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We introduce and study a new search-type problem with (n + 1)-robots on a disk. The searchers (robots) all start from the center of the disk, have unit speed, and can communicate wirelessly. The goal is for a distinguished robot (the queen) to reach and evacuate from an exit that is hidden on the perimeter of the disk in as little time as possible. The remaining n robots (servants) are there to facilitate the queen's objective and are not required to reach the hidden exit. We provide upper and lower bounds for the time required to evacuate the queen from a unit disk. Namely, we propose an algorithm specifying the trajectories of the robots which guarantees evacuation of the queen in time always better than 2 + 4 (2 − 1) π n for n ≥ 4 servants. We also demonstrate that for n ≥ 4 servants the queen cannot be evacuated in time less than 2 + π n + 2 n 2 . [ABSTRACT FROM AUTHOR]

Pathogenic variants in CHRNE encoding the epsilon subunit of acetyl choline receptor (AChR) result in impaired neuromuscular transmission and congenital myasthenic syndromes (CMS). Clinical manifestations include facial, ocular and limb fatigability and weakness, whereby severity of symptoms may vary in patients harboring the same pathogenic variant. Although the underlying pathophysiology is well-known, blood biomarkers enabling a patient-stratification are lacking. Previous studies revealed CHRNE protein in white blood cells (WBC) rendering these cells suitable for the study of cellular and minimal-invasive marker proteins. This retrospective two center-study includes 19 patients carrying biallelic pathogenic variants in CHRNE identified by molecular genetic testing. The patients were clinically characterized according to clinical severity (grade 1-4). Biomarker discovery was carried out on blood samples: proteomic profiling was performed on WBC (n =12) and on extracellular vesicles (EVs) purified from serum samples (n =7) in addition to amino acid profiling (n = 9) and miRNA screening (n = 18) on sera. In 19 patients (mean age 14.8 years) from 13 families seven known pathogenic variants in CHRNE were identified in addition to one variant previously not reported (c.1032+2_1032+3delTAinsGT). Whereas 15 patients were classified as mildly affected (group A: grade 1 and 2), 4 patients were classified as moderate or severely affected (group B: grade 3 and 4). Proteomics unveiled a significant increase of 7 and a decrease of 36 proteins in WBC in comparison to normal, age matched controls. GO-term based in silico studies of these dysregulated proteins indicated affection of secretory granules and the extracellular space. When comparing proteomic signatures of CHRNE-patients with a mild (A) versus moderate to severe phenotypes (B), 2 proteins (SCAMP2 and SNX2) were significantly increased in second group (B). These two proteins are involved in vesical transport. Prompted by this finding, proteomic profiling of EVs was initiated revealing a significant dysregulation of 20 proteins (7 are increased and 13 decreased). Three of these proteins (TARSH, ATRN & PLEC) are known to be important for synaptogenesis and synaptic function. Metabolic profiling of sera showed a decrease of 7 amino acids/ amino acid metabolites (aspartic and glutamic acids, phosphoserine, amino adipate, citrulline, ornithine & 1-methyhistidine) in terms of a metabolic fingerprint in CHRNE-related CMS patients. Moreover, miRNA screening unveiled increase of miR−365b−3p and miR−483−3p and decrease of miR-4433b-3p when comparing sera of CHRNE patients versus healthy controls. Moreover, a comparison of CHRNE patients versus other CMS-subtypes showed increase of miR−205−5p, miR−10b−5p, and miR−483−5 and decrease of miR−1290. Our combined data introduce a panel of minimal-invasive biomarkers on protein, metabolic and miRNA level with some of those play different roles along the neuromuscular axis. In the latter regard, impaired EV homeostasis impacting on synaptic function seems to be a molecular disease driver and two proteins in WBC correlate with disease severity. Our miRNA profiles introduce four miRNAs which may open new avenues in CMS patient stratification. [ABSTRACT FROM AUTHOR]

Abstract: We estimated the prevalence of Mycobacterium avium subsp. paratuberculosis (MAP) infected sheep and goats, older than 2 years, reared in the region effectively controlled by the Government of the Republic of Cyprus, in September 2005. The sera collected from 8011 animals (3429 sheep and 4582 goats) from 83 flocks, non-vaccinated against MAP, were examined for antibodies with a commercially available enzyme linked immunosorbent assay (Pourquier® paratuberculosis antibody screening ELISA). The true prevalence of MAP infection was calculated, in a Bayesian framework, separately in sheep and goats, with models that adjusted for the misclassification of animals because of the imperfect accuracy of the ELISA. The within-flock mean seroprevalence in sheep and goats was 9.9% (95% CI: 8.9; 10.9%) and 7.9% (7.2; 8.7%), respectively. There was at least one seropositive sheep in 52% (38; 66%) of flocks with sheep and one seropositive goat in 50% (39; 62%) of flocks with goats. Within the seropositive flocks the mean seroprevalence was 12.1% (10.9; 13.4%) and 10.3% (9.3; 11.4%) in sheep and goats, respectively. The calculated mean true prevalence of infected sheep and goats was 15.0 and 11.1%, respectively. There was at least one infected sheep in 60.8% (95% credible interval: 42.3; 78.8%) and at least an infected goat in 48.6% (30.4; 68.5%) of the flocks. In the infected flocks, the mean within flock true prevalence of infection in sheep and goats was estimated at 24.6% (16.3; 33.3%) and 23.1% (15.5; 33.6%), respectively. [Copyright &y& Elsevier]