The Basic Local Alignment Search Tool (BLAST) website at the National Center for Biotechnology (NCBI) is an important resource for searching and aligning sequences. A new BLAST report allows faster loading of alignments, adds navigation aids, allows easy downloading of subject sequences and reports and has improved usability. Here, we describe these improvements to the BLAST report, discuss design decisions, describe other improvements to the search page and database documentation and outline plans for future development. The NCBI BLAST URL is http://blast.ncbi.nlm.nih.gov.

Mammalian target of rapamycin (mTOR) regulates cell proliferation, autophagy, and apoptosis by participating in multiple signaling pathways in the body. Studies have shown that the mTOR signaling pathway is also associated with cancer, arthritis, insulin resistance, osteoporosis, and other diseases. The mTOR signaling pathway, which is often activated in tumors, not only regulates gene transcription and protein synthesis to regulate cell proliferation and immune cell differentiation but also plays an important role in tumor metabolism. Therefore, the mTOR signaling pathway is a hot target in anti-tumor therapy research. In recent years, a variety of newly discovered mTOR inhibitors have entered clinical studies, and a variety of drugs have been proven to have high activity in combination with mTOR inhibitors. The purpose of this review is to introduce the role of mTOR signaling pathway on apoptosis, autophagy, growth, and metabolism of tumor cells, and to introduce the research progress of mTOR inhibitors in the tumor field.

Empirical studies of information retrieval methods show that good retrieval performance is closely related to the use of various retrieval heuristics, such as TF-IDF weighting. One basic research question is thus what exactly are these "necessary" heuristics that seem to cause good retrieval performance. In this paper, we present a formal study of retrieval heuristics. We formally define a set of basic desirable constraints that any reasonable retrieval function should satisfy, and check these constraints on a variety of representative retrieval functions. We find that none of these retrieval functions satisfies all the constraints unconditionally. Empirical results show that when a constraint is not satisfied, it often indicates non-optimality of the method, and when a constraint is satisfied only for a certain range of parameter values, its performance tends to be poor when the parameter is out of the range. In general, we find that the empirical performance of a retrieval formula is tightly related to how well it satisfies these constraints. Thus the proposed constraints provide a good explanation of many empirical observations and make it possible to evaluate any existing or new retrieval formula analytically.

H19 RNA has been characterized as an oncogenic long non-coding RNA (lncRNA) in breast and colon cancer. However, the role and function of lncRNA H19 in glioma development remain unclear. In this study, we identified that H19/miR-675 signaling was critical for glioma progression. By analyzing glioma gene expression data sets, we found increased H19 in high grade gliomas. H19 depletion via siRNA inhibited invasion in glioma cells. Further, we found H19 positively correlated with its derivate miR-675 expression and reduction of H19 inhibited miR-675 expression. Bioinformatics and luciferase reporter assays showed that miR-675 modulated Cadherin 13 expression by directly targeting the binding site within the 3′ UTR. Finally, introduction of miR-675 abrogated H19 knockdown-induced cell invasion inhibition in glioma cells. To our knowledge, it is first time to demonstrate that H19 regulates glioma development by deriving miR-675 and provide important clues for understanding the key roles of lncRNA-miRNA functional network in glioma.

In most existing retrieval models, documents are scored primarily based on various kinds of term statistics such as within-document frequencies, inverse document frequencies, and document lengths. Intuitively, the proximity of matched query terms in a document can also be exploited to promote scores of documents in which the matched query terms are close to each other. Such a proximity heuristic, however, has been largely under-explored in the literature; it is unclear how we can model proximity and incorporate a proximity measure into an existing retrieval model. In this paper, we systematically explore the query term proximity heuristic. Specifically, we propose and study the effectiveness of five different proximity measures, each modeling proximity from a different perspective. We then design two heuristic constraints and use them to guide us in incorporating the proposed proximity measures into an existing retrieval model. Experiments on five standard TREC test collections show that one of the proposed proximity measures is indeed highly correlated with document relevance, and by incorporating it into the KL-divergence language model and the Okapi BM25 model, we can significantly improve retrieval performance.

Restriction-modification systems must be regulated to avoid autorestriction and death of the host cell. An open reading frame (ORF) in the PvuII restriction-modification system appears to code for a regulatory protein from a previously unrecognized family. First, interruptions of this ORF result in a nonrestricting phenotype. Second, this ORF can restore restriction competence to such interrupted mutants in trans. Third, the predicted amino acid sequence of this ORF resembles those of known DNA-binding proteins and includes a probable helix-turn-helix motif. A survey of unattributed ORFs in 15 other type II restriction-modification systems revealed three that closely resemble the PvuII ORF. All four members of this putative regulatory gene family have a common position relative to the endonuclease genes, suggesting a common regulatory mechanism.

Cerebral small vessel disease (CSVD) is composed of several diseases affecting the small arteries, arterioles, venules, and capillaries of the brain, and refers to several pathological processes and etiologies. Neuroimaging features of CSVD include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. The main clinical manifestations of CSVD include stroke, cognitive decline, dementia, psychiatric disorders, abnormal gait, and urinary incontinence. Currently, there are no specific preventive or therapeutic measures to improve this condition. In this review, we will discuss the pathophysiology, clinical aspects, neuroimaging, progress of research to treat and prevent CSVD and current treatment of this disease.

Language model information retrieval depends on accurate estimation of document models. In this paper, we propose a document expansion technique to deal with the problem of insufficient sampling of documents. We construct a probabilistic neighborhood for each document, and expand the document with its neighborhood information. The expanded document provides a more accurate estimation of the document model, thus improves retrieval accuracy. Moreover, since document expansion and pseudo feedback exploit different corpus structures, they can be combined to further improve performance. The experiment results on several different data sets demonstrate the effectiveness of the proposed document expansion method.