Solid State NMR Spectroscopy/Imaging in Situ Measuring Devices and Methods for Calibration and Determining One or More Quantitative Properties of a Target SampleAbstract

In situ measuring devices, methods of making the same, and methods of using the same are provided herein. The in situ measuring devices can include a capillary tube having a reference material sealed inside the capillary tube, where the capillary tube is positioned inside of a solid state or MAS NMR rotor. A target sample can also be positioned in the interior of the solid state or MAS NMR rotor but is sequestered from the reference material by a capillary tube wall. The in situ measuring devices can be used in solid state MAS NMR spectroscopy to quantify one or more parameters of a target sample, such as the quantity of a sample, chemical identity of a sample, or temperature of a sample

Capillary-Tube Package Devices for the Quantitative Performance Evaluation of Nuclear Magnetic Resonance Spectrometers and Pulse Sequences

With the increased sensitivity of modern nuclear magnetic resonance (NMR) spectrometers, the minimum amount needed for chemical-shift referencing of NMR spectra has decreased to a point where a few microliters can be sufficient to observe a reference signal. The reduction in the amount of required reference material is the basis for the NMR Capillary-tube Package (CapPack) platform that utilizes capillary tubes with inner diameters smaller than 150 µm as NMR-tube inserts for external reference standards. It is shown how commercially available electrophoresis capillary tubes with outer diameters of 360 µm are filled with reference liquids or solutions and then permanently sealed by the arc discharge plasma of a commercially available fusion splicer normally employed for joining optical fibers. The permanently sealed capillaries can be used as external references for chemical-shift, signal-to-noise, resolution, and concentration calibration. Combining a number of permanently sealed capillaries to form CapPack devices leads to additional applications such as performance evaluation of NMR spectrometers and NMR pulse sequences. A 10-capillary-tube side-by-side Gradient CapPack device is used in combination with one or two constant gradients, produced by room-temperature shim coils, to monitor the excitation profiles of shaped pulses. One example illustrates the performance of hyperbolic secant (sech) pulses in the EXponentially Converging Eradication Pulse Train (EXCEPT) solvent suppression sequence. The excitation profile of the pulse sequence is obtained in a single gradient NMR experiment. A clustered T1 CapPack device is introduced consisting of a coaxial NMR-tube insert that holds seven capillary tubes filled with aqueous solutions of different concentrations of the paramagnetic relaxation agent copper(ii) sulfate (CuSO4). The different CuSO4 concentrations lead to spin-lattice relaxation times in the seven capillary tubes that cover a range which extends to more than an order of magnitude. Clustered T1 CapPack devices are best suited to quantify the effects that relaxation has on magnetizations and coherences during the execution of NMR experiments, which is demonstrated for the order-of-magnitude T1 insensitivity of signal suppression with EXCEPT

In Situ NMR Parameter Monitoring Systems and Methods for Measuring PH and Temperature

Devices and methods are provided for measuring temperatures and pHs of a sample in situ using NMR spectroscopy, and for sealing one or more ends of a capillary tube after a reference material has been added to the capillary tube, which is used in an in situ NMR temperature measurement device. A method for measuring a pH of a sample in situ using NMR spectroscopy includes providing an in situ NMR pH measurement device. This device includes a sample housing member configured to house a target sample, at least one pH sensor configured to exhibit an NMR spectral change due to a change in pH value of the target sample, and a pH sensor containment member configured to house the at least one pH sensor. The target sample is added to the sample housing member. NMR spectra are obtained to then determine the pH of the target sample

The correlation of the gross opthalmometer anisometropia with the best far point acuity lens (O.E.P. #7A) anisometropia

Throughout the optometric examination, the examiner strives to obtain consistent findings, i.e., of the cylinder power, cylinder axis and also of the anisometropia of the subjective acuity lenses and objective findings. Tile experlmentors wish to show that the correlation between the far point subjective spherical equivalent anisometropia and the anisometropia of the average of the two principal meridians of the corneal power as determined by ophthalmometry is not high enough to be a check of internal consistency of the optometric analysis

Understanding earthquake hazards in southern California - the "LARSE" project - working toward a safer future for Los Angeles

The Los Angeles region is underlain by a network of active faults, including many that are deep and do not break the Earth’s surface. These hidden faults include the previously unknown one responsible for the devastating January 1994 Northridge earthquake, the costliest quake in U.S. history. So that structures can be built or strengthened to withstand the quakes that are certain in the future, the Los Angeles Region Seismic Experiment (LARSE) is locating hidden earthquake hazards beneath the region to help scientists determine where the strongest shaking will occur

Effector CD4+ T Cell Expression Signatures and Immune-Mediated Disease Associated Genes

Genome-wide association studies (GWAS) in immune-mediated diseases have identified over 150 associated genomic loci. Many of these loci play a role in T cell responses, and regulation of T cell differentiation plays a critical role in immune-mediated diseases; however, the relationship between implicated disease loci and T cell differentiation is incompletely understood. To further address this relationship, we examined differential gene expression in naïve human CD4+ T cells, as well as in in vitro differentiated Th1, memory Th17-negative and Th17-enriched CD4+ T cells subsets using microarray and RNASeq. We observed a marked enrichment for increased expression in memory CD4+ compared to naïve CD4+ T cells of genes contained among immune–mediated disease loci. Within memory T cells, expression of disease-associated genes was typically increased in Th17-enriched compared to Th17-negative cells. Utilizing RNASeq and promoter methylation studies, we identified a differential regulation pattern for genes solely expressed in Th17 cells (IL17A and CCL20) compared to genes expressed in both Th17 and Th1 cells (IL23R and IL12RB2), where high levels of promoter methylation are correlated to near zero RNASeq levels for IL17A and CCL20. These findings have implications for human Th17 celI plasticity and for the regulation of Th17-Th1 expression signatures. Importantly, utilizing RNASeq we found an abundant isoform of IL23R terminating before the transmembrane domain that was enriched in Th17 cells. In addition to molecular resolution, we find that RNASeq provides significantly improved power to define differential gene expression and identify alternative gene variants relative to microarray analysis. The comprehensive integration of differential gene expression between cell subsets with disease-association signals, and functional pathways provides insight into disease pathogenesis

Low levels of amyloid-beta and its transporters in neonatal rats with and without hydrocephalus

<p>Abstract</p> <p>Background</p> <p>Previous studies in aging animals have shown that amyloid-beta protein (Aβ) accumulates and its transporters, low-density lipoprotein receptor-related protein-1 (LRP-1) and the receptor for advanced glycation end products (RAGE) are impaired during hydrocephalus. Furthermore, correlations between astrocytes and Aβ have been found in human cases of normal pressure hydrocephalus (NPH) and Alzheimer's disease (AD). Because hydrocephalus occurs frequently in children, we evaluated the expression of Aβ and its transporters and reactive astrocytosis in animals with neonatal hydrocephalus.</p> <p>Methods</p> <p>Hydrocephalus was induced in neonatal rats by intracisternal kaolin injections on post-natal day one, and severe ventriculomegaly developed over a three week period. MRI was performed on post-kaolin days 10 and 21 to document ventriculomegaly. Animals were sacrificed on post-kaolin day 21. For an age-related comparison, tissue was used from previous studies when hydrocephalus was induced in a group of adult animals at either 6 months or 12 months of age. Tissue was processed for immunohistochemistry to visualize LRP-1, RAGE, Aβ, and glial fibrillary acidic protein (GFAP) and with quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR) to quantify expression of LRP-1, RAGE, and GFAP.</p> <p>Results</p> <p>When 21-day post-kaolin neonatal hydrocephalic animals were compared to adult (6–12 month old) hydrocephalic animals, immunohistochemistry demonstrated levels of Aβ, RAGE, and LRP-1 that were substantially lower in the younger animals; in contrast, GFAP levels were elevated in both young and old hydrocephalic animals. When the neonatal hydrocephalic animals were compared to age-matched controls, qRT-PCR demonstrated no significant changes in Aβ, LRP-1 and RAGE. However, immunohistochemistry showed very small increases or decreases in individual proteins. Furthermore, qRT-PCR indicated statistically significant increases in GFAP.</p> <p>Conclusion</p> <p>Neonatal rats with and without hydrocephalus had low expression of Aβ and its transporters when compared to adult rats with hydrocephalus. No statistical differences were observed in Aβ and its transporters between the control and hydrocephalic neonatal animals.</p

Multiple interactions between the alpha2C- and beta1-adrenergic receptors influence heart failure survival

<p>Abstract</p> <p>Background</p> <p>Persistent stimulation of cardiac β₁-adrenergic receptors by endogenous norepinephrine promotes heart failure progression. Polymorphisms of this gene are known to alter receptor function or expression, as are polymorphisms of the α_2C-adrenergic receptor, which regulates norepinephrine release from cardiac presynaptic nerves. The purpose of this study was to investigate possible synergistic effects of polymorphisms of these two intronless genes (<it>ADRB1 </it>and <it>ADRA2C</it>, respectively) on the risk of death/transplant in heart failure patients.</p> <p>Methods</p> <p>Sixteen sequence variations in <it>ADRA2C </it>and 17 sequence variations in <it>ADRB1 </it>were genotyped in a longitudinal study of 655 white heart failure patients. Eleven sequence variations in each gene were polymorphic in the heart failure cohort. Cox proportional hazards modeling was used to identify polymorphisms and potential intra- or intergenic interactions that influenced risk of death or cardiac transplant. A leave-one-out cross-validation method was utilized for internal validation.</p> <p>Results</p> <p>Three polymorphisms in <it>ADRA2C </it>and five polymorphisms in <it>ADRB1 </it>were involved in eight cross-validated epistatic interactions identifying several two-locus genotype classes with significant relative risks ranging from 3.02 to 9.23. There was no evidence of intragenic epistasis. Combining high risk genotype classes across epistatic pairs to take into account linkage disequilibrium, the relative risk of death or transplant was 3.35 (1.82, 6.18) relative to all other genotype classes.</p> <p>Conclusion</p> <p>Multiple polymorphisms act synergistically between the <it>ADRA2C </it>and <it>ADRB1 </it>genes to increase risk of death or cardiac transplant in heart failure patients.</p