Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Ice tank tests of a highly skewed propeller and a conventional ice-class propeller in four quadrants

Recent work to update regulations for ice-class ships has resulted in, amongst other things, new methods for dimensioning ice-class propellers. These methods have focussed on the more traditional propeller geometry and arrangements so that unconventional designs, such as highly skewed propeller blades and azimuthing propellers, have been excluded and must be treated as special cases. Also, elements of the design methods are based on limited empirical sources and as such need testing, verification, and perhaps modification. -- To address some of these issues, an experimental investigation was undertaken in the ice tank at the Institute for Marine Dynamics (IMD) using two different propeller models. A model of the propeller on the passenger ferry MV Caribou was tested specifically to investigate a highly skewed propeller under ice loading over a range of operating and ice conditions. The second propeller tested was a more conventional ice-class propeller from the R-Class icebreaker. The R-Class propeller model was tested over a wide range of operating conditions to give loading characteristics in all four quadrants. Such extreme loading might be experienced by fixed and controllable pitch propellers in off-design conditions, and by azimuthing propellers. The set of experiments involving the R-Class propeller were done over a range of ice strength conditions to examine nominal ice strength variation effects on the propeller loads. Based on the experimental results it is concluded that a highly skewed propeller behaves in a similar manner to that of a conventional ice-class propeller. In addition, the tests conducted in all four quadrants of propeller operation concluded propellers do not experience the greatest loads in quadrant 1, which is currently used as the design criterion. Rather, the largest loads are experienced in quadrants 2 and 3 and modifications to current design proposals should consider this detail

Platelet Function: Meloxicam Intravenous in Whole Blood Samples From Healthy Volunteers.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective treatments for pain but may induce bleeding events due to platelet dysfunction associated with inhibition of cyclooxygenase (COX)-1 impairing thromboxane production. An intravenous nanocrystal formulation of meloxicam, a COX-2 preferential nonsteroidal anti-inflammatory drug, is under development for the treatment of moderate to severe pain. This single-center ex vivo study evaluated the effect of meloxicam intravenous and ketorolac on platelet function in whole blood samples from healthy volunteers. Each whole blood sample was aliquoted to allow analysis using a platelet function analyzer under negative control (untreated), positive control (2 therapeutic ketorolac concentrations), and meloxicam intravenous (1 therapeutic, 3 supratherapeutic concentrations) using both collagen with epinephrine and collagen with adenosine diphosphate reagent cartridges. The platelet function analyzer determines closure time by simulating platelet adhesion and aggregation following vascular injury. The final analysis set included data from 8 subjects. The collagen with adenosine diphosphate analysis (sensitive to thrombocytopathies) showed no significant differences in closure time for meloxicam- or ketorolac-treated samples and untreated control. The collagen with epinephrine analysis (sensitive to aspirin-induced platelet abnormalities) produced no significant difference in closure time between any meloxicam concentration and untreated control. Ketorolac was associated with significantly longer closure times vs untreated control at both the 2.5- and 5-µg/mL concentrations (P = .003 and .0257, respectively) and vs meloxicam at several concentrations. Similar results were observed when all analyzed samples were included. Meloxicam intravenous had no significant effect on closure times at therapeutic or supratherapeutic concentrations in this ex vivo study

Additional file 1: of Safety, tolerability, pharmacokinetics, and efficacy of AMG 403, a human anti-nerve growth factor monoclonal antibody, in two phase I studies with healthy volunteers and knee osteoarthritis subjects

Ethical review boards that provided approval for this study. (DOC 22 kb

Theorizing Political Psychology: Doing Integrative Social Science Under the Condition of Postmodernity

At the beginning of the 21st century, the field of political psychology; like the social sciences more generally, is being challenged. New theoretical direction is being demanded from within and a greater epistemological sophistication and ethical relevance is being demanded from without. In response, direction for a reconstructed political psychology is offered here. To begin, a theoretical framework for a truly integrative political psychology is sketched. This is done in light of the apparent limits of cross-disciplinary or multidisciplinary inquiry. In the attempt to transcend these limits, the theoretical approach offered directly addresses the dually structured quality of social life as the singular product of both organizing social structures and defining discourse communities on the one hand and motivated, thinking individuals on the other. To further this theoretical effort, meta-theoretical considerations are addressed. The modernist-postmodernist debate regarding the status of truth and value is used as a point of departure for constructing the epistemological foundation for a truly political psychology. In this light, structural pragmatic guidelines for theory construction, empirical research and normative inquiry are presented