Giardia duodenalis mouse model for the development of novel antigiardial agents

This study describes a neonatal mouse model of Giardia infection for development of novel antigiardials. Mice were infected with the axenically cultured Assemblage A BAH2c2 strain, with 105 trophozoites per animal recovered. This model proved to be robust and consistent for use in preliminary drug efficacy trials and drug development

Altered renal hemodynamics and impaired myogenic responses in the fawn-hooded rat

The present study examined whether an abnormality in the myogenic response of renal arterioles that impairs autoregulation of renal blood flow (RBF) and glomerular capillary pressure (PGC) contributes to the development of renal damage in fawn-hooded hypertensive (FHH) rats. Autoregulation of whole kidney, cortical, and medullary blood flow and PGC were compared in young (12 wk old) FHH and fawn-hooded low blood pressure (FHL) rats in volume-replete and volume-expanded conditions. Baseline RBF, cortical and medullary blood flow, and PGC were significantly greater in FHH than in FHL rats. Autoregulation of renal and cortical blood flow was significantly impaired in FHH rats compared with results obtained in FHL rats. Myogenically mediated autoregulation of PGC was significantly greater in FHL than in FHH rats. PGC rose from 46 +/- 1 to 71 +/- 2 mmHg in response to an increase in renal perfusion pressure from 100 to 150 mmHg in FHH rats, whereas it only increased from 39 +/- 2 to 53 +/- 1 mmHg in FHL rats. Isolated perfused renal interlobular arteries from FHL rats constricted by 10% in response to elevations in transmural pressure from 70 to 120 mmHg. In contrast, the diameter of vessels from FHH rats increased by 15%. These results indicate that the myogenic response of small renal arteries is altered in FHH rats, and this contributes to an impaired autoregulation of renal blood flow and elevations in PGC in this strain

The assessment of intramolecular hydrogen bonding in ortho-substituted anilines by an NMR method

YesWe describe the Δlog P method for the assessment of intramolecular hydrogen bonds (IMHBs), and show that it is not a very general method of distinguishing between molecules in which there is an IMHB and molecules in which there is no IMHB. The ‘double’ Δlog P method of Shalaeva et al. is a much more reliable method for the assessment of IMHB but requires the synthesis of a model compound and the determination of no less than four water-solvent partition coefficients. In addition, it is difficult to apply to compounds that contain more than one hydrogen bond acidic group capable of IMHB. We then describe our NMR method of assessing IMHB, based on 1H NMR chemical shifts in solvents DMSO and CDCl3. We have determined 1H NMR chemical shifts for a number of ortho-substituted anilines and show that the only compound we have studied that forms an IMHB is methyl 2-methylaminobenzoate though there is no IMHB present in methyl 2-aminobenzoate. This apparently anomalous result is supported by both MM and ab initio calculations. The NMR method is much simpler and less time consuming than other methods for the assessment of IMHB. It provides a quantitative assessment of IMHB and can be applied to molecules with more than one hydrogen bond acidic group

Impaired autoregulation of renal blood flow in the fawn-hooded rat

The responses to changes in renal perfusion pressure (RPP) were compared in 12-wk-old fawn-hooded hypertensive (FHH), fawn-hooded low blood pressure (FHL), and August Copenhagen Irish (ACI) rats to determine whether autoregulation of renal blood flow (RBF) is altered in the FHH rat. Mean arterial pressure was significantly higher in conscious, chronically instrumented FHH rats than in FHL rats (121 +/- 4 vs. 109 +/- 6 mmHg). Baseline arterial pressures measured in ketamine-Inactin-anesthetized rats averaged 147 +/- 2 mmHg (n = 9) in FHH, 132 +/- 2 mmHg (n = 10) in FHL, and 123 +/- 4 mmHg (n = 9) in ACI rats. Baseline RBF was significantly higher in FHH than in FHL and ACI rats and averaged 9.6 +/- 0.7, 7.4 +/- 0.5, and 7.8 +/- 0.9 ml. min-1. g kidney wt-1, respectively. RBF was autoregulated in ACI and FHL but not in FHH rats. Autoregulatory indexes in the range of RPPs from 100 to 150 mmHg averaged 0.96 +/- 0.12 in FHH vs. 0.42 +/- 0.04 in FHL and 0.30 +/- 0.02 in ACI rats. Glomerular filtration rate was 20-30% higher in FHH than in FHL and ACI rats. Elevations in RPP from 100 to 150 mmHg increased urinary protein excretion in FHH rats from 27 +/- 2 to 87 +/- 3 microg/min, whereas it was not significantly altered in FHL or ACI rats. The percentage of glomeruli exhibiting histological evidence of injury was not significantly different in the three strains of rats. These results indicate that autoregulation of RBF is impaired in FHH rats before the development of glomerulosclerosis and suggest that an abnormality in the control of renal vascular resistance may contribute to the development of proteinuria and renal failure in this strain of rats

Demonstrating the Feasibility of Line Intensity Mapping Using Mock Data of Galaxy Clustering from Simulations

Visbal & Loeb (2010) have shown that it is possible to measure the clustering of galaxies by cross correlating the cumulative emission from two different spectral lines which originate at the same redshift. Through this cross correlation, one can study galaxies which are too faint to be individually resolved. This technique, known as intensity mapping, is a promising probe of the global properties of high redshift galaxies. Here, we test the feasibility of such measurements with synthetic data generated from cosmological dark matter simulations. We use a simple prescription for associating galaxies with dark matter halos and create a realization of emitted radiation as a function of angular position and wavelength over a patch of the sky. This is then used to create synthetic data for two different hypothetical instruments, one aboard the Space Infrared Telescope for Cosmology and Astrophysics (SPICA) and another consisting of a pair of ground based radio telescopes designed to measure the CO(1-0) and CO(2-1) emission lines. We find that the line cross power spectrum can be measured accurately from the synthetic data with errors consistent with the analytical prediction of Visbal & Loeb (2010). Removal of astronomical backgrounds and masking bright line emission from foreground contaminating galaxies do not prevent accurate cross power spectrum measurements.Comment: 12 pages, 6 figures, Submitted to JCA

The Use of MM/QM calculations of 13C chemical shifts in the analysis of Edaravone tautomers

YesThe 13C NMR chemical shifts of the three Edaravone tautomers (keto, enol, and amine) were calculated using a combined molecular mechanics (Pcmod 9.1/MMFF94) and ab initio (GIAO (B3LYP/DFT, 6–31 + G(d)) model. This method gave such good agreement with experiment that the assignment of the complex spectrum of Edaravone in solution, which is a mixture of the three tautomers could be made. This has been attempted previously by various methods with diverse results. In CDCl3 solution, the observed spectra show only one form, the keto tautomer, and this is also the case with acetonitrile solvent. Acetone solvent reacts with Edavarone in the NMR tube. In the other solvents studied, methanol, pyridine, DMSO, trifluoroethanol (TFE), there is a mixture of the tautomers with populations which vary with the solvent. The application of the shift predictions allows the assignment of the 13C spectra to the three tautomers and from this the proportions of the tautomers in the solution. The results at times differ significantly from previous studies, and this is discussed

Photoassociation spectroscopy of cold calcium atoms

Photoassociation spectroscopy experiments on 40Ca atoms close to the dissociation limit 4s4s 1S0 - 4s4p 1P1 are presented. The vibronic spectrum was measured for detunings of the photoassociation laser ranging from 0.6 GHz to 68 GHz with respect to the atomic resonance. In contrast to previous measurements the rotational splitting of the vibrational lines was fully resolved. Full quantum mechanical numerical simulations of the photoassociation spectrum were performed which allowed us to put constraints on the possible range of the calcium scattering length to between 50 a_0 and 300 a_0

Diagnosis and Management of Iliac Artery Endofibrosis: Results of a Delphi Consensus Study

Objective Iliac endofibrosis is a rare condition that may result in a reduction of blood flow to the lower extremity in young, otherwise healthy individuals. The data to inform everyday clinical management are weak and therefore a Delphi consensus methodology was used to explore areas of consensus and disagreement concerning the diagnosis and management of patients with suspected iliac endofibrosis. Methods A three-round Delphi questionnaire approach was used among vascular surgeons, sports physicians, sports scientists, radiologists, and clinical vascular scientists with experience of treating this condition to explore diagnosis and clinical management issues for patients with suspected iliac artery endofibrosis. Analysis is based on 18 responses to round 2 and 14 responses to round 3, with agreement reported when 70% of respondents were in agreement. Results Initially there was agreement on the typical symptoms at presentation and the need for an exercise test in the diagnosis. Round 3 clarified that duplex ultrasound was a useful tool in the diagnosis of endofibrosis. There was consensus on the most appropriate type of surgery (endarterectomy and vein patch) and that endovascular interventions were inadvisable. The final round helped to inform aspects of the natural history and post-operative surveillance. Progression of the disease was likely with continued exercise but cessation may prevent progression. Surveillance after surgery is generally recommended yearly with at least a clinical assessment. Conclusions There is broad agreement about the presenting symptoms and the investigations required to confirm (or exclude) the diagnosis of iliac endofibrosis. There was consensus on the surgical approach to repair. Disagreement existed about the specific diagnostic criteria that should be applied during non-invasive testing and about post-operative care and resumption of exercise

Rings and bars: unmasking secular evolution of galaxies

Secular evolution gradually shapes galaxies by internal processes, in contrast to early cosmological evolution which is more rapid. An important driver of secular evolution is the flow of gas from the disk into the central regions, often under the influence of a bar. In this paper, we review several new observational results on bars and nuclear rings in galaxies. They show that these components are intimately linked to each other, and to the properties of their host galaxy. We briefly discuss how upcoming observations, e.g., imaging from the Spitzer Survey of Stellar Structure in Galaxies (S4G), will lead to significant further advances in this area of research.Comment: Invited review at "Galaxies and their Masks", celebrating Ken Freeman's 70-th birthday, Sossusvlei, Namibia, April 2010. To be published by Springer, New York, editors D.L. Block, K.C. Freeman, & I. Puerari; minor change

Inflation and the Scale Dependent Spectral Index: Prospects and Strategies

We consider the running of the spectral index as a probe of both inflation itself, and of the overall evolution of the very early universe. Surveying a collection of simple single field inflationary models, we confirm that the magnitude of the running is relatively consistent, unlike the tensor amplitude, which varies by orders of magnitude. Given this target, we confirm that the running is potentially detectable by future large scale structure or 21 cm observations, but that only the most futuristic measurements can distinguish between these models on the basis of their running. For any specified inflationary scenario, the combination of the running index and unknown post-inflationary expansion history induces a theoretical uncertainty in the predicted value of the spectral index. This effect can easily dominate the statistical uncertainty with which Planck and its successors are expected to measure the spectral index. More positively, upcoming cosmological experiments thus provide an intriguing probe of physics between TeV and GUT scales by constraining the reheating history associated with any specified inflationary model, opening a window into the "primordial dark age" that follows the end of inflation.Comment: 32 pages. v2 and v3 Minor reference updates /clarification