Miracle-dz/UniFAR-FTUs huggingface dataset:
The Impact of Childhood Maltreatment: A Review of Neurobiological and Genetic Factors

Childhood maltreatment represents a significant risk factor for psychopathology. Recent research has begun to examine both the functional and structural neurobiological correlates of adverse care-giving experiences, including maltreatment, and how these might impact on a child’s psychological and emotional development. The relationship between such experiences and risk for psychopathology has been shown to vary as a function of genetic factors. In this review we begin by providing a brief overview of neuroendocrine findings, which indicate an association between maltreatment and atypical development of the hypothalamic–pituitary–adrenal axis stress response, which may predispose to psychiatric vulnerability in adulthood. We then selectively review the magnetic resonance imaging (MRI) studies that have investigated possible structural and functional brain differences in children and adults who have experienced childhood maltreatment. Differences in the corpus callosum identified by structural MRI have now been reliably reported in children who have experienced abuse, while differences in the hippocampus have been reported in adults with childhood histories of maltreatment. In addition, there is preliminary evidence from functional MRI studies of adults who have experienced childhood maltreatment of amygdala hyperactivity and atypical activation of frontal regions. These functional differences can be partly understood in the context of the information biases observed in event-related potential and behavioral studies of physically abused children. Finally we consider research that has indicated that the effect of environmental adversity may be moderated by genotype, reviewing pertinent studies pointing to gene by environment interactions. We conclude by exploring the extent to which the growing evidence base in relation to neurobiological and genetic research may be relevant to clinical practice and intervention.
Non-Markovian Rewards Expressed in LTL: Guiding Search Via Reward Shaping

We propose an approach to solving Markov Decision Processes with non-Markovian rewards specified in Linear Temporal Logic interpreted over finite traces (LTL-f). Our approach integrates automata representations of LTL-f formulae into compiled MDPs that can be solved by off-the-shelf MDP planners, exploiting reward shaping to help guide search. Experiments with state-of-the-art UCT-based MDP planner PROST show automata-based reward shaping to be an effective method to guide search, producing solutions of superior quality, while maintaining policy optimality guarantees.
CO Rebinding Kinetics and Molecular Dynamics Simulations Highlight Dynamic Regulation of Internal Cavities in Human Cytoglobin

Cytoglobin (Cygb) was recently discovered in the human genome and localized in different tissues. It was suggested to play tissue-specific protective roles, spanning from scavenging of reactive oxygen species in neurons to supplying oxygen to enzymes in fibroblasts. To shed light on the functioning of such versatile machinery, we have studied the processes supporting transport of gaseous heme ligands in Cygb. Carbon monoxide rebinding shows a complex kinetic pattern with several distinct reaction intermediates, reflecting rebinding from temporary docking sites, second order recombination, and formation (and dissociation) of a bis-histidyl heme hexacoordinated reaction intermediate. Ligand exit to the solvent occurs through distinct pathways, some of which exploit temporary docking sites. The remarkable change in energetic barriers, linked to heme bis-histidyl hexacoordination by HisE7, may be responsible for active regulation of the flux of reactants and products to and from the reaction site on the distal side of the heme. A substantial change in both protein dynamics and inner cavities is observed upon transition from the CO-liganded to the pentacoordinated and bis-histidyl hexacoordinated species, which could be exploited as a signalling state. These findings are consistent with the expected versatility of the molecular activity of this protein.
Sleep disordered breathing and hypertension: does self-reported sleepiness modify the association?

STUDY OBJECTIVES Epidemiologic studies that demonstrate increased risk of hypertension in persons with sleep disordered breathing indicate that only a minority of these persons report significant subjective sleepiness. Studies also suggest that presence of self-reported sleepiness may identify a subset of persons with sleep disordered breathing who are at greatest risk of cardiovascular sequelae, including hypertension. We explore whether self-reported sleepiness modifies the relationship between sleep disordered breathing and prevalent hypertension. DESIGN Cross-sectional. SETTING Multicenter study. PARTICIPANTS 6046 subjects from the Sleep Heart Health Study. MEASUREMENTS Polysomnography, systolic and diastolic blood pressure, antihypertensive medication use, questionnaire determined excessive sleepiness and Epworth Sleepiness Scale, and covariates. RESULTS The odds of hypertension at higher apnea hypopnea index categories were larger in participants identified as sleepy based on responses to a frequency of sleepiness question or the Epworth score. For example, for those with AHI > or =30 compared to AHI <1.5, the adjusted odds ratio for hypertension was 2.83 (1.33-6.04) among those reporting sleepiness > or =5 days per month, but only 1.22 (0.89-1.68) among those reporting less frequent daytime sleepiness. In adjusted logistic regression models, there was statistical evidence for effect modification by frequency of sleepiness (P = 0.033) of the association between apnea hypopnea index and hypertension. In adjusted models that included the Epworth score as a continuous variable, the interaction term fell slightly short of statistical significance (beta = 0.010, P = 0.07). CONCLUSION This study finds that the association of sleep disordered breathing with hypertension is stronger in individuals who report daytime sleepiness than in those who do not.
Bayesian Hierarchical Spatially Correlated Functional Data Analysis with Application to Colon Carcinogenesis

Summary In this article, we present new methods to analyze data from an experiment using rodent models to investigate the role of p27, an important cell‐cycle mediator, in early colon carcinogenesis. The responses modeled here are essentially functions nested within a two‐stage hierarchy. Standard functional data analysis literature focuses on a single stage of hierarchy and conditionally independent functions with near white noise. However, in our experiment, there is substantial biological motivation for the existence of spatial correlation among the functions, which arise from the locations of biological structures called colonic crypts: this possible functional correlation is a phenomenon we term crypt signaling. Thus, as a point of general methodology, we require an analysis that allows for functions to be correlated at the deepest level of the hierarchy. Our approach is fully Bayesian and uses Markov chain Monte Carlo methods for inference and estimation. Analysis of this data set gives new insights into the structure of p27 expression in early colon carcinogenesis and suggests the existence of significant crypt signaling. Our methodology uses regression splines, and because of the hierarchical nature of the data, dimension reduction of the covariance matrix of the spline coefficients is important: we suggest simple methods for overcoming this problem.
Clinical acumen and vestibular schwannoma.

OBJECTIVE This study aimed to quantify the atypical presentations of patients with vestibular schwannoma by applying the audiologic criteria for the treatment of patients to the Cambridge series of such tumors to show that clinical acumen is necessary for the effective screening of these tumors. STUDY DESIGN This study was a retrospective case review of 473 patients with vestibular schwannoma. SETTING The surgery was conducted at the Department of Otoneurological and Skull Base Surgery, University Hospital, Cambridge, a tertiary referral center. PATIENTS A total of 473 patients with a unilateral sporadic vestibular schwannoma were studied. MAIN OUTCOME MEASURES Measured were the principal presenting symptoms and the criteria for audiologic management. RESULTS Of this series of patients, 89.3% had a principal presenting symptom that was typical of vestibular schwannoma (hearing loss: progressive or sudden, imbalance or tinnitus) and 10.7% had an atypical principal presenting symptom. This group of patients had significantly larger tumors (Mann-Whitney U test; tied p value = 0.0002), shorter length of history (tied p value < 0.0001), and better preserved hearing (tied p value < 0.001) than the typical otologic presentation group. These clinical correlates are related to tumor morphology, and it is hypothesized that the site of the neurilemmal-glial junction (medial or lateral) has an effect here. If the U.S. criteria for the treatment of a patient by an audiologist are applied to this series of patients, then 7 patients (1.5%) would not have had the diagnosis of vestibular schwannoma. If the U.K. criteria are applied, this number of missed tumors is 17 (3.6%). The addition of unilateral tinnitus as an indicator of the need for otologic investigation reduced the number of patients who might be missed to 2 (0.42%) for the U.S. cases and 5 (1.1%) for the U.K. cases. CONCLUSIONS Of patients with vestibular schwannoma, 10.7% have an atypical principal presenting symptom, and this group of patients has significantly larger tumors than those patients who present typically. This finding is of particular relevance to the entry point of such cases to the healthcare system. A number of patients with vestibular schwannoma appear to pass the criteria for treatment by an audiologist without reference to an otologic opinion. These patients may not be investigated from an early stage with potential implications for increased morbidity.
Use of bacteriocin‐producing, probiotic strain Enterococcus faecium AL41 to control intestinal microbiota in farm ostriches

Probiotic enterococci can produce bacteriocins. Enterococcus faecium AL41 is an Enterocin M‐producing, probiotic strain which has previously shown beneficial effect in broiler chickens. In this study, it was used to control intestinal microbiota in farm ostriches in a 42‐day experiment with an experimental group (EG, 40 ostriches) and a control group (CG, 46). In addition to feed mixture, the ostriches in EG received Ent. faecium AL41 (109 CFU ml−1; by rifampicin‐marked variant) 400 μl per animal per day in their drinking water for 21 days. Sampling was carried out at the start of the experiment (at day 0/1), at day 21 (after 21 days of AL41 application) and at day 42 (21 days after AL41 cessation). Faeces (mixture, n = 6) were treated using the standard microbiological dilution method and cultivated on selective media (ISO). The highest count of AL41 was found at day 42. Its identity was confirmed with PCR and Maldi‐Tof. The ostriches were free of Salmonella and Campylobacter cells. At day 21, antimicrobial effect was demonstrated by significant reduction in coagulase‐positive and negative staphylococci in EG compared to CG (P < 0·001) and coliforms, Enterobacteria and Pseudomonas‐like bacteria (P < 0·001). We conclude that AL41 can be used to control intestinal microbiota in farm ostriches.
Structurally variant classes of pilus appendage fibers coexpressed from Burkholderia (Pseudomonas) cepacia

One or more of five morphologically distinct classes of appendage pili were determined to be peritrichously expressed by Burkholderia (formerly Pseudomonas) cepacia isolated from disparate sources. B. cepacia-encoded cblA pilin gene hybridization-based analysis revealed that one associated class, cable (Cbl) adhesin type IIB. cepacia pili, correlates with epidemically transmitted strains from a single cystic fibrosis (CF) center. When only phenotypic assays were available, correlations between the source and the pilus type were nonetheless observed: filamentous (Fil) type IIIB. cepacia pili correlated with CF-associated nonepidemic isolates, spine (Spn) type IVB. cepacia pili correlated with clinical (non-CF) isolates, and spike (Spk) type VB. cepacia pili correlated with environmental isolates. Further, Cbl, Fil, or Spk pili typically appear as an internal framework for constitutively coexpressed, peritrichously arranged dense mats of fine, curly mesh (Msh) type IB. cepacia pili. Constitutive coexpression of dense mats of Msh type IB. cepacia pili in association with a labyrinth of either Cbl, Fil, or Spk pili suggests possible cooperative pilus interactions mediating adhesion-based colonization in the differing environments from which the strains were isolated. Despite such correlations, phylogenetic analyses indicate that with the exception of the epidemically transmitted clusters of isolates, the remaining B. cepacia strains from the other three sources exhibited an equal degree of genetic relatedness independent of origin. As previously found for Escherichia coli, this discrepancy could be accounted for by selection-driven, in vivo horizontal transfer events between distantly related members of the species B. cepacia, leading to the genetic acquisition of environmentally appropriate adhesion-based colonization pilus operons.
A Sequential Approach to Random-Effects Meta-Analysis

The objective of meta-analysis is to combine results from several independent studies in order to create generalization and provide evidence base for decision making. But recent studies show that the magnitude of effect size estimates reported in many areas of research significantly changed over time and this can impair the results and conclusions of meta-analysis. A number of sequential methods have been proposed for monitoring the effect size estimates in meta-analysis. However they are based on statistical theory applicable only to fixed effect model (FEM) of meta-analysis. For random-effects model (REM), the analysis incorporates the heterogeneity variance, τ and its estimation create complications. In this paper we study the use of a truncated CUSUM-type test with asymptotically valid critical values for sequential monitoring in REM. Simulation results show that the test does not control the Type I error well, and is not recommended. Further work required to derive an appropriate test in this important area of applications.
Market Volatility and Feedback Effects from Dynamic Hedging

In this paper we analyze the manner in which the demand generated by dynamic hedging strategies affects the equilibrium price of the underlying asset. We derive an explicit expression for the transformation of market volatility under the impact of such strategies. It turns out that volatility increases and becomes time and price dependent. The strength of these effects however depends not only on the share of total demand that is due to hedging, but also significantly on the heterogeneity of the distribution of hedged payoffs. We finally discuss in what sense hedging strategies derived from the assumption of constant volatility may still be appropriate even though their implementation obviously violates this assumption.
Shock-Dispersed-Fuel Charges: Combustion in Chambers and Tunnels

In previous studies we have investigated after-burning effects of a fuel-rich explosive (TNT). In that case the detonation only releases about 30% of the available energy, but generates a hot cloud of fuel that can burn in the ambient air, thus evoking an additional energy release that is distributed in space and time. The current series of small-scale experiments can be looked upon as a natural generalization of this mechanism: a booster charge disperses a (non-explosive) fuel, provides mixing with air and, by means of the hot detonation products, the energy to ignite the fuel. The current version of our miniature Shock-Dispersed-Fuel (SDF) charges consists of a spherical booster charge of 0.5 g PETN, embedded in a paper cylinder of approximately 2.2 cm, which is filled with powdered fuel compositions. The main compositions studied up to now contain aluminum flakes, hydrocarbon powders like polyethylene or hexosen (sucrose) and/or carbon particles. These charges were studied in four different chambers: two cylindrical vessels of 6.6-1 and 40.5-1 volume with a height-to-diameter ratio of approximately 1, a rectangular chamber of 41 (10.5 x 10.5 x 38.6 cm) and a 299.6 cm long tunnel model with a cross section of 8 x 8 cmmore » (volume 19.21) closed at both ends. « less
Analysis of auditory fMRI recordings via ICA: a study on consistency

We apply a blind source separation approach to the identification of statistically independent spatial patterns of brain activation to auditory stimulation. Stimuli consisted of spoken text. The data was collected via functional magnetic resonance imaging (fMRI). As expected from standard processing of fMRI, we observe that independent component analysis (ICA) reveals spatial patterns with similar temporal activation as the stimulus. In these, ICA further distinguishes between the primary auditory areas and Broca's and Wernicke's, which are associated with speech production and understanding, respectively. Furthermore, we observe the activation of the thalamus, with a time course unrelated to the stimulus, hence hard to detect in a classical manner. We observe as well a temporally evolving artifact, related to inefficient filtering of the fMRI scans. The consistency of the estimated signals is tested by running the algorithm with many different initial conditions. The solutions found are combined according to their similarities. Estimates that differ greatly from run to run are less likely to correspond to true components, whereas those that present small variances are considered reliable ones.
Microstructural Investigation and Evaluation of Mechanical Properties in Friction Stir Welded Joints

Abstract : With involvement of the United States Military in various places in the world, increased improvements in personnel and vehicle protection are needed. Traditionally, armoring techniques have performed well against particular threats; however, a new threat has emerged from improvised explosive devices (IEDs), which has exposed the vulnerability of the undercarriage of the vehicle to explosions. Various solutions have been proposed to combat this problem, such as implementation of a unibody construction of the chassis. While traditional joining techniques have shown promise, the variability in mechanical properties of the weldment can be costly and needs to be addressed. Friction Stir Welding (FSW) is a solid-state welding technique, which involves local softening of the material subjected to severe plastic deformation, coupled with a localized heat flux, creates a unique microstructure in and around the weld that is dependent on the FSW parameters. The current work involves the characterization of the microstructures that develop during FSW as it relates to the locally spatial mechanical properties in the weld zone. The microstructure will be characterized by using scanning electron microscopy (SEM) and electron backscatter diffraction (EBSD) techniques, which, when coupled with mechanical testing data, can be used to shed light on the spatial stress-strain behavior of the welded sample.
Nerve Gas-Induced Seizures: Role of Acetylcholine in the Rapid Induction of Fos and Glial Fibrillary Acidic Protein in Piriform Cortex

Soman (pinacolymethylphosphonofluoridate), a highly potent irreversible inhibitor of acetylcholinesterase (AChE), causes seizures and rapidly increases Fos and glial fibrillary acidic protein (GFAP) staining in piriform cortex (PC). This suggests that the inhibition of AChE by soman leads to increased acetylcholine (ACh) and neuronal excitability in PC. The sole source of cholinergic input to PC is from the nucleus of the diagonal band (NDB). To investigate the role of ACh in soman-induced seizures, we lesioned cholinergic neurons in NDB unilaterally with 192-IgG-saporin. By 10 d, saporin eliminated staining for choline acetyltransferase (ChAT), the synthetic enzyme for ACh, in NDB ipsilateral to the lesion. Staining for AChE, the degradative enzyme for ACh, was eliminated in PC ipsilateral to the lesioned NDB. By 45–60 min after soman, increased Fos and GFAP staining in PC was evident only ipsilateral to the unlesioned NDB. By 90–120 min after soman, Fos and GFAP staining increased bilaterally in PC. In a second experiment, electrical stimulation electrodes were implanted unilaterally in the NDB to activate focally the projections to PC in unanesthetized rats. Within 5 min of NDB stimulation, there were clear behavioral and EEG signs of convulsions. After 45–60 min of NDB stimulation, there was increased Fos and GFAP staining in layer II of PC ipsilateral to the stimulation site. Pretreatment with the selective muscarinic receptor antagonist scopolamine blocked the convulsions and prevented increased Fos and GFAP staining in PC. These results suggest that ACh release in PC triggers the initiation of seizures and gliosis after soman administration, predominantly by the activation of muscarinic receptors.
High Levels of Apolipoprotein B/AI Ratio Are Associated With Intracranial Atherosclerotic Stenosis

Background and Purpose— The apolipoprotein B (apoB)/apoAI ratio is recognized as a better indicator of cardiovascular disease than other cholesterol measures. Whether intracranial or extracranial atherosclerosis is more closely associated with an increased apoB/apoAI ratio has not been investigated. Methods— A total of 464 statin or fibrate naïve Korean patients with acute ischemic stroke was categorized into 3 groups: intracranial (ICAS, n=236), extracranial (n=44), and no cerebral atherosclerotic stenosis (n=184). The apoB/apoAI ratio and demographics, including the presence of metabolic syndrome, were compared among the groups. Results— The ICAS group showed a higher apoB/apoAI ratio (0.81±0.02) than both the extracranial atherosclerotic stenosis (0.74±0.03) and no cerebral atherosclerotic stenosis (0.72±0.02) groups (P=0.002). The ratio was substantially increased (0.93±0.03) in patients with advanced ICAS (≥3 intracranial stenoses). With a multivariable analysis, the highest apoB/apoAI ratio quartile was an independent predictor of ICAS (OR, 2.13; 95% CI, 1.05 to 4.33). A dose–response relationship was observed between the presence of advanced ICAS and the apoB/apoAI ratio quartiles (OR, 4.03; 95% CI, 1.26 to 12.88 for the second quartile; OR, 4.88; 95% CI, 1.54 to 15.49 for the third quartile; and OR, 7.79; 95% CI, 2.41 to 25.16 for the fourth quartile when referenced to the first quartile). Patients having more metabolic syndrome components were more likely to have ICAS, advanced ICAS, and a higher apoB/apoAI ratio (P<0.001 for all). Conclusions— A higher apoB/apoAI ratio is a predictor of ICAS rather than of extracranial atherosclerotic stenosis or no cerebral atherosclerotic stenosis. The apoB/apoAI ratio might be a biomarker for ICAS in Asian patients with stroke.