Nowcasting daily minimum air and grass temperature.

Site-specific and accurate prediction of daily minimum air and grass temperatures, made available online several hours before their occurrence, would be of significant benefit to several economic sectors and for planning human activities. Site-specific and reasonably accurate nowcasts of daily minimum temperature several hours before its occurrence, using measured sub-hourly temperatures hours earlier in the morning as model inputs, was investigated. Various temperature models were tested for their ability to accurately nowcast daily minimum temperatures 2 or 4 h before sunrise. Temperature datasets used for the model nowcasts included sub-hourly grass and grass-surface (infrared) temperatures from one location in South Africa and air temperature from four subtropical sites varying in altitude (USA and South Africa) and from one site in central sub-Saharan Africa. Nowcast models used employed either exponential or square root functions to describe the rate of nighttime temperature decrease but inverted so as to determine the minimum temperature. The models were also applied in near real-time using an open web-based system to display the nowcasts. Extrapolation algorithms for the site-specific nowcasts were also implemented in a datalogger in an innovative and mathematically consistent manner. Comparison of model 1 (exponential) nowcasts vs measured daily minima air temperatures yielded root mean square errors (RMSEs) <1 °C for the 2-h ahead nowcasts. Model 2 (also exponential), for which a constant model coefficient (b = 2.2) was used, was usually slightly less accurate but still with RMSEs <1 °C. Use of model 3 (square root) yielded increased RMSEs for the 2-h ahead comparisons between nowcasted and measured daily minima air temperature, increasing to 1.4 °C for some sites. For all sites for all models, the comparisons for the 4-h ahead air temperature nowcasts generally yielded increased RMSEs, <2.1 °C. Comparisons for all model nowcasts of the daily grass and grass-surface minima yielded increased RMSEs compared to those for air temperature at 2 m. The sufficiently small RMSEs using the 2-h ahead nowcasts of the air temperature minimum, for the exponential model, demonstrate that the methodology used may be applied operationally but with increased errors for grass minimum temperature and the 4-h nowcasts.

Magnetic moments of light nuclei from lattice quantum chromodynamics.

We present the results of lattice QCD calculations of the magnetic moments of the lightest nuclei, the deuteron, the triton, and ^{3}He, along with those of the neutron and proton. These calculations, performed at quark masses corresponding to m_{π}∼800 MeV, reveal that the structure of these nuclei at unphysically heavy quark masses closely resembles that at the physical quark masses. In particular, we find that the magnetic moment of ^{3}He differs only slightly from that of a free neutron, as is the case in nature, indicating that the shell-model configuration of two spin-paired protons and a valence neutron captures its dominant structure. Similarly a shell-model-like moment is found for the triton, µ_{^{3}H}∼µ_{p}. The deuteron magnetic moment is found to be equal to the nucleon isoscalar moment within the uncertainties of the calculations. Furthermore, deviations from the Schmidt limits are also found to be similar to those in nature for these nuclei. These findings suggest that at least some nuclei at these unphysical quark masses are describable by a phenomenological nuclear shell model.

Hyperon-nucleon interactions from quantum chromodynamics and the composition of dense nuclear matter.

The low-energy nΣ(-) interactions determine, in part, the role of the strange quark in dense matter, such as that found in astrophysical environments. The scattering phase shifts for this system are obtained from a numerical evaluation of the QCD path integral using the technique of lattice QCD. Our calculations, performed at a pion mass of m(π)~389 MeV in two large lattice volumes and at one lattice spacing, are extrapolated to the physical pion mass using effective field theory. The interactions determined from lattice QCD are consistent with those extracted from hyperon-nucleon experimental data within uncertainties and strengthen model-dependent theoretical arguments that the strange quark is a crucial component of dense nuclear matter.

Evidence for a bound H dibaryon from lattice QCD.

We present evidence for the existence of a bound H dibaryon, an I=0, J=0, s=-2 state with valence quark structure uuddss, at a pion mass of m(π)∼389 MeV. Using the results of lattice QCD calculations performed on four ensembles of anisotropic clover gauge-field configurations, with spatial extents of L∼2.0, 2.5, 3.0, and 3.9 fm at a spatial lattice spacing of b(s)∼0.123 fm, we find an H dibaryon bound by B(∞)(H)=16.6±2.1±4.6 MeV at a pion mass of m(π)∼389 MeV.

Quality of life in advanced prostate cancer: results of a randomized therapeutic trial.

BACKGROUND: For patients with metastatic prostate cancer, treatment is primarily palliative, relying mainly on the suppression of systemic androgen hormone levels. To help document the achievement of palliation and to characterize positive and negative effects of treatment, we evaluated quality-of-life (QOL) parameters in patients with metastatic prostate cancer who were randomly assigned to two methods of androgen deprivation. METHODS: Patients (n = 739) with stage M1 (bone or soft tissue metastasis) prostate cancer were enrolled in a QOL protocol that was a companion to Southwest Oncology Group INT-0105, a randomized double-blind trial comparing treatment with bilateral orchiectomy (surgical castration) plus either flutamide or placebo. Patients completed a comprehensive battery of QOL questionnaires at random assignment to treatment and at 1, 3, and 6 months later. Data were collected on three treatment-specific symptoms (diarrhea, gas pain, and body image), on physical functioning, and on emotional functioning. All P values are two-sided. RESULTS: Questionnaire return rates for this study never dropped below 80%; only 2% of the patients did not submit baseline QOL assessments. Cross-sectional analyses (corrected for multiple testing) identified statistically significant differences that favored orchiectomy plus placebo for two of the five primary QOL parameters as follows: patients receiving flutamide reported more diarrhea at 3 months (P = .001) and worse emotional functioning at 3 and 6 months (both P<.003). Longitudinal analyses replicated these findings. Other analyzed QOL parameters favored the group receiving placebo but were not statistically significant after adjustment for multiple testing. CONCLUSIONS: We found a consistent pattern of better QOL outcomes at each follow-up assessment during the first 6 months of treatment for orchiectomized patients with metastatic prostate cancer who received placebo versus flutamide. Improvement over time was evident in both treatment groups but more so for patients receiving placebo.

Presenilin-1 P264L knock-in mutation: differential effects on abeta production, amyloid deposition, and neuronal vulnerability.

The pathogenic mechanism linking presenilin-1 (PS-1) gene mutations to familial Alzheimer's disease (FAD) is uncertain, but has been proposed to include increased neuronal sensitivity to degeneration and enhanced amyloidogenic processing of the beta-amyloid precursor protein (APP). We investigated this issue by using gene targeting with the Cre-lox system to introduce an FAD-linked P264L mutation into the endogenous mouse PS-1 gene, an approach that maintains normal regulatory controls over expression. Primary cortical neurons derived from PS-1 homozygous mutant knock-in mice exhibit basal neurodegeneration similar to their PS-1 wild-type counterparts. Staurosporine and Abeta1-42 induce apoptosis, and neither the dose dependence nor maximal extent of cell death is altered by the PS-1 knock-in mutation. Similarly, glutamate-induced neuronal necrosis is unaffected by the PS-1P264L mutation. The lack of effect of the PS-1P264L mutation is confirmed by measures of basal- and toxin-induced caspase and calpain activation, biochemical indices of apoptotic and necrotic signaling, respectively. To analyze the influence of the PS-1P264L knock-in mutation on APP processing and the development of AD-type neuropathology, we created mouse lines carrying mutations in both PS-1 and APP. In contrast to the lack of effect on neuronal vulnerability, cortical neurons cultured from PS-1P264L homozygous mutant mice secrete Abeta42 at an increased rate, whereas secretion of Abeta40 is reduced. Moreover, the PS-1 knock-in mutation selectively increases Abeta42 levels in the mouse brain and accelerates the onset of amyloid deposition and its attendant reactive gliosis, even as a single mutant allele. We conclude that expression of an FAD-linked mutant PS-1 at normal levels does not generally increase cortical neuronal sensitivity to degeneration. Instead, enhanced amyloidogenic processing of APP likely is critical to the pathogenesis of PS-1-linked FAD.

Isolation and characterization of poly(adenylic acid)-containing messenger ribonucleic acid from rat liver polysomes.

Undegraded rat liver polysomes were obtained after homogenizing the tissue in a medium containing NH4Cl, heparine, and yeast tRNA. Purification of poly(A)-containing RNA from polysomal RNA was accomplished by affinity chromatography on oligo(dT)-cellulose columns. Poly(A)-containing RNA molecules were monitored by the formation of ribonuclease-resistant hybrids with [3H]poly(U). To improve the separation of messenger RNA and ribosomal RNA by oligo(dT)-cellulose it was found essential to dissociate the aggregates formed between both molecular species by heat treatment in the presence of dimethylsulfoxide (Me2SO) prior to chromatography. Sucrose gradient analysis under denaturing conditions showed that the preparations obtained were virtually free of ribosomal RNA. Poly(A)-containing RNA constituted approx. 2.2% of the total polysomal RNA and the number average size was 1500--1800 nucleotides, as judged by sedimentation analysis on sucrose density gradients containing Me2SO. Approximately 8.2% of the purified preparation obtained was able to anneal with [3H]poly(U); the number average nucleotide length of the poly(A) segment of the RNA population was calculated to be 133 adenylate residues. Based on these values, our preparations appear to be greater than 90% pure. The RNA fractions obtained after oligo(dT)-cellulose chromatography were used to direct the synthesis of liver polypeptides in a heterologous cell-free system derived from wheat-germ. The system was optimized with respect to monovalent and divalent cations, and presence of polyamines (spermine). More than 65% of the translational activity present in the unfractionated polysomal RNA was recovered in the final poly(A)-containing RNA fraction. However, about 25% of the activity was found to be associated with the unbound fraction which was essentially free of poly(A)-containing RNA. Immunoprecipitation analysis with a specific antiserum to rat serum albumin demonstrated that about 6--8% of the labeled synthetic products translated from the poly(A)-containing RNA sample corresponded to serum albumin. Analysis of the translation products by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a heterogeneous distribution of molecular sizes ranging from 15 000 to greater than 70 000 daltons. Spermine not only increased the overall yield and extent of protein synthesis, but also resulted in higher yields of large protein products. Under optimal translation conditions a discrete peak representing about 7% of the total radioactivity was observed to migrate with rat serum albumin.

Carbonated soft drink consumption and bone mineral density in adolescence: the Northern Ireland Young Hearts project.

UNLABELLED: In an observational study of 1335 boys and girls aged 12 and 15 years, higher intakes of carbonated soft drinks (CSDs) were significantly associated with lower bone mineral density at the heel, but only in girls. Owing to the upward trend in CSD intake in adolescence, this finding may be of concern. INTRODUCTION: High consumption of carbonated soft drinks (CSD) during adolescence may reduce bone mineral accrual and increase fracture risk. The aim of this study was to examine the relationship between CSD consumption and bone mineral density (BMD) in a representative sample of adolescents. MATERIALS AND METHODS: This was a cross-sectional observational study in 36 postprimary schools in Northern Ireland. Participants included 591 boys and 744 girls either 12 or 15 years old. BMD was measured by DXA, and usual beverage consumption was assessed by the diet history method. Adjusted regression modeling was used to investigate the influence of CSD on BMD. RESULTS: A significant inverse relationship between total CSD intake and BMD was observed in girls at the dominant heel (beta, -0.099; 95% CI, -0.173 to -0.025). Non-cola consumption was inversely associated with dominant heel BMD in girls (beta, -0.121; 95% CI, -0.194 to -0.048), and diet drinks were also inversely associated with heel BMD in girls (beta, -0.087; 95% CI, -0.158 to -0.016). However, no consistent relationships were observed between CSD intake and BMD in boys. Cola consumption and nondiet drinks were not significantly related to BMD in either sex. CONCLUSION: CSD consumption seems to be inversely related to BMD at the dominant heel in girls. It is possible that the apparent association results from the displacement of more nutritious beverages from the diet. Although the inverse association observed between CSD consumption and BMD is modest and confined to girls, this finding may have important public health implications given the widespread use and current upward trend in CSD consumption in Western populations.

Diffuse plaques contain C-terminal A beta 42 and not A beta 40: evidence from cats and dogs.

Recent reports have suggested that beta-amyloid (A beta) species of variable length C-termini are differentially deposited within early and late-stage plaques and the cerebrovasculature. Specifically, longer C-terminal length A beta 42/3 fragments (i.e., A beta forms extending to residues 42 and/or 43) are thought to be predominant within diffuse plaques while both A beta 42/3 and A beta 40 (A beta forms terminating at residue 40) are present within a subset of neuritic plaques and cerebrovascular deposits. We sought to clarify the issue of differential A beta deposition using aged canines, a partial animal model of Alzheimer's disease that exhibits extensive diffuse plaques and frequent vascular amyloid, but does not contain neuritic plaques or neurofibrillary tangles. We examined the brains of 20 aged canines, 3 aged felines, and 17 humans for the presence of A beta immunoreactive plaques, using antibodies to A beta 1(-17), A beta 17(-24), A beta 1(-28), A beta 40, and A beta 42. We report that plaques within the canine and feline brain are immunopositive for A beta 42 but not A beta 40. This is the first observation of nascent AD pathology in the aged feline brain. Canine plaques also contained epitopes within A beta 1(-17), A beta 17(-24), and A beta 1(-28). In all species examined, vascular deposits were immunopositive for both A beta 40 and A beta 42. In the human brain, diffuse plaques were preferentially A beta 42 immunopositive, while neuritic plaques and vascular deposits were both A beta 40 and A beta 42 immunopositive. However, not all neuritic plaques contain A beta 40 epitopes.

Mutant and native human beta-amyloid precursor proteins in transgenic mouse brain.

Human beta-amyloid precursor protein (beta APP) has been targeted to transgenic neurons using synapsin I promoter-based chimeric transgenes. Native human beta APP was introduced as well as beta APP containing mutations genetically linked to familial Alzheimer's disease (AD) and to hereditary cerebral hemorrhage with amyloidosis-Dutch type. In mouse brain, human beta APP RNA was up to 60% as abundant as total endogenous beta APP RNA. Human beta APP gene expression was most abundant in the CA subfields of the hippocampus and in the piriform cortex. Correct processing of human beta APP at the beta-secretase cleavage site was demonstrated in transgenic mouse brains. Despite a 40% increase in total beta APP immunoreactivity in lines expressing mutant human beta APP, no evidence of amyloid deposition was found in brains of mice up to 14 months in age. Higher levels of mutant human beta APP, increased age, or other factors may be necessary to elicit beta-amyloid-related neuropathologies in the rodent brain.

Artifactual strain-specific signs of incipient brain amyloidosis in APP transgenic mice.

In an attempt to generate transgenic mice modeling Alzheimer-type amyloidogenesis, the COOH-terminal 103 residue human APP segment was expressed in brain regions known to be vulnerable in AD. Transfected cells overexpressing this transgene were previously shown to develop intracytoplasmic inclusions that were immunoreactive with antibodies to the APP COOH-terminus. Transgenic C57B6/SJL mice produced transgene-coded mRNA in their brains at levels up to sixfold above endogenous APP, most abundantly within cortical and hippocampal pyramidal neurons. Immunocytochemistry with anti-A beta antibodies revealed occasional structures that resembled diffuse amyloid, but which could not be detected on serial sections. Immunolabeling with antibodies to APP regions NH2-terminal to the transgene-coded domain revealed elevated immunoreactivity within perikarya and neurites in regions expressing the highest transgene and endogenous APP mRNA levels, similar to observations previously reported within vulnerable neurons in AD brain. However, subsequent breeding revealed that this phenotype segregated with the B6/SJL background rather than the transgene, thus emphasizing the importance of genetic background to observations of putative AD-type pathology in transgenic animals.

Cathepsin G: localization in human cerebral cortex and generation of amyloidogenic fragments from the beta-amyloid precursor protein.

Amyloid deposits in Alzheimer's disease, Down's syndrome and aged brain are composed largely of A beta protein, which is generated by proteolytic processing of beta-amyloid precursor protein. Proteases responsible for liberating the A beta protein from the precursor have not yet been identified. Here, we examined the ability of cathepsin G, a chymotrypsin-like protease, to cleave two protease substrates: (i) a fluorogenic hexapeptide, whose sequence spans the cleavage site in the precursor for generating the A beta NH2-terminus, and (ii) recombinant human beta-amyloid precursor protein purified from a baculovirus expression system. Unlike two other members of the chymotrypsin family, cathepsin G readily degraded the hexapeptide. Furthermore, cathepsin G cleaved the beta-amyloid precursor protein to generate several breakdown products, including a prominent 11,500 mol. wt fragment immunoreactive with antibodies directed against the COOH-terminus of the protein. This COOH-terminal fragment co-migrated using two-dimensional isoelectric focusing/sodium dodecyl sulfate-polyacrylamide gel electrophoresis with C-100, a recombinant COOH-terminal segment of the beta-amyloid precursor, whose NH2-terminus is one residue upstream of the NH2-terminus of the A beta domain. We also examined the localization of cathepsin G in human brain. The distribution of cathepsin G-containing cells was examined by immunohistochemistry in the temporal cortex of both Alzheimer's and aged control samples. Cathepsin G-like immunoreactivity was contained specifically within neutrophils. As visualized by double-labeling with antibodies to cathepsin G and Factor VIII, neutrophils were most frequently found within meningeal or cortical blood vessels. In addition, occasional neutrophils could be identified without an apparent vascular surround, in the brain parenchyma. By simultaneous labeling with antibodies to cathepsin G and A beta protein, neutrophils were also sometimes found associated with both parenchymal and vessel amyloid deposits; however, these associations were rare. These findings indicate that cathepsin G is capable of cleaving the beta-amyloid precursor protein to liberate the free NH2-terminus of the A beta protein and may have access to areas where this material is deposited in Alzheimer's disease. However, since there is no physical association between neutrophils and deposited amyloid and no increase in the number of neutrophils in an Alzheimer's brain, cathepsin G seems to be an unlikely mediator of amyloid deposition in this disease.

Abundance of the longer A beta 42 in neocortical and cerebrovascular amyloid beta deposits in Swedish familial Alzheimer's disease and Down's syndrome.

Recent studies have demonstrated the deposition of amyloid beta (A beta) protein with carboxyl- and aminoterminal heterogeneity in cortical and cerebrovascular deposits of Alzheimer's disease (AD). Using carboxyl end-terminal specific antibodies to A beta peptides, we examined the immunocytochemical distribution of A beta 40 and A beta 42 species in brain tissue from a Swedish subject with familial AD (FAD) bearing the double mutation at codons 670/671 in the amyloid beta precursor protein (A beta PP), and from subjects with Down's syndrome and sporadic AD. In the Swedish subject, we found profound parenchymal A beta deposits and cerebral amyloid angiopathy in all four cortical lobes and cerebellum. A beta 42 was evident in almost all parenchymal deposits as well as many vascular deposits. Although A beta 40 was present in meningeal and intraparenchymal vessels, deposits containing this shorter peptide reactivity were sparse. Surprisingly, our observations in Swedish FAD showing a remarkable abundance of A beta 42 in both parenchymal and vascular deposits were qualitatively similar to the Down's syndrome and most sporadic AD cases, and to previously published A beta PP717 FAD. While previous transfection studies in different cell cultures indicate substantially increased soluble A beta production and A beta 40 species to be predominant, it would appear that the double A beta PP mutations in Swedish FAD largely result in the deposition of the longer A beta 42 in vivo.

A beta 42 is the predominant form of amyloid beta-protein in the brains of short-term survivors of head injury.

Fatal head injury results in the formation of diffuse parenchymal deposits of amyloid beta-protein (A beta) in the brains of approximately 30% of individuals. We used carboxyl terminal-specific antisera to examine the exact nature of these deposits in paraffin sections of neocortex from seven head-injured patients. Immunostaining for A beta 42 was observed in all parenchymal deposits whereas staining for A beta 40, the form of the protein which predominates in serum and cerebrospinal fluid, was seen in only a small proportion of deposits. The relative paucity of A beta 40 suggests that post-traumatic deposits do not arise as a result of passive leakage from damaged cerebral blood vessels but are similar to the early A beta 42 parenchymal deposits seen in Down's syndrome and Alzheimer's disease.

Absolute specificity for retrograde fast axonal transport displayed by lipid droplets originating in the axon of an identified Aplysia neuron in vitro.

Lipid droplets were found to form all along the axon of the giant cerebral neuron (GCN) of the sea hare Aplysia californica when the cell was placed in culture. The emission of yellow fluorescence by the droplets after exposure of the neuron to Nile red and their uniformly dark appearance in electron micrographs of axons fixed with glutaraldehyde and osmium tetroxide identified them as lipid droplets. In contrast to lipid droplets in fat cells and certain other cell types, these droplets were bounded by a membrane, indicating that the lipid droplet is a type of organelle that is membranated in some situations but not others. As observed by video-enhanced contrast-differential interference contrast microscopy, the droplets grew manyfold in place in the axon to diameters of 1-3 micron within 2-3 days. Often they formed coherent tandem arrays of 3-15 droplets. Droplets were usually essentially stationary but occasionally moved tens of microns by fast axonal transport, the largest spherical organelles to have been observed to undergo transport. They usually moved as singlets, sometimes as tandem arrays. The direction of transport was always retrograde (towards the cell body). Thus, an organelle need neither originate nor be modified in the axon terminal to be specified for retrograde transport. Whether or not an organelle is formed in the cell body might determine directionality. Alternatively, size might be a determining factor, with large organelles specified for retrograde transport.

Physical activity, sports participation, and risk factors in adolescents.

The purpose of this study was to analyze the relationships between physical activity (ACT), including sports participation (SP) and antecedent risk factors for coronary heart disease (CHD), in a representative sample of adolescents from Northern Ireland, a region of high coronary mortality. Biological and behavioral risk factors were measured in a random sample of 1015 school children aged 12 and 15 yr. ACT and SP were assessed by self-report questionnaire, and relationships with biological risk factors were analyzed with stepwise multiple linear regression after controlling for potential confounders. Results showed that in 15-yr-old males ACT was beneficially associated with systolic blood pressure (P < 0.05), lipid profile, and cardiorespiratory fitness (both P < 0.01). In 15-yr-old females, SP was associated beneficially with fatness and cardiorespiratory fitness. Odds ratios calculated from logistic regression revealed that for the older children, a relatively small drop (-20%) in ACT (boys) or SP (girls) was significantly related to the probability of exposure to multiple risk factors. Overall, relationships were stronger for males rather than females and for older rather than younger children. This study provides further evidence for beneficial associations between ACT, SP, and CHD risk status in adolescents.