Activation of beta-catenin in CML granulocyte-macrophage progenitors appears to enhance the self-renewal activity and leukemic potential of these cells.

There are currently two dominant interface types for searching and browsing large image collections: keyword-based search, and searching by overall similarity to sample images. This paper presents an alternative in which users are able to navigate explicitly along conceptual dimensions that describe the images. The interface makes use of hierarchical faceted metadata and dynamically generated query previews. A usability study, conducted with 32 art history students exploring a collection of 35,000 fine arts images, compares this approach to a standard image search interface. Despite the unfamiliarity and power of the interface (attributes which often lead to rejection of new search interfaces), the study results show that 90% of the participants preferred the meta-data approach overall, 97% said that it helped them learn more about the collection, 75% found it more flexible and 72% found it easier to use than a standard baseline system. These results indicate that that a category-based approach is a successful way to provide access to image collections.

There are currently two dominant interface types for searching and browsing large image collections: keyword-based search, and searching by overall similarity to sample images. This paper presents an alternative in which users are able to navigate explicitly along conceptual dimensions that describe the images. The interface makes use of hierarchical faceted metadata and dynamically generated query previews. A usability study, conducted with 32 art history students exploring a collection of 35,000 fine arts images, compares this approach to a standard image search interface. Despite the unfamiliarity and power of the interface (attributes which often lead to rejection of new search interfaces), the study results show that 90% of the participants preferred the metadata approach overall, 97% said that it helped them learn more about the collection, 75% found it more flexible and 72% found it easier to use than a standard baseline system. These results indicate that that a category-based approach is a successful way to provide access to image collections.

DNA Double-Strand Break (DSB) repair is essential to safeguard genome integrity. Upon DSBs, the ATM PI3K kinase rapidly triggers the establishment of megabase-sized, γH2AX-decorated chromatin domains which further act as seeds for the formation of DNA Damage Response (DDR) foci 1 . How these foci are rapidly assembled in order to establish a “repair-prone” environment within the nucleus is yet unclear. Topologically Associating Domains (TADs) are a key feature of 3D genome organization that compartmentalize transcription and replication, but little is known about their contribution to DNA repair processes 2 , 3 . Here we found that TADs are functional units of the DDR, instrumental for the correct establishment of γH2AX/53BP1 chromatin domains in a manner that involves one-sided cohesin-mediated loop extrusion on both sides of the DSB. We propose a model whereby H2AX-containing nucleosomes are rapidly phosphorylated as they actively pass by DSB-anchored cohesin. Our work highlights the critical impact of chromosome conformation in the maintenance of genome integrity and provides the first example of a chromatin modification established by loop extrusion.

a b s t r a c tThis article proposes an approach to multiattribute decision making with incomplete attribute weight information where individual assessments are provided as interval-valued intuitionistic fuzzy numbers (IVIFNs). By employing a series of optimization models, the proposed approach derives a linear program for determining attribute weights. The weights are subsequently used to synthesize individual IVIFN assessments into an aggregated IVIFN value for each alternative. In order to rank alternatives based on their aggregated IVIFN values, a novel method is developed for comparing two IVIFNs by introducing two new functions: the membership uncertainty index and the hesitation uncertainty index. An illustrative investment decision problem is employed to demonstrate how to apply the proposed procedure and comparative studies are conducted to show its overall consistency with existing approaches.

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Existing research assessing human operators' trust in automation and robots has primarily examined trust as a steady-state variable, with little emphasis on the evolution of trust over time. With the goal of addressing this research gap, we present a study exploring the dynamic nature of trust. We defined trust of entirety as a measure that accounts for trust across a human's entire interactive experience with automation, and first identified alternatives to quantify it using real-time measurements of trust. Second, we provided a novel model that attempts to explain how trust of entirety evolves as a user interacts repeatedly with automation. Lastly, we investigated the effects of automation transparency on momentary changes of trust. Our results indicated that trust of entirety is better quantified by the average measure of "area under the trust curve" than the traditional post-experiment trust measure. In addition, we found that trust of entirety evolves and eventually stabilizes as an operator repeatedly interacts with a technology. Finally, we observed that a higher level of automation transparency may mitigate the "cry wolf" effect-wherein human operators begin to reject an automated system due to repeated false alarms.

Severe low-renin hypertension has few known causes. Apparent mineralocorticoid excess (AME) is a genetic disorder that results in severe juvenile low-renin hypertension, hyporeninemia, hypoaldosteronemia, hypokalemic alkalosis, low birth weight, failure to thrive, poor growth, and in many cases nephrocalcinosis. In 1995, it was shown that mutations in the gene (HSD11B2) encoding the 11␤-hydroxysteroid dehydrogenase type 2 enzyme (11␤-HSD2) cause AME. Typical patients with AME have defective 11␤-HSD2 activity, as evidenced by an abnormal ratio of cortisol to cortisone metabolites and by an exceedingly diminished ability to convert [11-3 H]cortisol to cortisone. Recently, we have studied an unusual patient with mild low-renin hypertension and a homozygous mutation in the HSD11B2 gene. The patient came from an inbred Mennonite family, and though the mutation identified her as a patient with AME, she did not demonstrate the typical features of AME. Biochemical analysis in this patient revealed a moderately elevated cortisol to cortisone metabolite ratio. The conversion of cortisol to cortisone was 58% compared with 0-6% in typical patients with AME whereas the normal conversion is 90-95%. Molecular analysis of the HSD11B2 gene of this patient showed a homozygous C3T transition in the second nucleotide of codon 227, resulting in a substitution of proline with leucine (P227L). The parents and sibs were heterozygous for this mutation. In vitro expression studies showed an increase in the K m (300 nM) over normal (54 nM). Because Ϸ40% of patients with essential hypertension demonstrate low renin, we suggest that such patients should undergo genetic analysis of the HSD11B2 gene.