Fire protection through modern day building codes

In this edition, fire protection regulations are not included and requirements of model codes and recommendations of code writing organizations are cited in the text. Much progress has been made in building construction techniques and in material development since the publication of the First Edition in 1944. While this Fifth Edition reflects that progress, it adheres to its original purpose to help develop construction standards for safeguarding life and property from fire

Effects of Trace Metal Limitation on Oxidative Stress in Zooxanthellae and Its Role in Coral Bleaching

Coral bleaching has increased dramatically in frequency, severity, and geographic extent since the 1980s and this trend is anticipated to continue, causing major environmental and economic impacts in tropical regions. This bleaching - the loss by corals of their photosynthetic endosymbiotic dinoflagellates (zooxanthellae; Symbiodinium spp.) - involves increased oxidative stress arising from the combined effects of elevated temperature at high light intensities. Although the production of reactive oxygen species (ROS) in corals and phytoplankton is routine during daylight hours, the failure of antioxidant defenses in zooxanthellae becomes catastrophic under comparatively small changes in environmental temperature, because reef corals live close to their upper thermal limits. The mechanisms underlying this failure are not understood, but fall into two categories: (1) the temperature/irradiance conditions lie beyond the capacity for thermal acclimatization by corals and their endo-symbionts, or (2) the necessary enhancement of antioxidant defenses in zooxanthellae is hindered by nutrient deficiencies. In this project, the working hypothesis is that low ambient concentrations of dissolved iron, zinc, copper and perhaps manganese (Fe, Zn, Cu, and Mn) in oligotrophic tropical surface waters, combined with regulation of metal supply to zooxanthellae by the coral host, restrict the compensatory elevation of metal-dependent antioxidant enzymes with rising ROS production, and this resource limitation contributes to coral bleaching. This hypothesis will be investigated in three stages: with pure clonal cultures of zooxanthella isolates; in coral colony culture experiments; and in samples on areas of the Great Barrier Reef, Australia, observed to be susceptible or resistant to coral bleaching. The primary goals of the pure culture experiments are to 1) identify which of the known metals involved in antioxidant enzymes (Fe, Cu, Zn, Mn) are important in zooxanthellae, 2) determine the thresholds of metal nutrition (both in supply and intracellular metal quotas) below which onset of uncontrolled oxidative stress occurs in the zooxanthellae, and 3) ascertain whether these relationships differ significantly among bleaching sensitive and insensitive Symbiodinium species. In addition to verifying the findings in coral/algal symbioses, coral experiments will be used to determine whether the timing and magnitude of bleaching indicators change with metal nutrition, and whether bleaching-sensitive corals can become more resistant by increasing their metal quotas. The linkage between trace metals and antioxidant enzymes is well established in other biological systems but has not been examined in coral/zooxanthellar associations. The proposed work brings together experts in trace metal/ phytoplankton interactions, phytoplankton photo-physiology and oxidative stress, photo-oxidative defenses in reef corals, and molecular biology of marine symbioses to provide mechanistic understanding of coral bleaching, increasing predictive insights to the global trend of coral bleaching. This project will support the education and research training of two Ph.D. students who would test hypotheses integral to the work as parts of their dissertations. Two postdoctoral scientists will participate in the planning, management, and research of the project, providing opportunities to refine their professional development and their mentoring skills necessary for career success. Public lectures on corals and global climate change are planned. The findings will provide insights to the factors influencing the severity of bleaching events, and may suggest realistic mitigation strategies to minimize bleaching in localized environmentally or economically sensitive regions

People of the British Isles: preliminary analysis of genotypes and surnames in a UK control population

There is a great deal of interest in fine scale population structure in the UK, both as a signature of historical immigration events and because of the effect population structure may have on disease association studies. Although population structure appears to have a minor impact on the current generation of genome-wide association studies, it is likely to play a significant part in the next generation of studies designed to search for rare variants. A powerful way of detecting such structure is to control and document carefully the provenance of the samples involved. Here we describe the collection of a cohort of rural UK samples (The People of the British Isles), aimed at providing a well-characterised UK control population that can be used as a resource by the research community as well as providing fine scale genetic information on the British population. So far, some 4,000 samples have been collected, the majority of which fit the criteria of coming from a rural area and having all four grandparents from approximately the same area. Analysis of the first 3,865 samples that have been geocoded indicates that 75% have a mean distance between grandparental places of birth of 37.3km, and that about 70% of grandparental places of birth can be classed as rural. Preliminary genotyping of 1,057 samples demonstrates the value of these samples for investigating fine scale population structure within the UK, and shows how this can be enhanced by the use of surnames

Tuba, a Cdc42 GEF, is required for polarized spindle orientation during epithelial cyst formation

An RNAi screen picks Tuba out of the GTPase exchange factor (GEF) orchestra as a regulator of cell polarity in epithelial morphogenesis. (See also a companion paper from Rodriguez-Fraticelli et al., in this issue.

Price and income policies

Discussion and objective debate is an important and necessary ingredient of social decision-making in a democracy. Only thus can the public, legislators, administrators and special interest groups inventory and understand the complete range of phenomena relevant for public decision. Discussion and analysis is a method of measurement, for a more complete inventory of goals and sub-goals of public policy and for expression of hypotheses and predictions in respect to outcomes of various policy means. Discussion is the most ancient and universal process for reasoned calculation in social policy, whether this be at the program committee of the 4-H Club or in presidential elections.https://lib.dr.iastate.edu/card_reports/1006/thumbnail.jp

Analogue peptides for the immunotherapy of human acute myeloid leukemia

Accepted manuscript. The final publication is available at: http://link.springer.com/article/10.1007%2Fs00262-015-1762-9The use of peptide vaccines, enhanced by adjuvants, has shown some efficacy in clinical trials. However, responses are often short-lived and rarely induce notable memory responses. The reason is that self-antigens have already been presented to the immune system as the tumor develops, leading to tolerance or some degree of host tumor cell destruction. To try to break tolerance against self-antigens, one of the methods employed has been to modify peptides at the anchor residues to enhance their ability to bind major histocompatibility complex molecules, extending their exposure to the T-cell receptor. These modified or analogue peptides have been investigated as stimulators of the immune system in patients with different cancers with variable but sometimes notable success. In this review we describe the background and recent developments in the use of analogue peptides for the immunotherapy of acute myeloid leukemia describing knowledge useful for the application of analogue peptide treatments for other malignancies

Calorimetric Investigation of Copper Binding in the N-Terminal Region of the Prion Protein at Low Copper Loading: Evidence for an Entropically Favorable First Binding Event

Although the Cu²⁺-binding sites of the prion protein have been well studied when the protein is fully saturated by Cu²⁺, the Cu²⁺-loading mechanism is just beginning to come into view. Because the Cu²⁺-binding modes at low and intermediate Cu²⁺ occupancy necessarily represent the highest-affinity binding modes, these are very likely populated under physiological conditions, and it is thus essential to characterize them in order to understand better the biological function of copper–prion interactions. Besides binding-affinity data, almost no other thermodynamic parameters (e.g., Δ<i>H</i> and Δ<i>S</i>) have been measured, thus leaving undetermined the enthalpic and entropic factors that govern the free energy of Cu²⁺ binding to the prion protein. In this study, isothermal titration calorimetry (ITC) was used to quantify the thermodynamic parameters (<i>K</i>, Δ<i>G</i>, Δ<i>H</i>, and <i>T</i>Δ<i>S</i>) of Cu²⁺ binding to a peptide, PrP­(23–28, 57–98), that encompasses the majority of the residues implicated in Cu²⁺ binding by full-length PrP. Use of the buffer <i>N</i>-(2-acetomido)-aminoethanesulfonic acid (ACES), which is also a well-characterized Cu²⁺ chelator, allowed for the isolation of the two highest affinity binding events. Circular dichroism spectroscopy was used to characterize the different binding modes as a function of added Cu²⁺. The <i>K</i>_d values determined by ITC, 7 and 380 nM, are well in line with those reported by others. The first binding event benefits significantly from a positive entropy, whereas the second binding event is enthalpically driven. The thermodynamic values associated with Cu²⁺ binding by the Aβ peptide, which is implicated in Alzheimer’s disease, bear striking parallels to those found here for the prion protein