The value of a small microkernel for dreamy memory and the RAMpage memory hierarchy

This paper explores potential for the RAMpage memory hierarchy to use a microkernel with a small memory footprint, in a specialized cache-speed static RAM (tightly-coupled memory, TCM). Dreamy memory is DRAM kept in low-power mode, unless referenced. Simulations show that a small microkernel suits RAMpage well, in that it achieves significantly better speed and energy gains than a standard hierarchy from adding TCM. RAMpage, in its best 128KB L2 case, gained 11% speed using TCM, and reduced energy 14%. Equivalent conventional hierarchy gains were under 1%. While 1MB L2 was significantly faster against lower-energy cases for the smaller L2, the larger SRAM's energy does not justify the speed gain. Using a 128KB L2 cache in a conventional architecture resulted in a best-case overall run time of 2.58s, compared with the best dreamy mode run time (RAMpage without context switches on misses) of 3.34s, a speed penalty of 29%. Energy in the fastest 128KB L2 case was 2.18J vs. 1.50J, a reduction of 31%. The same RAMpage configuration without dreamy mode took 2.83s as simulated, and used 2.39J, an acceptable trade-off (penalty under 10%) for being able to switch easily to a lower-energy mode.

Pax9 and Jagged1 act downstream of Gli3 in vertabrate limb development

From early in limb development the transcription factor Gli3 acts to define boundaries of gene expression along the anterior-posterior (AP) axis, establishing asymmetric patterns required to provide positional information. As limb development proceeds, posterior mesenchyme expression of Sonic hedgehog (Shh) regulates Gli3 transcription and post-translational processing to specify digit number and identity. The molecular cascades dependent on Gli3 at later stages of limb development, which link early patterning events with final digit morphogenesis, remain poorly characterised. By analysing the transcriptional consequences of loss of Gli3 in the anterior margin of the E11.5 and E12.5 limb bud in the polydactylous mouse mutant extra-toes (Gli3(Xt/Xt)), we have identified a number of known and novel transcripts dependent on Gli3 in the limb. In particular, we demonstrated that the genes encoding the paired box transcription factor Pax9, the Notch ligand Jagged1 and the cell surface receptor Cdo are dependent on Gli3 for correct expression in the anterior limb mesenchyme. Analysis of expression in compound Shh;Gli3 mutant mouse embryos and in both in vitro and in vivo Shh signaling assays, further defined the importance of Shh regulated processing of Gli3 in controlling gene expression. In particular Pax9 regulation by Shh and Gli3 was shown to be context dependent, with major differences between the limb and somite revealed by Shh bead implantation experiments in the chick. Jagged1 was shown to be induced by Shh in the chick limb and in a C3H10T1/2 cell based signaling assay, with Shh;Gli3 mutant analysis indicating that expression is dependent on Gli3 derepression. Our data have also revealed that perturbation of early patterning events within the Gli3(Xt/Xt), limb culminates in a specific delay of anterior chondrogenesis which is subsequently realised as extra digits. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Transcriptional profile reveals altered hepatic lipid and cholesterol metabolism in hyposulfatemic NaS1 null mice

Sulfate plays an essential role in human growth and development, and its circulating levels are maintained by the renal Na+-SO42- cotransporter, NaS1. We previously generated a NaS1 knockout ( Nas1(-/-)) mouse, an animal model for hyposulfatemia, that exhibits reduced growth and liver abnormalities including hepatomegaly. In this study, we investigated the hepatic gene expression profile of Nas1(-/-) mice using oligonucleotide microarrays. The mRNA expression levels of 92 genes with known functional roles in metabolism, cell signaling, cell defense, immune response, cell structure, transcription, or protein synthesis were increased ( n = 51) or decreased ( n = 41) in Nas1(-/-) mice when compared with Nas1(-/-) mice. The most upregulated transcript levels in Nas1(-/-) mice were found for the sulfotransferase genes, Sult3a1 ( approximate to 500% increase) and Sult2a2 ( 100% increase), whereas the metallothionein-1 gene, Mt1, was among the most downregulated genes ( 70% decrease). Several genes involved in lipid and cholesterol metabolism, including Scd1, Acly, Gpam, Elov16, Acsl5, Mvd, Insig1, and Apoa4, were found to be upregulated ( >= 30% increase) in Nas1(+/+) mice. In addition, Nas1(+/+) mice exhibited increased levels of hepatic lipid ( approximate to 16% increase), serum cholesterol ( approximate to 20% increase), and low-density lipoprotein ( approximate to 100% increase) and reduced hepatic glycogen ( approximate to 50% decrease) levels. In conclusion, these data suggest an altered lipid and cholesterol metabolism in the hyposulfatemic Nas1(-/-) mouse and provide new insights into the metabolic state of the liver in Nas1(-/-) mice.

Eph/Ephrin memhrane proteins: A mammalian expression vector pTIg-BOS-Fc allowing rapid protein purification

There is an urgent need for high purity, single chain, fully functional Eph/ephrin membrane proteins. This report outlines the pTIg-BOS-Fc vector and purification approach resulting in rapid increased production of fully functional single chain extracellular proteins that were isolated with high purity and used in structure-function analysis and pre-clinical studies.

Gene expression profiles in murine hematopoietic stem cells revisited: Analysis of cDNA libraries reveals high levels of translational and metabolic activities

Gene expression studies from hematopoietic stem cell (HSC) populations purified to variable degrees have defined a set of sternness genes. Unexpectedly, results also hinted toward a HSC chromatin poised in a wide-open state. With the aim of providing a robust tool for further studies into the molecular biology of HSCs, the studies herein describe the construction and comparative molecular analysis of A-phage cDNA libraries from highly purified HSCs that retained their long-term repopulating activities (long-term HSCs [LT-HSCs]) and from short-term repopulating HSCs that were largely depleted of these activities. Microarray analysis of the libraries confirmed the previous results but also revealed an unforeseen preferential expression of translation- and metabolism-associated genes in the LT-HSCs. Therefore, these data indicate that HSCs are quiescent only in regard of proliferative activities but are in a state of readiness to provide the metabolic and translational activities required after induction of proliferation and exit from the HSC pool.

Expression analysis of the Epha1 receptor tyrosine kinase and its high-affinity ligands Efna1 and Efna3 during early mouse development

Interaction of Eph receptor tyrosine kinases with their membrane bound ephrin ligands initiates bidirectional signaling events that regulate cell migratory and adhesive behavior. Whole-mount in situ hybridization revealed overlapping expression of the Epha1 receptor and its high-affinity ligands ephrin A1 (Efna1) and ephrin A3 (Efna3) in the primitive streak and the posterior paraxial mesoderm during early mouse development. These results show complex and dynamic expression for all three genes with expression domains that are successively complementary, overlapping, and divergent. (c) 2006 Elsevier B.V. All rights reserved.

Acupressure for the in-patient treatment of nausea and vomiting in early pregnancy: A randomized control trial

Objective: The purpose of this study was to evaluate the efficacy of acupressure at the P6 point for the in-patient treatment of severe nausea and vomiting in early pregnancy. Study design: This was a prospective single-blind randomized control trial that involved 80 patients with nausea and vomiting plus ketonuria before 14 weeks of gestation. Results: There was no difference between length of stay, amount of medication, or fluid required between the acupressure and placebo groups, although acupressure reduced the number of patients who stayed >= 4 nights in the hospital. Acupressure was well tolerated and not associated with an increase in perinatal morbidity or death. Conclusion: The use of acupressure Lit the P6 point does not reduce the amount of antiemetric medication that is required, the requirement for intravenous fluid, and median duration of inpatient stay more than the use of placebo. A small reduction was seen in the number of women who required >= 4 days in the hospital. (c) 2006 Mosby, Inc. All rights reserved.

An extensive repertoire of type III secretion effectors in Escherichia coli O157 and the role of lambdoid phages in their dissemination

Several pathogenic strains of Escherichia coli exploit type III secretion to inject effector proteins into human cells, which then subvert eukaryotic cell biology to the bacterium's advantage. We have exploited bioinformatics and experimental approaches to establish that the effector repertoire in the Sakai strain of enterohemorrhagic E. coli (EHEC) O157:H7 is much larger than previously thought. Homology searches led to the identification of > 60 putative effector genes. Thirteen of these were judged to be likely pseudogenes, whereas 49 were judged to be potentially functional. In total, 39 proteins were confirmed experimentally as effectors: 31 through proteomics and 28 through translocation assays. At the protein level, the EHEC effector sequences fall into > 20 families. The largest family, the NleG family, contains 14 members in the Sakai strain alone. EHEC also harbors functional homologs of effectors from plant pathogens (HopPtoH, HopW, AvrA) and from Shigella (OspD, OspE, OspG), and two additional members of the Map/IpgB family. Genes encoding proven or predicted effectors occur in > 20 exchangeable effector loci scattered throughout the chromosome. Crucially, the majority of functional effector genes are encoded by nine exchangeable effector loci that lie within lambdoid prophages. Thus, type III secretion in E. coli is linked to a vast phage metagenome, acting as a crucible for the evolution of pathogenicity.

Delivering culturally sensitive care: The perceptions of older Arabian Gulf Arabs concerning religion, health, and disease

Health professionals need to be cognizant of the varying perceptions of health shared by people from different religious, sociocultural, and linguistic backgrounds to deliver culturally sensitive health care. In this qualitative study, the authors used semistructured interviews to provide insight into how 10 older Arabian Gulf Muslim persons understand and perceive health and illness with emphasis on the role of Islam in formulating health behaviors. Participants' views were strongly influenced by their religious convictions. Good health was equated with the absence of visible disease, with participants demonstrating limited understanding of silent or insidious disease. They attended doctors for treatment of visible disease rather than seeking preventive health care for diseases such as hypertension, diabetes, and hyperlipidemia. Building oil the results from this study could help inform both health service planners and providers to improve the appropriateness, relevancy, and effectiveness of aged care services for these individuals.