Automated data pre-processing via meta-learning

The final publication is available at link.springer.comA data mining algorithm may perform differently on datasets with different characteristics, e.g., it might perform better on a dataset with continuous attributes rather than with categorical attributes, or the other way around. As a matter of fact, a dataset usually needs to be pre-processed. Taking into account all the possible pre-processing operators, there exists a staggeringly large number of alternatives and nonexperienced users become overwhelmed. We show that this problem can be addressed by an automated approach, leveraging ideas from metalearning. Specifically, we consider a wide range of data pre-processing techniques and a set of data mining algorithms. For each data mining algorithm and selected dataset, we are able to predict the transformations that improve the result of the algorithm on the respective dataset. Our approach will help non-expert users to more effectively identify the transformations appropriate to their applications, and hence to achieve improved results.Peer ReviewedPostprint (published version

T Cell Receptor-Independent, CD31/IL-17A-Driven Inflammatory Axis Shapes Synovitis in Juvenile Idiopathic Arthritis

T cells are considered autoimmune effectors in juvenile idiopathic arthritis (JIA), but the antigenic cause of arthritis remains elusive. Since T cells comprise a significant proportion of joint-infiltrating cells, we examined whether the environment in the joint could be shaped through the inflammatory activation by T cells that is independent of conventional TCR signaling. We focused on the analysis of synovial fluid (SF) collected from children with oligoarticular and rheumatoid factor-negative polyarticular JIA. Cytokine profiling of SF showed dominance of five molecules including IL-17A. Cytometric analysis of the same SF samples showed enrichment of αβT cells that lacked both CD4 and CD8 co-receptors [herein called double negative (DN) T cells] and also lacked the CD28 costimulatory receptor. However, these synovial αβT cells expressed high levels of CD31, an adhesion molecule that is normally employed by granulocytes when they transit to sites of injury. In receptor crosslinking assays, ligation of CD31 alone on synovial CD28nullCD31+ DN αβT cells effectively and sufficiently induced phosphorylation of signaling substrates and increased intracytoplasmic stores of cytokines including IL-17A. CD31 ligation was also sufficient to induce RORγT expression and trans-activation of the IL-17A promoter. In addition to T cells, SF contained fibrocyte-like cells (FLC) expressing IL-17 receptor A (IL-17RA) and CD38, a known ligand for CD31. Stimulation of FLC with IL-17A led to CD38 upregulation, and to production of cytokines and tissue-destructive molecules. Addition of an oxidoreductase analog to the bioassays suppressed the CD31-driven IL-17A production by T cells. It also suppressed the downstream IL-17A-mediated production of effectors by FLC. The levels of suppression of FLC effector activities by the oxidoreductase analog were comparable to those seen with corticosteroid and/or biologic inhibitors to IL-6 and TNFα. Collectively, our data suggest that activation of a CD31-driven, αβTCR-independent, IL-17A-mediated T cell-FLC inflammatory circuit drives and/or perpetuates synovitis. With the notable finding that the oxidoreductase mimic suppresses the effector activities of synovial CD31+CD28null αβT cells and IL-17RA+CD38+ FLC, this small molecule could be used to probe further the intricacies of this inflammatory circuit. Such bioactivities of this small molecule also provide rationale for new translational avenue(s) to potentially modulate JIA synovitis

The quest for companions to post-common envelope binaries: I. Searching a sample of stars from the CSS and SDSS

As part of an ongoing collaboration between student groups at high schools and professional astronomers, we have searched for the presence of circum-binary planets in a bona-fide unbiased sample of twelve post-common envelope binaries (PCEBs) from the Catalina Sky Survey (CSS) and the Sloan Digital Sky Survey (SDSS). Although the present ephemerides are significantly more accurate than previous ones, we find no clear evidence for orbital period variations between 2005 and 2011 or during the 2011 observing season. The sparse long-term coverage still permits O-C variations with a period of years and an amplitude of tens of seconds, as found in other systems. Our observations provide the basis for future inferences about the frequency with which planet-sized or brown-dwarf companions have either formed in these evolved systems or survived the common envelope (CE) phase.Comment: accepted by A&

Comparing Presenting Clinical Features in 48 Children With Microscopic Polyangiitis to 183 Children Who Have Granulomatosis With Polyangiitis (Wegener's) : an ARChiVe Cohort Study

OBJECTIVE: To uniquely classify children with microscopic polyangiitis (MPA), to describe their demographic characteristics, presenting clinical features, and initial treatments in comparison to patients with granulomatosis with polyangiitis (Wegener's) (GPA). METHODS: The European Medicines Agency (EMA) classification algorithm was applied by computation to categorical data from patients recruited to the ARChiVe (A Registry for Childhood Vasculitis: e-entry) cohort, with the data censored to November 2015. The EMA algorithm was used to uniquely distinguish children with MPA from children with GPA, whose diagnoses had been classified according to both adult- and pediatric-specific criteria. Descriptive statistics were used for comparisons. RESULTS: In total, 231 of 440 patients (64% female) fulfilled the classification criteria for either MPA (n\u2009=\u200948) or GPA (n\u2009=\u2009183). The median time to diagnosis was 1.6 months in the MPA group and 2.1 months in the GPA group (ranging to 39 and 73 months, respectively). Patients with MPA were significantly younger than those with GPA (median age 11 years versus 14 years). Constitutional features were equally common between the groups. In patients with MPA compared to those with GPA, pulmonary manifestations were less frequent (44% versus 74%) and less severe (primarily, hemorrhage, requirement for supplemental oxygen, and pulmonary failure). Renal pathologic features were frequently found in both groups (75% of patients with MPA versus 83% of patients with GPA) but tended toward greater severity in those with MPA (primarily, nephrotic-range proteinuria, requirement for dialysis, and end-stage renal disease). Airway/eye involvement was absent among patients with MPA, because these GPA-defining features preclude a diagnosis of MPA within the EMA algorithm. Similar proportions of patients with MPA and those with GPA received combination therapy with corticosteroids plus cyclophosphamide (69% and 78%, respectively) or both drugs in combination with plasmapheresis (19% and 22%, respectively). Other treatments administered, ranging in decreasing frequency from 13% to 3%, were rituximab, methotrexate, azathioprine, and mycophenolate mofetil. CONCLUSION: Younger age at disease onset and, perhaps, both gastrointestinal manifestations and more severe kidney disease seem to characterize the clinical profile in children with MPA compared to those with GPA. Delay in diagnosis suggests that recognition of these systemic vasculitides is suboptimal. Compared with adults, initial treatment regimens in children were comparable, but the complete reversal of female-to-male disease prevalence ratios is a provocative finding

Therapeutic use of etanercept in polyarticular course juvenile idiopathic arthritis over a two year period

Methods: 22 patients with polyarticular course JIA (19 females, three males; mean age 13.9 years; mean disease duration 6.3 years; 15 with polyarticular onset, seven with systemic onset, one with residual systemic activity; eight rheumatoid factor positive; eight with erosive disease) were treated with etanercept for up to 24 months. Etanercept was given subcutaneously at 0.4 mg/kg twice a week. Treatment response was ascertained in an open prospective study. Results: All patients showed impressive clinical improvement, with a decrease in swollen joint count by an average of 10.1 joints (mean of 49% decrease), a decrease in tender joint count by 9.3 joints (mean of 94%), and decrease in total joint count by 11.2 joints (mean of 48%). Duration of morning stiffness decreased to less than 10 minutes. Furthermore, haemoglobin concentration increased on average by 14 g/l (mean of 15.3%) and packed cell volume increased by 0.035 (mean increase of 12%), and erythrocyte sedimentation rate decreased on average by 42.8 mm/1st h (mean decrease of 64%). No major side effects were noted. Conclusion: Etanercept continues to be clinically effective and well tolerated in patients with polyarticular course JIA over a two year period

pH-dependence of inhibition by H₂DIDS of mouse erythroid band 3-mediated Cl^- transport in Xenopus oocytes. The effect of oligonucleotide-directed replacement of Lys-558 by an Asn residue

The rapid reversible inhibition of band 3-mediated inorganic anion transport by 4,4'-diisothiocyanodihydrostilbene-2,2'-disfulfonate (H2DIDS) turns slowly into irreversible inhibition. This is due to covalent bond formation of the two isothiocyanate groups of the inhibitor with two lysine residues on band 3, called Lys a and Lys b. In the red cell membrane, the pK value of Lys a is about 2.5 pK units lower than the pK value of Lys b. Hence the susceptibility of Lys a to irreversible modification by H2DIDS far exceeds the susceptibility to Lys b. In the present paper, we have expressed in Xenopus oocytes cRNA's derived from cDNA clones encoding wild-type mouse band 3 and mouse band 3 in which Lys a (Lys-558) had been replaced by an Asn residue by oligonucleotide-directed mutagenesis. In accord with previous findings, in the oocytes both wild-type and mutated band 3 mediate Cl- exchange. After determining the uninhibited exchange rate the oocytes were exposed for a fixed length of time to H2DIDS at a concentration (20 microM) which saturates all H2DIDS binding sites with reversibly bound H2DIDS (KI = 0.3 microM and 1.1 microM, respectively, for wild-type and mutant). Exposure was terminated by washing with a medium in which H2DIDS was replaced by bovine serum albumin to remove free and reversibly bound H2DIDS from the extracellular phase. Subsequent measurements of Cl- efflux yielded a measure for the irreversible inhibition that persisted. Since the transition from reversible to irreversible H2DIDS binding was found to follow first-order kinetics it was possible to calculate rate constants. From the pH dependence of the rate constants, pK values were calculated. These calculations could be made since in the wild-type, in which Lys a and Lys b are present, the exposure to H2DIDS could be confined to a pH range in which little if any covalent binding to Lys b takes place. The data could be represented by a single pK value of 8.3. In the mutant, Lys a is missing. Hence, covalent reaction can only take place with Lys b. Measurements over the appropriate pH range could be described by a single pK of 10.8. These values are 0.8-0.9 pK units higher than those previously obtained in experiments with band 3 in the red cell membran

The MiningMart Approach to Knowledge Discovery in Databases

Although preprocessing is one of the key issues in data analysis, it is still common practice to address this task by manually entering SQL statements and using a variety of stand-alone tools. The results are not properly documented and hardly re-usable. The MiningMart system presented in this chapter focusses on setting up and re-using best-practice cases of preprocessing data stored in very large databases. A meta-data model named M4 is used to declaratively define and document both, all steps of such a preprocessing chain and all the data involved. For data and applied operators there is an abstract level, understandable by human users, and an executable level, used by the meta-data compiler to run cases for given data sets. An integrated environment allows for a rapid development of preprocessing chains. Case adaptation to different environments is supported by just specifying all involved database entities in the target DBMS. This allows to re-use best-practice cases published on the Internet. 1 Acquiring Knowledge from Existing Databases The use of very large databases has enhanced in the last years from supporting transactions to additionally reporting business trends. The interest in analyzing the data has increased. One important topic is customer relationship management with the particular tasks of customer segmentation, customer profitability, customer retention, and customer acquisition (e.g. by direct mailing). Other tasks are the prediction of sales in order to minimize stocks, the prediction of electricity consumption or telecommunication services at particular day times in order to minimize the use of external services or optimize network routing, respectively. The health sector demands several analysis tasks for resource management, quality control, ..