Electron and ion microprobe analysis of calcium distribution and transport in coral tissues.

It is shown by x-ray microanalysis that a gradient of total intracellular Ca concentration exists from the outer oral ectoderm to the inner skeletogenic calicoblastic ectoderm in the coral Galaxea fascicularis. This suggests an increase in intracellular Ca stores in relation to calcification. Furthermore, Ca concentration in the fluid-filled space of the extrathecal coelenteron is approximately twice as high as in the surrounding seawater and higher than in the mucus-containing seawater layer on the exterior of the oral ectoderm. This is indicative of active Ca2+ transport across the oral epithelium. Polyps were incubated in artificial seawater in which all 40Ca was replaced by 44Ca. Imaging Ca2+ transport across the epithelia by secondary ion mass spectroscopy (SIMS) using 44Ca as a tracer showed that Ca2+ rapidly entered the cells of the oral epithelium and that 44Ca reached higher concentrations in the mesogloea and extrathecal coelenteron than in the external seawater layer. Very little Ca2+ was exchanged in the mucocytes, cnidocytes or zooxanthellae. These observations again suggest that Ca2+ transport is active and transcellular and also indicate a hitherto unsuspected role in Ca2+ transport for the mesogloea. © 2007, Company of Biologist

On the (Im)possibility of Obfuscating Programs

Informally, an obfuscator O is an (efficient, probabilistic) “compiler” that takes as input a program (or circuit) P and produces a new program O(P) that has the same functionality as P yet is “unintelligible” in some sense. Obfuscators, if they exist, would have a wide variety of cryptographic and complexity-theoretic applications, ranging from software protection to homomorphic encryption to complexity-theoretic analogues of Rice's theorem. Most of these applications are based on an interpretation of the “unintelligibility” condition in obfuscation as meaning that O(P) is a “virtual black box,” in the sense that anything one can efficiently compute given O(P), one could also efficiently compute given oracle access to P. In this work, we initiate a theoretical investigation of obfuscation. Our main result is that, even under very weak formalizations of the above intuition, obfuscation is impossible. We prove this by constructing a family of efficient programs P that are unobfuscatable in the sense that (a) given any efficient program P' that computes the same function as a program P ∈ p, the “source code” P can be efficiently reconstructed, yet (b) given oracle access to a (randomly selected) program P ∈ p, no efficient algorithm can reconstruct P (or even distinguish a certain bit in the code from random) except with negligible probability. We extend our impossibility result in a number of ways, including even obfuscators that (a) are not necessarily computable in polynomial time, (b) only approximately preserve the functionality, and (c) only need to work for very restricted models of computation (TC0). We also rule out several potential applications of obfuscators, by constructing “unobfuscatable” signature schemes, encryption schemes, and pseudorandom function families.Engineering and Applied Science

Issues in Cost Effectiveness in Health Care

Cost-effectiveness analysis (CEA) is becoming increasingly popular as society moves toward rationalizing health costs. This review describes the applications and limitations of the technique. Conceptually simple though frequently complicated in application, CEA compares the cost of a procedure with its effectiveness, thus helping an administrator to judge whether the procedure is worth its cost. CEA also permits comparison of various interventions that result in a similar health outcome. A major benefit of CEA is that it forces decision makers to confront the tradeoffs implicit in all decisions regarding alternative approaches. Limitations of the CEA philosophy and technique also have to be understood if it is to be employed effectively; it is not an assessment of cost savings, nor is it a decision-making technique because it does not incorporate value judgments. A number of potential applications to dentistry are described.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65700/1/j.1752-7325.1989.tb02085.x.pd

Selection on Coding and Regulatory Variation Maintains Individuality in Major Urinary Protein Scent Marks in Wild Mice

Recognition of individuals by scent is widespread across animal taxa. Though animals can often discriminate chemical blends based on many compounds, recent work shows that specific protein pheromones are necessary and sufficient for individual recognition via scent marks in mice. The genetic nature of individuality in scent marks (e.g. coding versus regulatory variation) and the evolutionary processes that maintain diversity are poorly understood. The individual signatures in scent marks of house mice are the protein products of a group of highly similar paralogs in the major urinary protein (Mup) gene family. Using the offspring of wild-caught mice, we examine individuality in the major urinary protein (MUP) scent marks at the DNA, RNA and protein levels. We show that individuality arises through a combination of variation at amino acid coding sites and differential transcription of central Mup genes across individuals, and we identify eSNPs in promoters. There is no evidence of post-transcriptional processes influencing phenotypic diversity as transcripts accurately predict the relative abundance of proteins in urine samples. The match between transcripts and urine samples taken six months earlier also emphasizes that the proportional relationships across central MUP isoforms in urine is stable. Balancing selection maintains coding variants at moderate frequencies, though pheromone diversity appears limited by interactions with vomeronasal receptors. We find that differential transcription of the central Mup paralogs within and between individuals significantly increases the individuality of pheromone blends. Balancing selection on gene regulation allows for increased individuality via combinatorial diversity in a limited number of pheromones

Comprehensive molecular testing for respiratory pathogens in community-acquired pneumonia

Funding: This work was supported by the Chief Scientist Office (grant number ETM/250).Background. The frequent lack of a microbiological diagnosis in community-acquired pneumonia (CAP) impairs pathogen-directed antimicrobial therapy. This study assessed the use of comprehensive multibacterial, multiviral molecular testing, including quantification, in adults hospitalized with CAP. Methods. Clinical and laboratory data were collected for 323 adults with radiologically-confirmed CAP admitted to 2 UK tertiary care hospitals. Sputum (96%) or endotracheal aspirate (4%) specimens were cultured as per routine practice and also tested with fast multiplex real-time polymerase-chain reaction (PCR) assays for 26 respiratory bacteria and viruses. Bacterial loads were also calculated for 8 bacterial pathogens. Appropriate pathogen-directed therapy was retrospectively assessed using national guidelines adapted for local antimicrobial susceptibility patterns. Results. Comprehensive molecular testing of single lower respiratory tract (LRT) specimens achieved pathogen detection in 87% of CAP patients compared with 39% with culture-based methods. Haemophilus influenzae and Streptococcus pneumoniae were the main agents detected, along with a wide variety of typical and atypical pathogens. Viruses were present in 30% of cases; 82% of these were codetections with bacteria. Most (85%) patients had received antimicrobials in the 72 hours before admission. Of these, 78% had a bacterial pathogen detected by PCR but only 32% were culture-positive (P < .0001). Molecular testing had the potential to enable de-escalation in number and/or spectrum of antimicrobials in 77% of patients. Conclusions. Comprehensive molecular testing significantly improves pathogen detection in CAP, particularly in antimicrobial-exposed patients, and requires only a single LRT specimen. It also has the potential to enable early de-escalation from broad-spectrum empirical antimicrobials to pathogen-directed therapy.Publisher PDFPeer reviewe

Selling Health Promotion to Corporate America: Uses and Abuses of the Economic Argument

Economic considerations constitute a significant factor in businesses' interest in adopting health promotion (HP) programs and in the wellness community's attempts to sell such programming to business. Substantial elements of both the business and wellness communities believe that HP programs are financially profitable, in addition to, and as a result of, improving employees' health. Examination of the foundation of this belief, however, leads to the conclusion that underlying analyses have been techni cally flawed and have ignored important costs of HP programs. This article discusses the limitations of these analyses and outlines the framework of a model that could provide a sound assessment of the economics of workplace HP programs. In general, it is expected that resultant analyses would find less direct profit potential in work place HP programs but would emphasize the cost-effectiveness of many such efforts. The latter would force recognition that health, and not profit, is the principal benefit of health promotion programming. The distinction between the cost-effectiveness and cost-saving potential of health promotion is one that all interested parties should master.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66785/2/10.1177_109019818701400106.pd

Comparative linkage analysis and visualization of high-density oligonucleotide SNP array data

Background: The identification of disease-associated genes using single nucleotide polymorphisms (SNPs) has been increasingly reported. In particular, the Affymetrix Mapping 10 K SNP microarray platform uses one PCR primer to amplify the DNA samples and determine the genotype of more than 10,000 SNPs in the human genome. This provides the opportunity for large scale, rapid and cost-effective genotyping assays for linkage analysis. However, the analysis of such datasets is nontrivial because of the large number of markers, and visualizing the linkage scores in the context of genome maps remains less automated using the current linkage analysis software packages. For example, the haplotyping results are commonly represented in the text format. Results: Here we report the development of a novel software tool called CompareLinkage for automated formatting of the Affymetrix Mapping 10 K genotype data into the "Linkage" format and the subsequent analysis with multi-point linkage software programs such as Merlin and Allegro. The new software has the ability to visualize the results for all these programs in dChip in the context of genome annotations and cytoband information. In addition we implemented a variant of the Lander-Green algorithm in the dChipLinkage module of dChip software (V1.3) to perform parametric linkage analysis and haplotyping of SNP array data. These functions are integrated with the existing modules of dChip to visualize SNP genotype data together with LOD score curves. We have analyzed three families with recessive and dominant diseases using the new software programs and the comparison results are presented and discussed. Conclusions: The CompareLinkage and dChipLinkage software packages are freely available. They provide the visualization tools for high-density oligonucleotide SNP array data, as well as the automated functions for formatting SNP array data for the linkage analysis programs Merlin and Allegro and calling these programs for linkage analysis. The results can be visualized in dChip in the context of genes and cytobands. In addition, a variant of the Lander-Green algorithm is provided that allows parametric linkage analysis and haplotyping

A Methodology for Risk Assessment to Improve the Resilience and Sustainability of Critical Infrastructure with Case Studies from the United States Army

Reliable performance of energy and water infrastructure is central to the mission readiness of the United States Army. These systems are vulnerable to coordinated attacks from an adversary as well as disruption from natural events. The objectives of this work were to investigate Army installations in North America, identify best practices for improving the resilience and sustainability of critical energy and water infrastructure, and develop a framework and methodology for analyzing the resilience of an installation under varying outage scenarios. This work was accomplished using a multi-layered decision process to identify unique case studies from the 117 active-duty domestic Army installations. A framework for analyzing and assessing the resilience of an installation was then developed to help inform stakeholders. Metered energy and water data from buildings across Fort Benning, GA were curated to inform the modeling framework, including a discrete-event simulation of the supply and demand for energy and water on the installation using ProModel. This simulation was used to study the scale of solutions required to address outage events of varying frequency, duration, and magnitude, the combination of which is described as the severity of outages at a given site. This project helps develop a framework to inform how installations might meet Army Directive 2020-03, which states that installations must be able to sustain mission requirements for a minimum of 14 days after a disruption has occurred