Intermolecular multiple-quantum coherences between bulk water and a glycoprotein fragment at modest concentration (20 mM) have been experimentally produced and detected, although such coherences are ...inconceivable in the normal theoretical framework of nuclear magnetic resonance. A density matrix treatment explains these results by including the long-range dipolar interaction between spins and by discarding the high-temperature approximation. These results imply that peak intensities (critical for structural determinations) can be distorted in many gradient experiments, and show that magic-angle gradients provide substantial improvements with reduced gradient strengths. They also suggest methods for contrast enhancement in magnetic resonance imaging.
the use of antihypertensive medication in older people in order to prevent cardiovascular events is well established. The use of such agents has been encouraged by incentive schemes in the United ...Kingdom including the Quality and Outcomes Framework. In addition, many guidelines recommend good blood pressure (BP) control in the elderly. However, in older people antihypertensives can cause adverse effects related to hypotension.
the aim of this study was to assess the prevalence of low BP and impact on outcomes, particularly in the presence of antihypertensive treatment, in a primary care population of older people.
a retrospective observational cohort study in people over the age of 70 years registered with primary care providers in Kent.
a total of 11,167 patients over 70 years old were analysed, 6,373 female (57%). Systolic blood pressure (SBP) was below 120 mmHg in 1,297 people (844 on antihypertensives), below 110 mmHg in 474 (313 on antihypertensives) and below 100 mmHg in 128 (89 on antihypertensives). Hypotension was independently associated with mortality, acute kidney injury and hospital admission.
the results demonstrate that low SBP is associated with adverse events, it is possible that the pursuit of BP control at a population level may lead to over-treatment in certain groups of patients. This may result in an increased incidence of adverse events particularly in older people.
The automated use of a matrix-assisted laser desorption ionization (MALDI) mass spectrometer (MS) is described for image analysis of samples through implementation of new software for instrument ...control, data acquisition, and data analysis. The software permits automated acquisition of MS MALDI spectra to form an ordered data array and contains display features to provide images at one or more mass-to-charge ratio values. The technique can be used to scan tissue samples, blotted samples, gels, or other sample surfaces where the image analysis of that sample is required. The program achieves a time of typically 1 s per image point, permitting an analysis made up of large numbers of points with high spatial resolution up to 850 dpi. The features of the software are demonstrated in this paper with samples of printed images, where visible images can be compared to those obtained by mass spectrometry. Quantitative aspects are introduced by analyzing a series of sample spots containing different amounts of several proteins.
This study explores how muscle and liver energy stores are linked with social status and the social environment in Neolamprologus pulcher, a cooperatively breeding fish that lives in colonies ...comprised of up to 200 distinct social groups. Subordinate muscle energy stores were positively correlated with the number of neighbouring social groups in the colony, but this pattern was not observed in dominant N. pulcher. Furthermore, liver energy stores were smaller in dominants living at the edge of the colony compared with those living in the colony centre, with no differences among subordinates in liver energy stores. Subordinate N. pulcher may build up large energy stores in the muscles to fuel rapid growth after dispersal, which could occur more frequently in high‐density environments. Dominant N. pulcher may use the more easily mobilized energy stores in the liver to fuel daily activities, which could be more energetically demanding on the edge of the colony as a result of the increased predation defence needed on the edge. Overall, this study demonstrates that both subordinate and dominant physiology in N. pulcher varies with characteristics of the social environment. Furthermore, dominant and subordinate energy storage strategies appear to differ due to status‐dependent variation in daily activities and variation in the need to prepare for future reproductive or dispersal opportunities.
A series of inhibitors of Pim-2 kinase identified by high-throughput screening is described. Details of the hit validation and lead generation process and structure-activity relationship (SAR) ...studies are presented. Disclosure of an unconventional binding mode for 1, as revealed by X-ray crystallography using the highly homologous Pim-1 protein, is also presented, and observed binding features are shown to correlate with the Pim-2 SAR. While highly selective within the kinase family, the series shows similar potency for both Pim-1 and Pim-2, which was expected on the basis of homology, but unusual in light of reports in the literature documenting a bias for Pim-1. A rationale for these observations based on Pim-1 and Pim-2 K(M(ATP)) values is suggested. Some interesting cross reactivity with casein kinase-2 was also identified, and structural features which may contribute to the association are discussed.
Astrocytes show a complex structural and physiological interplay with neurons and respond to neuronal activation in vitro and in vivo with intracellular calcium elevations. These calcium changes ...enable astrocytes to modulate synaptic transmission and plasticity through various mechanisms. However, the response pattern of astrocytes to single neuronal depolarization events still remains unresolved. This information is critical for fully understanding the coordinated network of neuron-glial signaling in the brain. To address this, we developed a system to map astrocyte calcium responses along apical dendrites of CA1 pyramidal neurons in hippocampal slices using single-neuron stimulation with channelrhodopsin-2. This technique allowed selective neuronal depolarization without invasive manipulations known to alter calcium levels in astrocytes. Light-evoked neuronal depolarization was elicited and calcium events in surrounding astrocytes were monitored using the calcium-sensitive dye Calcium Orange. Stimulation of single neurons caused calcium responses in populations of astrocytes along the apical axis of CA1 cell dendrites. Calcium responses included single events that were synchronized with neuronal stimulation and poststimulus changes in calcium event frequency, both of which were modulated by glutamatergic and purinergic signaling. Individual astrocytes near CA1 cells showed low ability to respond to repeated neuronal depolarization events. However, the response of the surrounding astrocyte population was remarkably accurate. Interestingly, the reliability of responses was graded with respect to astrocyte location along the CA1 cell dendrite, with astrocytes residing in the primary dendrite subregion being most responsive. This study provides a new perspective on the dynamic response property of astrocyte ensembles to neuronal activity.
Identification of acute kidney injury (AKI) is predominantly based on changes in plasma creatinine concentration, an insensitive marker. Alternative biomarkers have been proposed. The reference ...change value (RCV), the point at which biomarker change can be inferred to have occurred with statistical certainty, provides an objective assessment of change in serial tests results in an individual.
In 80 patients with chronic kidney disease, weekly measurements of blood and urinary biomarker concentrations were undertaken over 6 weeks. Variability was determined and compared before and after adjustment for urinary creatinine and across subgroups stratified by level of kidney function, proteinuria, and presence or absence of diabetes.
RCVs were determined for whole blood, plasma, and urinary neutrophil gelatinase-associated lipocalin (111%, 59%, and 693%, respectively), plasma cystatin C (14%), creatinine (17%), and urinary kidney injury molecule 1 (497%), tissue inhibitor of metalloproteinases 2 (454%), N-acetyl-β-d-glucosaminidase (361%), interleukin-18 (819%), albumin (430%), and α1-microglobulin (216%). Blood biomarkers exhibited lower variability than urinary biomarkers. Generally, adjusting urinary biomarker concentrations for creatinine reduced (P < 0.05) within-subject biological variability (CVI). For some markers, variation differed (P < 0.05) between subgroups.
These data can form a basis for application of these tests in clinical practice and research studies and are applicable across different levels of kidney function and proteinuria and in the presence or absence of diabetes. Most of the studied biomarkers have relatively high CVI (noise) but also have reported large concentration changes in response to renal insult (signal); thus progressive change should be detectable (high signal-to-noise ratio) when baseline data are available.
Corium strength is of interest in the context of a severe reactor accident in which molten core material melts through the reactor vessel and collects on the containment basemat. Some accident ...management strategies involve pouring water over the melt to solidify it and halt corium/concrete interactions. The effectiveness of this method could be influenced by the strength of the corium crust at the interface between the melt and coolant. A strong, coherent crust anchored to the containment walls could allow the yet-molten corium to fall away from the crust as it erodes the basemat, thereby thermally decoupling the melt from the coolant and sharply reducing the cooling rate. This paper presents a diverse collection of measurements of the mechanical strength of corium. The data is based on load tests of corium samples in three different contexts: (1) small blocks cut from the debris of the large-scale MACE experiments, (2) 30
cm-diameter, 75
kg ingots produced by SSWICS quench tests, and (3) high temperature crusts loaded during large-scale corium/concrete interaction (CCI) tests. In every case the corium consisted of varying proportions of UO
2, ZrO
2, and the constituents of concrete to represent a LWR melt at different stages of a molten core/concrete interaction. The collection of data was used to assess the strength and stability of an anchored, plant-scale crust. The results indicate that such a crust is likely to be too weak to support itself above the melt. It is therefore improbable that an anchored crust configuration could persist and the melt become thermally decoupled from the water layer to restrict cooling and prolong an attack of the reactor cavity concrete.
PDF
