1,107 research outputs found

    Optimum Shipment Patterns of Feeder Cattle and Feed Grains in South Dakota and Their Implications

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    Current data on the livestock and grain industries of South Dakota indicate that the state is a net exporter of feeder cattle and feed grains, suggesting that if the feeder cattle and feed grains were retained within the state, the state’s beef feeding and packing industries could be expanded considerably. This study divided the state into seven regions based on their natural resource similarities to determine the optimum movement of feed grains and feeder cattle in South Dakota

    Measuring Protein Binding to F-actin by Co-sedimentation

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    Filamentous actin (F-actin) organization within cells is regulated by a large number of actin-binding proteins that control actin nucleation, growth, cross-linking and/or disassembly. This protocol describes a technique – the actin co-sedimentation, or pelleting, assay – to determine whether a protein or protein domain binds F-actin and to measure the affinity of the interaction (i.e., the dissociation equilibrium constant). In this technique, a protein of interest is first incubated with F-actin in solution. Then, differential centrifugation is used to sediment the actin filaments, and the pelleted material is analyzed by SDS-PAGE. If the protein of interest binds F-actin, it will co-sediment with the actin filaments. The products of the binding reaction (i.e., F-actin and the protein of interest) can be quantified to determine the affinity of the interaction. The actin pelleting assay is a straightforward technique for determining if a protein of interest binds F-actin and for assessing how changes to that protein, such as ligand binding, affect its interaction with F-actin

    Pharmacokinetics of propofol in severely obese surgical patients

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    BACKGROUND: Existing PK models of propofol include sparse data from very obese patients. The aim of this study was to develop a PK model based on standardised surgical conditions and spanning from normal-weight up to, and including, a high number of very obese patients. METHODS: Adult patients scheduled for laparoscopic cholecystectomy or bariatric surgery were studied. Anaesthesia was induced with propofol 2 mg/kg adjusted body weight over 2 min followed by 6 mg/kg/h adjusted body weight over 30 min. For the remainder of the operation anaesthesia was maintained with sevoflurane. Remifentanil was dosed according to clinical need. Eight arterial samples were drawn in a randomised block sampling regimen over a span of 24 h. Time-concentration data were analysed by population PK modelling using non-linear mixed-effects modelling. RESULTS: Four hundred and seventy four serum propofol concentrations were collected from 69 patients aged 19-60 years with a BMI 21.6-67.3 kg/m2 . Twenty one patients had a BMI above 50 kg/m2 . A 3-compartment PK model was produced wherein three different body weight descriptors and sex were included as covariates in the final model. Total body weight was found to be a covariate for clearance and Q3; lean body weight for V1, V2 and Q2; predicted normal weight for V3 and sex for V1. The fixed allometric exponent of 0.75 applied to all clearance parameters improved the performance of the model. Accuracy and precision were 1.4% and 21.7% respectively in post-hoc performance evaluation. CONCLUSION: We have developed a new PK model of propofol that is suitable for all adult weight classes. Specifically, it is based on data from an unprecedented number of individuals with very high BMI

    Development of electrocardiogram intervals during growth of FVB/N neonate mice

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    <p>Abstract</p> <p>Background</p> <p>Electrocardiography remains the best diagnostic tool and therapeutic biomarker for a spectrum of pediatric diseases involving cardiac or autonomic nervous system defects. As genetic links to these disorders are established and transgenic mouse models produced in efforts to understand and treat them, there is a surprising lack of information on electrocardiograms (ECGs) and ECG abnormalities in neonate mice. This is likely due to the trauma and anaesthesia required of many legacy approaches to ECG recording in mice, exacerbated by the fragility of many mutant neonates. Here, we use a non-invasive system to characterize development of the heart rate and electrocardiogram throughout the growth of conscious neonate FVB/N mice.</p> <p>Results</p> <p>We examine ECG waveforms as early as two days after birth. At this point males and females demonstrate comparable heart rates that are 50% lower than adult mice. Neonatal mice exhibit very low heart rate variability. Within 12 days of birth PR, QRS and QTc interval durations are near adult values while heart rate continues to increase until weaning. Upon weaning FVB/N females quickly develop slower heart rates than males, though PR intervals are comparable between sexes until a later age. This suggests separate developmental events may contribute to these gender differences in electrocardiography.</p> <p>Conclusions</p> <p>We provide insight with a new level of detail to the natural course of heart rate establishment in neonate mice. ECG can now be conveniently and repeatedly used in neonatal mice. This should serve to be of broad utility, facilitating further investigations into development of a diverse group of diseases and therapeutics in preclinical mouse studies.</p

    Cyanine platelet single crystals: Growth, crystal structure and optical spectra

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    © the Owner Societies. Crystalline organic semiconducting materials are much in demand for multiple electronic and optoelectronic device applications. Here, solution grown ultrathin rhombic crystals of a trimethine carbocyanine anionic dye are used to establish relationships between structural and optical properties. The dye crystallized in the monoclinic space group P21/c featuring alternating layers of molecules in two different herringbone type patterns, with perchlorate counterions located mostly within one of the two layers. Micro transmittance spectroscopy revealed a broadened spectrum compared to those obtained in solution and in an amorphous thin film. Using polarized light, transmission spectroscopy revealed strong low-energy and weak high-energy bands polarized along the crystallographic b- and c-axis, respectively. Using the extended dipole approximation, significant exciton couplings are predicted between neighboring molecules in the crystal, of the order of the intrinsic monomer reorganization energies associated with nuclear relaxation after excitation, depicting a complex spectral scenario. The exciton coupling pattern explains the relative energies of the b- and c-polarized components but the observed intensities are opposite to expectations based on chromophore alignment within the crystal

    Randomized Trial to Evaluate Tandospirone in Geographic Atrophy Secondary to Age-Related Macular Degeneration: The GATE Study

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    Purpose To determine the safety and efficacy of AL-8309B (tandospirone) in the management of patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) and obtain standardized data on GA lesion growth progression. Design Prospective, controlled, double-masked, randomized, multicenter phase 3 clinical trial. Methods setting: Forty-eight clinical sites. patients: Patients with GA associated with AMD were enrolled. All patients were followed for a minimum of 30 months, and up to 36 months. intervention procedures: Patients were randomized (1:1:1) to receive AL-8309B ophthalmic solution 1.0%, 1.75%, or vehicle, administered as a twice-daily topical ocular drop. main outcome measures: The primary efficacy endpoint was mean annualized lesion enlargement from baseline as assessed with fundus autofluorescence (FAF) imaging. Results A total of 768 eyes of 768 patients were enrolled and treated with AL-8309B 1.0% (n = 250), AL-8309B 1.75% (n = 258), or vehicle (n = 260). An increase in mean lesion size was observed in both the AL-8309B and vehicle treatment groups, and growth rates were similar in all treatment groups. Annualized lesion growth rates were 1.73, 1.76, and 1.71 mm 2 for AL-8309B 1.0%, AL-8309B 1.75%, and vehicle, respectively. Conclusions AL-8309B 1.0% and 1.75% did not affect lesion growth in eyes with GA secondary to AMD. There were no clinically relevant safety issues identified for AL-8309B. The large natural history dataset from this study is a valuable repository for future comparisons

    Small bound for birational automorphism groups of algebraic varieties (with an Appendix by Yujiro Kawamata)

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    We give an effective upper bound of |Bir(X)| for the birational automorphism group of an irregular n-fold (with n = 3) of general type in terms of the volume V = V(X) under an ''albanese smoothness and simplicity'' condition. To be precise, |Bir(X)| < d_3 V^{10}. An optimum linear bound |Bir(X)|-1 < (1/3)(42)^3 V is obtained for those 3-folds with non-maximal albanese dimension. For all n > 2, a bound |Bir(X)| < d_n V^{10} is obtained when alb_X is generically finite, alb(X) is smooth and Alb(X) is simple.Comment: Mathematische Annalen, to appea

    Methodological approaches to determining the marine radiocarbon reservoir effect

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    The marine radiocarbon reservoir effect is an offset in 14C age between contemporaneous organisms from the terrestrial environment and organisms that derive their carbon from the marine environment. Quantification of this effect is of crucial importance for correct calibration of the &lt;sup&gt;14&lt;/sup&gt;C ages of marine-influenced samples to the calendrical timescale. This is fundamental to the construction of archaeological and palaeoenvironmental chronologies when such samples are employed in &lt;sup&gt;14&lt;/sup&gt;C analysis. Quantitative measurements of temporal variations in regional marine reservoir ages also have the potential to be used as a measure of process changes within Earth surface systems, due to their link with climatic and oceanic changes. The various approaches to quantification of the marine radiocarbon reservoir effect are assessed, focusing particularly on the North Atlantic Ocean. Currently, the global average marine reservoir age of surface waters, R(t), is c. 400 radiocarbon years; however, regional values deviate from this as a function of climate and oceanic circulation systems. These local deviations from R(t) are expressed as +R values. Hence, polar waters exhibit greater reservoir ages (&#948;R = c. +400 to +800 &lt;sup&gt;14&lt;/sup&gt;C y) than equatorial waters (&#948;R = c. 0 &lt;sup&gt;14&lt;/sup&gt;C y). Observed temporal variations in &#948;R appear to reflect climatic and oceanographic changes. We assess three approaches to quantification of marine reservoir effects using known age samples (from museum collections), tephra isochrones (present onshore/offshore) and paired marine/terrestrial samples (from the same context in, for example, archaeological sites). The strengths and limitations of these approaches are evaluated using examples from the North Atlantic region. It is proposed that, with a suitable protocol, accelerator mass spectrometry (AMS) measurements on paired, short-lived, single entity marine and terrestrial samples from archaeological deposits is the most promising approach to constraining changes over at least the last 5 ky BP

    Impact of Baseline Retinal Nonperfusion and Macular Retinal Capillary Nonperfusion on Outcomes in the COPERNICUS and GALILEO Studies

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    To evaluate the impact of baseline retinal capillary nonperfusion (RNP) and macular retinal capillary nonperfusion (MNP) status on outcomes at week&nbsp;24 (W24)

    IL-13-induced airway mucus production is attenuated by MAPK13 inhibition

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    Increased mucus production is a common cause of morbidity and mortality in inflammatory airway diseases, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis. However, the precise molecular mechanisms for pathogenic mucus production are largely undetermined. Accordingly, there are no specific and effective anti-mucus therapeutics. Here, we define a signaling pathway from chloride channel calcium-activated 1 (CLCA1) to MAPK13 that is responsible for IL-13–driven mucus production in human airway epithelial cells. The same pathway was also highly activated in the lungs of humans with excess mucus production due to COPD. We further validated the pathway by using structure-based drug design to develop a series of novel MAPK13 inhibitors with nanomolar potency that effectively reduced mucus production in human airway epithelial cells. These results uncover and validate a new pathway for regulating mucus production as well as a corresponding therapeutic approach to mucus overproduction in inflammatory airway diseases
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