Normally preordered spaces and utilities

In applications it is useful to know whether a topological preordered space is normally preordered. It is proved that every $k_\omega$-space equipped with a closed preorder is a normally preordered space. Furthermore, it is proved that second countable regularly preordered spaces are perfectly normally preordered and admit a countable utility representation.Comment: 17 pages, 1 figure. v2 contains a second proof to the main theorem with respect to the published version. The last section of v1 is not present in v2. It will be included in a different wor

Creating the Back Ward: The Triumph of Custodialism and the Uses of Therapeutic Failure in Nineteenth Century Idiot Asylums

My focus in this chapter is on the origin of the back ward rather than its demise. Where did the “back wards” that [Burton] Blatt and [Senator Robert] Kennedy witnessed come from in the first place? What 3 exactly were those “antecedents of the problems observed” that Blatt cited? This chapter reviews that history and argues that, in fact, there is a specific narrative to the evolution of the institutional “back ward” as an identifiable place where people with the most significant intellectual disabilities were to be incarcerated and largely forgotten.https://digitalcommons.chapman.edu/education_books/1006/thumbnail.jp

Inspired or foolhardy: sensemaking, confidence and entrepreneurs' decision-making.

The purpose of this paper is to investigate the role of confidence in how both new and experienced entrepreneurs interpret and make sense of their business environment to inform decision-making. We illustrate our conceptual arguments with descriptive results from a large-scale (n = 6289) survey on entrepreneurs' perception of business performance and their decisions taken at a time of uncertainty in an economic downturn. Quantitative findings are stratified along experiential lines to explore heterogeneity in entrepreneurial decision-making and directly inform our conceptual arguments, while qualitative data from open questions are used to explain the role of confidence. Newer entrepreneurs are found to be more optimistic in the face of environmental risk, which impacts on their decision-making and innovative capabilities. However, the more experienced entrepreneurs warily maintain margin and restructure to adapt to environmental changes. Instead of looking directly at the confidence of individuals, we show how confidence impacts sensemaking, and ultimately, decision-making. These insights inform research on the behaviour of novice and experienced entrepreneurs in relation to innovative business activities. Specifically, blanket assumptions on the role of confidence may be misplaced as its impact changes with experience to alter how entrepreneurs make sense of their environment

Plus- and Minus-End Directed Microtubule Motors Bind Simultaneously to Herpes Simplex Virus Capsids Using Different Inner Tegument Structures

Many viruses depend on host microtubule motors to reach their destined intracellular location. Viral particles of neurotropic alphaherpesviruses such as herpes simplex virus 1 (HSV1) show bidirectional transport towards the cell center as well as the periphery, indicating that they utilize microtubule motors of opposing directionality. To understand the mechanisms of specific motor recruitment, it is necessary to characterize the molecular composition of such motile viral structures. We have generated HSV1 capsids with different surface features without impairing their overall architecture, and show that in a mammalian cell-free system the microtubule motors dynein and kinesin-1 and the dynein cofactor dynactin could interact directly with capsids independent of other host factors. The capsid composition and surface was analyzed with respect to 23 structural proteins that are potentially exposed to the cytosol during virus assembly or cell entry. Many of these proteins belong to the tegument, the hallmark of all herpesviruses located between the capsid and the viral envelope. Using immunoblots, quantitative mass spectrometry and quantitative immunoelectron microscopy, we show that capsids exposing inner tegument proteins such as pUS3, pUL36, pUL37, ICP0, pUL14, pUL16, and pUL21 recruited dynein, dynactin, kinesin-1 and kinesin-2. In contrast, neither untegumented capsids exposing VP5, VP26, pUL17 and pUL25 nor capsids covered by outer tegument proteins such as vhs, pUL11, ICP4, ICP34.5, VP11/12, VP13/14, VP16, VP22 or pUS11 bound microtubule motors. Our data suggest that HSV1 uses different structural features of the inner tegument to recruit dynein or kinesin-1. Individual capsids simultaneously accommodated motors of opposing directionality as well as several copies of the same motor. Thus, these associated motors either engage in a tug-of-war or their activities are coordinately regulated to achieve net transport either to the nucleus during cell entry or to cytoplasmic membranes for envelopment during assembly

Web-based infectious disease surveillance systems and public health perspectives: a systematic review

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Abstract Background Emerging and re-emerging infectious diseases are a significant public health concern, and early detection and immediate response is crucial for disease control. These challenges have led to the need for new approaches and technologies to reinforce the capacity of traditional surveillance systems for detecting emerging infectious diseases. In the last few years, the availability of novel web-based data sources has contributed substantially to infectious disease surveillance. This study explores the burgeoning field of web-based infectious disease surveillance systems by examining their current status, importance, and potential challenges. Methods A systematic review framework was applied to the search, screening, and analysis of web-based infectious disease surveillance systems. We searched PubMed, Web of Science, and Embase databases to extensively review the English literature published between 2000 and 2015. Eleven surveillance systems were chosen for evaluation according to their high frequency of application. Relevant terms, including newly coined terms, development and classification of the surveillance systems, and various characteristics associated with the systems were studied. Results Based on a detailed and informative review of the 11 web-based infectious disease surveillance systems, it was evident that these systems exhibited clear strengths, as compared to traditional surveillance systems, but with some limitations yet to be overcome. The major strengths of the newly emerging surveillance systems are that they are intuitive, adaptable, low-cost, and operated in real-time, all of which are necessary features of an effective public health tool. The most apparent potential challenges of the web-based systems are those of inaccurate interpretation and prediction of health status, and privacy issues, based on an individuals internet activity. Conclusion Despite being in a nascent stage with further modification needed, web-based surveillance systems have evolved to complement traditional national surveillance systems. This review highlights ways in which the strengths of existing systems can be maintained and weaknesses alleviated to implement optimal web surveillance systems

Oxidation increases mucin polymer cross-links to stiffen airway mucus gels

Airway mucus in cystic fibrosis (CF) is highly elastic, but themechanism behind this pathology is unclear. We hypothesized that the biophysical properties of CF mucus are altered because of neutrophilic oxidative stress. Using confocal imaging, rheology, and biochemical measures of inflammation and oxidation, we found that CF airway mucus gels have a molecular architecture characterized by a core of mucin covered by a web of DNA and a rheological profile characterized by high elasticity that can be normalized by chemical reduction. We also found that high levels of reactive oxygen species in CF mucus correlated positively and significantly with high concentrations of the oxidized products of cysteine (disulfide cross-links). To directly determine whether oxidation can cross-link mucins to increase mucus elasticity, we exposed induced sputum from healthy subjects to oxidizing stimuli and found a marked and thiol-dependent increase in sputum elasticity. Targeting mucin disulfide cross-links using current thiol-amino structures such as N-acetylcysteine (NAC) requires high drug concentrations to have mucolytic effects. We therefore synthesized a thiol-carbohydrate structure (methyl 6-thio-6-deoxy-α-D-galactopyranoside) and found that it had stronger reducing activity than NAC and more potent and fast-acting mucolytic activity in CF sputum. Thus, oxidation arising from airway inflammation or environmental exposure contributes to pathologic mucus gel formation in the lung, which suggests that it can be targeted by thiol-modified carbohydrates