Dealing with sequence coordinates in different formats and reference genomes is challenging in genetic research. This complexity arises from the need to convert and harmonize datasets of different ...sources using alternating nomenclatures. Since manual processing is time-consuming and requires specialized knowledge, the Sequence Conversion and Analysis Toolbox (SeqCAT) was developed for daily work with genetic datasets. Our tool provides a range of functions designed to standardize and convert gene variant coordinates based on various sequence types. Its user-friendly web interface provides easy access to all functionalities, while the Application Programming Interface (API) enables automation within pipelines. SeqCAT provides access to human genomic, protein and transcript data, utilizing various data resources and packages and extending them with its own unique features. The platform covers a wide range of genetic research needs with its 14 different applications and 3 info points, including search for transcript and gene information, transition between reference genomes, variant mapping, and genetic event review. Notable examples are 'Convert Protein to DNA Position' for translation of amino acid changes into genomic single nucleotide variants, or 'Fusion Check' for frameshift determination in gene fusions. SeqCAT is an excellent resource for converting sequence coordinate data into the required formats and is available at: https://mtb.bioinf.med.uni-goettingen.de/SeqCAT/.
Epstein-Barr virus (EBV) associated diffuse large B-cell lymphoma (DLBCL) represents a rare aggressive B-cell lymphoma subtype characterized by an adverse clinical outcome. EBV infection of lymphoma ...cells has been associated with different lymphoma subtypes while the precise role of EBV in lymphomagenesis and specific molecular characteristics of these lymphomas remain elusive. To further unravel the biology of EBV associated DLBCL, we present a comprehensive molecular analysis of overall 60 primary EBV positive (EBV+) DLBCLs using targeted sequencing of cancer candidate genes (CCGs) and genome-wide determination of recurrent somatic copy number alterations (SCNAs) in 46 cases, respectively. Applying the LymphGen classifier 2.0, we found that less than 20% of primary EBV + DLBCLs correspond to one of the established molecular DLBCL subtypes underscoring the unique biology of this entity. We have identified recurrent mutations activating the oncogenic JAK-STAT and NOTCH pathways as well as frequent amplifications of 9p24.1 contributing to immune escape by PD-L1 overexpression. Our findings enable further functional preclinical and clinical studies exploring the therapeutic potential of targeting these aberrations in patients with EBV + DLBCL to improve outcome.
A comparative study of Me(=Ni/Cu/Ag)-based, W-alloyed, nanocrystalline, heavily faulted thin films was carried out to identify parameters stabilizing the nanocrystalline nature upon thermal ...treatment. The three systems, initially of comparably, heavily twinned (twin boundaries at spacings of 1–5 nm) microstructures showed similarities but also strikingly different behaviours upon annealing, as observed by application of in particular X-ray diffraction (line-broadening) analysis and (high resolution) transmission electron microscopy. During annealing in the range of 30–600 °C, (i) segregation at the planar faults (for Me = Ni) and at grain boundaries (for Me = Ni,Cu,Ag), as well as nanoscale phase separation (for Me = Cu,Ag) take place, (ii) distinct grain growth does not occur and (iii) the twin boundaries either are largely preserved ((Ni(W) and Ag(W)) or disappear totally (Cu(W))), which was ascribed to an altered faulting energy, due to change of the amount of W segregated at the twin boundaries, and to the evolution of nano-precipitates. The nanosized films exhibit very large internal (macro)stresses parallel to the surface, which change during annealing in the range of 1 GPa (tensile) to −3 GPa (compressive) and thus are sensitive to the microstructural changes in the films (decomposition and relaxation) that happen on a nanoscale. The results are discussed in terms of thermodynamic and/or kinetic constraints controlling these processes and thus the thermal stability of the systems concerned.
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WC–Co hardmetals are used for their combined high hardness and toughness. However, their poor corrosion resistance in aqueous solutions reduces the spectrum of their application. The goal of this ...work was a systematic investigation of the corrosion mechanisms of the WC–Co composite with electrochemical methods and analytical chemistry solution analysis characterization. WC–Co, Co and WC samples were investigated by electrochemical impedance spectroscopy, potentiodynamic polarization and inductively coupled plasma mass spectroscopy (ICP-MS). Concerning the corrosion susceptibility, the solution pH dominates the effect of specific ions. In neutral and acidic solution, the corrosion process of WC–Co consists mainly of Co dissolution. WC dissolution becomes more significant at alkaline pH. Degradation is mainly the result of selective uniform dissolution of the phases (Co or WC) not of localized corrosion because of the poor passivating ability of Co (except in alkaline pH). Synergistic effects due to galvanic coupling between the Co binder and WC are accelerating Co dissolution and hindering WC dissolution in the hardmetals compared to the pure compounds. This although the Co binder phase contains W and C, making it more corrosion resistant than pure Co. A further influence of the locally separated anodic and cathodic reactions is that the cathodic reduction on WC induces local pH increase which causes chemical dissolution of WC detected only by ICP-MS.
Abstract Background Stanford acute type A aortic dissection (ATAAD) is a potentially lethal condition. Epidemiology studies show a statistical incidence in Europe of approximately 2–16 cases/100,000 ...inhabitants/year. In Germany, the estimated incidence (here subsumed under “thoracic aortic dissection” with 4.63 cases/100,000 inhabitants/year) is mainly extracted from medical death certificates by the German Federal Statistical Office. The prehospital incidence of ATAAD deaths is largely unknown. Since patients often die in the pre-hospital setting, the incidence of ATAAD is therefore likely to be higher than current estimates. Material and methods For the period from 2010 to 2014, we retrospectively analyzed all in-hospital ATAAD data from two of the largest cardiac surgical centers that treat ATAAD in the Berlin-Brandenburg region. In addition, autopsy reports of all forensic medicine institutes and of one large pathological provider in the region were analyzed to identify additional non-hospitalized ATAAD patients. Based on these findings, the regional incidence of ATAAD was calculated. Results In addition to in-hospital ATAAD patients ( n = 405), we identified additional 145 lethal ATAAD cases among 14,201 autopsy reports. The total of 550 ATAAD cases led to an estimated incidence of 11.9 cases/100,000 inhabitants/year for the whole Berlin-Brandenburg region. Arterial hypertension, pre-existing aortic dilatation, and hereditary connective tissue disorder were found in, respectively, 62.7%, 10%, and 1.8% of patients. Conclusion ATAAD is more frequent than previously reported. Our results show that when patients who die outside of cardiac surgery centers are included, the incidence of ATAAD significantly exceeds the rate reported by the Federal Statistical Office.
The conceptual description of Follicular lymphoma (FL) in the 5th edition of the World Health Organization (WHO) classification of haematolymphoid tumors (WHO-HAEM5) has undergone significant ...revision. The vast majority of FL (85%) with a follicular growth pattern are composed of centrocytes and centroblasts, harbor the t(14;18)(q32;q21) translocation and are now termed classic FL (cFL). They are set apart from three related subtypes, FL with predominantly follicular growth pattern, FL with unusual cytological features (uFL) and follicular large B-cell lymphoma (FLBCL). In contrast to the revised 4th edition of the WHO classification of haematolymphoid tumors (WHO-HAEM4R), grading of cFL is no longer mandatory. FL with a predominantly diffuse growth pattern had been previously recognized in WHO-HAEM4R. It frequently occurs as a large tumor in the inguinal region and is associated with CD23 expression. An absence of the
fusion and frequent
mutations along with 1p36 deletion or
mutation is typical. The newly introduced subtype of uFL includes two subsets that significantly diverge from cFL: one with "blastoid" and one with "large centrocyte" variant cytological features. uFL more frequently displays variant immunophenotypic and genotypic features. FLBCL is largely identical to WHO-HAEM4R FL grade 3B and renaming was done for reasons of consistency throughout the classification. In-situ follicular B-cell neoplasm, pediatric-type FL, duodenal-type FL and primary cutaneous follicle center lymphoma are categorized as discrete entities. In addition, novel findings concerning underlying biological mechanisms in the pathogenesis of early and systemic follicular lymphoma will be presented.
Magnetron-sputtered Ni(W) films appear to possess a high density of nanotwins oriented parallel to the film surface which highly influences the properties of Ni(W) films. A sophisticated analysis ...method for describing the stacking sequence of close-packed atomic layers by statistical parameters has been developed which is based on the evaluation of intensity streaks in reciprocal space measured by (x-ray) synchrotron diffraction. In particular, the degree of hexagonality introduced by twinning into these ideally face-centered cubic-stacked films can be quantified. The validity of the proposed analysis has been confirmed by direct observation of the stacking sequences of close-packed layers using (high-resolution) transmission electron microscopy. It has been shown that the degree of hexagonality in the as-deposited state is practically proportional to the W content. Further, the thermal stability of the nanotwins increases with increasing W content which can be understood by the appearance of hexagonal close-packed-like domains exhibiting an intrinsic thermodynamic stability.
Canine infectious respiratory disease (CIRD) is an acute, highly contagious disease complex caused by a variety of infectious agents. At present, the role of viral and bacterial components as primary ...or secondary pathogens in CIRD is not fully understood. The aim of this study was to investigate the prevalence of canine parainfluenza virus (CPIV), canine adenovirus type 2 (CAV-2), canine influenza virus (CIV), canine respiratory coronavirus (CRCoV), canine herpes virus-1 (CHV-1), canine distemper virus (CDV) and Bordetella bronchiseptica in dogs with CIRD and to compare the data with findings in healthy dogs. Sixty-one dogs with CIRD and 90 clinically healthy dogs from Southern Germany were prospectively enrolled in this study. Nasal and pharyngeal swabs were collected from all dogs and were analysed for CPIV, CAV-2, CIV, CRCoV, CHV-1, CDV, and B. bronchiseptica by real-time PCR.
In dogs with acute respiratory signs, 37.7% tested positive for CPIV, 9.8% for CRCoV and 78.7% for B. bronchiseptica. Co-infections with more than one agent were detected in 47.9% of B. bronchiseptica-positive, 82.6% of CPIV-positive, and 100% of CRCoV-positive dogs. In clinically healthy dogs, 1.1% tested positive for CAV-2, 7.8% for CPIV and 45.6% for B. bronchiseptica. CPIV and B. bronchiseptica were detected significantly more often in dogs with CIRD than in clinically healthy dogs (P < 0.001 for each pathogen) and were the most common infectious agents in dogs with CIRD in Southern Germany. Mixed infections with several pathogens were common. In conclusion, clinically healthy dogs can carry respiratory pathogens and could act as sources of infection for susceptible dogs.
Current air traffic communication systems are mainly based on voice communication, with a newer digital communication technology called L-band digital aeronautical communication system (LDACS) being ...investigated in the single European sky air traffic management research project. An essential feature of this communication infrastructure is the encoding of data that guarantees reliable transport. While the encoding in the transmission path is straightforward, the decoding is computationally expensive due to the peculiarities of the convolutional codes used. As the target platform for the communication equipment is an embedded system, a proper system design is essential for the receiving path to ensure real-time processing. This article therefore focuses on the hardware/software codesign of the functional system parts needed for decoding in the LDACS radio receiver. We describe the fundamental design considerations, followed by the actual implementation in form of software and field-programmable gate array based hardware modules. Subsequently, the decoding solution was verified to prove a standard-compliant system. In an experimental validation, the actual system was fed with test data from a reference system. This allows conclusions to be drawn about system characteristics like data throughput, latency, and error correction. The resulting system demonstrates high-performance decoding that can exceed the desired requirements for quality and speed for use in the LDACS communication system.
Multi-drug resistant (MDR), gram-negative
Enterobacteriaceae
, such as
Escherichia coli
(
E. coli
) limit therapeutic options and increase morbidity, mortality, and treatment costs worldwide. They ...pose a serious burden on healthcare systems, especially in developing countries like Rwanda. Several studies have shown the effects caused by the global spread of extended-spectrum beta-lactamase (ESBL)-producing
E. coli
. However, limited data is available on transmission dynamics of these pathogens and the mobile elements they carry in the context of clinical and community locations in Sub-Saharan Africa. Here, we examined 120 ESBL-producing
E. coli
strains from patients hospitalized in the University Teaching Hospital of Butare (Rwanda), their attending caregivers as well as associated community members and livestock. Based on whole-genome analysis, the genetic diversification and phylogenetics were assessed. Moreover, the content of carried plasmids was characterized and investigated for putative transmission among strains, and for their potential role as drivers for the spread of antibiotic resistance. We show that among the 30 different sequence types (ST) detected were the pandemic clonal lineages ST131, ST648 and ST410, which combine high-level antimicrobial resistance with virulence. In addition to the frequently found resistance genes
bla
CTX–M–15
,
tet
(34), and
aph(6)-Id
, we identified
csg
genes, which are required for curli fiber synthesis and thus biofilm formation. Numerous strains harbored multiple virulence-associated genes (VAGs) including
pap
(P fimbriae adhesion cluster),
fim
(type I fimbriae) and
chu
(Chu heme uptake system). Furthermore, we found phylogenetic relationships among strains from patients and their caregivers or related community members and animals, which indicates transmission of pathogens. Also, we demonstrated the presence and potential transfer of identical/similar ESBL-plasmids in different strains from the Rwandan setting and when compared to an external plasmid. This study highlights the circulation of clinically relevant, pathogenic ESBL-producing
E. coli
among patients, caregivers and the community in Rwanda. Combining antimicrobial resistance with virulence in addition to the putative exchange of mobile genetic elements among bacterial pathogens poses a significant risk around the world.
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