2,392 research outputs found

    Fixing Rule 702: The PCAST Report and Steps to Ensure the Reliability of Forensic Feature-Comparison Methods in the Criminal Courts

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    In response to PCAST’s recommendation, the Standing Advisory Committee on Evidence Rules convened a meeting on forensic expert testimony, Daubert, and Rule 702 on October 27, 2017, at Boston College Law School to inform itself about the issues.22 The meeting included presentations by twenty-six speakers (including myself) and discussion among the attendees. The purpose of this Article is to summarize aspects of the PCAST report relevant to its recommendation to the Standing Advisory Committee on Evidence Rules and to propose a path forward with respect to Rule 702

    Vietnamese and the NP/DP parameter

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    This paper investigates the place of Vietnamese in the NP/DP typology as formulated by Bošković (2005, 2008, 2009, 2010). We show that Bošković’s NP/DP parameter breaks down into at least three separate parameters. In many languages, these three parameters line up in a consistent manner and conspire to give the impression that there is a single macro-parameter at work. However, due to its mixed status, Vietnamese reveals that there are in fact three smaller parameters (nominal, clausal, and quantificational) at work, and that these are independently fixed (as [–DP], [+TP], and [–movement], respectively). Moreover, Vietnamese can in general be classified as a topic-prominent language, a classification which requires more research but which plays an important role in determining the behavior of Vietnamese with regard to many of the syntactic properties discussed

    The nanosyntax of the Northwest Germanic reinforced demonstrative

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    ​The reinforced demonstrative pronoun (RDem) 'this' is a morphological innovation common to the North and West Germanic languages. Though RDem is a defining characteristic of the Northwest branch of Germanic, there is no detailed treatment of its internal structure in the literature. In this dissertation I perform a fine-grained morphological decomposition of RDem in Old Norse, Runic Norse, Old English, Old Frisian, Old Saxon, and Old High German. First I identify the individual morphological ingredients making up RDem in each language. Next the different orders in which these ingredients can combine are identified. Making use first of the U20 framework (Cinque 2005) and then the theory of nanosyntax, I show that all of the various morphological structures observed (both intra- and interparadigmatically) can be derived from a single universal functional sequence of grammatical features, altered in constrained ways by movement operations, which are influenced by the way these features are lexically packaged. In sum, the nanosyntactic approach allows us to account for the crosslinguistic variation and similarities in the Northwest Germanic RDem in a precise and restrictive way.

    Clonal evolution in patients with chronic lymphocytic leukaemia developing resistance to BTK inhibition

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    Resistance to the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib has been attributed solely to mutations in BTK and related pathway molecules. Using whole-exome and deep-targeted sequencing, we dissect evolution of ibrutinib resistance in serial samples from five chronic lymphocytic leukaemia patients. In two patients, we detect BTK-C481S mutation or multiple PLCG2 mutations. The other three patients exhibit an expansion of clones harbouring del(8p) with additional driver mutations (EP300, MLL2 and EIF2A), with one patient developing trans-differentiation into CD19-negative histiocytic sarcoma. Using droplet-microfluidic technology and growth kinetic analyses, we demonstrate the presence of ibrutinib-resistant subclones and estimate subclone size before treatment initiation. Haploinsufficiency of TRAIL-R, a consequence of del(8p), results in TRAIL insensitivity, which may contribute to ibrutinib resistance. These findings demonstrate that the ibrutinib therapy favours selection and expansion of rare subclones already present before ibrutinib treatment, and provide insight into the heterogeneity of genetic changes associated with ibrutinib resistance.University of Texas M.D. Anderson Cancer Center (Support Grant CA016672)National Science Foundation (U.S.) (DMR-1310266)Harvard University. Materials Research Science and Engineering Center (DMR-1420570)National Natural Science Foundation (China) (81372496

    Complementary genomic approaches highlight the PI3K/mTOR pathway as a common vulnerability in osteosarcoma

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    Osteosarcoma is the most common primary bone tumor, yet there have been no substantial advances in treatment or survival in three decades. We examined 59 tumor/normal pairs by whole-exome, whole-genome, and RNA-sequencing. Only the TP53 gene was mutated at significant frequency across all samples. The mean nonsilent somatic mutation rate was 1.2 mutations per megabase, and there was a median of 230 somatic rearrangements per tumor. Complex chains of rearrangements and localized hypermutation were detected in almost all cases. Given the intertumor heterogeneity, the extent of genomic instability, and the difficulty in acquiring a large sample size in a rare tumor, we used several methods to identify genomic events contributing to osteosarcoma survival. Pathway analysis, a heuristic analytic algorithm, a comparative oncology approach, and an shRNA screen converged on the phosphatidylinositol 3-kinase/mammalian target of rapamycin (PI3K/mTOR) pathway as a central vulnerability for therapeutic exploitation in osteosarcoma. Osteosarcoma cell lines are responsive to pharmacologic and genetic inhibition of the PI3K/mTOR pathway both in vitro and in vivo

    The Mutational Landscape of Head and Neck Squamous Cell Carcinoma

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    2012 August 09 Author ManuscriptHead and neck squamous cell carcinoma (HNSCC) is a common, morbid, and frequently lethal malignancy. To uncover its mutational spectrum, we analyzed whole-exome sequencing data from 74 tumor-normal pairs. The majority exhibited a mutational profile consistent with tobacco exposure; human papillomavirus was detectable by sequencing DNA from infected tumors. In addition to identifying previously known HNSCC genes (TP53, CDKN2A, PTEN, PIK3CA, and HRAS), our analysis revealed many genes not previously implicated in this malignancy. At least 30% of cases harbored mutations in genes that regulate squamous differentiation (for example, NOTCH1, IRF6, and TP63), implicating its dysregulation as a major driver of HNSCC carcinogenesis. More generally, the results indicate the ability of large-scale sequencing to reveal fundamental tumorigenic mechanisms

    Brief for Amicus Curiae Eric S. Lander in Support of Neither Party

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    Amicus ("friend of the court") brief written by Professor Eric S. Lander in support of petitioners in AMP v. Myriad Genetics (Supreme Court Case Docket No. 12-398)

    Nanosyntax: the basics

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    This chapter offers a thorough introduction to nanosyntactic theory, a development of the cartographic program in generative grammar. It discusses the foundations on which nanosyntax was conceived, such as the “one feature–one head” maxim and the universal functional sequence (fseq). It also provides a brief comparison of theoretical and terminological issues in nanosyntax vs. the competing framework of Distributed Morphology. It is seen that the syntactic component according to nanosyntax unifies aspects of (what are traditionally called) syntax, morphology, and formal semantics. This is reflected in the tools used to probe linguistic structure in the nanosyntactic approach, such as morphological decomposition, syncretism, and containment. The chapter also discusses the technical details of the syntax–lexicon relation, detailing the matching or spellout process and Starke’s view of spellout-driven movement. This chapter is meant to provide readers with the necessary background to understand and navigate the rest of the chapters in this volume

    The distribution of clusters in random graphs

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    AbstractGiven a random graph, we investigate the occurrence of subgraphs especially rich in edges. Specifically, given a ϵ [0,1], a set of k points in a graph G is defined to be an a-cluster of cardinality k if the induced subgraph contains at least ak2 edges, so that in the extreme case a = 1, an a-cluster is the same as a clique. We let G = G(n, p) be a random graph on n vertices with edges chosen independently with probability p. Let W denote the number of a-clusters of cardinality k in G, where k and n tend to infinity so that the expected number λ of a-clusters of cardinality k does not grow or decay too rapidly. We prove that W is asymptotically distributed as Zλ, whose distribution is Poisson with mean λ, which is the same result that Bollobás and Erdös have proved for cliques. In contrast to the situation for cliques (a = 1) however, for all a < 1 the second moment of W blows up, i.e., the expected number of neighbors of a given cluster tends to infinity. Nevertheless, the probability that there exists at least one pair of neighboring clusters tends to zero, and a Poisson approximation for W is valid
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