Modeling recursive RNA interference.

An important application of the RNA interference (RNAi) pathway is its use as a small RNA-based regulatory system commonly exploited to suppress expression of target genes to test their function in vivo. In several published experiments, RNAi has been used to inactivate components of the RNAi pathway itself, a procedure termed recursive RNAi in this report. The theoretical basis of recursive RNAi is unclear since the procedure could potentially be self-defeating, and in practice the effectiveness of recursive RNAi in published experiments is highly variable. A mathematical model for recursive RNAi was developed and used to investigate the range of conditions under which the procedure should be effective. The model predicts that the effectiveness of recursive RNAi is strongly dependent on the efficacy of RNAi at knocking down target gene expression. This efficacy is known to vary highly between different cell types, and comparison of the model predictions to published experimental data suggests that variation in RNAi efficacy may be the main cause of discrepancies between published recursive RNAi experiments in different organisms. The model suggests potential ways to optimize the effectiveness of recursive RNAi both for screening of RNAi components as well as for improved temporal control of gene expression in switch off-switch on experiments

A Cross-Sectional Study of People with Epilepsy and Neurocysticercosis in Tanzania: Clinical Characteristics and Diagnostic Approaches.

Neurocysticercosis (NCC) is a major cause of epilepsy in regions where pigs are free-ranging and hygiene is poor. Pork production is expected to increase in the next decade in sub-Saharan Africa, hence NCC will likely become more prevalent. In this study, people with epilepsy (PWE, n=212) were followed up 28.6 months after diagnosis of epilepsy. CT scans were performed, and serum and cerebrospinal fluid (CSF) of selected PWE were analysed. We compared the demographic data, clinical characteristics, and associated risk factors of PWE with and without NCC. PWE with NCC (n=35) were more likely to be older at first seizure (24.3 vs. 16.3 years, p=0.097), consumed more pork (97.1% vs. 73.6%, p=0.001), and were more often a member of the Iraqw tribe (94.3% vs. 67.8%, p=0.005) than PWE without NCC (n=177). PWE and NCC who were compliant with anti-epileptic medications had a significantly higher reduction of seizures (98.6% vs. 89.2%, p=0.046). Other characteristics such as gender, seizure frequency, compliance, past medical history, close contact with pigs, use of latrines and family history of seizures did not differ significantly between the two groups. The number of NCC lesions and active NCC lesions were significantly associated with a positive antibody result. The electroimmunotransfer blot, developed by the Centers for Disease Control and Prevention, was more sensitive than a commercial western blot, especially in PWE and cerebral calcifications. This is the first study to systematically compare the clinical characteristics of PWE due to NCC or other causes and to explore the utility of two different antibody tests for diagnosis of NCC in sub-Saharan Africa

The Distances of the Magellanic Clouds

The present status of our knowledge of the distances to the Magellanic Clouds is evaluated from a post-Hipparcos perspective. After a brief summary of the effects of structure, reddening, age and metallicity, the primary distance indicators for the Large Magellanic Cloud are reviewed: The SN 1987A ring, Cepheids, RR Lyraes, Mira variables, and Eclipsing Binaries. Distances derived via these methods are weighted and combined to produce final "best" estimates for the Magellanic Clouds distance moduli.Comment: Invited review article to appear in ``Post Hipparcos Cosmic Candles'', F. Caputo & A. Heck (Eds.), Kluwer Academic Publ., Dordrecht, in pres

Spatio-temporal Models of Lymphangiogenesis in Wound Healing

Several studies suggest that one possible cause of impaired wound healing is failed or insufficient lymphangiogenesis, that is the formation of new lymphatic capillaries. Although many mathematical models have been developed to describe the formation of blood capillaries (angiogenesis), very few have been proposed for the regeneration of the lymphatic network. Lymphangiogenesis is a markedly different process from angiogenesis, occurring at different times and in response to different chemical stimuli. Two main hypotheses have been proposed: 1) lymphatic capillaries sprout from existing interrupted ones at the edge of the wound in analogy to the blood angiogenesis case; 2) lymphatic endothelial cells first pool in the wound region following the lymph flow and then, once sufficiently populated, start to form a network. Here we present two PDE models describing lymphangiogenesis according to these two different hypotheses. Further, we include the effect of advection due to interstitial flow and lymph flow coming from open capillaries. The variables represent different cell densities and growth factor concentrations, and where possible the parameters are estimated from biological data. The models are then solved numerically and the results are compared with the available biological literature.Comment: 29 pages, 9 Figures, 6 Tables (39 figure files in total

MICE: The muon ionization cooling experiment. Step I: First measurement of emittance with particle physics detectors

Copyright @ 2011 APSThe Muon Ionization Cooling Experiment (MICE) is a strategic R&D project intended to demonstrate the only practical solution to providing high brilliance beams necessary for a neutrino factory or muon collider. MICE is under development at the Rutherford Appleton Laboratory (RAL) in the United Kingdom. It comprises a dedicated beamline to generate a range of input muon emittances and momenta, with time-of-flight and Cherenkov detectors to ensure a pure muon beam. The emittance of the incoming beam will be measured in the upstream magnetic spectrometer with a scintillating fiber tracker. A cooling cell will then follow, alternating energy loss in Liquid Hydrogen (LH2) absorbers to RF cavity acceleration. A second spectrometer, identical to the first, and a second muon identification system will measure the outgoing emittance. In the 2010 run at RAL the muon beamline and most detectors were fully commissioned and a first measurement of the emittance of the muon beam with particle physics (time-of-flight) detectors was performed. The analysis of these data was recently completed and is discussed in this paper. Future steps for MICE, where beam emittance and emittance reduction (cooling) are to be measured with greater accuracy, are also presented.This work was supported by NSF grant PHY-0842798

Gastric stimulation: influence of electrical parameters on gastric emptying in control and diabetic rats

BACKGROUND: The aim of this study was to test the effect of different pulse frequencies and amplitudes during gastric stimulation (GS) on gastric emptying in the rat. METHODS: GS was performed in 2 groups of laparotomized rats: healthy control animals, and rats with acute diabetes. The effects of four pulse frequencies (0.5, 1, 10, 20 Hz) and three pulse amplitudes (5, 20, 40 mA) were tested. The volumes emptied from the stomach after the oro-gastric instillation of a nutrient solution were compared to those obtained in animals without GS. Intragastric pH values were assessed under basal conditions and after GS. RESULTS: In both groups, GS increased emptied volumes compared to conditions without stimulation (p < 0.05) for pulse frequencies above 0.5 Hz. Increases in pulse frequencies accelerated gastric emptying (p < 0.01) with a plateau at around 10 Hz. The increase in pulse amplitudes resulted in larger emptied volumes only when the pulse frequency was 1 Hz (p < 0.04) while the opposite effect was observed at 20 Hz (p < 0.04). The most effective combinations to enhance gastric emptying compared to baseline conditions were 10 Hz with 5 or 20 mA. The overall effect of GS on gastric emptying compared to baseline conditions without stimulation, was greater in diabetic than in controls rats (p < 0.05). During stimulation, intragastric pH values were not different from basal conditions during fasting or after a meal in control and diabetic rats. CONCLUSIONS: Although both pulse frequency and amplitude should be considered during GS, frequency appears to be the most critical point. The possibility of increasing gastric emptying by electrical stimulation in diabetic rats suggests potential clinical applications for this method

Postural development in school children: a cross-sectional study

BACKGROUND: Little information on quantitative sagittal plane postural alignment and evolution in children exists. The objectives of this study are to document the evolution of upright, static, sagittal posture in children and to identify possible critical phases of postural evolution (maturation). METHODS: A total of 1084 children (aged 4–12 years) received a sagittal postural evaluation with the Biotonix postural analysis system. Data were retrieved from the Biotonix internet database. Children were stratified and analyzed by years of age with n = 36 in the youngest age group (4 years) and n = 184 in the oldest age group (12 years). Children were analyzed in the neutral upright posture. Variables measured were sagittal translation distances in millimeters of: the knee relative to the tarsal joint, pelvis relative to the tarsal joint, shoulder relative to the tarsal joint, and head relative to the tarsal joint. A two-way factorial ANOVA was used to test for age and gender effects on posture, while polynomial trend analyses were used to test for increased postural displacements with years of age. RESULTS: Two-way ANOVA yielded a significant main effect of age for all 4 sagittal postural variables and gender for all variables except head translation. No age × gender interaction was found. Polynomial trend analyses showed a significant linear association between child age and all four postural variables: anterior head translation (p < 0.001), anterior shoulder translation (p < 0.001), anterior pelvic translation (p < 0.001), anterior knee translation (p < 0.001). Between the ages of 11 and 12 years, for anterior knee translation, T-test post hoc analysis revealed only one significant rough break in the continuity of the age related trend. CONCLUSION: A significant linear trend for increasing sagittal plane postural translations of the head, thorax, pelvis, and knee was found as children age from 4 years to 12 years. These postural translations provide preliminary normative data for the alignment of a child's sagittal plane posture

Mechanistic modelling of dynamic MRI data predicts that tumour heterogeneity decreases therapeutic response

Mechanistic modelling of dynamic MRI data predicts that tumour heterogeneity decreases therapeutic respons

Limits on WWZ and WW\gamma couplings from p\bar{p}\to e\nu jj X events at \sqrt{s} = 1.8 TeV

We present limits on anomalous WWZ and WW-gamma couplings from a search for WW and WZ production in p-bar p collisions at sqrt(s)=1.8 TeV. We use p-bar p -> e-nu jjX events recorded with the D0 detector at the Fermilab Tevatron Collider during the 1992-1995 run. The data sample corresponds to an integrated luminosity of 96.0+-5.1 pb^(-1). Assuming identical WWZ and WW-gamma coupling parameters, the 95% CL limits on the CP-conserving couplings are -0.33<lambda<0.36 (Delta-kappa=0) and -0.43<Delta-kappa<0.59 (lambda=0), for a form factor scale Lambda = 2.0 TeV. Limits based on other assumptions are also presented.Comment: 11 pages, 2 figures, 2 table