Biosynthesis and enzymology of the Caenorhabditis elegans cuticle: identification and characterization of a novel serine protease inhibitor.

The nematode Caenorhabditis elegans represents an excellent model in which to examine nematode gene expression and function. A completed genome, straightforward transgenesis, available mutants and practical genome-wide RNAi approaches provide an invaluable toolkit in the characterization of nematode genes. We have performed a targeted RNAi screen in an attempt to identify components of the cuticle collagen biosynthetic pathway. Collagen biosynthesis and cuticle assembly are multi-step processes that involve numerous key enzymes involved in post-translational modification, trimer folding, procollagen processing and subsequent cross-linking stages. Many of these steps, the modifications and the enzymes are unique to nematodes and may represent attractive targets for the control of parasitic nematodes. A novel serine protease inhibitor was uncovered during our targeted screen, which is involved in collagen maturation, proper cuticle assembly and the moulting process. We have confirmed a link between this inhibitor and the previously uncharacterized bli-5 locus in C. elegans. The mutant phenotype, spatial expression pattern and the over-expression phenotype of the BLI-5 protease inhibitor and their relevance to collagen biosynthesis are discussed

Symptom Domain Groups of the Patient-Reported Outcomes Measurement Information System Tools Independently Predict Hospitalizations and Re-hospitalizations in Cirrhosis

Background Patient-Reported Outcomes Measurement Information System (PROMIS) tools can identify health-related quality of life (HRQOL) domains that could differentially affect disease progression. Cirrhotics are highly prone to hospitalizations and re-hospitalizations, but the current clinical prognostic models may be insufficient, and thus studying the contribution of individual HRQOL domains could improve prognostication. Aim Analyze the impact of individual HRQOL PROMIS domains in predicting time to all non-elective hospitalizations and re-hospitalizations in cirrhosis. Methods Outpatient cirrhotics were administered PROMIS computerized tools. The first non-elective hospitalization and subsequent re-hospitalizations after enrollment were recorded. Individual PROMIS domains significantly contributing toward these outcomes were generated using principal component analysis. Factor analysis revealed three major PROMIS domain groups: daily function (fatigue, physical function, social roles/activities and sleep issues), mood (anxiety, anger, and depression), and pain (pain behavior/impact) accounted for 77% of the variability. Cox proportional hazards regression modeling was used for these groups to evaluate time to first hospitalization and re-hospitalization. Results A total of 286 patients [57 years, MELD 13, 67% men, 40% hepatic encephalopathy (HE)] were enrolled. Patients were followed at 6-month (mth) intervals for a median of 38 mths (IQR 22–47), during which 31% were hospitalized [median IQR mths 12.5 (3–27)] and 12% were re-hospitalized [10.5 mths (3–28)]. Time to first hospitalization was predicted by HE, HR 1.5 (CI 1.01–2.5, p = 0.04) and daily function PROMIS group HR 1.4 (CI 1.1–1.8, p = 0.01), independently. In contrast, the pain PROMIS group were predictive of the time to re-hospitalization HR 1.6 (CI 1.1–2.3, p = 0.03) as was HE, HR 2.1 (CI 1.1–4.3, p = 0.03). Conclusions Daily function and pain HRQOL domain groups using PROMIS tools independently predict hospitalizations and re-hospitalizations in cirrhotic patients

Making the great transformation, November 13, 14, and 15, 2003

This repository item contains a single issue of the Pardee Conference Series, a publication series that began publishing in 2006 by the Boston University Frederick S. Pardee Center for the Study of the Longer-Range Future. This Conference took place during November 13, 14, and 15, 2003. Co-organized by Cutler Cleveland and Adil Najam.The conference discussants and participants analyze why transitions happen, and why they matter. Transitions are those wide-ranging changes in human organization and well being that can be convincingly attributed to a concerted set of choices that make the world that was significantly and recognizably different from the world that becomes. Transition scholars argue that that history does not just stumble along a pre-determined path, but that human ingenuity and entrepreneurship have the ability to fundamentally alter its direction. However, our ability to ‘will’ such transitions remains in doubt. These doubts cannot be removed until we have a better understanding of how transitions work

Economic development, human development, and the pursuit of happiness, April 1, 2, and 3, 2004

This repository item contains a single issue of the Pardee Conference Series, a publication series that began publishing in 2006 by the Boston University Frederick S. Pardee Center for the Study of the Longer-Range Future. This was the Center's spring conference, which took place during April 1, 2, and 3, 2004.The conference asks the questions, how can we make sure that the benefits of economic growth flow into health, education, welfare, and other aspects of human development; and what is the relationship between human development and economic development? Speakers and participants discuss the role that culture, legal and political institutions, the UN Developmental Goals, the level of decision-making, and ethics, play in development

Looking ahead: forecasting and planning for the longer-range future, April 1, 2, and 3, 2005

This repository item contains a single issue of the Pardee Conference Series, a publication series that began publishing in 2006 by the Boston University Frederick S. Pardee Center for the Study of the Longer-Range Future. This was the Center's spring Conference that took place during April 1, 2, and 3, 2005.The conference allowed for many highly esteemed scholars and professionals from a broad range of fields to come together to discuss strategies designed for the 21st century and beyond. The speakers and discussants covered a broad range of subjects including: long-term policy analysis, forecasting for business and investment, the National Intelligence Council Global Trends 2020 report, Europe’s transition from the Marshal plan to the EU, forecasting global transitions, foreign policy planning, and forecasting for defense

Human cloning in film: horror, ambivalence, hope

Fictional filmic representations of human cloning have shifted in relation to the 1997 announcement of the birth of Dolly the cloned sheep, and since therapeutic human cloning became a scientific practice in the early twentieth century. The operation and detail of these shifts can be seen through an analysis of the films The Island (2005) and Aeon Flux (2005). These films provide a site for the examination of how these changes in human cloning from fiction to practice, and from horror to hope, have been represented and imagined, and how these distinctions have operated visually in fiction, and in relation to genre

Simulating Subhalos at High Redshift: Merger Rates, Counts, and Types

Galaxies are believed to be in one-to-one correspondence with simulated dark matter subhalos. We use high-resolution N-body simulations of cosmological volumes to calculate the statistical properties of subhalo (galaxy) major mergers at high redshift (z=0.6-5). We measure the evolution of the galaxy merger rate, finding that it is much shallower than the merger rate of dark matter host halos at z>2.5, but roughly parallels that of halos at z<1.6. We also track the detailed merger histories of individual galaxies and measure the likelihood of multiple mergers per halo or subhalo. We examine satellite merger statistics in detail: 15%-35% of all recently merged galaxies are satellites and satellites are twice as likely as centrals to have had a recent major merger. Finally, we show how the differing evolution of the merger rates of halos and galaxies leads to the evolution of the average satellite occupation per halo, noting that for a fixed halo mass, the satellite halo occupation peaks at z~2.5.Comment: 17 pages, 12 figures, accepted in MNRAS, version matches published on

Lagos and the Uncertain New Modernism of Teju Cole

This article offers an innovative account of the work of the Nigerian American writer, Teju Cole, and argues that his fiction demonstrates an ‘uncertain new’ modernism of the city. In particular, the article analyses how Every Day is for the Thief (2007/14) and Open City (2011) draw upon the techniques and categories of earlier forms of modernist writing in order to depict the complexities of the urban experience. It focuses upon the representation of the Nigerian city of Lagos in Every Day is for the Thief, and argues that Cole’s spatial stories of this city demonstrate a fascinating new development in the history of modernism and the city

Domain Knowledge Injection in Bayesian Search for New Materials

In this paper we propose DKIBO, a Bayesian optimization (BO) algorithm that accommodates domain knowledge to tune exploration in the search space. Bayesian optimization has recently emerged as a sample-efficient optimizer for many intractable scientific problems. While various existing BO frameworks allow the input of prior beliefs to accelerate the search by narrowing down the space, incorporating such knowledge is not always straightforward and can often introduce bias and lead to poor performance. Here we propose a simple approach to incorporate structural knowledge in the acquisition function by utilizing an additional deterministic surrogate model to enrich the approximation power of the Gaussian process. This is suitably chosen according to structural information of the problem at hand and acts a corrective term towards a better-informed sampling. We empirically demonstrate the practical utility of the proposed method by successfully injecting domain knowledge in a materials design task. We further validate our method's performance on different experimental settings and ablation analyses.Comment: 8 pages, 5 figures, published in ECAI2

Galaxy Formation Theory

We review the current theory of how galaxies form within the cosmological framework provided by the cold dark matter paradigm for structure formation. Beginning with the pre-galactic evolution of baryonic material we describe the analytical and numerical understanding of how baryons condense into galaxies, what determines the structure of those galaxies and how internal and external processes (including star formation, merging, active galactic nuclei etc.) determine their gross properties and evolution. Throughout, we highlight successes and failings of current galaxy formation theory. We include a review of computational implementations of galaxy formation theory and assess their ability to provide reliable modelling of this complex phenomenon. We finish with a discussion of several "hot topics" in contemporary galaxy formation theory and assess future directions for this field.Comment: 58 pages, to appear in Physics Reports. This version includes minor corrections and a handful of additional reference