal, Goldman and Benz.)

Langerhans cell histiocytosis (LCH) is a diagnostic and therapeutic challenge. We report on a rare case of its primary oral manifestation that was treated successfully with the BRAF-specific agent, vemurafenib, after insufficient standard LCH treatment. This case underlines the importance of proper diagnosis and the evaluation of targeted therapy as a valuable tool in LCH treatment. Furthermore, the close collaboration of surgeons, oncologists, and dentists is mandatory to ensure adequate treatment, restore the stomatognathic system in debilitating post-treatment situations, improve quality of life, and ensure effective disease control in infants and young patients., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2019.)

Introduction: The treatment of facial fractures is an integral part of the oral and maxillofacial surgical treatment spectrum. In the case of complex fractures that involve multiple levels of the facial skeleton associated with severe concomitant injuries, an individual and interdisciplinary treatment approach is needed, which requires the infrastructure of a national trauma center., Objective: The aim of this study was to analyze the incidence and management of patients with complex facial fractures and considering the concomitant injury pattern., Material and Methods: A retrospective analysis of patients with complex facial fractures during the years 2009-2015 admitted to the emergency surgical department of a national trauma center was carried out. The identification of appropriate patient cases was based on the International Statistical Classification of Diseases and Related Health Problems (ICD) coding of electronic patient data. Only patients with at least a combination of mandibular and midfacial fractures (2-level fractures) were considered. Patients with mainly dentoalveolar fractures and simple nasal bone fractures were not included. The evaluation of the electronic medical records included the etiology, fracture pattern, associated severe injuries on the basis of the injury severity score (ISS), treatment regimen as well as the length of the hospital stay., Results: In the 7‑year study period, 3382 patients were identified with facial fractures. Of these, 128 patients (3.78%) presented with a complex fracture pattern with a combination of mandibular fractures and fractures of the midface. The majority of these patients (n = 92) had less severe concomitant injuries (ISS ≤ 16), while 36 patients showed severe concomitant injuries (ISS > 16). The incidence of a 3-level fracture involving the mandible, midface and anterior skull base was only 0.47% and could be detected in 16 patients, of which 10 were classified as polytrauma (ISS > 16)., Conclusion: The incidence of complex fractures of the facial skeleton was comparatively low with almost 4%. More than one in four patients with complex injury patterns of the facial skeleton exhibited severe concomitant life-threatening injuries, necessitating an interdisciplinary management with the specialized infrastructure of a nationwide trauma center.

Crystal growth processes can profit from an electromagnetically driven melt flow since controlling them allows optimizing the mass and heat transfers in the melt and, thereby, improves the structural and electrical properties of the grown crystals. This process optimization requires a precise understanding of magnetohydrodynamics (MHD) phenomena in crystal growth. Studying time-dependent MHD demands for a high temporal resolution combined with a long measurement duration to analyze the transitional flow behavior. Furthermore, a spatially resolved measurement of the global flow structure is desired to capture the complex 3-D flow structures. We present an ultrasound array Doppler velocimeter (UADV) for time-resolved flow imaging in MHD model experiments with low-melting metals. Flow imaging at frame rates of several Hertz is achieved by using a combined spatial and temporal multiplexing scheme. Long-running measurements are enabled by a field-programmable gate array (FPGA)-based signal processing that reduces the measurement data rate by a factor of 5. A reconstruction of the 3-D flow structure in cylindrical containers with a rotation-symmetric flow is proposed. The UADV is demonstrated at an MHD experiment with a melt flow in a cylindrical container driven by a traveling magnetic field. The transition from a laminar to a time-dependent flow is studied, revealing an oscillating flow. The demonstration of the 3-D reconstruction gives comprehensive insight into the global flow structure. Hence, the UADV method is shown to be a valuable tool for measuring complex, time-dependent melt flows, which can contribute to a better understanding of the flow phenomena during crystal growth.

Background: Congenital cysts and fistulas of the neck are common in children, often located in the head and neck area. Belonging to the group of tumor-like conditions, dermoid and epidermoid cysts are dysontogenetic lesions with seldom multiple co-occurrences in infants., Case Report: We report on a nine-month-old female with a persisting congenital fistula of the tongue. The patient was admitted with acute poor feeding and hypersalivation, which started within the last 24 h. Magnetic resonance imaging detected a fistula of the tongue connected to sublingual cystic lesions. Intraoral surgical removal of three cystic lesions and the fistula was performed under general anesthesia. Histopathological analysis confirmed the coexistence of an epidermoid cyst and two dermoid cysts., Conclusion: Sudden feeding difficulties in combination with dysphagia and tongue displacement in pediatric patients pose an emergency situation that requires prompt diagnostic clarification. A persisting congenital fistula of the tongue is a clear indication of dysontogenetic lesions, including malformations, tumors, and tumor-like lesions. Congenital sublingual cysts are rare in infants, but can be life threatening when present. Surgical excision with histopathological analysis is essential to exclude any form of malignancy and malignant transformation., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Penetrating foreign bodies of different origins in the head and neck are rare and potentially dangerous injuries, which might pose problems for their detection, primary care, and final treatment. Depending on the severity of the underlying trauma, some injuries present a higher risk for the presence of foreign bodies. Minor wounds, including common lacerations, are likely to be contaminated with loose gravel debris or dental fragments, and need to be distinguished from severe wounds caused by impalement, shootings, stabbings, and explosions. Blast injuries resulting from terror attacks are challenging recent therapeutic concepts. Even though these injury patterns are uncommon, they carry the risk of impacted objects with dramatic consequences. Despite improving medical imaging techniques, detection remains a challenge as it is dependent on the material of the foreign body, the affected anatomical site, and the injury severity. Therefore, a detailed history of the circumstances leading to trauma is essential when foreign objects are not visible during clinical examination. Precise detection of the foreign body, its anatomical position, and the affected surrounding structures are vital, especially for impalement injuries of the head and neck area. Therefore, an interdisciplinary planning approach is essential prior to removal of the foreign object. Finally, tension-free anatomical adaptation of the corresponding structures is crucial for maintaining and restoring aesthetic and function. Here, we give an overview of the diagnosis and treatment of cases of foreign body injuries encountered in our department.

Purpose: Despite the advantages and broad applications of alloplastic resorbable implants, postoperative radiological control is challenging due to its radiolucency. The aim of the present study was to evaluate the radiographic visibility of newly developed materials for orbital floor reconstruction., Materials and Methods: The radiographic visibility of four different material combinations consisting of poly-(L-lactic acid)/poly-glycolic acid (PLLA/PGA) or poly(D,L-lactic acid) (PDLLA) enriched with magnesium (Mg), hydroxyapatite (HA) or β-tricalcium phosphate (β-TCP) with various layers of thicknesses (0.3, 0.6, and 1 mm), surgically placed above the orbital floor of a human head specimen, was evaluated using computed tomography (CT) and cone beam computed tomography (CBCT). The visibility was rated on a scale of 0-10 in CT/CBCT and by Hounsfield Units in CT for each subject., Results: All of the materials were clearly detectable in CT scans. Visibility was significantly higher (p < 0.001) in the standard soft tissue window (mean score: 7.3, ranging from 2 to 10) in comparison to the standard bone window (mean score: 5.2, ranging from 1 to 10). In CBCT (mean score: 3.3, ranging from 0 to 7), there was significantly lower but still sufficient visibility of the materials compared to the CT soft tissue window (p < 0.001) and CT bone window (p < 0.001). Comparing the different materials' visibility among the group of same layer thicknesses with each other, in the majority of cases, PDLLA enriched with β-TCP appeared to be most visible in both CT and CBCT., Conclusion: The incorporation of radiopaque elements to PLLA/PGA and PDLLA polymers is a promising strategy to improve their visibility in CT and CBCT. Our data suggest that the reconstruction of the orbital floor with these new materials could provide an advantageous postoperative radiographic control., (Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Mitogen-activated protein kinases (MAPKs) are conserved regulators of proliferation, differentiation and adaptation in eukaryotic cells. Their activity often involves changes in their subcellular localization, indicating an important role for these spatio-temporal dynamics in signal transmission. A striking model illustrating these dynamics is somatic cell fusion in Neurospora crassa Germinating spores of this fungus rapidly alternate between signal sending and receiving, thereby establishing a cell-cell dialog, which involves the alternating membrane recruitment of the MAPK MAK-2 in both fusion partners. Here, we show that the dynamic translocation of MAK-2 is essential for coordinating the behavior of the fusion partners before physical contact. The activation and function of the kinase strongly correlate with its subcellular localization, indicating a crucial contribution of the MAPK dynamics in establishing regulatory feedback loops, which establish the oscillatory signaling mode. In addition, we provide evidence that MAK-2 not only contributes to cell-cell communication, but also mediates cell-cell fusion. The MAK-2 dynamics significantly differ between these two processes, suggesting a role for the MAPK in switching of the cellular program between communication and fusion., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Background: The industrial applications of cellulases are mostly limited by the costs associated with their production. Optimized production pathways are therefore desirable. Based on their enzyme inducing capacity, celluloses are commonly used in fermentation media. However, the influence of their physiochemical characteristics on the production process is not well understood. In this study, we examined how physical, structural and chemical properties of celluloses influence cellulase and hemicellulase production in an industrially-optimized and a non-engineered filamentous fungus: Trichoderma reesei RUT-C30 and Neurospora crassa . The performance was evaluated by quantifying gene induction, protein secretion and enzymatic activities., Results: Among the three investigated substrates, the powdered cellulose was found to be the most impure, and the residual hemicellulosic content was efficiently perceived by the fungi. It was furthermore found to be the least crystalline substrate and consequently was the most readily digested cellulose in vitro. In vivo however, only RUT-C30 was able to take full advantage of these factors. When comparing carbon catabolite repressed and de-repressed strains of T. reesei and N. crassa , we found that cre1 / cre - 1 is at least partially responsible for this observation, but that the different wiring of the molecular signaling networks is also relevant., Conclusions: Our findings indicate that crystallinity and hemicellulose content are major determinants of performance. Moreover, the genetic background between WT and modified strains greatly affects the ability to utilize the cellulosic substrate. By highlighting key factors to consider when choosing the optimal cellulosic product for enzyme production, this study has relevance for the optimization of a critical step in the biotechnological (hemi-) cellulase production process.

Purpose: There are insufficient data concerning risk factors for contralateral regional metastases in laryngeal cancer. The aim of this study was to investigate the frequency and risk factors for contralateral lymph node metastases and their dependence on midline involvement of the primary tumor in patients with advanced laryngeal squamous cell carcinoma., Methods: 58 consecutive patients (8 females, 50 males; mean age 64.2 ± 9.8 years; AJCC stage III disease in 43.1%, IVA disease in 54.4%) undergoing primary total laryngectomy with bilateral neck dissection between 2002 and 2016 have been retrospectively investigated at one of the largest university medical centers in Europe. Preoperative staging computed tomography (CT) scans were analyzed for midline involvement of the primary laryngeal cancer. As a result, a classification scheme has been established (type A: clear, type B: involved, type C: exceeded, and type D: bilateral/origin side indeterminable)., Results: Contralateral lymph node metastases (pN2c necks) were found in six cases (10.3%), from which four were diagnosed with type D (23.5% of type D cases), and one each with type B and type C midline involvement. In cases with no midline involvement (type A), a risk ratio reduction of 100% was seen. CT-based midline typing resulted in fourfold increased sensitivity for predicting contralateral metastases compared to conventional staging. Positive nodal status (pN+) significantly reduced overall and disease-free survival (HR 2.706, p < 0.05)., Conclusions: As a consequence, for type A category, a contralateral neck dissection might be avoidable accompanied by a reduction in surgical complications and operating time.

Background: Pectin is an abundant component in many fruit and vegetable wastes and could therefore be an excellent resource for biorefinery, but is currently underutilized. Fungal pectinases already play a crucial role for industrial purposes, such as for foodstuff processing. However, the regulation of pectinase gene expression is still poorly understood. For an optimal utilization of plant biomass for biorefinery and biofuel production, a detailed analysis of the underlying regulatory mechanisms is warranted. In this study, we applied the genetic resources of the filamentous ascomycete species Neurospora crassa to screen for transcription factors that play a major role in pectinase induction., Results: The pectin degradation regulator-1 (PDR-1) was identified through a transcription factor mutant screen in N. crassa . The Δ pdr - 1 mutant exhibited a severe growth defect on pectin and all tested pectin-related poly- and monosaccharides. Biochemical as well as transcriptional analyses of WT and the Δ pdr - 1 mutant revealed that while PDR-1-mediated gene induction was dependent on the presence of l-rhamnose, it also strongly affected the degradation of the homogalacturonan backbone. The expression of the endo-polygalacturonase gh28 - 1 was greatly reduced in the Δ pdr - 1 mutant, while the expression levels of all pectate lyase genes increased. Moreover, a pdr - 1 overexpression strain displayed substantially increased pectinase production. Promoter analysis of the PDR-1 regulon allowed refinement of the putative PDR-1 DNA-binding motif., Conclusions: PDR-1 is highly conserved in filamentous ascomycete fungi and is present in many pathogenic and industrially important fungi. Our data demonstrate that the function of PDR-1 in N. crassa combines features of two recently described transcription factors in Aspergillus niger (RhaR) and Botrytis cinerea (GaaR). The results presented in this study contribute to a broader understanding of how pectin degradation is orchestrated in filamentous fungi and how it could be manipulated for optimized pectinase production.

A high energy conversion and cost efficiency are keys for the transition to renewable energy sources, e.g., solar cells. The efficiency of multicrystalline solar cells can be improved by enhancing the understanding of its crystallization process, especially the directional solidification. In this paper, a novel measurement system for the characterization of flow phenomena and solidification processes in low-temperature model experiments on the basis of ultrasound (US) Doppler velocimetry is described. It captures turbulent flow phenomena in two planes with a frame rate of 3.5 Hz and tracks the shape of the solid-liquid interface during multihour experiments. Time-resolved flow mapping is performed using four linear US arrays with a total of 168 transducer elements. Long duration measurements are enabled through an online, field-programmable gate array (FPGA)-based signal processing. Nine single US transducers allow for in situ tracking of a solid-liquid interface. Results of flow and solidification experiments in the model experiment are presented and compared with numerical simulation. The potential of the developed US system for measuring turbulent flows and for tracking the solidification front during a directional crystallization process is demonstrated. The results of the model experiments are in good agreement with numerical calculations and can be used for the validation of numerical models, especially the selection of the turbulence model.

The rhodium-catalyzed atom-economic asymmetric N-selective intermolecular addition of purine derivatives to terminal allenes is reported. Branched allylic purines were obtained in high yields, regioselectivity and outstanding enantioselectivity utilizing a Rh/Josiphos catalyst. Conversely, linear selective allylation of purines could be realized in good to excellent regio- and E/Z-selectivity with a Pd/dppf catalyst system. Furthermore, the new methodology was applied to a straightforward asymmetric synthesis of carbocyclic nucleoside abacavir., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: The purpose of this study was to evaluate risk factors for and the incidence of osteoradionecrosis (ORN) of the jaw in patients with head and neck cancer., Study Design: This study was a retrospective analysis of the risk for ORN and outcome for 149 of 540 patients with head and neck cancer of the oral cavity (65%), oropharynx (26%), or other head and neck sites (9%) treated with radiotherapy between 2004 and 2009. ORN was graded according to Late Effects of Normal Tissues/Somatic Objective Management Analytic Scale (LENT/SOMA) criteria., Results: Within a median follow-up of 41 months (95% confidence interval: 27.4-54.6), 38 patients (25.5%) had developed ORN, 37 patients (25%) had a local recurrence, and 53 patients (36%) had died. The median time to diagnosis of ORN was 14.5 months (range: 3-80), and 79% were diagnosed within 2 years of RT. Eleven of these patients had undergone previous mandibular surgery. Univariate significant risk factors for ORN were any comorbidity, poor oral hygiene, pre-radiotherapy osteotomy, close tumor-to-bone proximity, post-radiotherapy dentoalveolar surgery (DAS), DAS without sufficient wound closure, alcohol consumption, and denture pressure sores. In multivariate analysis, comorbidities, pre-radiotherapy mandibular surgery, poor oral hygiene, and insufficient DAS remained significant., Conclusions: Reducing the risk of ORN calls for maintaining optimal oral hygiene, ensuring good denture fit, receiving proper training in DAS, and helping patients to stop drinking and smoking., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Computer-assisted preoperative planning (CAPP) usually relies on computed tomography (CT) or cone beam CT (CBCT) and has already become an established technique in craniomaxillofacial surgery. The purpose of this study was to implement CT-based virtual fracture reduction as a key planning feature in patients with bimandibular fractures., Material and Methods: Nine routine preoperative CT scans of patients with bilateral mandibular fractures were acquired and post-processed using a mean model of the mandible and Amira software extended by custom-made scripting and programming modules., Results: A computerized technique was developed that allowed three-dimensional modeling, separation of the mandible from the cranium, distinction of the fracture fragments, and virtual fracture reduction. User interaction was required to label the mandibular fragments by landmarks. Virtual fracture reduction was achieved by optionally using the landmarks or the contralateral unaffected side as anatomical references., Conclusion: We successfully elaborated an effective technique for virtual fracture reduction of the mandible using a standard CT protocol. It offers expanded planning options for osteosynthesis construction or the manufacturing of personalized rapid prototyping guides in fracture reduction procedures. CAPP is justified in complex mandibular fractures and may be adopted in addition to routine preoperative CT assessment., (Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

The marine-derived Scopulariopsis brevicaulis strain LF580 produces scopularides A and B, which have anticancerous properties. We carried out genome sequencing using three next-generation DNA sequencing methods. De novo hybrid assembly yielded 621 scaffolds with a total size of 32.2 Mb and 16298 putative gene models. We identified a large non-ribosomal peptide synthetase gene (nrps1) and supporting pks2 gene in the same biosynthetic gene cluster. This cluster and the genes within the cluster are functionally active as confirmed by RNA-Seq. Characterization of carbohydrate-active enzymes and major facilitator superfamily (MFS)-type transporters lead to postulate S. brevicaulis originated from a soil fungus, which came into contact with the marine sponge Tethya aurantium. This marine sponge seems to provide shelter to this fungus and micro-environment suitable for its survival in the ocean. This study also builds the platform for further investigations of the role of life-style and secondary metabolites from S. brevicaulis.

The rhodium-catalyzed, highly N(2) - and N(1) -selective coupling of benzotriazoles with allenes is reported. The exceptionally high N(2) and N(1) selectivities were achieved by using a rhodium(I)/DPEphos and rhodium(I)/JoSPOphos catalyst, respectively. This method permits the atom-economic synthesis of valuable branched N(2) - and N(1) -allylated benzotriazole derivatives and allows for preliminary studies of their reactivity., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The fine tuning of neural networks during development and learning relies upon both functional and structural plastic processes. Changes in the number as well as in the size and shape of dendritic spines are associated to long-term activity-dependent synaptic plasticity. However, the molecular mechanisms translating functional into structural changes are still largely unknown. In this context, neurotrophins, like Brain-Derived Neurotrophic Factor (BDNF), are among promising candidates. Specifically BDNF-TrkB receptor signaling is crucial for activity-dependent strengthening of synapses in different brain regions. BDNF application has been shown to positively modulate dendritic and spine architecture in cortical and hippocampal neurons as well as structural plasticity in vitro. However, a global BDNF deprivation throughout the central nervous system (CNS) resulted in very mild structural alterations of dendritic spines, questioning the relevance of the endogenous BDNF signaling in modulating the development and the mature structure of neurons in vivo. Here we show that a loss-of-function approach, blocking BDNF results in a significant reduction in dendritic spine density, associated with an increase in spine length and a decrease in head width. These changes are associated with a decrease in F-actin levels within spine heads. On the other hand, a gain-of-function approach, applying exogenous BDNF, could not reproduce the increase in spine density or the changes in spine morphology previously described. Taken together, we show here that the effects exerted by BDNF on the dendritic architecture of hippocampal neurons are dependent on the neuron's maturation stage. Indeed, in mature hippocampal neurons in vitro as shown in vivo BDNF is specifically required for the activity-dependent maintenance of the mature spine phenotype.

New Rh- and Pd-catalyzed regiodivergent and stereoselective intermolecular coupling reactions of imidazole derivatives with mono-substituted allenes are herein reported. Using a Rh(I)/Josiphos system, perfect regioselectivities and high enantiomeric excess were obtained, while a Pd(II)/dppf system gave linear products with high regioselectivities and high E/Z selectivities. This method permits the atom economic synthesis of valuable branched and linear allylic imidazole derivatives., (Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: New technologies for analyzing biological samples, like next generation sequencing, are producing a growing amount of data together with quality scores. Moreover, software tools (e.g., for mapping sequence reads), calculating transcription factor binding probabilities, estimating epigenetic modification enriched regions or determining single nucleotide polymorphism increase this amount of position-specific DNA-related data even further. Hence, requesting data becomes challenging and expensive and is often implemented using specialised hardware. In addition, picking specific data as fast as possible becomes increasingly important in many fields of science. The general problem of handling big data sets was addressed by developing specialized databases like HBase, HyperTable or Cassandra. However, these database solutions require also specialized or distributed hardware leading to expensive investments. To the best of our knowledge, there is no database capable of (i) storing billions of position-specific DNA-related records, (ii) performing fast and resource saving requests, and (iii) running on a single standard computer hardware., Results: Here, we present DRUMS (Disk Repository with Update Management and Select option), satisfying demands (i)-(iii). It tackles the weaknesses of traditional databases while handling position-specific DNA-related data in an efficient manner. DRUMS is capable of storing up to billions of records. Moreover, it focuses on optimizing relating single lookups as range request, which are needed permanently for computations in bioinformatics. To validate the power of DRUMS, we compare it to the widely used MySQL database. The test setting considers two biological data sets. We use standard desktop hardware as test environment., Conclusions: DRUMS outperforms MySQL in writing and reading records by a factor of two up to a factor of 10000. Furthermore, it can work with significantly larger data sets. Our work focuses on mid-sized data sets up to several billion records without requiring cluster technology. Storing position-specific data is a general problem and the concept we present here is a generalized approach. Hence, it can be easily applied to other fields of bioinformatics.

The effect of the transition metal valence electron concentration on the energy of formation, effective charge of B icosahedra, elastic properties, surface energy and fracture toughness was calculated using density functional theory for icosahedral transition metal borides of AlXB14 (X=Sc, Ti, V, Cr, Y, Zr, Nb, Mo). Consistent with previous work on AlYB14 (Kölpin et al 2009 J. Phys.: Condens. Matter 21 355006) it is shown that phase stability is generally dependent on the effective charge of the icosahedral transition metal borides. Also, ionization potential and electronegativity are identified as parameters affecting the effective charge of B icosahedra suitable for use in predicting the phase stability. Al0.75Y0.75B14, Al0.75Sc0.75B14 and Al0.75Zr0.75B14 have been identified as promising phases for application as protective coatings as they exhibit high phase stability and stiffness combined with a comparatively high fracture toughness.

Bone metastases are a class of cancerous metastases that result from the invasion of a tumor into bone. The solid mass which forms inside the bone is often associated with a constant dull ache and severe spikes in pain, which greatly reduce the quality of life of the patient. Numerous (99m)Tc-labeled bisphosphonate functionalised complexes are well established tracers for bone metastases imaging. The objective of this research was to evaluate the pharmacokinetics and behaviour of three DOTA based bisphosphonate functionalised ligands (BPAMD, BPAPD and BPPED), using both (68)Ga μ-PET in vivo imaging and ex vivo biodistribution studies in healthy Wistar rats. The compounds were labelled with (68)Ga in high yields using an ammonium acetate buffer, and subsequently purified using a cation exchange resin. High bone uptake values were observed for all (68)Ga-labelled bisphosphonates at 60 minutes p.i. The highest uptake was observed for [(68)Ga]BPPED (2.6 ± 0.3% ID/g) which compares favourably with that of [(99m)Tc]MDP (2.7 ± 0.1 ID/g) and [(18)F]fluoride (2.4 ± 0.2% ID/g). The (68)Ga-labelled DOTA-bisphosphonates showed rapid clearance from the blood and renal system, as well as low binding to soft tissue, resulting in a high bone to blood ratio (9.9 at 60 minutes p.i. for [(68)Ga]BPPED, for example). Although further studies are required to assess their performance in tumor models, the results obtained suggest that these ligands could be useful both in imaging ((68)Ga) and therapeutic treatment ((177)Lu) of bone metastases., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To evaluate 3-dimensional inner ear visualization by volume rendering of high-resolution magnetic resonance data in patients with clinically suspected inner ear abnormality., Design: Prospective comparative study of different postprocessing techniques, based on blinded film readings., Setting: Tertiary referral hospital., Subjects: Fifty patients (17 females and 33 males) aged 1 to 77 years (average age, 42 years) with sensorineural hearing loss, vertigo, and/or tinnitus., Intervention: Postprocessing of magnetic resonance data to inner ear reconstructions by the use of volume rendering as well as maximum-intensity projection; caloric testing by electronystagmography., Main Outcome Measures: Film was read blindly by 4 radiologists using a 5-point parameter scale for image quality and diagnostic value. The assessibility of inner ear subsegments was evaluated. The specificity of volume-rendered reconstructions for detecting semicircular canal obliterations was assessed in a subgroup of 9 patients by caloric testing. The time required for data postprocessing as well as film reading was recorded by means of a stopwatch., Results: Volume-rendered inner ear reconstructions were superior in image quality (P<.001), diagnostic value (P<.001), subsegment inner ear assessment (P<.01 to P<.001), and film reading time (P<.001) compared with maximum-intensity projections. The data postprocessing time was comparable for both techniques. Caloric weakness was noted in all patients assessed by electronystagmography., Conclusion: Volume rendering is the postprocessing technique of choice for 3-dimensional inner ear visualization, performing better than maximum-intensity projections with respect to various parameters.

Unlabelled: Virtual postprocessing techniques combine the advantages of condensing the large amounts of data provided by high-resolution (HR) cross-sectional imaging modalities with those of three-dimensional (3D) imaging. The techniques and indications for virtual representations in imaging of the middle ear (ME), internal ear (IE), and cerebellopontine angle (CPA) are presented together with practical examples., Material and Methods: HR data sets acquired by computed tomography (CT) and magnetic resonance imaging (MRI) in patients with ME, IE, and CPA pathologies were transferred to a workstation via an internal network to generate endo- or extraluminal 3D views by means of the volume rendering technique (VRT). The source data were acquired using scanners and imaging protocols with the highest resolution available at present: a multislice spiral CT (MSCT) with a slice thickness of 0.5 mm and a reconstruction increment of 0.2 mm and a 3D CISS sequence with a slice thickness of 0.5 mm for MRI., Results: Virtual endoscopy was superior to cross-sectional images for assessing ME pathologies like dysplasia, postoperative changes, and destructive bone processes with extensive soft-tissue involvement; fibrous obliterations of the internal ear and labyrinthine dysplasia were depicted with a superior image quality on 3D renderings compared to conventional reconstruction techniques. Virtual endoscopy of the CPA and external acoustic meatus (EAM) was helpful in detecting and visualizing neurovascular conflicts and in assigning small intrameatal tumors to components of the acousticofacial bundle. A common feature of all applications was that the large numbers of source images could be reduced to a few 3D reconstructions for documentation and optimized communication of the findings between the radiologist and otologist., Conclusion: Virtual rendering makes an important contribution towards establishing, presenting, and documenting the findings when certain otologic pathologies have to be assessed. It can be used for routine imaging and allows for more efficient handling of the large amounts of imaging data generated by high-resolution cross-sectional imaging modalities.