Inconsistency of the MLE for the joint distribution of interval censored survival times and continuous marks

This paper considers the nonparametric maximum likelihood estimator (MLE) for the joint distribution function of an interval censored survival time and a continuous mark variable. We provide a new explicit formula for the MLE in this problem. We use this formula and the mark specific cumulative hazard function of Huang and Louis (1998) to obtain the almost sure limit of the MLE. This result leads to necessary and sufficient conditions for consistency of the MLE which imply that the MLE is inconsistent in general. We show that the inconsistency can be repaired by discretizing the marks. Our theoretical results are supported by simulations.Comment: 27 pages, 4 figure

Wheat straw hemicellulose films as affected by citric acid.

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Automatic de-identification of textual documents in the electronic health record: a review of recent research

<p>Abstract</p> <p>Background</p> <p>In the United States, the Health Insurance Portability and Accountability Act (HIPAA) protects the confidentiality of patient data and requires the informed consent of the patient and approval of the Internal Review Board to use data for research purposes, but these requirements can be waived if data is de-identified. For clinical data to be considered de-identified, the HIPAA "Safe Harbor" technique requires 18 data elements (called PHI: Protected Health Information) to be removed. The de-identification of narrative text documents is often realized manually, and requires significant resources. Well aware of these issues, several authors have investigated automated de-identification of narrative text documents from the electronic health record, and a review of recent research in this domain is presented here.</p> <p>Methods</p> <p>This review focuses on recently published research (after 1995), and includes relevant publications from bibliographic queries in PubMed, conference proceedings, the ACM Digital Library, and interesting publications referenced in already included papers.</p> <p>Results</p> <p>The literature search returned more than 200 publications. The majority focused only on structured data de-identification instead of narrative text, on image de-identification, or described manual de-identification, and were therefore excluded. Finally, 18 publications describing automated text de-identification were selected for detailed analysis of the architecture and methods used, the types of PHI detected and removed, the external resources used, and the types of clinical documents targeted. All text de-identification systems aimed to identify and remove person names, and many included other types of PHI. Most systems used only one or two specific clinical document types, and were mostly based on two different groups of methodologies: pattern matching and machine learning. Many systems combined both approaches for different types of PHI, but the majority relied only on pattern matching, rules, and dictionaries.</p> <p>Conclusions</p> <p>In general, methods based on dictionaries performed better with PHI that is rarely mentioned in clinical text, but are more difficult to generalize. Methods based on machine learning tend to perform better, especially with PHI that is not mentioned in the dictionaries used. Finally, the issues of anonymization, sufficient performance, and "over-scrubbing" are discussed in this publication.</p

Configuration of the Northern Antarctic Peninsula Ice Sheet at LGM based on a new synthesis of seabed imagery

We present a new seafloor map for the northern Antarctic Peninsula (AP), including swath multibeam data sets from five national programs. Our map allows for the examination and interpretation of Last Glacial Maximum (LGM) paleo-ice-flow paths developed on the seafloor from the preservation of mega-scale glacial lineations, drumlinized features, and selective linear erosion. We combine this with terrestrial observations of flow direction to place constraints on ice divides and ice domes on the AP continental shelf during the LGM time interval. The results show a flow bifurcation as ice exits the Larsen B embayment. Flow emanating off the Seal Nunataks (including Robertson Island) is directed toward the southeast, then eastward as the flow transits toward the Robertson Trough. A second, stronger “streaming flow” is directed toward the southeast, then southward as ice overflowed the tip of the Jason Peninsula to reach the southern perimeter of the embayment. Our reconstruction also refines the extent of at least five other distinct paleo-icestream systems that, in turn, serve to delineate seven broad regions where contemporaneous ice domes must have been centered on the continental shelf at LGM. Our reconstruction is more detailed than other recent compilations because we followed specific ice-flow indicators and have kept tributary flow paths parallel

Ell3 Enhances Differentiation of Mouse Embryonic Stem Cells by Regulating Epithelial-Mesenchymal Transition and Apoptosis

Ell3 is a testis-specific RNA polymerase II elongation factor whose cellular function is not clear. The present study shows that Ell3 is activated during the differentiation of mouse embryonic stem cells (mESCs). Furthermore, Ell3 plays a critical role in stimulating lineage differentiation of mESCs by promoting epithelial-mesenchymal transition (EMT) and suppressing apoptosis. Mouse ESCs engineered to stably express Ell3 were rapidly differentiated compared with control cells either under spontaneous differentiation or neural lineage-specific differentiation conditions. Gene expression profile and quantitative RT-PCR analysis showed that the expression of EMT markers, such as Zeb1 and Zeb2, two major genes that regulate EMT, was upregulated in Ell3-overexpressing mESCs. Remarkably, knockdown of Zeb1 attenuated the enhanced differentiation capacity of Ell3-overexpressing mESCs, which indicates that Ell3 plays a role in the induction of mESC differentiation by inducing EMT. In contrast to Ell3-overexpressing mESCs, Ell3-knock down mESCs could not differentiate under differentiation conditions and, instead, underwent caspase-dependent apoptosis. In addition, apoptosis of differentiating Ell3-knock out mESCs was associated with enhanced expression of p53. The present results suggest that Ell3 promotes the differentiation of mESCs by activating the expression of EMT-related genes and by suppressing p53 expression

Emergence of terpene cyclization in Artemisia annua

The emergence of terpene cyclization was critical to the evolutionary expansion of chemical diversity yet remains unexplored. Here we report the first discovery of an epistatic network of residues that controls the onset of terpene cyclization in Artemisia annua. We begin with amorpha-4,11-diene synthase (ADS) and (E)-b-farnesene synthase (BFS), a pair of terpene synthases that produce cyclic or linear terpenes, respectively. A library of B27,000 enzymes is generated by breeding combinations of natural amino-acid substitutions from the cyclic into the linear producer. We discover one dominant mutation is sufficient to activate cyclization, and together with two additional residues comprise a network of strongly epistatic interactions that activate, suppress or reactivate cyclization. Remarkably, this epistatic network of equivalent residues also controls cyclization in a BFS homologue from Citrus junos. Fitness landscape analysis of mutational trajectories provides quantitative insights into a major epoch in specialized metabolism

TGF-ß induces miR-100 and miR-125b but blocks let-7a through LIN28B controlling PDAC progression.

Abstract TGF-ß/Activin induces epithelial-to-mesenchymal transition (EMT) and stemness in pancreatic ductal adenocarcinoma (PDAC). However, the microRNAs (miRNAs) regulated during this response have remained yet undetermined. Here, we show that TGF-ß transcriptionally induces MIR100HG lncRNA, containing miR-100, miR-125b and let-7a in its intron, via SMAD2/3. Interestingly, we find that although the pro-tumourigenic miR-100 and miR-125b accordingly increase, the amount of anti-tumourigenic let-7a is unchanged, as TGF-ß also induces LIN28B inhibiting its maturation. Notably, we demonstrate that inactivation of miR-125b or miR-100 affects the TGF-ß-mediated response indicating that these miRNAs are important TGF-ß effectors. We integrated AGO2-RIP-seq with RNA-seq to identify the global regulation exerted by these miRNAs in PDAC cells. Transcripts targeted by miR-125b and miR-100 significantly overlap and mainly inhibit p53 and cell-cell junctions’ pathways. Together, we uncover that TGF-ß induces an lncRNA, whose encoded miRNAs, miR-100, let-7a and miR-125b, play opposing roles in controlling PDAC tumourigenesis