Orbital dynamics of "smart dust" devices with solar radiation pressure and drag

This paper investigates how perturbations due to asymmetric solar radiation pressure, in the presence of Earth shadow, and atmospheric drag can be balanced to obtain long-lived Earth centred orbits for swarms of micro-scale 'smart dust' devices, without the use of active control. The secular variation of Keplerian elements is expressed analytically through an averaging technique. Families of solutions are then identified where Sun-synchronous apse-line precession is achieved passively to maintain asymmetric solar radiation pressure. The long-term orbit evolution is characterized by librational motion, progressively decaying due to the non-conservative effect of atmospheric drag. Long-lived orbits can then be designed through the interaction of energy gain from asymmetric solar radiation pressure and energy dissipation due to drag. In this way, the usual short drag lifetime of such high area-to-mass spacecraft can be greatly extended (and indeed selected). In addition, the effect of atmospheric drag can be exploited to ensure the rapid end-of-life decay of such devices, thus preventing long-lived orbit debris

Rapid Publication The Transmembrane pH Gradient Drives Uphill Folate Transport in Rabbit Jejunum Direct Evidence for Folate/Hydroxyl Exchange in Brush Border Membrane Vesicles

Abstract In rabbit jejunal, but not ileal brush border membrane vesicles, an outwardly directed OH-gradient (pH 7.7 inside, pH 5.5 outside) markedly stimulated the initial velocity of folate (0.1 tiM) uptake compared with uptake in the absence of a pH gradient. Under pH gradient conditions, folate was transiently accumulated at a concentration four times that found at equilibrium (overshoot), implying uphill transport of the vitamin. Equilibrium folate uptake was inversely proportional to medium osmolality, suggesting uptake into an osmotically sensitive space. pH gradient-stimulated folate uptake was markedly reduced by inhibitors of anion exchange (4,4'-diisothiocyano-2,2'-disulfonic acid stilbene; 4-acetamido-4-isothiocyanostilbene-2,2'-disulfonic acid; furosemide), and was saturable (folate K., = 0.19±0.02 gsM; V, = 12.8±0.4 pmol -mg protein-' . min-). Imposition of an inside-positive electrical potential did not stimulate folate uptake, suggesting that stimulation by a pH gradient was not due to an induced electrical potential. In contrast, an inwardly directed Na' or K' gradient did not stimulate folate uptake. These findings provide evidence for a carrier on the jejunal brush border membrane that mediates folate/OH-exchange (or HW/folate co-transport), and are consonant with the known presence of an outwardly directed OH-gradient in vivo (brush border acid microclimate), an acidic pH optimum for intestinal folate uptake, and the primary role of the jejunum in folate absorption

Tocotrienol-rich fraction (TRF) improves the viability of wild-type Saccharomyces cerevisiae in the initial stationary phase

Palm oil tocotrienol-rich fraction (TRF) containing majorly of αα, β, γ andδδ-tocotrienols and some αα-tocopherols, was reported to have anti-ageing effects in both human and non-human model organisms, but still remains unexplored in the yeast model. It was reported to have the ability to extend the lifespan of several organisms. Chronological lifespan is one of the means to measure ageing in yeasts. The effect of TRF on the viability of three strains of Saccharomyces cerevisiae (wild-type, CTT1ΔΔand GPx2Δ) was studied. Phenotypic growth analysis of all strains was carried out for 15 hours by measuring the absorbance at OD600nm and cell counting. The optimum dose of TRF was optimised by determining the number of colony-forming unit by the wild-type strain at the end of a 24-hour treatment with TRF (ranging from 0μg/ml to 300μg/ml). TRF at 300 μg/mL showed the best result, and selected as a working dose. Treatment of cells with 300 μg/mL of TRF improved the viability of the wild-type strain in the initial stationary phase, but not on the knockout strains. These finding suggests that TRF has a potential in prolonging the chronological lifespan of S. cerevisiae, and perhaps other organisms as well

Effect of ranitidine on acetaminophen-induced hepatotoxicity in dogs

The effect of ranitidine administration upon the hepatotoxic effect produced by a multidose acetaminophen administration regimen was examined. Seventy-two dogs received three subcutaneous injections of acetaminophen (750, 200, 200 mg/kg body wt) in DMSO (600 mg/ml) at time zero, 9 hr later, and 24 hr after the first dose. Ten control animals (group I) were not given ranitidine, the remaining 62 dogs received an intramus-cular injection of ranitidine 30 min before each acetaminophen dose. Three different doses of ranitidine were used (mg/kg body wt): 50 mg, group II (33 dogs); 75 mg, group III (14 dogs); 120 mg, group IV (15 dogs). Ranitidine reduced the expected acetaminophen-induced hepatoxicity in a dose-response manner. Moreover, a significant correlation was found between the ranitidine dose and the survival rate, as evidenced by transaminase levels in the serum and histology of the liver. This model of fulminant hepatic failure induced by acetaminophen and its modulation with ranitidine provides clinical investigators with a research tool that will be useful in the future investigation of putative medical and surgical therapies being investigated for use in the clinical management of fulminant hepatic failure. Because of the size of the animal used in this model, frequent and serial analyses of blood and liver were available for study to determine the effect of therapy within a given animal as opposed to within groups of animals. © 1990 Plenum Publishing Corporation

Inferring latent task structure for Multitask Learning by Multiple Kernel Learning

<p>Abstract</p> <p>Background</p> <p>The lack of sufficient training data is the limiting factor for many Machine Learning applications in Computational Biology. If data is available for several different but related problem domains, Multitask Learning algorithms can be used to learn a model based on all available information. In Bioinformatics, many problems can be cast into the Multitask Learning scenario by incorporating data from several organisms. However, combining information from several tasks requires careful consideration of the degree of similarity between tasks. Our proposed method simultaneously learns or refines the similarity between tasks along with the Multitask Learning classifier. This is done by formulating the Multitask Learning problem as Multiple Kernel Learning, using the recently published <it>q</it>-Norm MKL algorithm.</p> <p>Results</p> <p>We demonstrate the performance of our method on two problems from Computational Biology. First, we show that our method is able to improve performance on a splice site dataset with given hierarchical task structure by refining the task relationships. Second, we consider an MHC-I dataset, for which we assume no knowledge about the degree of task relatedness. Here, we are able to learn the task similarities<it> ab initio</it> along with the Multitask classifiers. In both cases, we outperform baseline methods that we compare against.</p> <p>Conclusions</p> <p>We present a novel approach to Multitask Learning that is capable of learning task similarity along with the classifiers. The framework is very general as it allows to incorporate prior knowledge about tasks relationships if available, but is also able to identify task similarities in absence of such prior information. Both variants show promising results in applications from Computational Biology.</p

A critical role for endocytosis in Wnt signaling

BACKGROUND: The Wnt signaling pathway regulates many processes during embryonic development, including axis specification, organogenesis, angiogenesis, and stem cell proliferation. Wnt signaling has also been implicated in a number of cancers, bone density maintenance, and neurological conditions during adulthood. While numerous Wnts, their cognate receptors of the Frizzled and Arrow/LRP5/6 families and downstream pathway components have been identified, little is known about the initial events occurring directly after receptor activation. RESULTS: We show here that Wnt proteins are rapidly endocytosed by a clathrin- and dynamin-mediated process. While endocytosis has traditionally been considered a principal mechanism for receptor down-regulation and termination of signaling pathways, we demonstrate that interfering with clathrin-mediated endocytosis actually blocks Wnt signaling at the level of β-catenin accumulation and target gene expression. CONCLUSION: A necessary component of Wnt signaling occurs in a subcellular compartment distinct from the plasma membrane. Moreover, as internalized Wnts transit partially through the transferrin recycling pathway, it is possible that a "signaling endosome" serves as a nexus for activated Wnt pathway components

Erythrocyte uridine diphosphate galactose-4-epimerase deficiency identified by newborn screening for galactosemia in the United States

Eight infants (two whites and six blacks) with erythrocyte uridine diphosphate galactose-4-epimerase (epimerase) deficiency were identified in four newborn screening programs for galactosemia in the United States. The initial biochemical findings in all cases were elevated blood galactose-l-phosphate with normal or only slightly increased blood galactose and normal galactose-l-phosphate uridyltransferase (GALT) activity. Epimerase deficiency was confirmed in erythrocytes by a two-step enzymatic assay involving fluorometric measurements of NADH generated by coupling the uridine diphosphate glucose dehydrogenase reaction to epimerase. Seven of the eight infants appeared to be clinically normal at birth and one newborn had neonatal jaundice. The infrequent recognition of epimerase deficiency is likely due to the methods of newborn screening for galactosemia which are often only for GALT deficiency and perhaps also due to incomplete follow-up of increased metabolite levels in newborn blood specimens with normal GALT activity. Our results confirm a preliminary report of a high frequency of erythrocyte epimerase deficiency in the American black population.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30522/1/0000153.pd

Monte Carlo simulations of membrane signal transduction events: Effect of receptor blockers on G-protein activation

Cells have evolved elaborate strategies for sensing, responding to, and interacting with their environment. In many systems, interaction of cell surface receptors with extracellular ligand can activate cellular signal transduction pathways leading to G-protein activation and calcium mobilization. In BC 3 H1 smooth muscle-like cells, we find that the speed of calcium mobilization as well as the fraction of cells which mobilize calcium following phenylephrine stimulation is dependent upon receptor occupation. To determine whether receptor inactivation affects calcium mobilization, we use the receptor antagonist prazosin to block a fraction of cell surface receptors prior to phenylephrine stimulation. For cases of equal receptor occupation by agonist, cells with inactivated or blocked receptors show diminished calcium mobilization following phenylephrine stimulation as compared to cells without inactivated receptors. Ligand/receptor binding and two-dimensional diffusion of receptors and G-proteins in the cell membrane are studied using a Monte Carlo model. The model is used to determine if receptor inactivation affects G-protein activation and thus the following signaling events for cases of equal equilibrium receptor occupation by agonist. The model predicts that receptor inactivation by antagonist binding results in lower G-protein activation not only by reducing the number of receptors able to bind agonist but also by restricting the movement of agonist among free receptors. The latter process is important to increasing the access of bound receptors to G-proteins.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43997/1/10439_2006_Article_BF00000009.pd

Dkk1 Stabilizes Wnt Co-Receptor LRP6: Implication for Wnt Ligand-Induced LRP6 Down-Regulation

The low density lipoprotein receptor-related protein-6 (LRP6) is an essential co-receptor for canonical Wnt signaling. Dickkopf 1 (Dkk1), a major secreted Wnt signaling antagonist, binds to LRP6 with high affinity and prevents the Frizzled-Wnt-LRP6 complex formation in response to Wnts. Previous studies have demonstrated that Dkk1 promotes LRP6 internalization and degradation when it forms a ternary complex with the cell surface receptor Kremen.In the present study, we found that transfected Dkk1 induces LRP6 accumulation while inhibiting Wnt/LRP6 signaling. Treatment with Dkk1-conditioned medium or recombinant Dkk1 protein stabilized LRP6 with a prolonged half-life and induces LRP6 accumulation both at the cell surface and in endosomes. We also demonstrated that Kremen2 co-expression abrogated the effect of Dkk1 on LRP6 accumulation, indicating that the effect of Kremen2 is dominant over Dkk1 regulation of LRP6. Furthermore, we found that Wnt3A treatment induces LRP6 down-regulation, an effect paralleled with a Wnt/LRP6 signaling decay, and that Dkk1 treatment blocked Wnt3A-induced LRP6 down-regulation. Finally, we found that LRP6 turnover was blocked by an inhibitor of caveolae-mediated endocytosis.Our results reveal a novel role for Dkk1 in preventing Wnt ligand-induced LRP6 down-regulation and contribute significantly to our understanding of Dkk1 function in Wnt/LRP6 signaling

Dysregulation of the mTOR Pathway Mediates Impairment of Synaptic Plasticity in a Mouse Model of Alzheimer's Disease

Background: The mammalian target of rapamycin (mTOR) is an evolutionarily conserved Ser/Thr protein kinase that plays a pivotal role in multiple fundamental biological processes, including synaptic plasticity. We explored the relationship between the mTOR pathway and b-amyloid (Ab)-induced synaptic dysfunction, which is considered to be critical in the pathogenesis of Alzheimer’s disease (AD). Methodology/Principal Findings: We provide evidence that inhibition of mTOR signaling correlates with impairment in synaptic plasticity in hippocampal slices from an AD mouse model and in wild-type slices exposed to exogenous Ab1-42. Importantly, by up-regulating mTOR signaling, glycogen synthase kinase 3 (GSK3) inhibitors rescued LTP in the AD mouse model, and genetic deletion of FK506-binding protein 12 (FKBP12) prevented Ab-induced impairment in long-term potentiation (LTP). In addition, confocal microscopy demonstrated co-localization of intraneuronal Ab42 with mTOR. Conclusions/Significance: These data support the notion that the mTOR pathway modulates Ab-related synaptic dysfunctio