Miracle-dz/UniFAR-FTUs huggingface dataset:
Loss of Antibiotic Tolerance in Sod-Deficient Mutants Is Dependent on the Energy Source and Arginine Catabolism in Enterococci

ABSTRACT Enterococci are naturally tolerant to typically bactericidal cell wall-active antibiotics, meaning that their growth is inhibited but they are not killed even when exposed to a high concentration of the drug. The molecular reasons for this extraordinary tolerance are still incompletely understood. Previous work showed that resistance to killing collapsed specifically in mutants affected in superoxide dismutase (Sod) activity, arguing that bactericidal antibiotic treatment led to induction of a superoxide burst. In the present work, we show that loss of antibiotic tolerance in ΔsodA mutants of pathogenic enterococci is dependent on the energy source present during antibiotic treatment. Hexoses induce greater killing than the pentose ribose, and no killing was observed with glycerol as the energy source. These results point to glycolytic reactions as crucial for antibiotic-mediated killing of ΔsodA mutants. A transposon mutant library was constructed in Enterococcus faecalis ΔsodA mutants and screened for restored tolerance of vancomycin. Partially restored tolerance was observed in mutants with transposon integrations into intergenic regions upstream of regulators implicated in arginine catabolism. In these mutants, the arginine deiminase operon was highly upregulated. A model for the action of cell wall-active antibiotics in tolerant and nontolerant bacteria is proposed. IMPORTANCE Antibiotic tolerance is a serious clinical concern, since tolerant bacteria have considerably increased abilities to resist killing by bactericidal drugs. Using enterococci as models for highly antibiotic-tolerant pathogens, we showed that tolerance of these bacteria is linked to their superoxide dismutase (Sod), arguing that bactericidal antibiotics induce generation of reactive oxygen species inside cells. Wild-type strains are tolerant because they detoxify these deleterious molecules by the activity of Sod, whereas Sod-deficient strains are killed. This study showed that killing depends on the energy source present during treatment and that an increase in arginine catabolism partially restored tolerance of the Sod mutants. These results are used to propose a mode-of-action model of cell wall-active antibiotics in tolerant and nontolerant bacteria.
Chinese automobile demand prediction based on ARIMA model

Chinese automobile industry is a pillar industry of national economy. Forecasting on automobile demand of China is helpful for government to draft automobile industry policies and for automobile enterprises to plan their output. In this paper, based on autoregressive integrated moving average (ARIMA) time series model, I build a forecast model of automobile demand of China by using the monthly data of automobile sales from China Association of Automobile Manufactures (CAAM) in 2001.01–2011.06. Furthermore, I evaluate the forecasting performance of established model and find that it is very well.
Understanding Public Opinions from Geosocial Media

Increasingly, social media data are linked to locations through embedded GPS coordinates. Many local governments are showing interest in the potential to repurpose these firsthand geo-data to gauge spatial and temporal dynamics of public opinions in ways that complement information collected through traditional public engagement methods. Using these geosocial data is not without challenges since they are usually unstructured, vary in quality, and often require considerable effort to extract information that is relevant to local governments’ needs from large data volumes. Understanding local relevance requires development of both data processing methods and their use in empirical studies. This paper addresses this latter need through a case study that demonstrates how spatially-referenced Twitter data can shed light on citizens’ transportation and planning concerns. A web-based toolkit that integrates text processing methods is used to model Twitter data collected for the Region of Waterloo (Ontario, Canada) between March 2014 and July 2015 and assess citizens’ concerns related to the planning and construction of a new light rail transit line. The study suggests that geosocial media can help identify geographies of public perceptions concerning public facilities and services and have potential to complement other methods of gauging public sentiment.
Broad domain generality in focal regions of frontal and parietal cortex

Significance One of the oldest debates in cognitive neuroscience concerns the degree of functional specialization present in the human brain. Prior work has discovered several highly specialized components dedicated to particular mental functions, like face recognition or motion perception. However, our cognitive versatility suggests the additional existence of more general-purpose machinery. Building on prior neuroimaging evidence, along with neurophysiological evidence from non-human primates, we searched for such domain-general brain regions in humans. Seven diverse demanding cognitive tasks produced overlapping activation at the individual-subject level in a number of frontal and parietal brain regions. Thus, human cognition arises from hardware that includes not only specialized components, but also very general-purpose ones that plausibly enable us to solve novel problems. Unlike brain regions that respond selectively to specific kinds of information content, a number of frontal and parietal regions are thought to be domain- and process-general: that is, active during a wide variety of demanding cognitive tasks. However, most previous evidence for this functional generality in humans comes from methods that overestimate activation overlap across tasks. Here we present functional MRI evidence from single-subject analyses for broad functional generality of a specific set of brain regions: the same sets of voxels are engaged across tasks ranging from arithmetic to storing information in working memory, to inhibiting irrelevant information. These regions have a specific topography, often lying directly adjacent to domain-specific regions. Thus, in addition to domain-specific brain regions tailored to solve particular problems of longstanding importance to our species, the human brain also contains a set of functionally general regions that plausibly endow us with the cognitive flexibility necessary to solve novel problems.
CuikSLAM: A Kinematics-based Approach to SLAM

In this paper, we depart from the fact that Simultaneous Localization and Mapping (SLAM) is a sub-case of the general kinematic problem, and, thus, all techniques used in kinematics are potentially applicable to SLAM. We describe how to formalize a SLAM problem as a typical kinematic problem and we propose a simple SLAM algorithm based on an interval-based kinematic method called Cuik previously developed in our group. This new algorithm solves the SLAM problem taking advantage of the structure imposed in the SLAM problem by the motion and sensing capabilities of the autonomous robots. However, since we use a kinematic approach instead of a probabilistic one (the usual approach for SLAM) we can perfectly model the constraints between robot poses and between robot poses and landmarks, including the nonlinearities, and we can ensure those constraints to be fulfilled at any time during the map construction and refinement. The viability of the new algorithm is shown with a small test.
Exported Epoxide Hydrolases Modulate Erythrocyte Vasoactive Lipids during Plasmodium falciparum Infection

ABSTRACT Erythrocytes are reservoirs of important epoxide-containing lipid signaling molecules, including epoxyeicosatrienoic acids (EETs). EETs function as vasodilators and anti-inflammatory modulators in the bloodstream. Bioactive EETs are hydrolyzed to less active diols (dihydroxyeicosatrienoic acids) by epoxide hydrolases (EHs). The malaria parasite Plasmodium falciparum infects host red blood cells (RBCs) and exports hundreds of proteins into the RBC compartment. In this study, we show that two parasite epoxide hydrolases, P. falciparum epoxide hydrolases 1 (PfEH1) and 2 (PfEH2), both with noncanonical serine nucleophiles, are exported to the periphery of infected RBCs. PfEH1 and PfEH2 were successfully expressed in Escherichia coli, and they hydrolyzed physiologically relevant erythrocyte EETs. Mutations in active site residues of PfEH1 ablated the ability of the enzyme to hydrolyze an epoxide substrate. Overexpression of PfEH1 or PfEH2 in parasite-infected RBCs resulted in a significant alteration in the epoxide fatty acids stored in RBC phospholipids. We hypothesize that the parasite disruption of epoxide-containing signaling lipids leads to perturbed vascular function, creating favorable conditions for binding and sequestration of infected RBCs to the microvascular endothelium. IMPORTANCE The malaria parasite exports hundreds of proteins into the erythrocyte compartment. However, for most of these proteins, their physiological function is unknown. In this study, we investigate two “hypothetical” proteins of the α/β-hydrolase fold family that share sequence similarity with epoxide hydrolases (EHs)—enzymes that destroy bioactive epoxides. Altering EH expression in parasite-infected erythrocytes resulted in a significant change in the epoxide fatty acids stored in the host cell. We propose that these EH enzymes may help the parasite to manipulate host blood vessel opening and inflame the vessel walls as they pass through the circulation system. Understanding how the malaria parasite interacts with its host RBCs will aid in our ability to combat this deadly disease. The malaria parasite exports hundreds of proteins into the erythrocyte compartment. However, for most of these proteins, their physiological function is unknown. In this study, we investigate two “hypothetical” proteins of the α/β-hydrolase fold family that share sequence similarity with epoxide hydrolases (EHs)—enzymes that destroy bioactive epoxides. Altering EH expression in parasite-infected erythrocytes resulted in a significant change in the epoxide fatty acids stored in the host cell. We propose that these EH enzymes may help the parasite to manipulate host blood vessel opening and inflame the vessel walls as they pass through the circulation system. Understanding how the malaria parasite interacts with its host RBCs will aid in our ability to combat this deadly disease.
A Cognitive Model Based on Neuromodulated Plasticity

Associative learning, including classical conditioning and operant conditioning, is regarded as the most fundamental type of learning for animals and human beings. Many models have been proposed surrounding classical conditioning or operant conditioning. However, a unified and integrated model to explain the two types of conditioning is much less studied. Here, a model based on neuromodulated synaptic plasticity is presented. The model is bioinspired including multistored memory module and simulated VTA dopaminergic neurons to produce reward signal. The synaptic weights are modified according to the reward signal, which simulates the change of associative strengths in associative learning. The experiment results in real robots prove the suitability and validity of the proposed model.
Vigorous Innate and Virus-Specific Cytotoxic T-Lymphocyte Responses to Murine Cytomegalovirus in the Submaxillary Salivary Gland

ABSTRACT To better understand the immunological mechanisms that permit prolonged shedding of murine cytomegalovirus (MCMV) from the salivary gland, the phenotypic and functional characteristics of leukocytes infiltrating the submaxillary gland (SMG) were analyzed in infected BALB/c mice. A robust innate immune response, comprised of CD11c+ major histocompatibility complex class II+ CD11b− CD8α+ dendritic cells and γ/δ T-cell receptor-bearing CD3+ T cells was prominent through at least 28 days postinfection. Concurrently, a dramatic increase in pan-NK (DX5+) CD3+ and CD8+ T cells was observed, while CD4+ T cells, known to be essential for viral clearance from this tissue, increased slightly. The expression particularly of gamma interferon but also of interleukin-10 and CC chemokines was extraordinarily high in the SMG in response to MCMV infection. The gamma interferon was produced primarily by CD4+ and CD8+ T lymphocytes and DX5+ CD3+ T cells. The SMG CD8+ T cells were highly cytolytic ex vivo, and a significant proportion of these cells were specific to an immunodominant MCMV peptide. These peptide-specific clones were not exhausted by the presence of high virus titers, which persisted in the SMG despite the strength of the cell-mediated responses. In contrast, MCMV replication was efficiently cleared from the draining cervical and periglandular lymph nodes, a tissue displaying a substantially weaker antiviral response. Our data indicated that vigorous innate and acquired immune responses are elicited, activated, and retained in response to mucosal inflammation from persistent MCMV infection of the submaxillary gland.
Modelling and Optimization of Magnetic Abrasive Finishing Process

Finishing is final operation involved in the manufacturing of components and is most labour intensive, time consuming and least controllable area. The need of better finishing of complicated shapes made of advanced materials and high accuracy are the main factors responsible for using advanced abrasive fine finishing processes (Jain, 2002). MAF is an unconventional finishing process in which the cutting force is primarily controlled by the magnetic field. It reduces the possibility of microcracks on the surface of the workpiece, specially in hard brittle material, due to low forces acting on abrasive particles (Jain, 2002). This process is capable of producing surface roughness in the nanometer range on flat surfaces as well as internal and external cylindrical surfaces (Jain et al., 2001). The MAF process offers many advantages, such as self-sharpening, selfadaptability, controllability and the finishing tools require neither compensation nor dressing (Chang et al., 2002). In MAF, the workpiece is kept between the two poles of a magnet. The working gap between the workpiece and the magnet is filled with magnetic abrasive particles, composed of ferromagnetic particles and abrasive powder. Bonded or unbounded Magnetic abrasive particles can be used. In this process, usually ferromagnetic particles are sintered with fine abrasive particles (Al2O3, SiC, CBN, or diamond) and such particles are called ferromagnetic abrasive particles (Shinmura et al., 1986, 1990; Chang et al., 2002; Jain, 2009). Finishing pressure can be controlled via a magnetic field applications (Shinmura et al., 1993; Chang et al., 2002). Workpiece materials can be both magnetic (e.g., steel) as well as nonmagnetic (e.g., ceramics) and the material removal can be adjusted based on the size of the magnetic abrasives. Thus, MAF is a multi-functional precise finishing method one can use to obtain quality surface finishes efficiently (Lieh-Dai et al., 2007). Jayswal et al. (2005) also proposed a mathematical
The Clustering of Galaxies in the SDSS-III DR10 Baryon Oscillation Spectroscopic Survey: No Detectable Colour Dependence of Distance Scale or Growth Rate Measurements

We study the clustering of galaxies, as a function of their colour, from Data Release Ten (DR10) of the Sloan Digital Sky Survey III (SDSS-III) Baryon Oscillation Spectroscopic Survey. DR10 contains 540 505 galaxies with 0.43 < z < 0.7; from these we select 122 967 for a ‘Blue’ sample and 131 969 for a ‘Red’ sample based on k + e corrected (to z =0.55) r − i colours and i-band magnitudes. The samples are chosen such that both contain more than 100 000 galaxies, have similar redshift distributions and maximize the difference in clustering amplitude. The Red sample has a 40 per cent larger bias than the Blue (bRed/bBlue = 1.39 ± 0.04), implying that the Red galaxies occupy dark matter haloes with an average mass that is 0.5 log10 M⊙ greater. Spherically averaged measurements of the correlation function, ξ0, and the power spectrum are used to locate the position of the baryon acoustic oscillation (BAO) feature of both samples. Using ξ0, we obtain distance scales, relative to the distance of our reference Λ cold dark matter cosmology, of 1.010 ± 0.027 for the Red sample and 1.005 ± 0.031 for the Blue. After applying reconstruction, these measurements improve to 1.013 ± 0.020 for the Red sample and 1.008 ± 0.026 for the Blue. For each sample, measurements of ξ0 and the second multipole moment, ξ2, of the anisotropic correlation function are used to determine the rate of structure growth, parametrized by fσ8. We find fσ8,Red = 0.511 ± 0.083, fσ8, Blue = 0.509 ± 0.085 and fσ8, Cross = 0.423 ± 0.061 (from the cross-correlation between the Red and Blue samples). We use the covariance between the bias and growth measurements obtained from each sample and their cross-correlation to produce an optimally combined measurement of fσ8, comb = 0.443 ± 0.055. This result compares favourably to that of the full 0.43 < z < 0.7 sample (fσ8, full = 0.422 ± 0.051) despite the fact that, in total, we use less than half of the number of galaxies analysed in the full sample measurement. In no instance do we detect significant differences in distance scale or structure growth measurements obtained from the Blue and Red samples. Our results are consistent with theoretical predictions and our tests on mock samples, which predict that any colour-dependent systematic uncertainty on the measured BAO position is less than 0.5 per cent.
An Introduction to Bε-trees and Write-Optimization

A B-tree is an example of a write-optimized data structure and can be used to organize on-disk storage for an application such as a database or file system. A B-tree provides a key-value API, similar to a Btree, but with better performance, particularly for inserts, range queries, and key-value updates. This article describes the B-tree, compares its asymptotic performance to B-trees and Log-Structured Merge trees (LSM-trees), and presents real-world performance measurements. After finishing this article, a reader should have a basic understanding of how a B-tree works, its performance characteristics, how it compares to other key-value stores, and how to design applications to gain the most performance from a B-tree.
Plasminogen Activator Inhibitor-1 and Thrombotic Cerebrovascular Diseases

Alterations in thrombosis and fibrinolysis comprise important parts of stroke pathophysiology. A key step in the fibrinolytic process includes the tissue-type plasminogen activator (tPA)-mediated conversion of the proenzyme plasminogen into the active protease plasmin, which in turn degrades the fibrin structure of intravascular thrombi. There are a number of review articles well summarizing molecular mechanisms of the fibrinolytic system.1,2 Inhibition of the fibrinolytic system may occur at the level of plasminogen activation, mainly by a direct inhibition of tPA by plasminogen activator inhibitor 1 (PAI-1) or indirectly by thrombin-activatable fibrinolysis inhibitor and, at the level of plasmin, by α2-antiplasmin. The roles of these 3 inhibitors are complementary in thrombolysis.3 PAI-1 has become recognized as a central molecule linking pathogenesis and progression of thrombotic vascular events including stroke. As a main endogenous inhibitor of tPA, PAI-1 might be related to reperfusion efficacy and hemorrhagic risk of tPA thrombolytic therapy. Moreover, a clear association has been observed between elevated PAI-1 plasma levels and prothrombotic disease conditions such as hypertension, obesity, insulin resistance, and diabetes.4–7 Clinical and experimental studies show that PAI-1 deficiencies cause accelerated fibrinolysis and bleeding, whereas elevated PAI-1 plasma levels are associated with vascular thrombosis.8 Concentrations of active PAI-1 in newly formed thrombi can be several thousandfold greater than active PAI-1 concentrations in normal plasma9 and thus high enough to inhibit doses of tPA used for clinical thrombolysis. Furthermore, beyond its effects in modulating the activity of tPA and the functionally related urokinase-type plasminogen activator, which predominantly catalyzes plasmin formation in the extravascular space, PAI-1 also plays diverse roles in metabolic and vascular disease and may participate in the evolution of brain damage and recovery after stroke.4 …
Disrupted Modularity and Local Connectivity of Brain Functional Networks in Childhood-Onset Schizophrenia

Modularity is a fundamental concept in systems neuroscience, referring to the formation of local cliques or modules of densely intra-connected nodes that are sparsely inter-connected with nodes in other modules. Topological modularity of brain functional networks can quantify theoretically anticipated abnormality of brain network community structure – so-called dysmodularity – in developmental disorders such as childhood-onset schizophrenia (COS). We used graph theory to investigate topology of networks derived from resting-state fMRI data on 13 COS patients and 19 healthy volunteers. We measured functional connectivity between each pair of 100 regional nodes, focusing on wavelet correlation in the frequency interval 0.05–0.1 Hz, then applied global and local thresholding rules to construct graphs from each individual association matrix over the full range of possible connection densities. We show how local thresholding based on the minimum spanning tree facilitates group comparisons of networks by forcing the connectedness of sparse graphs. Threshold-dependent graph theoretical results are compatible with the results of a k-means unsupervised learning algorithm and a multi-resolution (spin glass) approach to modularity, both of which also find community structure but do not require thresholding of the association matrix. In general modularity of brain functional networks was significantly reduced in COS, due to a relatively reduced density of intra-modular connections between neighboring regions. Other network measures of local organization such as clustering were also decreased, while complementary measures of global efficiency and robustness were increased, in the COS group. The group differences in complex network properties were mirrored by differences in simpler statistical properties of the data, such as the variability of the global time series and the internal homogeneity of the time series within anatomical regions of interest.
Growth hormone-secreting variants of a mammotropic tumor.

Three investigators described independently somatotropic variants (mutants) of the originally typical mammotropic MtT.W5, which was isolated from a rat that had been X-rayed (800 R) over the head and neck. Studies of one of these variants (W5/St.H) led us to conclude that the three variants are basically identical; all possess high somatotropic hormone (growth hormone, StH) and very low mammotropic hormone (prolactin, MtH) activity. However, persistence of secretion of some MtH is indicated by our tests with the highly sensitive radioimmunoassay and immunohistochemical staining. The mammary gland stimulation of the variant studied by us is characterized by slight to moderate alveolar hyperplasia with some milk secretion, periglandular and perivascular fibrosis, some ability to support the growth of a hormone-responsive mammary tumor, and serum levels of MtH elevated 8 to 23 times normal. The variant is stable and fully autonomous, growing equally well in rats of both sexes. StH secretion was about as high as that of the original tumor as judged by similar criteria. StH serum levels were increased to about 220 times normal in rats of both sexes. Immunohistochemical staining of the tumors was distinct for StH but not for MtH. Staining of the pituitaries of tumor hosts for MtH was reduced as compared with normal pituitaries. These findings suggest that the quantity of this hormone secreted per cell in the tumors was very small. This study supports our earlier findings of the intimate relation of MtH and StH production and is consistent with the hypothesis that the same neoplastic acidophils can produce both hormones.