Quadratic tranverse anisotropy term due to dislocations in Mn12 acetate crystals directly observed by EPR spectroscopy

High-sensitivity electron paramagnetic resonance experiments have been carried out in fresh and stressed Mn12 acetate single crystals for frequencies ranging from 40 GHz up to 110 GHz. The high number of crystal dislocations formed in the stressing process introduces a E(Sx2-Sy2) transverse anisotropy term in the spin Hamiltonian. From the behavior of the resonant absorptions on the applied transverse magnetic field we have obtained an average value for E=22 mK, corresponding to a concentration of dislocations per unit cell of c=10-3.

In defense of the "tunneling" wave function of the universe

The tunneling approach to the wave function of the Universe has been recently criticized by Bousso and Hawking who claim that it predicts a catastrophic instability of de Sitter space with respect to pair production of black holes. We show that this claim is unfounded. First, we argue that different horizon size regions in de Sitter space cannot be treated as independently created, as they contend. And second, the WKB tunneling wave function is not simply the inverse of the Hartle-Hawking one, except in very special cases. Applied to the related problem of pair production of massive particles, we argue that the tunneling wave function leads to a small constant production rate, and not to a catastrophe as the argument of Bousso and Hawking would suggest.

Preoperative assessment of neurovesical function in children with anorectal malformation: association with vertebral and spinal malformations.

PURPOSE: We preoperatively assessed neurovesical function and spinal cord function in children with anorectal malformations. In cases of neurovesical dysfunction we looked for an association with vertebral malformation or myelodysplasia. MATERIALS AND METHODS: We prospectively evaluated 80 children with anorectal malformations via preoperative urodynamics and magnetic resonance imaging of the spine. Bladder compliance and volume, detrusor activity and vesicosphincteric synergy during voiding allowed urodynamic evaluation. Results were reported according to Wingspread and Krickenbeck classifications of anorectal malformations. RESULTS: Urodynamic findings were pathological in 14 children (18%). Pathological evaluations did not seem related to type of fistula or level of anorectal malformation. Vertebral anomalies were seen in 34 patients (43%) and myelodysplasia in 16 (20%). Neither vertebral anomaly nor myelodysplasia seemed associated with type of fistula or severity of anorectal malformation. Of 14 children with pathological urodynamics no vertebral anomaly or myelodysplasia was found in 7. Of 66 children with normal urodynamics 40 presented with vertebral or spinal malformation. CONCLUSIONS: Lower urinary tract dysfunction is common in patients with anorectal malformations. Normal spine or spinal cord does not exclude neurovesical dysfunction. Myelodysplasia or vertebral anomaly does not determine lower urinary tract dysfunction. Thus, we recommend preoperative urodynamic assessment of the bladder and magnetic resonance imaging of the spine in children with anorectal malformations.

Sleep function: current questions and new approaches.

The mammalian brain oscillates through three distinct global activity states: wakefulness, non-rapid eye movement (NREM) sleep and REM sleep. The regulation and function of these 'vigilance' or 'behavioural' states can be investigated over a broad range of temporal and spatial scales and at different levels of functional organization, i.e. from gene expression to memory, in single neurons, cortical columns or the whole brain and organism. We summarize some basic questions that have arisen from recent approaches in the quest for the functions of sleep. Whereas traditionally sleep was viewed to be regulated through top-down control mechanisms, recent approaches have emphasized that sleep is emerging locally and regulated in a use-dependent (homeostatic) manner. Traditional markers of sleep homeostasis, such as the electroencephalogram slow-wave activity, have been linked to changes in connectivity and plasticity in local neuronal networks. Thus waking experience-induced local network changes may be sensed by the sleep homeostatic process and used to mediate sleep-dependent events, benefiting network stabilization and memory consolidation. Although many questions remain unanswered, the available data suggest that sleep function will best be understood by an analysis which integrates sleep's many functional levels with its local homeostatic regulation.

Dual Blockade of PD-1 and CTLA-4 Combined with Tumor Vaccine Effectively Restores T-Cell Rejection Function in Tumors.

Tumor progression is facilitated by regulatory T cells (Treg) and restricted by effector T cells. In this study, we document parallel regulation of CD8(+) T cells and Foxp3(+) Tregs by programmed death-1 (PD-1, PDCD1). In addition, we identify an additional role of CTL antigen-4 (CTLA-4) inhibitory receptor in further promoting dysfunction of CD8(+) T effector cells in tumor models (CT26 colon carcinoma and ID8-VEGF ovarian carcinoma). Two thirds of CD8(+) tumor-infiltrating lymphocytes (TIL) expressed PD-1, whereas one third to half of CD8(+) TIL coexpressed PD-1 and CTLA-4. Double-positive (PD-1(+)CTLA-4(+)) CD8(+) TIL had characteristics of more severe dysfunction than single-positive (PD-1(+) or CTLA-4(+)) TIL, including an inability to proliferate and secrete effector cytokines. Blockade of both PD-1 and CTLA-4 resulted in reversal of CD8(+) TIL dysfunction and led to tumor rejection in two thirds of mice. Double blockade was associated with increased proliferation of antigen-specific effector CD8(+) and CD4(+) T cells, antigen-specific cytokine release, inhibition of suppressive functions of Tregs, and upregulation of key signaling molecules critical for T-cell function. When used in combination with GVAX vaccination (consisting of granulocyte macrophage colony-stimulating factor-expressing irradiated tumor cells), inhibitory pathway blockade induced rejection of CT26 tumors in 100% of mice and ID8-VEGF tumors in 75% of mice. Our study indicates that PD-1 signaling in tumors is required for both suppressing effector T cells and maintaining tumor Tregs, and that PD-1/PD-L1 pathway (CD274) blockade augments tumor inhibition by increasing effector T-cell activity, thereby attenuating Treg suppression. Cancer Res; 73(12); 3591-603. ©2013 AACR.

Common variants in mendelian kidney disease genes and their association with renal function.

Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.

Hydrodynamic fluctuations in fluids under external gradients

Temperature and velocity correlation functions in a fluid subjected to conditions creating both a temperature and a velocity gradient are computed up to second order in the gradients. Temperature and velocity fluctuations are coupled due to convection and viscous heating. When the viscosity goes to infinity one gets the temperature correlation function for a solid under a temperature gradient, which contains a long-ranged contribution, quadratic in the temperature gradient. The velocity correlation function also exhibits long-range behavior. In a particular case its equilibrium term is diagonal whereas the nonequilibrium correction contains nondiagonal terms.

Soil fertility, nutrition and yield of maize and barley with gypsum application on soil surface in no-till

Annual crop yield and nutrition have shown differentiated responses to modifications in soil chemical properties brought about by gypsum application. The aim of this study was to evaluate the effect of gypsum application rates on the chemical properties of a Latossolo Bruno (Clayey Oxisol), as well as on the nutrition and yield of a maize-barley succession under no-till. The experiment was set up in November 2009 in Guarapuava, Parana, Brazil, applying gypsum rates of 0.0, 1.5, 3.0, 4.5, and 6.0 Mg ha-1 to the soil surface upon sowing maize, with crop succession of barley. Gypsum application decreased the levels of Al3+ and Mg2+ in the 0.0-0.1 m layer and increased soil pH in the layers from 0.2-0.6 m depth. Gypsum application has increased the levels of Ca2+ in all soil layers up to 0.6 m, and the levels of S-SO4(2-) up to 0.8 m. In both crops, the leaf concentrations of Ca and S were increased while Mg concentrations have decreased as a function of gypsum rates. There was also an effect of gypsum rates on grain yield, with a quadratic response of maize and a linear increase for barley. Yield increases were up to 11 and 12 % in relation to control for the maximum technical efficiency (MTE) rates of 3.8 and 6.0 Mg ha-1 of gypsum, respectively. Gypsum application improved soil fertility in the profile, especially in the subsurface, as well as plant nutrition, increasing the yields of maize and barley.

Cross-cultural adaptation, reliability, internal consistency and validation of the Spinal Function Sort (SFS) for French- and German-speaking patients with back complaints.

Introduction Functional subjective evaluation through questionnaire is fundamental, but not often realized in patients with back complaints, lacking validated tools. The Spinal Function Sort (SFS) was only validated in English. We aimed to translate, adapt and validate the French (SFS-F) and German (SFS-G) versions of the SFS. Methods Three hundred and forty-four patients, experiencing various back complaints, were recruited in a French (n = 87) and a German-speaking (n = 257) center. Construct validity was estimated via correlations with SF-36 physical and mental scales, pain intensity and hospital anxiety and depression scales (HADS). Scale homogeneities were assessed by Cronbach's α. Test-retest reliability was assessed on 65 additional patients using intraclass correlation (IC). Results For the French and German translations, respectively, α were 0.98 and 0.98; IC 0.98 (95% CI: [0.97; 1.00]) and 0.94 (0.90; 0.98). Correlations with physical functioning were 0.63 (0.48; 0.74) and 0.67 (0.59; 0.73); with physical summary 0.60 (0.44; 0.72) and 0.52 (0.43; 0.61); with pain -0.33 (-0.51; -0.13) and -0.51 (-0.60; -0.42); with mental health -0.08 (-0.29; 0.14) and 0.25 (0.13; 0.36); with mental summary 0.01 (-0.21; 0.23) and 0.28 (0.16; 0.39); with depression -0.26 (-0.45; -0.05) and -0.42 (-0.52; -0.32); with anxiety -0.17 (-0.37; -0.04) and -0.45 (-0.54; -0.35). Conclusions Reliability was excellent for both languages. Convergent validity was good with SF-36 physical scales, moderate with VAS pain. Divergent validity was low with SF-36 mental scales in both translated versions and with HADS for the SFS-F (moderate in SFS-G). Both versions seem to be valid and reliable for evaluating perceived functional capacity in patients with back complaints.

The 5th anniversary of "Patient Safety in Surgery" - from the Journal's origin to its future vision.

A prospective study was undertaken to determine prognostic markers for patients with obstructive jaundice. Along with routine liver function tests, antipyrine clearance was determined in 20 patients. Four patients died after basal investigations. Five patients underwent definitive surgery. The remaining 11 patients were subjected to percutaneous transhepatic biliary decompression. Four patients died during the drainage period, while surgery was carried out for seven patients within 1-3 weeks of drainage. Of 20 patients, only six patients survived. Basal liver function tests were comparable in survivors and nonsurvivors. Discriminant analysis of the basal data revealed that plasma bilirubin, proteins and antipyrine half-life taken together had a strong association with mortality. A mathematical equation was derived using these variables and a score was computed for each patient. It was observed that a score value greater than or equal to 0.84 indicated survival. Omission of antipyrine half-life from the data, however, resulted in prediction of false security in 55% of patients. This study highlights the importance of addition of antipyrine elimination test to the routine liver function tests for precise identification of high risk patients.

MODELING OF SOIL LOAD-BEARING CAPACITY AS A FUNCTION OF SOIL MECHANICAL RESISTANCE TO PENETRATION

Estimation of soil load-bearing capacity from mathematical models that relate preconsolidation pressure (σp) to mechanical resistance to penetration (PR) and gravimetric soil water content (U) is important for defining strategies to prevent compaction of agricultural soils. Our objective was therefore to model the σp and compression index (CI) according to the PR (with an impact penetrometer in the field and a static penetrometer inserted at a constant rate in the laboratory) and U in a Rhodic Eutrudox. The experiment consisted of six treatments: no-tillage system (NT); NT with chiseling; and NT with additional compaction by combine traffic (passing 4, 8, 10, and 20 times). Soil bulk density, total porosity, PR (in field and laboratory measurements), U, σp, and CI values were determined in the 5.5-10.5 cm and 13.5-18.5 cm layers. Preconsolidation pressure (σp) and CI were modeled according to PR in different U. The σp increased and the CI decreased linearly with increases in the PR values. The correlations between σp and PR and PR and CI are influenced by U. From these correlations, the soil load-bearing capacity and compaction susceptibility can be estimated by PR readings evaluated in different U.

The transcription factor c-Maf controls touch receptor development and function.

The sense of touch relies on detection of mechanical stimuli by specialized mechanosensory neurons. The scarcity of molecular data has made it difficult to analyze development of mechanoreceptors and to define the basis of their diversity and function. We show that the transcription factor c-Maf/c-MAF is crucial for mechanosensory function in mice and humans. The development and function of several rapidly adapting mechanoreceptor types are disrupted in c-Maf mutant mice. In particular, Pacinian corpuscles, a type of mechanoreceptor specialized to detect high-frequency vibrations, are severely atrophied. In line with this, sensitivity to high-frequency vibration is reduced in humans carrying a dominant mutation in the c-MAF gene. Thus, our work identifies a key transcription factor specifying development and function of mechanoreceptors and their end organs.

Food for thought: the importance of glucose and other energy substrates for sustaining brain function under varying levels of activity.

The brain requires a constant and substantial energy supply to maintain its main functions. For decades, it was assumed that glucose was the major if not the only significant source of energy for neurons. This view was supported by the expression of specific facilitative glucose transporters on cerebral blood vessels, as well as neurons. Despite the fact that glucose remains a key energetic substrate for the brain, growing evidence suggests a different scenario. Thus astrocytes, a major type of glial cells that express their own glucose transporter, play a critical role in coupling synaptic activity with glucose utilization. It was shown that glutamatergic activity triggers an enhancement of aerobic glycolysis in this cell type. As a result, lactate is provided to neurons as an additional energy substrate. Indeed, lactate has proven to be a preferential energy substrate for neurons under various conditions. A family of proton-linked carriers known as monocarboxylate transporters has been described and specific members have been found to be expressed by endothelial cells, astrocytes and neurons. Moreover, these transporters are subject to fine regulation of their expression levels and localization, notably in neurons, which suggests that lactate supply could be adjusted as a function of their level of activity. Considering the importance of energetics in the aetiology of several neurodegenerative diseases, a better understanding of its cellular and molecular underpinnings might have important implications for the future development of neuroprotective strategies.