Miracle-dz/UniFAR-FTUs huggingface dataset:
On reliability in publish/subscribe systems: a survey

In recent years, publish/subscribe (pub/sub) systems have evolved as serious candidate for the implementation of group communication for distributed systems. However, they have not yet been properly evaluated with respect to the critical dimension of reliability. In particular, existing surveys do not consider the case of selfish behaviour of the nodes. This paper aims to bridge this gap by reviewing 25 pub/sub systems of the literature in order to evaluate their Byzantine, altruistic, rational tolerance capabilities, i.e. how well they are able to prevent or tolerate Byzantine failures as well as rational (selfish) behaviour. To this end, we also provide the foundations required for systematically evaluating such capabilities: we define a comprehensive classification scheme of pub/sub systems and a taxonomy of elementary failures. The latter covers not only failures that may be caused by arbitrary faults but also those arising from selfish behaviour of the nodes.
Quantitative assessment of CA1 local circuits: Knowledge base for interneuron‐pyramidal cell connectivity

In this work, through a detailed literature review, data‐mining, and extensive calculations, we provide a current, quantitative estimate of the cellular and synaptic constituents of the CA1 region of the rat hippocampus. Beyond estimating the cell numbers of GABAergic interneuron types, we calculate their convergence onto CA1 pyramidal cells and compare it with the known input synapses on CA1 pyramidal cells. The convergence calculation and comparison are also made for excitatory inputs to CA1 pyramidal cells. In addition, we provide a summary of the excitatory and inhibitory convergence onto interneurons. The quantitative knowledge base assembled and synthesized here forms the basis for data‐driven, large‐scale computational modeling efforts. Additionally, this work highlights specific instances where the available data are incomplete, which should inspire targeted experimental projects toward a more complete quantification of the CA1 neurons and their connectivity. © 2013 Wiley Periodicals, Inc.
Implementing the weakest failure detector for solving the consensus problem

The concept of unreliable failure detector was introduced by Chandra and Toueg as a mechanism that provides information about process failures. This mechanism has been used to solve several agreement problems, such as the consensus problem. In this paper, algorithms that implement failure detectors in partially synchronous systems are presented. First two simple algorithms of the weakest class to solve the consensus problem, namely the Eventually Strong class (⋄S), are presented. While the first algorithm is wait-free, the second algorithm is f-resilient, where f is a known upper bound on the number of faulty processes. Both algorithms guarantee that, eventually, all the correct processes agree permanently on a common correct process, i.e. they also implement a failure detector of the class Omega (Ω). They are also shown to be optimal in terms of the number of communication links used forever. Additionally, a wait-free algorithm that implements a failure detector of the Eventually Perfect class (⋄P) is presented. This algorithm is shown to be optimal in terms of the number of bidirectional links used forever.
Speed modulation of hippocampal theta frequency correlates with spatial memory performance

Hippocampal theta rhythm is believed to play a critical role in learning and memory. In animal models of temporal lobe epilepsy (TLE), there is evidence that alterations of hippocampal theta oscillations are involved in the cognitive impairments observed in this model. However, hippocampal theta frequency and amplitude at both the local field potential (LFP) and single unit level are strongly modulated by running speed, suggesting that the integration of locomotor information into memory processes may also be critical for hippocampal processing. Here, we investigate whether hippocampal speed‐theta integration influences spatial memory and whether it could account for the memory deficits observed in TLE rats. LFPs were recorded in both Control (CTR) and TLE rats as they were trained in a spatial alternation task. TLE rats required more training sessions to perform the task at CTR levels. Both theta frequency and power were significantly lower in the TLE group. In addition, speed/theta frequency correlation coefficients and regression slopes varied from session to session and were worse in TLE. Importantly, there was a strong relationship between speed/theta frequency parameters and performance. Our analyses reveal that speed/theta frequency correlation with performance cannot merely be explained by the direct influence of speed on behavior. Therefore, variations in the coordination of theta frequency with speed may participate in learning and memory processes. Impairments of this function could explain at least partially memory deficits in epilepsy. © 2013 Wiley Periodicals, Inc.
Effects of Hydrochloric Acid and Formic Acid Decalcification on Breast Tumor Biomarkers and HER2 Fluorescence In Situ Hybridization

Biomarker analysis of metastatic breast carcinoma (MBC) is routinely recommended by ASCO/CAP guidelines, and establishing a diagnosis of MBC often requires immunohistochemistry (IHC). The reliability of breast tumor biomarkers and breast-specific markers on decalcified tissues has not been extensively studied. We performed IHC studies on breast tumors exposed to hydrochloric acid (HCl) and formic acid (FA) decalcification solutions, and HER2 fluorescence in situ hybridization on a subset of these tumors to establish a protocol for handling bone specimens with suspicion for MBC. Fifteen fresh cases of primary breast carcinoma and 8 HER2+ paraffin-embedded core biopsy cases were studied. Fresh tissue was divided into 5 fragments to approximate a bone core biopsy. One fragment (control) was fixed in 10% neutral buffered formalin. The remaining fragments were also exposed to FA or HCl decalcification for 1 or 5 hours. All fragments were embedded in 1 block and tested with an IHC panel. The known HER2+ cases were exposed to either 1 or 5 hours of FA, and HER2 fluorescence in situ hybridization was also performed. Results were interpreted as follows: H-scores for estrogen receptor, progesterone receptor, and GATA-3 were assigned from 0 to 300; HER2, cytokeratin 7, gross cystic disease fluid protein-15, Pax-8, TTF-1, cytokeratin 20, and mammaglobin were scored from 0 to 3+; and Ki67 from 0% to 100%. Mean scores were compared using the t test or Wilcoxon test for paired samples. No significant differences in mean score were seen between NF and 1 hour FA for any IHC immunoreactivity. After 5 hours of FA, only Ki67 average score was significantly less than NF. Mean scores for estrogen receptor, progesterone receptor, HER2, Ki67, and GATA-3 were significantly lower than NF in the tissue after either 1 or 5 hours of HCl. Mean scores for gross cystic disease fluid protein-15, mammaglobin, and cytokeratin 7 staining were not significantly lower than NF after 1 or 5 hours of HCl.
Transcriptome profiling analysis of the mechanisms underlying the BDNF Val66Met polymorphism induced dysfunctions of the central nervous system

Brain‐derived neurotrophic factor (BDNF) Val66Met polymorphism affects postnatal behaviors and is associated with a variety of neuropsychiatric disorders. However, the mechanisms underlying the BDNFMet variant induced dysfunctions of the central nervous system remain obscure. In order to identify the candidate genes and pathways responsible for the dysfunctions associated with this BDNF variation, we analyzed the expression of genes in the hippocampus, prefrontal cortex, and amygdala of the BDNFMet variant mice in comparison with the wild‐type mice using Illumina bead microarray. Transcriptome profiling analysis revealed region‐distinctive and gene‐dose dependent changes of gene expression associated with the BDNFMet variant. BDNFMet variant mice exhibited altered expression of genes associated with translational machinery, neuronal plasticity and mitochondrial function based on the gene ontology (GO) annotation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the chemokine, cell adhesion, ubiquitin‐proteosome and wnt signaling pathways were altered in the BDNFMet variant mice brain. Finally, the CX3CL1/CX3CR1 signaling was identified to be impaired in the hippocampus and microinjection of CX3CL1 into the hippocampus could rescue the hippocampal dependent memory deficits in BDNFMet/Met mice, indicating that CX3CL1 may be an effective treatment option for memory disorders in humans with this genetic BDNF variation. These findings will help us further understanding the molecular mechanisms involved in the BDNFMet associated behavior and neuroanatomy alternations. © 2013 Wiley Periodicals, Inc.
β-Agonists and metabolism

Abstract This review presents recent concepts of how β-agonists affect glucose homeostasis by modulating insulin secretion, liver metabolism, and uptake of glucose into muscle, with attention to the influence of hypoglycemia on β-agonist sensitivity and the effects of β 3 -adrenergic receptor (β 3 AR) polymorphisms on adipocyte metabolism. Specific β 2 -agonist effects on the pancreatic β cell result in increased insulin secretion, yet other mechanisms, such as increased glucagon secretion and hepatic effects, cause an overall increase in serum glucose and an apparent decrease in insulin sensitivity. Human studies confirm the presence of β 2 ARs on pancreatic β cells. Intensive treatment of diabetes mellitus with insulin, especially in type 1 diabetes, has led to increased incidence of hypoglycemia. Repeated episodes of hypoglycemia lead to unawareness of neuroglycopenia, a major limitation to intensive treatment. Hypoglycemic unawareness is associated with reduced β-agonist sensitivity. Scrupulous avoidance of hypoglycemia over many weeks to months can restore β-agonist sensitivity and improve detection of hypoglycemia. β-agonists have also been employed to prevent hypoglycemia. β-agonists can increase thermogenesis and lipolysis, leading to increased energy expenditure and decreased fat stores. While β 1 ARs and β 2 ARs mediate many of these actions, it is likely that β 3 ARs in the adipocyte membrane also play an important role. Specific β 3 AR subtypes have been associated with obesity and the metabolic syndrome. (J Allergy Clin Immunol 2002;110:S313-7.)
The Plight of Rural Parents Caring for Adult Children with HIV

The author used a qualitative research design to study the impact of an HIV-seropositive adult child on parents living in rural communities. In-depth, informal conversational interviews were conducted with eight mothers and two fathers of eight seropositive adult children on two separate occasions during a four-month period in three mid' western states. The author discusses three themes: physical and mental problems related to HIV/AIDS, HIV/AIDS stigma, and health care. Although no single theme was dominant in the interviews, HIV/AIDS stigma showed the highest degree of interrelatedness. Rural parents of HIV-seropositive children have few places or people in their communities to turn to in dealing with the consequences of their child's HIV status. Recommendations for rural health care professionals are provided.
Role of low‐ and high‐frequency oscillations in the human hippocampus for encoding environmental novelty during a spatial navigation task

The hippocampus plays a key role in the encoding and retrieval of information related to novel environments during spatial navigation. However, the neural basis for these processes in the human hippocampus remains unknown because it is difficult to directly measure neural signals in the human hippocampus. This study investigated hippocampal neural oscillations involved in encoding novel environments during spatial navigation in a virtual environment. Seven epileptic patients with implanted intracranial hippocampal depth electrodes performed three sessions of virtual environment navigation. Each session consisted of a navigation task and a location‐recall task. The navigation task consisted of eight blocks, and in each block, the participant navigated to the location of four different objects and was instructed to remember the location of the objects. After the eight blocks were completed, a location‐recall task was performed for each of the four objects. Intracranial electroencephalography data were monitored during the navigation tasks. Theta (5–8 Hz) and delta (1–4 Hz) oscillations were lower in the first block (novel environment) than in the eighth block (familiar environment) of the navigation task, and significantly increased from block one to block eight. By contrast, low‐gamma (31–50 Hz) oscillations were higher in the first block than in the eighth block of the navigation task, and significantly decreased from block one to block eight. Comparison of sessions with high recall performance (low error between identified and actual object location) and low recall performance revealed that high‐gamma (51–100 Hz) oscillations significantly decreased from block one to block eight only in sessions with high recall performance. These findings suggest that delta, theta, and low‐gamma oscillations were associated with encoding of environmental novelty and high‐gamma oscillations were important for the successful encoding of environmental novelty. © 2014 Wiley Periodicals, Inc.
Docking of Protein Kinase B Inhibitors: Implications in the Structure‐Based Optimization of a Novel Scaffold

Protein kinase B (PKB/AKT) is an attractive therapeutic target in anticancer drug development. We have recently identified by docking‐based virtual screening a low micromolar AKT‐2 inhibitor. Additionally, the virtual screening hit represents a novel AKT‐2 inhibitor scaffold. In this work, we discuss a structure‐based design strategy toward the optimization of this hit. Following this strategy and using a herein validated docking protocol, we conducted the design of novel compounds with expected improved activity over the parent compound. The newly designed molecules have high predicted affinity for AKT‐2; are synthetically accessible and are contained within the kinase‐relevant property space.
Finding the maximum subsequence sum on interconnection networks

We develop parallel algorithms for the maximum subsequence sum (or maximum sum for short) problem on several interconnection networks. For the 1-D version of the problem, we find an algorithm that computes the maximum sum of N elements on these networks of size p, where p ≤ N, with a running time of , which is optimal in view of the lower bound. When , our algorithm computes the maximum sum in O(log N) time, resulting in an optimal cost of O(N). This result also matches the performance of two previous algorithms that are designed to run on the more powerful PRAM model. Our 1-D maximum sum algorithm can be used to solve the problem of maximum subarray, the 2-D version of the problem. In particular, for the same interconnection networks studied here, our parallel algorithm finds the maximum subarray of an N × N array in time O(log N) with processors, once again, matching the performance of a previous PRAM algorithm.
Chemical Space Sampling in Virtual Screening by Different Crystal Structures

Retrospective virtual screening experiments were carried out to investigate the effects of combining hit lists from different crystal structures of the same target using consensus scoring. An in‐house High Throughput Screening (HTS) dataset from PI3K‐γ was used and docked against five diverse PI3K‐γ crystal structures. The results show that consensus scoring prioritizes compounds that score moderately against individual crystal structures and is thus complementary to individual crystal structure screening leading to an increase in the diversity of hits. Enrichment factors (EFs) of the consensus score for two or three structures are often as high as or higher than the EF of the individual structures used in the consensus score. Combining four or five structures in the consensus score generally yields lower enrichments. Compounds in the top 500 of the consensus score that are also found in the top 500 of an individual X‐ray structure used in the consensus score calculations yield the largest number of hits with the lowest number of false positives.
Post‐training, intrahippocampal HDAC inhibition differentially impacts neural circuits underlying spatial memory in adult and aged mice

Converging evidence indicates that pharmacologically elevating histone acetylation using post‐training, systemic or intrahippocampal, administration of histone deacetylase inhibitor (HDACi) can enhance memory consolidation processes in young rodents but it is not yet clear, whether such treatment is sufficient to prevent memory impairments associated with aging. To address this question, we used a 1‐day massed spatial learning task in the water maze to investigate the effects of immediate post‐training injection of the HDACi trichostatin A (TSA) into the dorsal hippocampus on long‐term memory consolidation in 3–4 and 18–20 month‐old mice. We show that TSA improved the 24 h‐memory retention for the hidden platform location in young‐adults, but failed to rescue memory impairments in older mice. The results further indicate that Young‐TSA mice sacrificed 1 h after training had a robust increase in histone H4 acetylation in the dorsal hippocampal CA1 region (dCA1) and the dorsomedial part of the striatum (DMS), a structure important for spatial information processing. Importantly, TSA infusion in aged mice completely rescued altered H4 acetylation in the dCA1 but failed to alleviate age‐associated decreased H4 acetylation in the DMS. Moreover, intrahippocampal TSA infusion produced concomitant decreases (in adults) or increases (in older mice) of acetylated histone levels in the ventral hippocampus (vCA1 and vCA3) and the lateral amygdala, two structures critically involved in stress and emotional responses. These data suggest that the failure of post‐training, intrahippocampal TSA injection to reverse age‐associated memory impairments may be related to an inability to recruit appropriate circuit‐specific epigenetic patterns during early consolidation processes. © 2014 Wiley Periodicals, Inc.
The functioning of the hypothalamic-pituitary-adrenal (HPA) axis in postpartum depressive states: a systematic review

ABSTRACT Introduction: A large body of literature suggests the role of the hypothalamic-pituitary-adrenal (HPA) axis in postpartum depression (PPD). Nonetheless, these studies present discrepant methodology and results; thus, this hypothesis deserves further exploration. Areas covered: This review included studies investigating the HPA axis in PPD or postpartum blues published until November 2016. In total, 48 studies met the inclusion criteria. The HPA axis was mostly investigated in the immediate postpartum period (62.5%), and the majority of studies collected samples in the morning (43.8%), with one measure in a single day (43.8%), and blood was the fluid more often collected (58.4%). Seven out of 21 studies evaluating postpartum blues, and 15 out of 28 studies evaluating PPD detected abnormalities in the HPA axis functioning. Expert commentary: We found a significant heterogeneity in the methodology adopted by studies and consequently, in the results. Despite that, the majority of studies reported HPA changes in women with PPD during the remote period. Notably, reactivity tests pointed to attenuated HPA axis response. Ideally, future investigations should use validated reactivity tests, include larger sample sizes, consider many measures of cortisol throughout the day, and more than one day of collection. We also recommend that studies continue to use validated scales for mood assessment.
Semantic retrieval over time in the aging brain: Structural evidence of hippocampal contribution

This study investigates relationship between regional cerebral volumes and performances over time of a categorical fluency task, in a sample of older adults (n = 316). Using voxel‐wise technique, the relationship between local grey matter volume and Isaacs Set Test (IST) scores at its early (first 15 sec) and late (last 15 sec) phase production was analyzed with a linear regression model adjusting for age, sex, educational level, ApoEɛ4 allele, handedness and Grey Matter atrophy. Lower early IST scores were associated with smaller volumes in bilateral inferior frontal gyri and in right thalamus, whereas lower late IST scores were associated to smaller left inferior parietal gyrus and left anterior hippocampus. An analysis based on automatic segmentation of hippocampus confirmed the latest relationship which cannot be attributed to the correlation of each variable with global cognitive impairment because it remained when MMSE was accounted for. We observed a switch from frontal to temporo‐parietal regions as words retrieval become more difficult over time. Automatic speech production of the early phase of the category fluency task is dependent on executive networks integrity whereas controlled speech production of the late phase is dependent on memory networks integrity, including left hippocampus. These results are concordant with recent imaging studies expanding the implication of hippocampus to semantic memory performances and they underlie the need to consider verbal fluency task over time. © 2015 Wiley Periodicals, Inc.
Integrating In Silico and In vitro Approaches to Dissect the Stereoselectivity of Bacillus subtilis Lipase A toward Ketoprofen Vinyl Ester

The asymmetric catalysis, as the character of enzyme, attracts increasing attention from the scientific and industrial communities. In this study, the Bacillus subtilis lipase A, as a model enzyme, is studied systematically to dissect its stereoselectivity toward (rac)‐ketoprofen vinyl ester using a combination scheme of molecular docking and quantum mechanical/molecular mechanical (QM/MM) analysis. In this procedure, the rational orientation of the two enantiomers of ketoprofen vinyl ester is obtained with the AutoDock performing, and then, the steric contacts between the enzyme and substrate in the docking outputs are examined visually at the atomic level with a small‐probe technique. Subsequently, the binding energies of the enzyme–substrate complexes are calculated using an ONIOM (Our own N‐layered Integrated Molecular Orbital + Molecular mechanics)‐based QM/MM protocol. The results obtained from the theoretical studies show that the B. subtilis lipase A prefer to hydrolyze the (R )‐ketoprofen vinyl ester when compared to its (S )‐enantiomer, with a relatively high E (stereoselectivity) value of 31.28 charactering its enantioselectivity. Furthermore, to verify the conclusions from the computational analysis, the B. subtilis lipase A gene is cloned to overexpress the recombinant B. subtilis lipase A, and its stereoselectivity was determined. Satisfactorily, the experimental results are in well agreement with the theoretical predictions because the (R )‐ketoprofen vinyl ester is found as the preferring enantiomer of the B. subtilis lipase A, with experimentally measured E value of 36.7. We therefore expect that this in silico–in vitro hybrid approach can provide a new and effective avenue to predict the catalytic activity of and to investigate the molecular mechanism of enzyme‐mediated asymmetric catalysis and help in understanding the enzymatic process and in rational enzyme design.