Generation of tumor immunity by bone marrow-derived dendritic cells correlates with dendritic cell maturation stage

The mutational pattern of IgVH and IgVL genes from synovial tissue B cell hybridomas (n = 8) of patients (n = 4) with rheumatoid arthritis (RA) was analysed, which had been produced by the electrofusion technique without prior in vitro stimulation. The molecular data were correlated with immunohistopathological data and parameters of local disease activity. The IgVH genes of the B cell hybridomas belonged to the VH3 family (DP42; DP47, n = 2; DP53), the VH1 family (DP75), the VH4 family (DP71) and the VH5 family (DP73); 7/7 IgVH genes showed somatic mutations, the R/S ratio (CDR) was > 3 in 4/7 IgVH genes and the mean R/S ratio of all IgVH genes was 9.3 (CDR) and 1.0 (FR), suggesting an antigen-dependent selection. The IgVL/lambda genes belonged to the Vlambda1 family (DPL2, DPL5, DPL8nf), the Vlambda2 family (DPL11, n = 2) and to the Vlambda6 family (IGLV6S1); 6/6 IgVL genes showed somatic mutations, the R/S ratio (CDR) was > 3 in 3/6 IgVL genes and the mean R/S ratio of all IgVL was 3.0 (CDR) and 2.3 (FR), suggesting an antigen-dependent selection. The synovial tissue exhibited germinal centres in the follicles (3/4), with the unique distribution of Ki-M4+ follicular dendritic cells and Ki-67+ proliferating cells and a dominance of IgA+ plasma cells (3/3). All patients were positive for RF in serum and exhibited severe local symptoms (swelling 4/4; warmth 4/4; effusion 2/4), whereas the hybridomas were negative for RF. Since B cell hybridomas showed hypermutation and affinity selection for IgVH and IgVL/lambda genes and the patients exhibited severe local symptoms with germinal centres in synovial tissue, this study indicates that an antigen-driven process is behind the B cell expansion in the synovial tissue of clinically affected joints. These mutated B hybridomas were negative for RF, thus suggesting that antigens different from RF are also involved in the local B cell expansion and in the chronic synovitis of RA.     

Median‐unbiased Estimation and Exact Inference Methods for First‐order Autoregressive Models with Conditional Heteroscedasticity of Unknown Form

Abstract. Consider the first‐order autoregressive model y_t = φy_t?1 + ?_t, t = 1,…, T, with arbitrary initial non‐zero value y₀. Assuming that the error terms ?_t are independently distributed according to median‐zero distributions [ Zieliński (1999) Journal of Time Series Analysis, Vol. 20, p. 477] shows that the estimator conjectured by Hurwicz (1950) Statistical Inference in Dynamic Economic Models. New York, NY: Wiley – the median of the consecutive ratios y_t/y_t?1– is an exactly median‐unbiased estimator of the autoregressive parameter φ. This paper shows that the Hurwicz estimator remains median‐unbiased under more general distributional assumptions, without assuming statistical independence. In particular, no restrictions are placed on the degree of heterogeneity and dependence of the conditional variance process. A computationally efficient method is also proposed to build exact confidence intervals for the autoregressive parameter which are valid in finite samples for any value of φ on the real line.     

Crystal structure of the nucleosome core particle at 2.8 A resolution

The X-ray crystal structure of the nucleosome core particle of chromatin shows in atomic detail how the histone protein octamer is assembled and how 146 base pairs of DNA are organized into a superhelix around it. Both histone/histone and histone/DNA interactions depend on the histone fold domains and additional, well ordered structure elements extending from this motif. Histone amino-terminal tails pass over and between the gyres of the DNA superhelix to contact neighbouring particles. The lack of uniformity between multiple histone/DNA-binding sites causes the DNA to deviate from ideal superhelix geometry.     

AVOCADO: Visualization of Workflow–Derived Data Provenance for Reproducible Biomedical Research

A major challenge in data‐driven biomedical research lies in the collection and representation of data provenance information to ensure that findings are reproducibile. In order to communicate and reproduce multi‐step analysis workflows executed on datasets that contain data for dozens or hundreds of samples, it is crucial to be able to visualize the provenance graph at different levels of aggregation. Most existing approaches are based on node‐link diagrams, which do not scale to the complexity of typical data provenance graphs. In our proposed approach, we reduce the complexity of the graph using hierarchical and motif‐based aggregation. Based on user action and graph attributes, a modular degree‐of‐interest (DoI) function is applied to expand parts of the graph that are relevant to the user. This interest‐driven adaptive approach to provenance visualization allows users to review and communicate complex multi‐step analyses, which can be based on hundreds of files that are processed by numerous workflows. We have integrated our approach into an analysis platform that captures extensive data provenance information, and demonstrate its effectiveness by means of a biomedical usage scenario.     

Mechanical property characterization of LPCVD silicon nitride thin films at cryogenic temperatures

T-shape, LPCVD silicon nitride cantilevers are fabricated to determine Young's modulus and fracture strength of silicon nitride thin films at room and cryogenic temperatures. A helium-cooled measurement setup is developed and installed inside a focused-ion-beam (FIB) system. A lead-zirconate-titanate (PZT) translator powered by a function generator and a dc voltage is utilized as an actuator, and a silicon diode is used as a temperature sensor in this setup. Resonant frequencies of identical cantilevers with different "milling masses" are measured to obtain thickness and Young's modulus of the silicon nitride thin films, while a bending test is performed to obtain fracture strength. From the experiment, the average Young's modulus of low-pressure chemical-vapor deposition (LPCVD) silicon nitride thin films varies from 260.5 GPa at room temperature (298 K) to 266.6 GPa at 30 K, and the average fracture strength ranges from 6.9 GPa at room temperature to 7.9 GPa at 30 K. The measurement setup and technique presented here can be used to characterize the mechanical properties of different MEMS materials at cryogenic temperatures.     

Transplantation rate of the blood group B waiting list is increased by using A2 and A2B kidneys

BACKGROUND: We have increased the transplantation rate for blood group B cadaveric waiting list candidates by transplanting them with A2 and A2B kidneys. METHODS: Since 1991, five of the seven renal transplant programs in our organ procurement organization service area have preferentially transplanted blood group A2 and A2B cadaveric kidneys to B blood group waiting list candidates with histories of low anti-A isoagglutinin titers. RESULTS: Between 1991 and 1997, these five centers performed transplantations on 71 patients from the B cadaveric waiting list. Of those 71 patients, 29% (21 of 71) underwent transplantation with either A2 (n=18) or A2B (n=3) cadaveric kidneys. In 1997 alone, 48% (11 of 23) of the B patient transplant recipients received A2 or A2B kidneys. CONCLUSIONS: Transplantation of A2 and A2B kidneys into B waiting list patients has successfully increased access of B patients to kidneys. Such an allocation algorithm implemented nationally may similarly increase the transplantation rate of B waiting list candidates.     

From Alan Turing to modern AI: practical solutions and an implicit epistemic stance

It has been just over 100 years since the birth of Alan Turing and more than 65 years since he published in Mind his seminal paper, Computing Machinery and Intelligence (Turing in Computing machinery and intelligence. Oxford University Press, Oxford, 1950). In the Mind paper, Turing asked a number of questions, including whether computers could ever be said to have the power of “thinking” (“I propose to consider the question, Can computers think?” ...Alan Turing, Computing Machinery and Intelligence, Mind, 1950). Turing also set up a number of criteria—including his imitation game—under which a human could judge whether a computer could be said to be “intelligent”. Turing’s paper, as well as his important mathematical and computational insights of the 1930s and 1940s led to his popular acclaim as the “Father of Artificial Intelligence”. In the years since his paper was published, however, no computational system has fully satisfied Turing’s challenge. In this paper we focus on a different question, ignored in, but inspired by Turing’s work: How might the Artificial Intelligence practitioner implement “intelligence” on a computational device? Over the past 60 years, although the AI community has not produced a general-purpose computational intelligence, it has constructed a large number of important artifacts, as well as taken several philosophical stances able to shed light on the nature and implementation of intelligence. This paper contends that the construction of any human artifact includes an implicit epistemic stance. In AI this stance is found in commitments to particular knowledge representations and search strategies that lead to a product’s successes as well as its limitations. Finally, we suggest that computational and human intelligence are two different natural kinds, in the philosophical sense, and elaborate on this point in the conclusion.     

Depoteffect of benzathine-penicillin (author's transl)

15 test persons received an injection of 2,400,000 units of benzathine penicillin. Serum levels were subsequently assayed, as well as the excretion of the antibiotic in the urine. The samples were stored in liquid-nitrogen between collection and examination. Each of the speciemens was tested 5 to 10 times and the results were ascertained by empirical evaluation of every single analysis. This assay showed the existence of mean levels above 0.036 I.U./ml in the serum and above 19.75 I.U./ml in the urine for the duration of 26 days. The evaluation of serum levels after the administration of antibiotics is difficult due to several sources of error. Reliable results can, therefore, be obtained only by examination at special institutes which possess experienced technical personnel. The establishment of reference laboratories for this purpose is suggested. The results of the study confirm the efficacy of one-shot treatment of the syphilis by administration of 2,400,000 to units of benzathine penicillin.     

The influence of task variation on manifestation of fatigue is ambiguous – a literature review

Task variation has been proposed to reduce shoulder fatigue resulting from repetitive hand–arm tasks. This review analyses the effect of task variation, both ‘temporal (i.e. change of work–rest ratio)’ and ‘activity (i.e. job rotation)’ variation, on physiological responses, endurance time (ET) and subjective feelings. Pubmed was searched and complemented with references from selected articles, resulting in 17 articles. Temporal variation had some positive effects on the objective parameters, as blood pressure decreased and ET increased, and on the subjective feelings, as perceived discomfort decreased. The observed findings of activity variation showed both positive and negative effects of increased activity variation, while hardly any effects were found on electromyography manifestations of fatigue. In conclusion, the evidence for positive effects of increasing the level of variation is scarce. The number of studies on variation is limited, while in most studies the findings were not controlled for the amount or intensity of work.