Identification of a target antigen in human anti-tubular basement membrane nephritis

Identification of a target antigen in human anti-tubular basement membrane nephritis. Sera from two patients with primary anti-tubular–basement–membrane–mediated tubulointerstitial nephritis, one a renal allograft recipient and the other with spontaneous anti-tubular–basement–membrane disease, were analyzed for the specificity of their autoantibodies. Both sera had circulating antibodies that reacted by ELISA with extracts of tubular basement membrane from several species, but failed to react significantly with extracts of glomerular basement membrane. Reactive antigen was solubilized with 6 M guanidine-HCl, 6 M urea, with reduction and alkylation, and with sodium dodecylsulfate. Digestion of the basement membrane with collagenase released relatively small quantities of antigen from the membrane, and trypsin and pepsin destroyed its antigenicity. The antigenic activity was characterized with respect to its size distribution by gel filtration and by immuno-overlay analysis of protein blots. Collectively, the results indicate that the major reactivity of both sera is directed towards a Mr 58,000 component that is unique to the tubular basement membrane. Minor reactivities toward high molecular weight components common to both glomerular and tubular basement membranes were detected by immuno-overlay analysis. This study identifies an antigen that is involved in human anti-tubular–basement–membrane–mediated tubulointerstitial nephritis, and demonstrates an advantage of the use of denaturing extraction over proteolytic methods to prepare the antigen

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Antigen restriction and IgG subclasses among anti-GBM autoantibodies

Thirty-seven sera positive for anti-GBM antibodies (antibodies against the ‘Goodpasture antigen’ = NCI-domain of collagen IV) in routine analysis were studied for antigen restriction and IgG subclasses. Four different polypeptides, the four α-chains (α1, α2, α3 and α4) of human collagen IV NCI, were used as coating in ELISA assays. Autoantibodies were detected with monoclonal antibodies towards human IgG subclasses. All patients had antibodies to the α3 chain, and most patients reacted much more to the α3 peptide than to any of the other three peptides. This shows that the NCI domain of the α3 chain of collagen IV is the major target for anti-GBM antibodies. A minor group of patients, 6 of 37, showed no antigen restriction and had only moderate titres. It remains to be studied, however, whether they have antibodies to another epitope and a different clinical picture. All four subclasses of IgG antibodies were present, but IgGl antibodies dominated. A group, consisting of females mainly, had relatively high titres of IgG4 antibodies to the NCI domain of the α3 chain of collagen IV

Implementation of the Beam Loading Compensation Algorithm in the LLRF System of the European XFEL

In the European XFEL, a maximum number of 2700 electron bunches per RF pulse with beam currents up to 4.5mA can be accelerated. Such large beam currents can cause a significant drop of the accelerating gradients, which results in large energy changes across the macro-pulse. But, the electron bunch energies should not deviate from the nominal energy to guarantee stable and reproducible generation of photon pulses for the European XFEL users. To overcome this issue, the Low Level RF system (LLRF) compensates in real-time the beam perturbation using a Beam Loading Compensation algorithm (BLC) minimizing the transient gradient variations. The algorithm takes the charge information obtained from beam diagnostic systems e.g. Beam Position Monitors (BPM) and information from the timing system. The BLC is a part of the LLRF controller implemented in the FPGA. The article presents the implementation of the algorithm in the FPGA and shows the results achieved with the BLC in the European XFEL