The Effectiveness of fMRI Data when Combined with Polygraph Data

The Integrated Zone Comparison Technique (IZCT) was utilized with computerized polygraph instrumentation and the Academy for Scientific Investigative Training’s Horizontal Scoring System ASIT PolySuite algorithm, as part of a blind study in the detection of deception. This paper represents a synergy analysis of combining fMRI only deception data with each of the three individual physiological parameters that are used in polygraph. They include the electro-dermal response (EDR), pneumo, and cardio measurements. In addition, we compared the detection accuracy analysis using each single parameter by itself. Th e fMRI score and each individual polygraph parameter score on individual subjects were averaged to establish an overall score

Association of Reported Fish Intake and Supplementation Status with the Omega-3 Index

Background: An Omega-3 Index (O3I; EPA+DHA as a % of erythrocyte total fatty acids) in the desirable range (8%-12%) has been associated with improved heart and brain health. Objective: To determine the combination of fish intake and supplement use that is associated with an O3I of \u3e8%. Design: Two cross-sectional studies comparing the O3I to EPA+DHA/fish intake. Participants/setting: The first study included 28 individuals and assessed their fish and EPA+DHA intake using both a validated triple-pass 24-hr recall dietary survey and a single fish-intake question. The second study used de-identified data from 3,458 adults (84% from US) who self-tested their O3I and answered questions about their fish intake and supplement use. Statistical analyses performed: Study 1, chi-squared, one-way ANOVA, and Pearson correlations were computed. In Study 2, multi-variable regression models were used to predict O3I levels from reported fish/supplement intakes. Results: The mean ± SD O3I was 4.87 ± 1.32%, and 5.99 ± 2.29% in the first and second studies, respectively. Both studies showed that for every increase in fish intake category the O3I increased by 0.50–0.65% (p \u3c 0.0001). In the second study, about half of the population was taking omega-3 supplements, 32% reported no fish intake and 17% reported eating fish \u3e2 times per week. Taking an EPA+DHA supplement increased the O3I by 2.2% (p \u3c 0.0001). The odds of having an O3I of ≥8% were 44% in the highest intake group (≥3 servings/week and supplementation) and 2% in the lowest intake group (no fish intake or supplementation); and in those consuming 2 fish meals per week but not taking supplements (as per recommendations), 10%. Conclusion: Current AHA recommendations are unlikely to produce a desirable O3I. Consuming at least 3 fish servings per week plus taking an EPA+DHA supplement markedly increases the likelihood of achieving this target level

Thermodynamics as an alternative foundation for zero-temperature density functional theory and spin density functional theory

Thermodynamics provides a transparent definition of the free energy of density functional theory (DFT), and of its derivatives - the potentials, at finite temperatures T. By taking the T to 0 limit, it is shown here that both DFT and spin-dependent DFT (for ground states) suffer from precisely the same benign ambiguities: (a) charge and spin quantization lead to "up to a constant" indeterminacies in the potential and the magnetic field respectively, and (b) the potential in empty subspaces is undetermined but irrelevant. Surprisingly, these simple facts were inaccessible within the standard formulation, leading to recent discussions of apparent difficulties within spin-DFT.Comment: RevTeX, to appear in Phys. Rev.

Eulerian simulation of the fluid dynamics of helicopter brownout

A computational model is presented that can be used to simulate the development of the dust cloud that can be entrained into the air when a helicopter is operated close to the ground in desert or dusty conditions. The physics of this problem, and the associated pathological condition known as ‘brownout’ where the pilot loses situational awareness as a result of his vision being occluded by dust suspended in the flow around the helicopter, is acknowledged to be very complex. The approach advocated here involves an approximation to the full dynamics of the coupled particulate-air system. Away from the ground, the model assumes that the suspended particles remain in near equilibrium under the action of aerodynamic forces. Close to the ground, this model is replaced by an algebraic sublayer model for the saltation and entrainment process. The origin of the model in the statistical mechanics of a distribution of particles governed by aerodynamic forces allows the validity of the method to be evaluated in context by comparing the physical properties of the suspended particulates to the local properties of the flow field surrounding the helicopter. The model applies in the Eulerian frame of reference of most conventional Computational Fluid Dynamics codes and has been coupled with Brown’s Vorticity Transport Model. Verification of the predictions of the coupled model against experimental data for particulate entrainment and transport in the flow around a model rotor are encouraging. An application of the coupled model to analyzing the differences in the geometry and extent of the dust clouds that are produced by single main rotor and tandem-rotor configurations as they decelerate to land has shown that the location of the ground vortex and the size of any regions of recirculatory flow, should they exist, play a primary role in governing the extent of the dust cloud that is created by the helicopter

Transfer of noncoding DNA drives regulatory rewiring in bacteria

Understanding the mechanisms that generate variation is a common pursuit unifying the life sciences. Bacteria represent an especially striking puzzle, because closely related strains possess radically different metabolic and ecological capabilities. Differences in protein repertoire arising from gene transfer are currently considered the primary mechanism underlying phenotypic plasticity in bacteria. Although bacterial coding plasticity has been extensively studied in previous decades, little is known about the role that regulatory plasticity plays in bacterial evolution. Here, we show that bacterial genes can rapidly shift between multiple regulatory modes by acquiring functionally divergent nonhomologous promoter regions. Through analysis of 270,000 regulatory regions across 247 genomes, we demonstrate that regulatory “switching” to nonhomologous alternatives is ubiquitous, occurring across the bacterial domain. Using comparative transcriptomics, we show that at least 16% of the expression divergence between Escherichia coli strains can be explained by this regulatory switching. Further, using an oligonucleotide regulatory library, we establish that switching affects bacterial promoter architecture. We provide evidence that regulatory switching can occur through horizontal regulatory transfer, which allows regulatory regions to move across strains, and even genera, independently from the genes they regulate. Finally, by experimentally characterizing the fitness effect of a regulatory transfer on a pathogenic E. coli strain, we demonstrate that regulatory switching elicits important phenotypic consequences. Taken together, our findings expose previously unappreciated regulatory plasticity in bacteria and provide a gateway for understanding bacterial phenotypic variation and adaptation.National Science Foundation (U.S.) (Grant DEB-0936234

Biomarkers of lupus nephritis determined by serial urine proteomics

Lupus nephritis is a frequent and serious complication of systemic lupus erythematosus (SLE), the treatment of which often requires the use of immunosuppressives that can have severe side effects. Here we determined the low-molecular weight proteome of serial lupus urine samples to uncover novel and predictive biomarkers of SLE renal flare. Urine from 25 flare cycles of 19 patients with WHO Class III, IV, and V SLE nephritis were obtained at baseline, pre-flare, flare and post-flare. Each sample was first fractionated to remove proteins larger than 30kDa, then applied onto weak cation exchanger protein chips for analysis by SELDI-TOF mass spectrometry. We found 176 protein ions of which 27 were differentially expressed between specific flare intervals. On-chip peptide sequencing by integrated tandem mass spectrometry positively identified the 20 and 25 amino-acid isoforms of hepcidin, as well as fragments of α1-antitrypsin and albumin among the selected differentially expressed protein ions. Hepcidin 20 increased 4 months before renal flare and returned to baseline at renal flare, whereas hepcidin 25 decreased at renal flare and returned to baseline 4 months after the flare. These studies provide a beginning proteomic analysis aimed at predicting impending renal relapse, relapse severity, and the potential for recovery after SLE nephritis flare

Characterization of glycan substrates accumulating in GM1 Gangliosidosis

Introduction: GM1 gangliosidosis is a rare autosomal recessive genetic disorder caused by the disruption of the GLB1 gene that encodes β-galactosidase, a lysosomal hydrolase that removes β-linked galactose from the non-reducing end of glycans. Deficiency of this catabolic enzyme leads to the lysosomal accumulation of GM1 and its asialo derivative GA1 in β-galactosidase deficient patients and animal models. In addition to GM1 and GA1, there are other glycoconjugates that contain β-linked galactose whose metabolites are substrates for β-galactosidase. For example, a number of N-linked glycan structures that have galactose at their non-reducing end have been shown to accumulate in GM1 gangliosidosis patient tissues and biological fluids. Objective: In this study, we attempt to fully characterize the broad array of GLB1 substrates that require GLB1 for their lysosomal turnover. Results: Using tandem mass spectrometry and glycan reductive isotope labeling with data-dependent mass spectrometry, we have confirmed the accumulation of glycolipids (GM1 and GA1) and N-linked glycans with terminal beta-linked galactose. We have also discovered a novel set of core 1 and 2 O-linked glycan metabolites, many of which are part of structurally-related isobaric series that accumulate in disease. In the brain of GLB1 null mice, the levels of these glycan metabolites increased along with those of both GM1 and GA1 as a function of age. In addition to brain tissue, we found elevated levels of both N-linked and O-linked glycan metabolites in a number of peripheral tissues and in urine. Both brain and urine samples from human GM1 gangliosidosis patients exhibited large increases in steady state levels for the same glycan metabolites, demonstrating their correlation with this disease in humans as well. Conclusions: Our studies illustrate that GLB1 deficiency is not purely a ganglioside accumulation disorder, but instead a broad oligosaccharidosis that include representatives of many β-linked galactose containing glycans and glycoconjugates including glycolipids, N-linked glycans, and various O-linked glycans. Accounting for all β-galactosidase substrates that accumulate when this enzyme is deficient increases our understanding of this severe disorder by identifying metabolites that may drive certain aspects of the disease and may also serve as informative disease biomarkers to fully evaluate the efficacy of future therapies

Is High Blood Pressure Self-Protection for the Brain?

Rationale: Data from animal models of hypertension indicate that high blood pressure may develop as a vital mechanism to maintain adequate blood flow to the brain. We propose that congenital vascular abnormalities of the posterior cerebral circulation and cerebral hypoperfusion could partially explain the etiology of essential hypertension, which remains enigmatic in 95% of patients. Objective: To evaluate the role of the cerebral circulation in the pathophysiology of hypertension. Methods and Results: We completed a series of retrospective and mechanistic case-control magnetic resonance imaging and physiological studies, in normotensive and hypertensive humans (n=259). Interestingly, in humans with hypertension, we report a higher prevalence of congenital cerebrovascular variants; vertebral artery hypoplasia and an incomplete posterior circle of Willis, which were coupled with increased cerebral vascular resistance, reduced cerebral blood flow and a higher incidence of lacunar type infarcts. Causally, cerebral vascular resistance was elevated before the onset of hypertension and elevated sympathetic nerve activity (n=126). Interestingly, untreated hypertensive patients (n=20) had a cerebral blood flow similar to age-matched controls (n=28). However, participants receiving anti-hypertensive therapy (with blood pressure controlled below target levels) had reduced cerebral perfusion (n=19). Finally, elevated cerebral vascular resistance was a predictor of hypertension suggesting it may be a novel prognostic and/or diagnostic marker (n=126). < Conclusions: Our data indicate that congenital cerebrovascular variants in the posterior circulation and the associated cerebral hypoperfusion may be a factor in triggering hypertension. Therefore lowering blood pressure may worsen cerebral perfusion in susceptible individuals

Probing host pathogen cross-talk by transcriptional profiling of both Mycobacterium tuberculosis and infected human dendritic cells and macrophages

This study provides the proof of principle that probing the host and the microbe transcriptomes simultaneously is a valuable means to accessing unique information on host pathogen interactions. Our results also underline the extraordinary plasticity of host cell and pathogen responses to infection, and provide a solid framework to further understand the complex mechanisms involved in immunity to M. tuberculosis and in mycobacterial adaptation to different intracellular environments