Parathyroid tumors are rare endocrine neoplasms affecting 0.1–0.3% of the general population, including benign parathyroid adenomas (PAs; about 98% of cases), intermediate atypical parathyroid adenomas (aPAs; 1.2–1.3% of cases) and malignant metastatic parathyroid carcinomas (PCs; less than 1% of cases). These tumors are characterized by a variable spectrum of clinical phenotypes and an elevated cellular, histological and molecular heterogeneity that make it difficult to pre-operatively distinguish PAs, aPAs and PCs. Thorough knowledge of genetic, epigenetic, and molecular signatures, which characterize different parathyroid tumor subtypes and drive different tumorigeneses, is a key step to identify potential diagnostic biomarkers able to distinguish among different parathyroid neoplastic types, as well as provide novel therapeutic targets and strategies for these rare neoplasms, which are still a clinical and therapeutic challenge. Here, we review the current knowledge on gene mutations and epigenetic changes that have been associated with the development of different clinical types of parathyroid tumors, both in familial and sporadic forms of these endocrine neoplasms. 相似文献
Activation-induced deaminase (AID) is required for somatic hypermutation in immunoglobulin genes, but also induces off-target mutations. Follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL), the most frequent types of indolent B-cell tumors, are exposed to AID activity during lymphomagenesis. We designed a workflow integrating de novo mutational signatures extraction and fitting of COSMIC (Catalogue Of Somatic Mutations In Cancer) signatures, with tridimensional chromatin conformation data (Hi-C). We applied the workflow to exome sequencing data from lymphoma samples. In 33 FL and 30 CLL samples, 42% and 34% of the contextual mutations could be traced to a known AID motif. We demonstrate that both CLL and FL share mutational processes dominated by spontaneous deamination, failures in DNA repair, and AID activity. The processes had equiproportional distribution across active and nonactive chromatin compartments in CLL. In contrast, canonical AID activity and failures in DNA repair pathways in FL were significantly higher within the active chromatin compartment. Analysis of DNA repair genes revealed a higher prevalence of base excision repair gene mutations (p = 0.02) in FL than CLL. These data indicate that AID activity drives the genetic landscapes of FL and CLL. However, the final result of AID-induced mutagenesis differs between these lymphomas depending on chromatin compartmentalization and mutations in DNA repair pathways. 相似文献
Minghua Qu and Vanstone [2] have proposed a public-key cryptosystem (FGM) which is based on factorizations of a binary vector space (i.e., transversal logarithmic signatures of an elementary abelian 2-group). In this paper a generalized (basis-independent) decryption algorithm is given, which shows that there are many equivalent private keys, and a method of efficiently obtaining such an equivalent private key is given. The FGM cryptosystem is thus rendered insecure. Although the FGM cryptosystem is defined in terms of linear algebra, the attack given here is essentially group-theoretic in nature. Thus this attack throws doubt on any cryptosystem which relies on the security of transversal logarithmic signatures.This author was supported by S.E.R.C. Research Grant GR/H23719. 相似文献
In this paper we consider parallel processing of a graph represented by a database relation, and we achieved two objectives. First, we propose a methodology for analyzing the speedup of a parallel processing strategy with the purpose of selecting at runtime one of several candidate strategies, depending on the hardware architecture and the input graph. Second, we study the single-source reachability problem, namely the problem of computing the set of nodes reachable from a given node in a directed graph. We propose several parallel strategies for solving this problem, and we analyze their performance using our new methodology. The analysis is confirmed experimentally in a UNIX-Ethernet environment. We also extend the results to the transitive closure problem.A preliminary shortened version of this paper has appeared inPDIS. See Ref. 1.This author's work was supported in part by NSF Grant 90-03341.This author's work was supported in part by the Natural Sciences and Engineering Research Council of Canada.This author's work was supported in part by NSF Grant 90-03341. 相似文献
Over the past few years, much attention has been paid to deductive databases. They offer a logic-based interface, and allow formulation of complex recursive queries. However, they do not offer appropriate update facilities, and do not support existing applications. To overcome these problems an SQL-like interface is required besides a logic-based interface.
In the PRISMA project we have developed a tightly-coupled distributed database, on a multiprocessor machine, with two user interfaces: SQL and PRISMAlog. Query optimization is localized in one component: the relational query optimizer. Therefore, we have defined an eXtended Relational Algebra that allows recursive query formulation and can also be used for expressing executable schedules, and we have developed algebraic optimization strategies for recursive queries. In this paper we describe an optimization strategy that rewrites regular (in the context of formal grammars) mutually recursive queries into standard Relational Algebra and transitive closure operations. We also describe how to push selections into the resulting transitive closure operations.
The reason we focus on algebraic optimization is that, in our opinion, the new generation of advanced database systems will be built starting from existing state-of-the-art relational technology, instead of building a completely new class of systems. 相似文献