A General Framework for the Derivation of Regular Expressions

The aim of this paper is to design a theoretical framework that allows us to perform the computation of regular expression derivatives through a space of generic structures. Thanks to this formalism, the main properties of regular expression derivation, such as the finiteness of the set of derivatives, need only be stated and proved one time, at the top level. Moreover, it is shown how to construct an alternating automaton associated with the derivation of a regular expression in this general framework. Finally, Brzozowski's derivation and Antimirov's derivation turn out to be a particular case of this general scheme and it is shown how to construct a DFA, a NFA and an AFA for both of these derivations.Comment: 22 page

Bottom Up Quotients and Residuals for Tree Languages

In this paper, we extend the notion of tree language quotients to bottom-up quotients. Instead of computing the residual of a tree language from top to bottom and producing a list of tree languages, we show how to compute a set of k-ary trees, where k is an arbitrary integer. We define the quotient formula for different combinations of tree languages: union, symbol products, compositions, iterated symbol products and iterated composition. These computations lead to the definition of the bottom-up quotient tree automaton, that turns out to be the minimal deterministic tree automaton associated with a regular tree language in the case of the 0-ary trees

Functional Assemblages of Collembola Determine Soil Microbial Communities and Associated Functions

Soil processes such as decomposition are mainly performed by soil biota. Although soils worldwide are extremely biodiverse, the relationship between decomposers (fauna and microorganisms), and ecosystem function is poorly understood. Collembola are abundant and ubiquitous microarthropods that are found in terrestrial ecosystems. They can affect the amount of biomass and the activity of microbial communities, either directly through selectively feeding on fungi and bacteria, or indirectly by dissemination of microbial propagules, and the alteration of nutrient availability. However, despite the functional role they play in belowground food webs, the interactions between natural assemblages of soil microbes and Collembola receive little attention. This study, conducted in microcosm conditions, examines the effects of two distinct natural assemblages of functional groups of Collembola (ep- and euedaphic) upon microbial communities using PLFA markers and their associated soil functions (e.g., enzymatic activities and C mineralization rate) over a 2-month period. Our principal objective was to determine whether different functional groups of Collembola had varying effects on microbial soil community abundance, structure and activity, resulting in potentially important effects on ecosystem processes. Our findings show that the interactions of the functional groups of Collembola with microbial communities vary significantly whether they are alone or combined. A distinct response in the composition of the microbial communities was found at the end of the 2-month period. The communities were significantly different from each other in terms of PLFA marker composition. We found that the epedaphic species were related to and promoted Gram+ bacteria whereas euedaphic species were related to Gram- bacterial markers. This had further repercussions on soil function, such as nutrient recycling. Combining both functional groups did not lead to a complementary effect on soil microbial properties, with a drastically different outcome between the first and the second month of the experiment. Additional research dealing with the interactions between decomposers using natural assemblages will help to predict the functional outcomes of soil biota structure and composition

A genomic and transcriptomic approach for a differential diagnosis between primary and secondary ovarian carcinomas in patients with a previous history of breast cancer

<p>Abstract</p> <p>Background</p> <p>The distinction between primary and secondary ovarian tumors may be challenging for pathologists. The purpose of the present work was to develop genomic and transcriptomic tools to further refine the pathological diagnosis of ovarian tumors after a previous history of breast cancer.</p> <p>Methods</p> <p>Sixteen paired breast-ovary tumors from patients with a former diagnosis of breast cancer were collected. The genomic profiles of paired tumors were analyzed using the Affymetrix GeneChip^®Mapping 50 K Xba Array or Genome-Wide Human SNP Array 6.0 (for one pair), and the data were normalized with ITALICS (ITerative and Alternative normaLIzation and Copy number calling for affymetrix Snp arrays) algorithm or Partek Genomic Suite, respectively. The transcriptome of paired samples was analyzed using Affymetrix GeneChip^®Human Genome U133 Plus 2.0 Arrays, and the data were normalized with gc-Robust Multi-array Average (gcRMA) algorithm. A hierarchical clustering of these samples was performed, combined with a dataset of well-identified primary and secondary ovarian tumors.</p> <p>Results</p> <p>In 12 of the 16 paired tumors analyzed, the comparison of genomic profiles confirmed the pathological diagnosis of primary ovarian tumor (n = 5) or metastasis of breast cancer (n = 7). Among four cases with uncertain pathological diagnosis, genomic profiles were clearly distinct between the ovarian and breast tumors in two pairs, thus indicating primary ovarian carcinomas, and showed common patterns in the two others, indicating metastases from breast cancer. In all pairs, the result of the transcriptomic analysis was concordant with that of the genomic analysis.</p> <p>Conclusions</p> <p>In patients with ovarian carcinoma and a previous history of breast cancer, SNP array analysis can be used to distinguish primary and secondary ovarian tumors. Transcriptomic analysis may be used when primary breast tissue specimen is not available.</p

SLC35A2â CDG: Functional characterization, expanded molecular, clinical, and biochemical phenotypes of 30 unreported Individuals

Pathogenic de novo variants in the Xâ linked gene SLC35A2 encoding the major Golgiâ localized UDPâ galactose transporter required for proper protein and lipid glycosylation cause a rare type of congenital disorder of glycosylation known as SLC35A2â congenital disorders of glycosylation (CDG; formerly CDGâ IIm). To date, 29 unique de novo variants from 32 unrelated individuals have been described in the literature. The majority of affected individuals are primarily characterized by varying degrees of neurological impairments with or without skeletal abnormalities. Surprisingly, most affected individuals do not show abnormalities in serum transferrin Nâ glycosylation, a common biomarker for most types of CDG. Here we present data characterizing 30 individuals and add 26 new variants, the single largest study involving SLC35A2â CDG. The great majority of these individuals had normal transferrin glycosylation. In addition, expanding the molecular and clinical spectrum of this rare disorder, we developed a robust and reliable biochemical assay to assess SLC35A2â dependent UDPâ galactose transport activity in primary fibroblasts. Finally, we show that transport activity is directly correlated to the ratio of wildâ type to mutant alleles in fibroblasts from affected individuals.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150498/1/humu23731_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150498/2/humu23731-sup-0001-Supp_Mat__2019.2.10_.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150498/3/humu23731.pd

Clinical spectrum of MTOR-related hypomelanosis of Ito with neurodevelopmental abnormalities.

PURPOSE: Hypomelanosis of Ito (HI) is a skin marker of somatic mosaicism. Mosaic MTOR pathogenic variants have been reported in HI with brain overgrowth. We sought to delineate further the pigmentary skin phenotype and clinical spectrum of neurodevelopmental manifestations of MTOR-related HI. METHODS: From two cohorts totaling 71 patients with pigmentary mosaicism, we identified 14 patients with Blaschko-linear and one with flag-like pigmentation abnormalities, psychomotor impairment or seizures, and a postzygotic MTOR variant in skin. Patient records, including brain magnetic resonance image (MRI) were reviewed. Immunostaining (n = 3) for melanocyte markers and ultrastructural studies (n = 2) were performed on skin biopsies. RESULTS: MTOR variants were present in skin, but absent from blood in half of cases. In a patient (p.[Glu2419Lys] variant), phosphorylation of p70S6K was constitutively increased. In hypopigmented skin of two patients, we found a decrease in stage 4 melanosomes in melanocytes and keratinocytes. Most patients (80%) had macrocephaly or (hemi)megalencephaly on MRI. CONCLUSION: MTOR-related HI is a recognizable neurocutaneous phenotype of patterned dyspigmentation, epilepsy, intellectual deficiency, and brain overgrowth, and a distinct subtype of hypomelanosis related to somatic mosaicism. Hypopigmentation may be due to a defect in melanogenesis, through mTORC1 activation, similar to hypochromic patches in tuberous sclerosis complex

Construction progress of WEAVE: the next generation wide-field spectroscopy facility for the William Herschel Telescope

We present an update on the overall construction progress of the WEAVE next-generation spectroscopy facility for the William Herschel Telescope (WHT), now that all the major fabrication contracts are in place. We also present a summary of the current planning behind the 5-year initial phase of survey operations, and some detailed end-to-end science simulations that have been effected to evaluate the final on-sky performance after data processing. WEAVE will provide optical ground-based follow up of ground-based (LOFAR) and space-based (Gaia) surveys. WEAVE is a multi-object and multi-IFU facility utilizing a new 2-degree prime focus field of view at the WHT, with a buffered pick-and-place positioner system hosting 1000 multi-object (MOS) fibres, 20 integral field units, or a single large IFU for each observation. The fibres are fed to a single (dual-beam) spectrograph, with total of 16k spectral pixels, located within the WHT GHRIL enclosure on the telescope Nasmyth platform, supporting observations at R 5000 over the full 370-1000nm wavelength range in a single exposure, or a high resolution mode with limited coverage in each arm at R 20000. The project has experienced some delays in procurement and now has first light expected for the middle of 2019

Twist exome capture allows for lower average sequence coverage in clinical exome sequencing

Background Exome and genome sequencing are the predominant techniques in the diagnosis and research of genetic disorders. Sufficient, uniform and reproducible/consistent sequence coverage is a main determinant for the sensitivity to detect single-nucleotide (SNVs) and copy number variants (CNVs). Here we compared the ability to obtain comprehensive exome coverage for recent exome capture kits and genome sequencing techniques. Results We compared three different widely used enrichment kits (Agilent SureSelect Human All Exon V5, Agilent SureSelect Human All Exon V7 and Twist Bioscience) as well as short-read and long-read WGS. We show that the Twist exome capture significantly improves complete coverage and coverage uniformity across coding regions compared to other exome capture kits. Twist performance is comparable to that of both short- and long-read whole genome sequencing. Additionally, we show that even at a reduced average coverage of 70× there is only minimal loss in sensitivity for SNV and CNV detection. Conclusion We conclude that exome sequencing with Twist represents a significant improvement and could be performed at lower sequence coverage compared to other exome capture techniques

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock