Analyzing Foreign Policy Crisis Situations: The Bay of Pigs

Here, the author will offer a view of the Bay of Pigs crisis within the analytical framework of the prescriptive model. There are two major objectives for undertaking this study. The first objective is to further explore the Bay of Pigs crisis. The Bay of Pigs was a prelude to the Cuban Missile crisis. The handling of the missile crisis and the various models of decision-making that have emerged from the study of that October crisis can possibly be best understood from a more careful viewing of Bay of Pigs. The second objective is to lay the groundwork for a comparative study of other similar crisis situations through the perspective of the prescriptive model. The prescriptive model has two distinct aspects. The first aspect concerns the evolution of “general strategy” for dealing with crisis situations in the nuclear age. Each aspect of the model has a number of components and sub-components. These various components will be used as the illustrative tools of analysis to measure and elucidate the Bay of Pigs operation

A Nonlinear Force-Free Magnetic Field Approximation Suitable for Fast Forward-Fitting to Coronal Loops. II. Numeric Code and Tests

Based on a second-order approximation of nonlinear force-free magnetic field solutions in terms of uniformly twisted field lines derived in Paper I, we develop here a numeric code that is capable to forward-fit such analytical solutions to arbitrary magnetogram (or vector magnetograph) data combined with (stereoscopically triangulated) coronal loop 3D coordinates. We test the code here by forward-fitting to six potential field and six nonpotential field cases simulated with our analytical model, as well as by forward-fitting to an exactly force-free solution of the Low and Lou (1990) model. The forward-fitting tests demonstrate: (i) a satisfactory convergence behavior (with typical misalignment angles of $\mu \approx 1^\circ-10^\circ$), (ii) relatively fast computation times (from seconds to a few minutes), and (iii) the high fidelity of retrieved force-free $\alpha$-parameters ($\alpha_{\rm fit}/\alpha_{\rm model} \approx 0.9-1.0$ for simulations and $\alpha_{\rm fit}/\alpha_{\rm model} \approx 0.7\pm0.3$ for the Low and Lou model). The salient feature of this numeric code is the relatively fast computation of a quasi-forcefree magnetic field, which closely matches the geometry of coronal loops in active regions, and complements the existing {\sl nonlinear force-free field (NLFFF)} codes based on photospheric magnetograms without coronal constraints.Comment: Solar PHysics, (in press), 25 pages, 11 figure

Single-subject analysis of N400 event-related potential component with five different methods

There are several different approaches to analyze event-related potentials (ERPs) at single-subject level, and the aim of the current study is to provide information for choosing a method based on its ability to detect ERP effects and factors influencing the results. We used data from 79 healthy participants with EEG referenced to mastoid average and investigated the detection rate of auditory N400 effect in single-subject analysis using five methods: visual inspection of participant-wise averaged ERPs, analysis of variance (ANOVA) for amplitude averages in a time window, cluster-based non-parametric testing, a novel Bayesian approach and Studentized continuous wavelet transform (t-CWT). Visual inspection by three independent raters yielded N400 effect detection in 85% of the participants in at least one paradigm (active responding or passive listening), whereas ANOVA identified the effect in 68%, the cluster-method in 59%, the Bayesian method in 89%, and different versions of t-CWT in 22–59% of the participants. Thus, the Bayesian method was the most liberal and also showed the greatest concordance between the experimental paradigms (active/passive). ANOVA detected significant effect only in cases with converging evidence from other methods. The t-CWT and cluster-based method were the most conservative methods. As we show in the current study, different analysis methods provide results that do not completely overlap. The method of choice for determining the presence of an ERP component at single-subject level thus remains unresolved. Relying on a single statistical method may not be sufficient for drawing conclusions on single-subject ERPs.</p

The PDZ domain of the SpoIVB serine peptidase facilitates multiple functions

During spore formation in Bacillus subtilis, the SpoIVB protein is a critical component of the sigma (K) regulatory checkpoint. SpoIVB has been shown to be a serine peptidase that is synthesized in the spore chamber and which self-cleaves, releasing active forms. These forms can signal proteolytic processing of the transcription factor sigma (K) in the outer mother cell chamber of the sporulating cell. This forms the basis of the sigma (K) checkpoint and ensures accurate sigma (K)-controlled gene expression. SpoIVB has also been shown to activate a second distinct process, termed the second function, which is essential for the formation of heat-resistant spores. In addition to the serine peptidase domain, SpoIVB contains a PDZ domain. We have altered a number of conserved residues in the PDZ domain by site-directed mutagenesis and assayed the sporulation phenotype and signaling properties of mutant SpoIVB proteins. Our work has revealed that the SpoIVB PDZ domain could be used for up to four distinct processes, (i) targeting of itself for trans proteolysis, (11) binding to the protease inhibitor BofC, (iii) signaling of pro-sigma (K) processing, and (iv) signaling of the second function of SpoIVB

Maternal corticotropin-releasing hormone is associated with LEP DNA methylation at birth and in childhood: an epigenome-wide study in Project Viva

BackgroundCorticotropin-releasing hormone (CRH) plays a central role in regulating the secretion of cortisol which controls a wide range of biological processes. Fetuses overexposed to cortisol have increased risks of disease in later life. DNA methylation may be the underlying association between prenatal cortisol exposure and health effects. We investigated associations between maternal CRH levels and epigenome-wide DNA methylation of cord blood in offsprings and evaluated whether these associations persisted into mid-childhood.MethodsWe investigated mother-child pairs enrolled in the prospective Project Viva pre-birth cohort. We measured DNA methylation in 257 umbilical cord blood samples using the HumanMethylation450 Bead Chip. We tested associations of maternal CRH concentration with cord blood cells DNA methylation, adjusting the model for maternal age at enrollment, education, maternal race/ethnicity, maternal smoking status, pre-pregnancy body mass index, parity, gestational age at delivery, child sex, and cell-type composition in cord blood. We further examined the persistence of associations between maternal CRH levels and DNA methylation in children's blood cells collected at mid-childhood (n = 239, age: 6.7-10.3 years) additionally adjusting for the children's age at blood drawn.ResultsMaternal CRH levels are associated with DNA methylation variability in cord blood cells at 96 individual CpG sites (False Discovery Rate &lt;0.05). Among the 96 CpG sites, we identified 3 CpGs located near the LEP gene. Regional analyses confirmed the association between maternal CRH and DNA methylation near LEP. Moreover, higher maternal CRH levels were associated with higher blood-cell DNA methylation of the promoter region of LEP in mid-childhood (P &lt; 0.05, β = 0.64, SE = 0.30).ConclusionIn our cohort, maternal CRH was associated with DNA methylation levels in newborns at multiple loci, notably in the LEP gene promoter. The association between maternal CRH and LEP DNA methylation levels persisted into mid-childhood

Visual Evoked Potentials Change as Heart Rate and Carotid Pressure Change

The relationship between cardiovascular activity and the brain was explored by recording visual evoked potentials from the occipital regions of the scalp during systolic and diastolic pressure (Experiment I) and during fast and slow heartbeats at systolic and diastolic pressure (Experiment II). Visual evoked potentials changed significantly as heart rate and carotid pressure fluctuated normally, and these changes were markedly different in the right and left cerebral hemispheres. Evoked potentials recorded from the right hemisphere during various cardiac events differed significantly, whereas those recorded from the left did not. In both experiments, differences in the right hemisphere were due primarily to the P1 component, which was larger at diastolic than at systolic pressure. The present findings are consistent with formulations from behavioral studies suggesting that baroreceptor activity can influence sensory intake, and suggest that hemispheric specialization may play an important role in the relationship between cardiac events, the brain and behavior.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73146/1/j.1469-8986.1982.tb02579.x.pd

Pediatric Microdose Study of [14C]Paracetamol to Study Drug Metabolism Using Accelerated Mass Spectrometry: Proof of Concept

Results: Ten infants (aged 0.1–83.1 months) were included; one was excluded as he vomited shortly after administration. In nine patients, [14C]AAP and metabolites in blood samples were detectable at expected concentrations: median (range) maximum concentration (Cmax) [14C]AAP 1.68 (0.75–4.76) ng/L, [14C]AAP-Glu 0.88 (0.34–1.55) ng/L, and [14C]AAP-4Sul 0.81 (0.29–2.10) ng/L. Dose-normalized oral [14C]AAP Cmax approached median intravenous average concentrations (Cav): 8.41 mg/L (3.75–23.78 mg/L) and 8.87 mg/L (3.45–12.9 mg/L), respectively.Conclusions: We demonstrate the feasibility of using a [14C]labeled microdose to study AAP pharmacokinetics, including metabolite disposition, in young children.Background: Pediatric drug development is hampered by practical, ethical, and scientific challenges. Microdosing is a promising new method to obtain pharmacokinetic data in children with minimal burden and minimal risk. The use of a labeled oral microdose offers the added benefit to study intestinal and hepatic drug disposition in children already receiving an intravenous therapeutic drug dose for clinical reasons.Methods: In an open-label microdose pharmacokinetic pilot study, infants (0–6 years of age) received a single oral [14C]AAP microdose (3.3 ng/kg, 60 Bq/kg) in addition to intravenous therapeutic doses of AAP (15 mg/kg intravenous every 6 h). Blood samples were taken from an indwelling catheter. AAP blood concentrations were measured by liquid chromatography–tandem mass spectrometry (LC-MS/MS) and [14C]AAP and metabolites ([14C]AAP-Glu and [14C]AAP-4Sul) were measured by accelerator mass spectrometry.Objective: The objective of this study was to present pilot data of an oral [14C]paracetamol [acetaminophen (AAP)] microdosing study as proof of concept to study developmental pharmacokinetics in children

Pandemic dreams: network analysis of dream content during the COVID-19 lockdown

We used crowdsourcing (CS) to examine how COVID-19 lockdown affects the content of dreams and nightmares. The CS took place on the 6th week of the lockdown. Over the course of one week, 4275 respondents (mean age 43, SD=14 years) assessed their sleep and 811 reported their dream content. Overall, respondents slept substantially more (54.2%) but reported an average increase of awakenings (28.6%) and nightmares (26%) from the pre-pandemic situation. We transcribed the content of the dreams into word lists and performed unsupervised computational network and cluster analysis of word associations, which suggested 33 dream clusters including 20 bad dream clusters, of which 55% were pandemic specific (e.g. Disease Management, Disregard of Distancing, Elderly in Trouble). The dream association networks were more accentuated for those who reported an increase in perceived stress. This CS survey on dream-association networks and pandemic stress introduces novel, collectively shared COVID-19 bad dream contents. </p