Existence of r-fold perfect (v,K,1)-Mendelsohn designs with K⊆{4,5,6,7}

AbstractLet v be a positive integer and let K be a set of positive integers. A (v,K,1)-Mendelsohn design, which we denote briefly by (v,K,1)-MD, is a pair (X,B) where X is a v-set (of points) and B is a collection of cyclically ordered subsets of X (called blocks) with sizes in the set K such that every ordered pair of points of X are consecutive in exactly one block of B. If for all t=1,2,…,r, every ordered pair of points of X are t-apart in exactly one block of B, then the (v,K,1)-MD is called an r-fold perfect design and denoted briefly by an r-fold perfect (v,K,1)-MD. If K={k} and r=k−1, then an r-fold perfect (v,{k},1)-MD is essentially the more familiar (v,k,1)-perfect Mendelsohn design, which is briefly denoted by (v,k,1)-PMD. In this paper, we investigate the existence of r-fold perfect (v,K,1)-Mendelsohn designs for a specified set K which is a subset of {4, 5, 6, 7} containing precisely two elements

A salvage pathway maintains highly functional respiratory complex I

Regulation of the turnover of complex I (CI), the largest mitochondrial respiratory chain complex, remains enigmatic despite huge advancement in understanding its structure and the assembly. Here, we report that the NADH-oxidizing N-module of CI is turned over at a higher rate and largely independently of the rest of the complex by mitochondrial matrix protease ClpXP, which selectively removes and degrades damaged subunits. The observed mechanism seems to be a safeguard against the accumulation of dysfunctional CI arising from the inactivation of the N-module subunits due to attrition caused by its constant activity under physiological conditions. This CI salvage pathway maintains highly functional CI through a favorable mechanism that demands much lower energetic cost than de novo synthesis and reassembly of the entire CI. Our results also identify ClpXP activity as an unforeseen target for therapeutic interventions in the large group of mitochondrial diseases characterized by the CI instability. Maintenance and quality control of the mitochondrial respiratory chain complexes responsible for bulk energy production are unclear. Here, the authors show that the mitochondrial protease ClpXP is required for the rapid turnover of the core N-module of respiratory complex I, which happens independently of other modules in the complex

Scaleable Code Clone Detection

Code clone detection helps connect developers across projects, if we do it on a large scale. The cornerstones that allow clone detection to work on a large scale are: (1) bad hashing (2) lightweight parsing using regular expressions and (3) MapReduce pipelines. Bad hashing means to determine whether or not two artifacts are similar by checking whether their hashes are identical. We show a bad hashing scheme that works well on source code. Lightweight parsing using regular expressions is our technique of obtaining entire parse trees from regular expressions, robustly and efficiently. We detail the algorithm and implementation of one such regular expression engine. MapReduce pipelines are a way of expressing a computation such that it can automatically and simply be parallelized. We detail the design and implementation of one such MapReduce pipeline that is efficient and debuggable. We show a clone detector that combines these cornerstones to detect code clones across all projects, across all versions of each project

Validation of the high-dose heparin confirmatory step for the diagnosis of heparin-induced thrombocytopenia

The diagnosis of heparin-induced thrombocytopenia (HIT) requires detection of antibodies to the heparin/platelet factor 4 (PF4) complexes via enzyme-linked immunosorbent assay. Addition of excess heparin to the sample decreases the optical density by 50% or more and confirms the presence of these antibodies. One hundred fifteen patients with anti-heparin/PF4 antibodies detected by enzyme-linked immunosorbent assay were classified as clinically HIT-positive or HIT-negative, followed by confirmation with excess heparin. A multivariate logistic regression model was fitted to estimate relationships between patient characteristics, laboratory findings, and clinical HIT status. This model was validated on an independent sample of 97 patients with anti-heparin/PF4 antibodies. No relationship between age, race, or sex and clinical HIT status was found. Maximal optical density and confirmatory positive status independently predicted HIT in multivariate analysis. Predictive accuracy on the training set (c-index 0.78, Brier score 0.17) was maintained when the algorithm was applied to the independent validation population (c-index 0.80, Brier score 0.20). This study quantifies the clinical utility of the confirmatory test to diagnose HIT. On the basis of data from the heparin/PF4 enzyme-linked immunosorbent assay and confirmatory assays, a predictive computer algorithm could distinguish patients likely to have HIT from those who do not