Miracle-dz/UniFAR-FTUs huggingface dataset:
The immediate early gene Egr3 mediates adaptation to stress and novelty

Stress and exploration of novel environments induce neural expression of immediate early gene transcription factors (IEG-TFs). However, as yet no IEG-TF has been shown to be required for the normal biological or behavioral responses to these stimuli. Here we show that mice deficient for the IEG-TF early growth response gene (Egr) 3, display accentuated behavioral responses to the mild stress of handling paralleled by increased release of the stress hormone corticosterone. Egr3 − / − mice also display abnormal responses to novelty, including heightened reactivity to novel environments and failure to habituate to social cues or startling acoustic stimuli. In a Y-maze spontaneous alternation task, they perform fewer sequential arm entries than controls, suggesting defects in immediate memory. Because stress and novelty stimulate hippocampal long-term depression (LTD), and because abnormalities in habituation to novelty and Y-maze performance have been associated with LTD deficits, we examined this form of synaptic plasticity in Egr3 − / − mice. We found that Egr3 − / − mice fail to establish hippocampal LTD in response to low frequency stimulation and exhibit dysfunction of an ifenprodil-sensitive (NR1/NR2B) NMDA receptor subclass. LTP induction was not altered. The NR2B-dependent dysfunction does not result from transcriptional regulation of this subunit by Egr3, because NR2B mRNA levels did not differ in the hippocampi of Egr3 − / − and control mice. These findings are the first demonstration of the requirement for an IEG-TF in mediating the response to stress and novelty, and in the establishment of LTD.
Andre-Quillen homology for simplicial algebras and ring spectra

We discuss Andre-Quillen homology for simplicial algebras and algebras over simplicial algebras, extending the classical notion for rings. This extension is also discussed by Goerss and Hopkins, however our statements are proven in a more explicit way. We are then further able to construct spectral sequences for Andre-Quillen homology like the spectral sequence for the indecomposables or the Fundamental spectral sequence according to Quillen. The Andre-Quillen homology for algebras constructed as cellular complexes is calculated and we apply this homology theory to obtain notions of atomic and nuclear algebras, thus extending results from Baker and May. We define the notion of i-stable algebras and are able to give a comparison theorem between Andre-Quillen homology, stabilisation and Gamma-homology for i-stable algebras up to degree i. In the second part of the thesis we discuss topological Andre-Quillen homology and extend certain results by Gilmour about cellular complexes in this setting.
Is Gray Matter Volume an Intermediate Phenotype for Schizophrenia? A VBM Study of Patients with Schizophrenia and their Healthy Siblings

Objective: Shared neuropathological characteristics of patients with schizophrenia and their siblings may represent intermediate phenotypes that could be used to investigate genetic susceptibility to the illness. We sought to discover previously unidentified gray matter volume differences in patients with schizophrenia and their siblings using optimized Voxel-Based Morphometry (VBM). Methods: We studied 169 patients with schizophrenia, 213 of their unaffected siblings, and 212 healthy volunteers from the CBDB/NIMH Genetic Study of Schizophrenia with magnetic resonance imaging (MRI). Results: Patients with schizophrenia had significant regional gray matter decreases in the frontal, temporal, and parietal cortices compared with healthy volunteers. Their unaffected siblings tended to share gray matter decreases in the medial frontal, superior temporal and insular cortices, but these decreases were not significant after correction for multiple comparisons, even when we looked at a subgroup of siblings with a past history of mood disorder. As an exploratory analysis, we estimated heritability using regions of interest from the VBM analysis, as well as from the hippocampus. Hippocampal volume was significantly correlated within sibling-pairs.
Cells from long-lived mutant mice exhibit enhanced repair of UV lesions

Fibroblasts isolated from long-lived hypopituitary dwarf mice are resistant to many cell stresses, including UV light and MMS, which induce cell death by producing DNA damage. Here we report that cells from Snell dwarf mice recover more rapidly than controls from the inhibition of RNA synthesis induced by UV damage. Recovery of mRNA synthesis in particular is more rapid in dwarf cells, suggesting enhanced repair of the actively transcribing genes in dwarf-derived cells. At early timepoints, there was no difference in the repair of CPD or 6-4PP in the whole genome, nor was there any significant difference in the repair of UV lesions in specific genes. However, at later time points we found that more lesions had been removed from the genome of dwarf-derived cells. We have also found that cells from dwarf mice express higher levels of the nucleotide excision repair proteins XPC and CSA, suggesting a causal link to enhanced DNA repair. Overall, these data suggest a mechanism for the UV resistance of Snell dwarf-derived fibroblasts that could contribute to the delay of aging and neoplasia in these mice.
Regression from Pre-diabetes to Normal Glucose Regulation is Associated with Long-term Reduction in Diabetes Risk: Results from the Diabetes Prevention Program Outcomes Study

Background— Our objective was to quantify and predict diabetes risk reduction during the Diabetes Prevention Program Outcomes Study (DPPOS) among those who returned to normal glucose regulation (NGR) at least once during DPP compared to those who were consistently considered to have pre-diabetes. Methods— Diabetes cumulative incidence in DPPOS was calculated for subjects with NGR or pre-diabetes status during DPP with and without stratification by prior randomized treatment group. Cox proportional hazards modeling and generalized linear mixed models were used to quantify the impact of previous (DPP) glycemic status on risk of later (DPPOS) diabetes and NGR status, respectively, per standard deviation in change. Included in this analysis are 1990 participants of DPPOS (who had been randomized during DPP: N=736 in intensive lifestyle (ILS), N=647 to metformin (MET), and N=607 to placebo (PLB)). Findings— Diabetes risk during DPPOS was 56% lower in NGR vs. pre-diabetes (HR=0.44, 95% CI 0.37-0.55, p<0.0001) and was unaffected by prior group assignment (interaction test for NGR*ILS, p=0.1722; NGR*MET, p=0.3304). Many, but not all, of the variables that increased diabetes risk were inversely associated with 1.08-1.25, p<0.0001) were associated with NGR in DPPOS, whereas the opposite was true for predicting diabetes (HR=0.80, 95% CI 0.71-0.89; HR=0.83, 95% CI 0.74-0.94, respectively, p<0.0001 for both). Surprisingly, among subjects who failed to return to NGR in DPP, those randomized to ILS had a higher diabetes risk (HR=1.31, 95% CI 1.03-1.68, p=0.0304) and lower chance of NGR (OR=0.59, 95% CI 0.42-0.82, p=0.0014) vs. placebo in DPPOS. Interpretation— We conclude that pre-diabetes represents a high-risk state for diabetes, especially among those who remain so despite ILS. Reversion to NGR, even if transient, is associated with a significantly lower risk of future diabetes independent of prior treatment group.
Hospital-based surveillance of malaria-related

Although Plasmodium falciparum malaria is a leading cause of paediatric morbidity and mortality in Africa, few quantitative estimates are available about the impact of malaria on childhood health. To quantify the impact of the disease in an urban African setting, we reviewed the paediatric ward and mortuary records at Mama Yemo Hospital in Kinshasa, Zaire. From June 1985 to May 1986, 6208 children were admitted to the hospital, 2374 (38.2%) of whom had malaria; 500 of those with malaria died (case fatality rate, 21.1%). During this same period, there were 10036 paediatric deaths, 1323 (13.2%) of which were attributed to malaria; 823 (62.2%) of these occurred in the emergency ward prior to hospitalization. Minimum population-based malaria mortality rates were highest for children aged < 1 year (4.0 per 1000 per year). Over 70% of children admitted with malaria and >80% of children who died from the disease were <5 years old. The total number of paediatric admissions and deaths remained relatively constant between 1982 and 1986; however, the proportional malaria admission rate increased from 29.5% in 1983 to 56.4% in 1986, and the proportional malaria mortality rate, from 48% in 1982 to 15.3% in 1986. These increases were temporally related to the emergence of chloroquine-resistant Plasmodium falciparum malaria in Kinshasa. Malaria is therefore a major cause of paediatric morbidity and mortality in the city, and this study indicates that hospital-based surveillance may be useful in monitoring disease-specific morbidity and mortality elsewhere in Africa.
The role of submicroscopic malaria in malaria transmission: what is the evidence?

Achieving malaria elimination requires targeting the human reservoir of infection, including those with asymptomatic infection. Smear-positive asymptomatic infections detectable by microscopy are an important reservoir because they often persist for months and harbor gametocytes, the parasite stage infectious to mosquitoes. However, many asymptomatic infections are submicroscopic and can only be detected by molecular methods. While there is some evidence that persons with submicroscopic malaria can infect mosquitoes, transmission is much less likely to occur at submicroscopic gametocyte levels. As malaria elimination programs pursue mass screening and treatment of asymptomatic individuals, further research should strive to define the degree to which submicroscopic malaria contributes to the infectious reservoir, and in turn, what diagnostic detection threshold is needed to effectively interrupt transmission.
Preferential labeling of inhibitory and excitatory cortical neurons by endogenous tropism of AAV and lentiviral vectors

Despite increasingly widespread use of recombinant adeno-associated virus (AAV) and lentiviral (LV) vectors for transduction of neurons in a wide range of brain structures and species, the diversity of cell types within a given brain structure is rarely considered. For example, the ability of a vector to transduce neurons within a brain structure is often assumed to indicate that all neuron types within the structure are transduced. We have characterized the transduction of mouse somatosensory cortical neuron types by recombinant AAV pseudotyped with serotype 1 capsid (rAAV2/1) and by recombinant lentivirus pseudotyped with the VSV glycoprotein. Both vectors utilized human synapsin (hSyn) promoter driving DsRed-Express. We demonstrate that high titer rAAV2/1 efficiently transduces both cortical excitatory and inhibitory neuronal populations, but use of lower titers exposes a strong preference for transduction of cortical inhibitory neurons and layer 5 pyramidal neurons. In contrast, we find that VSV-GLV-hSyn principally labels excitatory cortical neurons at the highest viral titer generated. These findings demonstrate that endogenous tropism of rAAV2/1 and VSV-GLV can be used to obtain preferential gene expression in mouse somatosensory cortical inhibitory and excitatory neuron populations, respectively.
Is There an Association Between Maternal Pap Test Use and Adolescent Human Papillomavirus Vaccination? Implications and Contribution

Purpose— To identify the association between mother’s recent receipt of a Pap test and daughter’s uptake and completion of the three-shot human papillomavirus (HPV) vaccination series. Methods— We used cross-sectional data from the 2008 to 2010 Behavioral Risk Factor Surveillance System from 9 U.S. states and Puerto Rico and logistic regression models to examine the association between mother’s receipt of a Pap test in the past 3 years and daughter’s uptake and completion of the three-shot HPV vaccination series among adolescent girls aged 9-17 years (N = 4,776). Results— Approximately one-quarter of adolescent girls began the HPV vaccination series, and 13.6% completed the three-shot series. Uptake and completion were more likely among girls whose mothers had obtained a Pap test within the past 3 years—for HPV uptake, odds ratio: 1.342, 95% confidence interval: 1.073-1.692; for HPV completion, odds ratio: 1.904; 95% confidence interval: 1.372-2.721—but the relationship between mother’s recent Pap test and vaccine uptake was explained by the mother’s use of a personal doctor and obtaining a routine physical examination in the past year. Conclusions— HPV vaccination uptake and completion were more likely among adolescent girls whose mothers obtained a recent Pap test. Interventions designed to educate mothers on the importance of HPV vaccination and to facilitate relationships between physicians and mothers may prove successful at increasing HPV vaccination among adolescent girls.
A method for in vitro assembly of HCV core protein and for screening of inhibitors

The assembly of hepatitis C virus (HCV) is not well understood. We investigated HCV nucleocapsid assembly in vitro and the role of electrostatic/hydrophobic interactions in this process. A simple and rapid in vitro assay was developed in which the progress of assembly is monitored by measuring an increase in turbidity, thus allowing the kinetics of assembly to be determined. Assembly is performed using a truncated HCV core (C1-82), containing the minimal assembly domain, purified from E. coli . The increase in turbidity is linked to the formation of nucleocapsid-like particles (NLPs) in solution, and nucleic acids are essential to initiate nucleocapsid assembly under the experimental conditions used. The sensitivity of NLP formation to salt strongly suggests that electrostatic forces govern in vitro assembly. Mutational analysis of C1-82 demonstrated that it is the global positive charge of C1-82 rather than any specific basic residue that is important for the assembly process. Our in vitro assembly assay provides an easy and efficient means of screening for assembly inhibitors; we have identified several inhibitory peptides that could represent a starting point for drug design.
ICU Exposures for Long-Term Outcomes Research: Development and Description of Exposures for 150 ALI Patients

Purpose— Long-term follow-up studies in critical care have described survivors’ outcomes, but provided less insight into the patient/disease characteristics and intensive care therapies (“exposures”) associated with these outcomes. Such insights are essential for improving patients’ long-term outcomes. This report describes the development of a strategy for comprehensively measuring relevant exposures for long-term outcomes research, and presents empirical results from its implementation. Materials and Methods— A multi-step, iterative process was used to develop the exposures strategy. First, a comprehensive list of potential exposures was generated and subsequently reduced based on feasibility, redundancy, and relevance criteria. Next, data abstraction methods were designed and tested. Finally, the strategy was implemented in 150 acute lung injury patients with iterative refinement. Results— The strategy resulted in development of >60 unique exposures requiring <45 minutes per patient-day for data collection. The vast majority of exposures had minimal missing data and adequate reliability. These data revealed that evidence-based practices including lower tidal volume ventilation, spontaneous breathing trials, sedation interruption, adequate nutrition, multi-step,
Cholinergic Modulation of non-NMDA Glutamatergic Transmission in the Chick Ventral Lateral Geniculate Nucleus

Neurotransmission between glutamatergic terminals of retinal ganglion cells and principal neurons of the ventral lateral geniculate nucleus (LGNv) was examined with patch clamp recordings in chick brain slices during electrical stimulation of the optic tract. Since muscarinic and nicotinic receptors are present in high densities in LGNv, the present study examined possible roles of both receptors in modulating retinogeniculate transmission. During whole-cell recordings from LGNv neurons, acetylcholine (ACh, 100 μ M) caused an initial increase in amplitudes of optic tract-evoked non-NMDA glutamatergic postsynaptic currents (PSCs). This increase was unchanged when 1 μ M atropine was present, indicating that this initial enhancement of PSCs was due entirely to activation of nicotinic receptors. However, during washout of ACh the amplitudes of evoked PSCs became significantly decreased by 40.4±5.0% for several minutes before recovering to their original amplitudes, an effect blocked by 1 μ M atropine. Exogenously applied muscarine (10 μ M) markedly depressed optic tract-evoked PSCs, and this decrease in amplitude was blocked by atropine. In a second set of experiments, we examined effects of releasing endogenous ACh prior to optic tract stimulation. This was accomplished by stimulation of the lateral portion of LGNv via a separate conditioning electrode. Following a brief train of low intensity conditioning stimuli, non-NMDA glutamatergic PSCs evoked by optic tract stimulation were potentiated. However, at higher conditioning stimulus intensities the PSCs were markedly decreased compared with control, and this decrease was partially blocked by atropine (1 μ M). Neither ACh nor muscarine altered amplitudes of PSCs elicited by exogenously applied glutamate. Muscarine significantly reduced the frequency but not the amplitudes of miniature PSCs, consistent with a presynaptic location for muscarinic receptors mediating these effects. Thus while activation of nicotinic receptors potentiates retinogeniculate transmission, activation of muscarinic receptors mediates depression of transmission, demonstrating a complex cholinergic modulation of sensory information in LGNv. by exogenously applied glutamate (p>0.05, n=4 for both). The results suggest that activation of presynaptically located muscarinic receptors was responsible for the observed decreases in optic tract-evoked glutamatergic transmission in the LGNv.
Correlates of Root Caries Experience in Middle-Aged and Older Adults within the Northwest PRECEDENT

Methods—This observational cross-sectional study focused on adult patients ages 45–97 years recruited from the Northwest PRECEDENT (N=775 adults). The outcome variable was any root caries experience (no/yes). Sociodemographic, intraoral, and behavioral factors were hypothesized as potential root caries correlates. We used Poisson regression models to generate overall and agestratified prevalence ratios (PR) of root caries and Generalized Estimating Equations to account for practice-level clustering of participants.
Aminoflavone, a ligand of the Aryl Hydrocarbon Receptor (AhR), inhibits HIF-1 α expression in an AhR-independent fashion

Aminoflavone (AF), the active component of a novel anticancer agent (AFP464) in phase I clinical trials, is a ligand of the aryl hydrocarbon receptor (AhR). AhR dimerizes with HIF-1 β /ARNT, which is shared with HIF-1 α , a transcription factor critical for the response of cells to oxygen deprivation. To address whether pharmacological activation of the AhR pathway might be a potential mechanism for inhibition of HIF-1, we tested the effects of AF on HIF-1 expression. AF inhibited HIF-1 α transcriptional activity and protein accumulation in MCF-7 cells. However, inhibition of HIF-1 α by AF was independent from a functional AhR pathway. Indeed, AF inhibited HIF-1 α expression in Ah R100 cells, in which the AhR pathway is functionally impaired, yet did not induce cytotoxicity, providing evidence that these effects are mediated by distinct signaling pathways. Moreover, AF was inactive in MDA-MB-231 cells, yet inhibited HIF-1 α in MDA-MB-231 cells transfected with the SULT1A1 gene. AF inhibited HIF-1 α mRNA expression by approximately 50%. Notably, actinomycin-D completely abrogated the ability of AF to down-regulate HIF-1 α mRNA, indicating that active transcription was required for the inhibition of HIF-1 α expression. Finally, AF inhibited HIF-1 α protein accumulation and the expression of HIF-1-target genes in MCF-7 xenografts. These results demonstrate that AF inhibits HIF-1 α in an AhR-independent fashion and they unveil additional activities of AF that may be relevant for its further clinical development.
interleukin-8 concentrations cystic fibrosis are associated with high bronchoalveolar lavage fluid from children with High concentrations of pepsin in http : / / thorax

Background Gastro-oesophageal reflux is common in children with cystic fibrosis (CF) and is thought to be associated with pulmonary aspiration of gastric contents. The measurement of pepsin in bronchoalveolar lavage (BAL) fluid has recently been suggested to be a reliable indicator of aspiration. The prevalence of pulmonary aspiration in a group of children with CF was assessed and its association with lung inflammation investigated. Methods This was a cross-sectional caseecontrol study. BAL fluid was collected from individuals with CF (n1⁄431) and healthy controls (n1⁄47). Interleukin-8 (IL-8), pepsin, neutrophil numbers and neutrophil elastase activity levels were measured in all samples. Clinical, microbiological and lung function data were collected
A Lightweight Perceptron-Based Intrusion Detection System for Fog Computing

Fog computing is a paradigm that extends cloud computing and services to the edge of the network in order to address the inherent problems of the cloud, such as latency and lack of mobility support and location-awareness. The fog is a decentralized platform capable of operating and processing data locally and can be installed in heterogeneous hardware which makes it ideal for Internet of Things (IoT) applications. Intrusion Detection Systems (IDSs) are an integral part of any security system for fog and IoT networks to ensure the quality of service. Due to the resource limitations of fog and IoT devices, lightweight IDS is highly desirable. In this paper, we present a lightweight IDS based on a vector space representation using a Multilayer Perceptron (MLP) model. We evaluated the presented IDS against the Australian Defense Force Academy Linux Dataset (ADFA-LD) and Australian Defense Force Academy Windows Dataset (ADFA-WD), which are new generation system calls datasets that contain exploits and attacks on various applications. The simulation shows that by using a single hidden layer and a small number of nodes, we are able to achieve a 94% Accuracy, 95% Recall, and 92% F1-Measure in ADFA-LD and 74% Accuracy, 74% Recall, and 74% F1-Measure in ADFA-WD. The performance is evaluated using a Raspberry Pi.
Distributed Reconciliation in Day-Ahead Wind Power Forecasting

With increasing renewable energy generation capacities connected to the power grid, a number of decision-making problems require some form of consistency in the forecasts that are being used as input. In everyday words, one expects that the sum of the power generation forecasts for a set of wind farms is equal to the forecast made directly for the power generation of that portfolio. This forecast reconciliation problem has attracted increased attention in the energy forecasting literature over the last few years. Here, we review the state of the art and its applicability to day-ahead forecasting of wind power generation, in the context of spatial reconciliation. After gathering some observations on the properties of the game-theoretical optimal projection reconciliation approach, we propose to readily rethink it in a distributed setup by using the Alternating Direction Method of Multipliers (ADMM). Three case studies are considered for illustrating the interest and performance of the approach, based on simulated data, the National Renewable Energy Labaratory (NREL) Wind Toolkit dataset, and a dataset for a number of geographically distributed wind farms in Sardinia, Italy.