Regulation of Sphingosine-1-phosphate Lyase Gene Expression by Members of the GATA Family of Transcription Factors

Sphingosine-1-phosphate is a bioactive sphingolipid that regulates proliferation, differentiation, migration, and apoptosis. Sphingosine-1-phosphate is irreversibly degraded by the highly conserved enzyme sphingosine-1-phosphate lyase. Recent studies have suggested that sphingosine-1-phosphate lyase expression affects animal development and cell fate decisions. Despite its crucial role, mechanisms affecting expression of sphingosine-1-phosphate lyase remain poorly understood. In this study, regulation of sphingosine-1-phosphate lyase gene expression was investigated in Caenorhabditis elegans, where lyase expression is spatially restricted to cells of the developing and adult gut and is essential for normal development. Deletion analysis and generation of transgenic worms combined with fluorescence microscopy identified a 350-nucleotide sequence upstream of the ATG start site necessary for maximal lyase expression in adult worms. Site-specific mutagenesis of a GATA transcription factor-binding motif in the promoter led to loss of reporter expression. Knockdown of the gut-specific GATA transcription factor ELT-2 by RNA interference similarly led to loss of reporter expression. ELT-2 interacted with the GATA factor-binding motif in vitro and was also capable of driving expression of a Caenorhabditis elegans lyase promoter-{beta}-galactosidase reporter in a heterologous yeast system. These studies demonstrate that ELT-2 regulates sphingosine-1-phosphate lyase expression in vivo. Additionally, we demonstrate that the human sphingosine-1-phosphate lyase gene is regulated by a GATA transcription factor. Overexpression of GATA-4 led to both an increase in activity of a reporter gene as well as an increase in endogenous sphingosine-1-phosphate lyase protein

Status of magnetically-insulated power transmission theory

The theory of magnetically-insulated power flow has improved dramatically over the last two decades since the early works of Creedon, Lovelace and Ott, Ron, Mondelli, and Rostoker, and of Bergeron. During the intervening years theoretical improvements included a complete general kinetic theory that involved distributions of electrons based on quasi-conserved canonical variables and was used to study flow stability and to analyze simulations and pulsers with voltage adders. The status of theory at this time allowed them to understand many features of these flows, but did not allow detailed analysis for design and data interpretation. Recent theoretical advances have drastically changed this situation. Two recent static models based on layered flows have allowed them to understand and to improve power coupling in voltage adders, current adders, plasma opening switches and in systems where the vacuum impedance varies along the flow. A dynamic model based upon electrons flowing in one or more thin layers has permitted detailed self-consistent time-dependent calculations which include electron flow. This model accurately predicts experimental and simulational data

Chemical durability of zinc borosilicate nuclear waste glass

Chemical durability is of primary concern when evaluating the safety of waste glass. For this reason, testing the leachability of waste glasses is a fundamental part of their development and characterization. The leachability is also very much a function of glass composition as previously discussed. This discussion is limited to a representative waste glass composition, a high-zinc borosilicate formulation which has been studied in detail by Battelle Pacific Northwest Laboratories. (GHT

Precision electron flow measurements in a disk transmission line.

An analytic model for electron flow in a system driving a fixed inductive load is described and evaluated with particle in cell simulations. The simple model allows determining the impedance profile for a magnetically insulated transmission line given the minimum gap desired, and the lumped inductance inside the transition to the minimum gap. The model allows specifying the relative electron flow along the power flow direction, including cases where the fractional electron flow decreases in the power flow direction. The electrons are able to return to the cathode because they gain energy from the temporally rising magnetic field. The simulations were done with small cell size to reduce numerical heating. An experiment to compare electron flow to the simulations was done. The measured electron flow is {approx}33% of the value from the simulations. The discrepancy is assumed to be due to a reversed electric field at the cathode because of the inductive load and falling electron drift velocity in the power flow direction. The simulations constrain the cathode electric field to zero, which gives the highest possible electron flow

State-of-the-art review of materials properties of nuclear waste forms.

The Materials Characterization Center (MCC) was established at the Pacific Northwest Laboratory to assemble a standardized nuclear waste materials data base for use in research, systems and facility design, safety analyses, and waste management decisions. This centralized data base will be provided through the means of a Nuclear Waste Materials Handbook. The first issue of the Handbook will be published in the fall of 1981 in looseleaf format so that it can be updated as additional information becomes available. To ensure utmost reliability, all materials data appearing in the Handbook will be obtained by standard procedures defined in the Handbook and approved by an independent Materials Review Board (MRB) comprised of materials experts from Department of Energy laboratories and from universities and industry. In the interim before publication of the Handbook there is need for a report summarizing the existing materials data on nuclear waste forms. This review summarizes materials property data for the nuclear waste forms that are being developed for immobilization of high-level radioactive waste. It is intended to be a good representation of the knowledge concerning the properties of HLW forms as of March 1981. The table of contents lists the following topics: introduction which covers waste-form categories, and important waste-form materials properties; physical properties; mechanical properties; chemical durability; vaporization; radiation effects; and thermal phase stability

Applying a brain-computer interface to support motor imagery practice in people with stroke for upper limb recovery: A feasibility study

<p>Abstract</p> <p>Background</p> <p>There is now sufficient evidence that using a rehabilitation protocol involving motor imagery (MI) practice in conjunction with physical practice (PP) of goal-directed rehabilitation tasks leads to enhanced functional recovery of paralyzed limbs among stroke sufferers. It is however difficult to confirm patient engagement during an MI in the absence of any on-line measure. Fortunately an EEG-based brain-computer interface (BCI) can provide an on-line measure of MI activity as a neurofeedback for the BCI user to help him/her focus better on the MI task. However initial performance of novice BCI users may be quite moderate and may cause frustration. This paper reports a pilot study in which a BCI system is used to provide a computer game-based neurofeedback to stroke participants during the MI part of a protocol.</p> <p>Methods</p> <p>The participants included five chronic hemiplegic stroke sufferers. Participants received up to twelve 30-minute MI practice sessions (in conjunction with PP sessions of the same duration) on 2 days a week for 6 weeks. The BCI neurofeedback performance was evaluated based on the MI task classification accuracy (CA) rate. A set of outcome measures including action research arm test (ARAT) and grip strength (GS), was made use of in assessing the upper limb functional recovery. In addition, since stroke sufferers often experience physical tiredness, which may influence the protocol effectiveness, their fatigue and mood levels were assessed regularly.</p> <p>Results</p> <p>Positive improvement in at least one of the outcome measures was observed in all the participants, while improvements approached a minimal clinically important difference (MCID) for the ARAT. The on-line CA of MI induced sensorimotor rhythm (SMR) modulation patterns in the form of lateralized event-related desynchronization (ERD) and event-related synchronization (ERS) effects, for novice participants was in a moderate range of 60-75% within the limited 12 training sessions. The ERD/ERS change from the first to the last session was statistically significant for only two participants.</p> <p>Conclusions</p> <p>Overall the crucial observation is that the moderate BCI classification performance did not impede the positive rehabilitation trends as quantified with the rehabilitation outcome measures adopted in this study. Therefore it can be concluded that the BCI supported MI is a feasible intervention as part of a post-stroke rehabilitation protocol combining both PP and MI practice of rehabilitation tasks. Although these findings are promising, the scope of the final conclusions is limited by the small sample size and the lack of a control group.</p

Behavioral Consequences of NMDA Antagonist-Induced Neuroapoptosis in the Infant Mouse Brain

Background: Exposure to NMDA glutamate antagonists during the brain growth spurt period causes widespread neuroapoptosis in the rodent brain. This period in rodents occurs during the first two weeks after birth, and corresponds to the third trimester of pregnancy and several years after birth in humans. The developing human brain may be exposed to NMDA antagonists through drug-abusing mothers or through anesthesia. Methodology/Principal Findings: We evaluated the long-term neurobehavioral effects of mice exposed to a single dose of the NMDA antagonist, phencyclidine (PCP), or saline, on postnatal day 2 (P2) or P7, or on both P2 and P7. PCP treatment on P2 + P7 caused more severe cognitive impairments than either single treatment. Histological examination of acute neuroapoptosis resulting from exposure to PCP indicated that the regional pattern of degeneration induced by PCP in P2 pups was different from that in P7 pups. The extent of damage when evaluated quantitatively on P7 was greater for pups previously treated on P2 compared to pups treated only on P7. Conclusions: These findings signify that PCP induces different patterns of neuroapoptosis depending on the developmental age at the time of exposure, and that exposure at two separate developmental ages causes more severe neuropathologica

The place of VEGF inhibition in the current management of renal cell carcinoma

Vascular endothelial growth factor (VEGF) is overexpressed in around 80% of patients with clear cell carcinoma of the kidney owing to the inactivation of von Hippel Lindau gene activity. VEGF stimulates angiogenesis and acts as an autocrine growth factor. A number of different agents are now available which target VEGF and its signalling pathways. A significant body of evidence has accumulated demonstrating that antagonism of VEGF and its downstream pathways is clinically useful in a significant proportion of patients with metastatic clear cell carcinoma of the kidney. Enough data is now available to recommend that patients with metastatic clear cell carcinoma of the kidney should at some point during the course of their disease be offered entry into a clinical trial enabling exposure to a targeted inhibitor of VEGF or its signalling pathways. Assuming early clinical trial data is substantiated by ongoing registration studies, efforts should be made to minimise the time taken between licensing and general availability of these active agents

Giant breast tumors: Surgical management of phyllodes tumors, potential for reconstructive surgery and a review of literature

<p>Abstract</p> <p>Background</p> <p>Phyllodes tumors are biphasic fibroepithelial neoplasms of the breast. While the surgical management of these relatively uncommon tumors has been addressed in the literature, few reports have commented on the surgical approach to tumors greater than ten centimeters in diameter – the giant phyllodes tumor.</p> <p>Case presentation</p> <p>We report two cases of giant breast tumors and discuss the techniques utilized for pre-operative diagnosis, tumor removal, and breast reconstruction. A review of the literature on the surgical management of phyllodes tumors was performed.</p> <p>Conclusion</p> <p>Management of the giant phyllodes tumor presents the surgeon with unique challenges. The majority of these tumors can be managed by simple mastectomy. Axillary lymph node metastasis is rare, and dissection should be limited to patients with pathologic evidence of tumor in the lymph nodes.</p