Deterministically Counting Satisfying Assignments for Constant-Depth Circuits with Parity Gates, with Implications for Lower Bounds

We give a deterministic algorithm for counting the number of satisfying assignments of any AC^0[oplus] circuit C of size s and depth d over n variables in time 2^(n-f(n,s,d)), where f(n,s,d) = n/O(log(s))^(d-1), whenever s = 2^o(n^(1/d)). As a consequence, we get that for each d, there is a language in E^{NP} that does not have AC^0[oplus] circuits of size 2^o(n^(1/(d+1))). This is the first lower bound in E^{NP} against AC^0[oplus] circuits that beats the lower bound of 2^Omega(n^(1/2(d-1))) due to Razborov and Smolensky for large d. Both our algorithm and our lower bounds extend to AC^0[p] circuits for any prime p

Measuring Audit Quality

This study first provides detailed descriptive analyses on 45 specific audit deficiency allegations based on GAAS as detailed in 141 AAERs and 153 securities class action lawsuits over the violation years 1978-2016, and then uses these allegations to validate existing popular proxies of audit quality. Of all the audit quality proxies, we find that restatements consistently predict all the top six most cited audit violations. The ratio of audit fees to total fees and the presence of city specialist auditor predict five of the most cited violations. Overall, our results suggest that the predictive power of audit quality proxies depends on (i) the settings that researchers are interested in; and (ii) the specific audit violations hypothesized to matter in the investigated setting. For example, for future studies related to auditor independence, we recommend the use of restatements and audit fees to total fees ratio as proxies of audit quality

Read Mapping on Genome Variation Graphs

Genome variation graphs are natural candidates to represent a pangenome collection. In such graphs, common subsequences are encoded as vertices and the genomic variations are captured by introducing additional labeled vertices and directed edges. Unlike a linear reference, a reference graph allows a rich representation of the genomic diversities and avoids reference bias. We address the fundamental problem of mapping reads to genome variation graphs. We give a novel mapping algorithm V-MAP for efficient identification of small subgraph of the genome graph for optimal gapped alignment of the read. V-MAP creates space efficient index using locality sensitive minimizer signatures computed using a novel graph winnowing and graph embedding onto metric space for fast and accurate mapping. Experiments involving graph constructed from the 1000 Genomes data and using both real and simulated reads show that V-MAP is fast, memory efficient and can map short reads, as well as PacBio/Nanopore long reads with high accuracy. V-MAP performance was significantly better than the state-of-the-art, especially for long reads

Non-audit services and financial reporting quality: evidence from 1978 to 1980

We provide evidence for the long-standing concern on auditor conflicts of interest from providing non-audit services (NAS) to audit clients by using rarely explored NAS fee data from 1978 to 1980. Using this earlier setting, we find cross-sectional evidence of improved earnings quality when auditors provide NAS, especially those related to information services. This is consistent with better audit quality from knowledge spillovers due to the joint offering of audit and consulting services. Events related to the repeal of these NAS disclosures in 1982 are associated with a small positive stock price reaction suggesting no adverse economic consequences of withdrawing NAS disclosures. Further, following the repeal of disclosure requirements we find no change in the earnings quality of client firms. In sum, data drawn from an earlier time period suggest that auditors' reputational incentives, possible synergies, and knowledge transfers imply that NAS offered by audit firms can be associated with improved audit and reporting quality in client firms

TPX: Biomedical literature search made easy

TPX is a web-based PubMed search enhancement tool that enables faster article searching using an alysis and exploration features . These features include identification of relevant biomedical concepts from search results with linkouts to source databases, concept based article categorization, concept assisted search and filtering, query refinement. A distinguishing feature here is the ability to add user-defined concept names and/or concept types for named entity recognition. The tool allows contextual exploration of knowledge sources by providing concept association maps derived from the MEDLINE repository. It also has a full-text search mode that can be configured on request to access local text repositories, incorporating entity co-occurrence search at sentence/paragraph levels. Local text files can also be analyzed on-the-fly

An Integrated Pipeline of Open Source Software Adapted for Multi-CPU Architectures: Use in the Large-Scale Identification of Single Nucleotide Polymorphisms

The large amounts of EST sequence data available from a single species of an organism as well as for several species within a genus provide an easy source of identification of intra- and interspecies single nucleotide polymorphisms (SNPs). In the case of model organisms, the data available are numerous, given the degree of redundancy in the deposited EST data. There are several available bioinformatics tools that can be used to mine this data; however, using them requires a certain level of expertise: the tools have to be used sequentially with accompanying format conversion and steps like clustering and assembly of sequences become time-intensive jobs even for moderately sized datasets. We report here a pipeline of open source software extended to run on multiple CPU architectures that can be used to mine large EST datasets for SNPs and identify restriction sites for assaying the SNPs so that cost-effective CAPS assays can be developed for SNP genotyping in genetics and breeding applications. At the International Crops Research Institute for the Semi-Arid Tropics (ICRISAT), the pipeline has been implemented to run on a Paracel high-performance system consisting of four dual AMD Opteron processors running Linux with MPICH. The pipeline can be accessed through user-friendly web interfaces at http://hpc.icrisat.cgiar.org/PBSWeb and is available on request for academic use. We have validated the developed pipeline by mining chickpea ESTs for interspecies SNPs, development of CAPS assays for SNP genotyping, and confirmation of restriction digestion pattern at the sequence level

Nijmegen Breakage Syndrome Detected by Newborn Screening for T Cell Receptor Excision Circles (TRECs)

PURPOSE: Severe combined immunodeficiency (SCID) encompasses a group of disorders characterized by reduced or absent T-cell number and function and identified by newborn screening utilizing T-cell receptor excision circles (TRECs). This screening has also identified infants with T lymphopenia who lack mutations in typical SCID genes. We report an infant with low TRECs and non-SCID T lymphopenia, who proved upon whole exome sequencing to have Nijmegen breakage syndrome (NBS). METHODS: Exome sequencing of DNA from the infant and his parents was performed. Genomic analysis revealed deleterious variants in the NBN gene. Confirmatory testing included Sanger sequencing and immunoblotting and radiosensitivity testing of patient lymphocytes. RESULTS: Two novel nonsense mutations in NBN were identified in genomic DNA from the family. Immunoblotting showed absence of nibrin protein. A colony survival assay demonstrated radiosensitivity comparable to patients with ataxia telangiectasia. CONCLUSIONS: Although TREC screening was developed to identify newborns with SCID, it has also identified T lymphopenic disorders that may not otherwise be diagnosed until later in life. Timely identification of an infant with T lymphopenia allowed for prompt pursuit of underlying etiology, making possible a diagnosis of NBS, genetic counseling, and early intervention to minimize complications

Combined Immunodeficiency Due to MALT1 Mutations, Treated by Hematopoietic Cell Transplantation

PURPOSE: A male infant developed generalized rash, intestinal inflammation and severe infections including persistent cytomegalovirus. Family history was negative, T cell receptor excision circles were normal, and engraftment of maternal cells was absent. No defects were found in multiple genes associated with severe combined immunodeficiency. A 9/10 HLA matched unrelated hematopoietic cell transplant (HCT) led to mixed chimerism with clinical resolution. We sought an underlying cause for this patient’s immune deficiency and dysregulation. METHODS: Clinical and laboratory features were reviewed. Whole exome sequencing and analysis of genomic DNA from the patient, parents and 2 unaffected siblings was performed, revealing 2 MALT1 variants. With a host-specific HLA-C antibody, we assessed MALT1 expression and function in the patient’s post-HCT autologous and donor lymphocytes. Wild type MALT1 cDNA was added to transformed autologous patient B cells to assess functional correction. RESULTS: The patient had compound heterozygous DNA variants affecting exon 10 of MALT1 (isoform a, NM_006785.3), a maternally inherited splice acceptor c.1019-2A > G, and a de novo deletion of c.1059C leading to a frameshift and premature termination. Autologous lymphocytes failed to express MALT1 and lacked NF-κB signaling dependent upon the CARMA1, BCL-10 and MALT1 signalosome. Transduction with wild type MALT1 cDNA corrected the observed defects. CONCLUSIONS: Our nonconsanguineous patient with early onset profound combined immunodeficiency and immune dysregulation due to compound heterozygous MALT1 mutations extends the clinical and immunologic phenotype reported in 2 prior families. Clinical cure was achieved with mixed chimerism after nonmyeloablative conditioning and HCT. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10875-014-0125-1) contains supplementary material, which is available to authorized users