95 research outputs found

    LiDAR-Guided Cross-Attention Fusion for Hyperspectral Band Selection and Image Classification

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    The fusion of hyperspectral and light detection and range (LiDAR) data has been an active research topic. Existing fusion methods have ignored the high-dimensionality and redundancy challenges in hyperspectral images (HSIs), despite that band selection methods have been intensively studied for HSI processing. This article addresses this significant gap by introducing a cross-attention mechanism from the transformer architecture for the selection of HSI bands guided by LiDAR data. LiDAR provides high-resolution vertical structural information, which can be useful in distinguishing different types of land cover that may have similar spectral signatures but different structural profiles. In our approach, the LiDAR data are used as the “query” to search and identify the “key” from the HSI to choose the most pertinent bands for LiDAR. This method ensures that the selected HSI bands drastically reduce redundancy and computational requirements while working optimally with the LiDAR data. Extensive experiments have been undertaken on three paired HSI and LiDAR datasets: Houston 2013, Trento, and MUUFL. The results highlight the superiority of the cross-attention mechanism, underlining the enhanced classification accuracy of the identified HSI bands when fused with the LiDAR features. The results also show that the use of fewer bands combined with LiDAR surpasses the performance of state-of-the-art fusion models

    Interpolative multidimensional scaling techniques for the identification of clusters in very large sequence sets

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    <p>Abstract</p> <p>Background</p> <p>Modern pyrosequencing techniques make it possible to study complex bacterial populations, such as <it>16S rRNA</it>, directly from environmental or clinical samples without the need for laboratory purification. Alignment of sequences across the resultant large data sets (100,000+ sequences) is of particular interest for the purpose of identifying potential gene clusters and families, but such analysis represents a daunting computational task. The aim of this work is the development of an efficient pipeline for the clustering of large sequence read sets.</p> <p>Methods</p> <p>Pairwise alignment techniques are used here to calculate genetic distances between sequence pairs. These methods are pleasingly parallel and have been shown to more accurately reflect accurate genetic distances in highly variable regions of <it>rRNA </it>genes than do traditional multiple sequence alignment (MSA) approaches. By utilizing Needleman-Wunsch (NW) pairwise alignment in conjunction with novel implementations of interpolative multidimensional scaling (MDS), we have developed an effective method for visualizing massive biosequence data sets and quickly identifying potential gene clusters.</p> <p>Results</p> <p>This study demonstrates the use of interpolative MDS to obtain clustering results that are qualitatively similar to those obtained through full MDS, but with substantial cost savings. In particular, the wall clock time required to cluster a set of 100,000 sequences has been reduced from seven hours to less than one hour through the use of interpolative MDS.</p> <p>Conclusions</p> <p>Although work remains to be done in selecting the optimal training set size for interpolative MDS, substantial computational cost savings will allow us to cluster much larger sequence sets in the future.</p

    Nuclear-Targeted Deleted in Liver Cancer 1 (DLC1) Is Less Efficient in Exerting Its Tumor Suppressive Activity Both In Vitro and In Vivo

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    BACKGROUND: Deleted in liver cancer 1 (DLC1) serves as an important RhoGTPase activating protein (RhoGAP) protein that terminates active RhoA signaling in human cancers. Increasing evidence has demonstrated that the tumor suppressive activity of DLC1 depends not only on RhoGAP activity, but also relies on proper focal adhesion localization through its interaction with tensin family proteins. Recently, there are reports showing that DLC1 can also be found in the nucleus; however, the existence and the relative tumor suppressive activity of nuclear DLC1 have never been clearly addressed. METHODOLOGY AND PRINCIPAL FINDINGS: We herein provide new evidence that DLC1 protein, which predominantly associated with focal adhesions and localized in cytosol, dynamically shuttled between cytoplasm and nucleus. Treatment of cells with nuclear export blocker, Leptomycin B (LMB), retained DLC1 in the nucleus. To understand the nuclear entry of DLC1, we identified amino acids 600-700 of DLC1 as a novel region that is important for its nuclear localization. The tumor suppressive activity of nuclear DLC1 was directly assessed by employing a nuclear localization signal (NLS) fusion variant of DLC1 (NLS-DLC1) with preferential nuclear localization. In SMMC-7721 HCC cells, expression of NLS-DLC1 failed to suppress colony formation and actin stress fiber formation in vitro. The abrogated tumor suppressive activity of nuclear DLC1 was demonstrated for the first time in vivo by subcutaneously injecting p53(-/-) RasV12 hepatoblasts with stable NLS-DLC1 expression in nude mice. The injected hepatoblasts with NLS-DLC1 expression effectively formed tumors when compared with the non-nuclear targeted DLC1. CONCLUSIONS/SIGNIFICANCE: Our study identified a novel region responsible for the nuclear entry of DLC1 and demonstrated the functional difference of DLC1 in different cellular compartments both in vitro and in vivo

    Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

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    Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

    Combined linkage and linkage disequilibrium analysis of a motor speech phenotype within families ascertained for autism risk loci

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    Using behavioral and genetic information from the Autism Genetics Resource Exchange (AGRE) data set we developed phenotypes and investigated linkage and association for individuals with and without Autism Spectrum Disorders (ASD) who exhibit expressive language behaviors consistent with a motor speech disorder. Speech and language variables from Autism Diagnostic Interview-Revised (ADI-R) were used to develop a motor speech phenotype associated with non-verbal or unintelligible verbal behaviors (NVMSD:ALL) and a related phenotype restricted to individuals without significant comprehension difficulties (NVMSD:C). Using Affymetrix 5.0 data, the PPL framework was employed to assess the strength of evidence for or against trait-marker linkage and linkage disequilibrium (LD) across the genome. Ingenuity Pathway Analysis (IPA) was then utilized to identify potential genes for further investigation. We identified several linkage peaks based on two related language-speech phenotypes consistent with a potential motor speech disorder: chromosomes 1q24.2, 3q25.31, 4q22.3, 5p12, 5q33.1, 17p12, 17q11.2, and 17q22 for NVMSD:ALL and 4p15.2 and 21q22.2 for NVMSD:C. While no compelling evidence of association was obtained under those peaks, we identified several potential genes of interest using IPA. Conclusion: Several linkage peaks were identified based on two motor speech phenotypes. In the absence of evidence of association under these peaks, we suggest genes for further investigation based on their biological functions. Given that autism spectrum disorders are complex with a wide range of behaviors and a large number of underlying genes, these speech phenotypes may belong to a group of several that should be considered when developing narrow, well-defined, phenotypes in the attempt to reduce genetic heterogeneity

    Consensus guidelines for the use and interpretation of angiogenesis assays

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    The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

    Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

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    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

    A comparison of the clinical effectiveness and cost of specialised individually-delivered parent training for preschool attention-deficit/hyperactivity disorder and a generic, group-based programme: a multi-centre, randomised controlled trial of the New Forest Parenting Programme versus Incredible Years

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    Objective: To compare the efficacy and cost of specialised individually-delivered parent training (PT) for preschool children with attention-deficit/ hyperactivity disorder (ADHD) against generic group-based PT and treatment as usual (TAU). Design: Multi-centre, three-arm parallel group randomised controlled trial. Research Setting: National Health Service Trusts. Participants: Preschool children (33-54 months) fulfilling ADHD research diagnostic criteria. Interventions: New Forest Parenting Programme (NFPP) – 12 week individual, home-delivered ADHD PT programme; Incredible Years (IY) – 12 week group-based, PT programme initially designed for children with behaviour problems. Main outcome measures: Primary outcome - Parent ratings of child’s ADHD symptoms (Swanson, Nolan & Pelham Questionnaire - SNAP-IV). Secondary outcomes - teacher ratings (SNAP-IV) and direct observations of ADHD symptoms and parent/teacher ratings of conduct problems. NFPP, IY and TAU outcomes were measured at baseline (T1) and post-treatment (T2). NFPP and IY outcomes only were measured 6 months post treatment (T3). Researchers, but not therapists or parents, were blind to treatment allocation. Analysis employed mixed effect regression models (multiple imputation). Intervention and other costs were estimated using standardized approaches. Results: NFPP and IY did not differ on parent-rated SNAP-IV, ADHD combined symptoms (mean difference -0.009 95%CI [-0.191, 0.173], p=0.921) or any other measure. Small, non-significant, benefits of NFPP over TAU were seen for parent-rated SNAP-IV, ADHD combined symptoms (-0.189 95%CI [-0.380, 0.003], p=0.053). NFPP significantly reduced parent-rated conduct-problems compared to TAU across scales (p-values.05). The cost per family of providing NFPP in the trial was significantly lower than IY (£1,591 versus £2,103). Conclusions: Although, there were no differences between NFPP and IY with regards clinical effectiveness, individually-delivered NFPP cost less. However, this difference may be reduced when implemented in routine clinical practice. Clinical decisions should take into account parental preferences between delivery approaches. Funding: National Institute of Health Research. Trial Registration: Trial name: COPPI Trial; ISRCTN39288126
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