Miracle-dz/UniFAR-FTUs huggingface dataset:
A novel DNA gyrase inhibitor rescues Escherichia coli dnaAcos mutant cells from lethal hyperinitiation.

OBJECTIVES In order to search for novel antibacterial compounds we used a previously developed screening strain designed specifically to discover inhibitors of the bacterial initiator protein, DnaA. This strain (SF53) is not viable at 30 degrees C due to overinitiation. Therefore, compounds that are able to restore growth to SF53 cells are likely to cause either partial or complete inhibition of DnaA function. In this study we used SF53 cells to screen the Library of Pharmacologically Active Compounds (LOPAC). METHODS An SF53 screen of LOPAC in 384-well plates was performed. The effects of compounds identified as positive were studied further by growth assays specific for replication proteins as well as an in vitro assay of the activity of purified DNA gyrase. RESULTS One of the compounds that tested positive in this screening was the benzazepine derivate (+/-)-6-chloro-PB hydrobromide (S143). We found that the substance did not target DnaA directly, but that it most probably reduces overinitiation by inhibiting DNA gyrase. Benzazepines have not previously been reported as gyrase inhibitors. CONCLUSIONS These findings indicate that a screening with SF53 will be able to identify compounds that also target other replication proteins (in addition to DnaA). Screening of LOPAC with SF53 cells led to the discovery of a novel DNA gyrase inhibitor.
Is Education Associated With Improvements in General Cognitive Ability, or in Specific Skills?

Previous research has indicated that education influences cognitive development, but it is unclear what, precisely, is being improved. Here, we tested whether education is associated with cognitive test score improvements via domain-general effects on general cognitive ability (g), or via domain-specific effects on particular cognitive skills. We conducted structural equation modeling on data from a large (n = 1,091), longitudinal sample, with a measure of intelligence at age 11 years and 10 tests covering a diverse range of cognitive abilities taken at age 70. Results indicated that the association of education with improved cognitive test scores is not mediated by g, but consists of direct effects on specific cognitive skills. These results suggest a decoupling of educational gains from increases in general intellectual capacity.
Concentric left ventricular morphology in aerobically trained kayak canoeists

The aim of the present study was to test the hypothesis that upper body aerobically trained athletes (kayak canoeists) would have greater left ventricular wall thickness, but similar left ventricular diastolic chamber dimensions, compared with recreationally active and sedentary men. Ultrasound echocardiography was used to determine cardiac structure and function in highly trained kayak canoeists (n = 10), moderately active (n = 10) and sedentary men (n = 10). The septal and posterior left ventricular walls were ∼0.2 cm thicker in kayak canoeists (P < 0.05), and left ventricular mass was 51% and 32% greater (P < 0.05) in canoeists than in the sedentary and moderately trained participants, respectively. There were no differences in left ventricular chamber dimension, suggesting that the kayak canoeists had a concentric pattern of left ventricular adaptation to aerobic upper body training. Scaling the data to body composition indices had no effect on the outcome of the statistical analysis. There were no differences in resting Doppler left ventricular diastolic or systolic function among the groups. Ejection fraction was lower in the kayak canoeists, but the magnitude of the difference was within the normal variability for this measurement. Thus aerobically upper body trained athletes demonstrated a concentric pattern of cardiac enlargement, but resting left ventricle function was not different between athletes, moderately active and sedentary individuals.
Inspection of Surfaces with a Manipulator Mounted on a Climbing Robot

The non-destructive inspection of large bridges with autonomous systems is still an unsolved problem. One of the main difficulties is to develop a very flexible platform, which is able to move at horizontal and vertical areas and can inspect the surface. For precise inspection of concrete walls it is essential to have a manipulator to perform a 2D scan with adequate sensors. In this paper a climbing robot with a manipulation arm will be presented. The platform consists of a vacuum system for the adhesion and omni directional driven wheels for the locomotion. The manipulator base on parallel kinematic techniques and is able to make scans with different types of inspection sensor. For controlling the platform and the manipulator there are coupled algorithm implemented to generate adequate inspection trajectories. The paper ends with test results, done with a manipulator mounted on a vehicle which drives on the floor.
Hall-Petch Relationship in an Al-Mg-Sc Alloy Subjected to ECAP

Effect of extensive grain refinement on mechanical properties of an Al-Mg-Sc alloy subjected to equal-channel angular pressing (ECAP) at 300°C is considered in detail. It was shown that the Hall-Petch relationship with the coefficient, ky, of 0.2 MPa×m1/2 is valid in a wide strain range despite a great difference in deformation structures. Volume fraction of fine grains with an average size of ∼1 μm gradually increases with strain. It is caused by the fact that additive contributions of grain size strengthening and dislocation strengthening to the overall strengthening take place in this alloy. Upon ECAP the extensive grain refinement is accompanied by increasing dislocation density. Superposition of deformation and structural strengthening mechanisms provides achieving very high strength in the alloy. It was shown that ECAP at 300°C has no remarkable effect on a dispersion of coherent dispersoids. Al3(Sc,Zr), which gives a significant contribution to overall strength through dispersion strengthening. Contributions of different strengthening mechanisms to overall strength of the material are analyzed.
Efficient Exploration With Latent Structure

When interacting with a new environment, a robot can improve its online performance by efficiently exploring the effects of its actions. The efficiency of exploration can be expanded significantly by modeling and using latent structure to generalize experiences. We provide a theoretical development of the problem of exploration with latent structure, analyze several algorithms and prove matching lower bounds. We demonstrate our algorithmic ideas on a simple robot car repeatedly traversing a path with two different surface properties.
An NoC Traffic Compiler for Efficient FPGA Implementation of Sparse Graph-Oriented Workloads

Parallel graph-oriented applications expressed in the Bulk-Synchronous Parallel (BSP) and Token Dataflow compute models generate highly-structured communication workloads from messages propagating along graph edges. We can statially expose this structure to traffic compilers and optimization tools to reshape and reduce traffic for higher performance (or lower area, lower energy, lower cost). Such offline traffic optimization eliminates the need for complex, runtime NoC hardware and enables lightweight, scalable NoCs. We perform load balancing, placement, fanout routing, and fine-grained synchronization to optimize our workloads for large networks up to 2025 parallel elements for BSP model and 25 parallel elements for Token Dataflow. This allows us to demonstrate speedups between 1.2× and 22× (3.5× mean), area reductions (number of Processing Elements) between 3× and 15× (9× mean) and dynamic energy savings between 2× and 3.5× (2.7× mean) over a range of real-world graph applications in the BSP compute model. We deliver speedups of 0.5–13× (geomean 3.6×) for Sparse Direct Matrix Solve (Token Dataflow compute model) applied to a range of sparse matrices when using a high-quality placement algorithm. We expect such traffic optimization tools and techniques to become an essential part of the NoC application-mapping flow.
The evolutionary ecology of alternative migratory tactics in salmonid fishes

Extensive individual variation in spatial behaviour is a common feature among species that exhibit migratory life cycles. Nowhere is this more evident than in salmonid fishes; individual fish may complete their entire life cycle in freshwater streams, others may migrate variable distances at sea and yet others limit their migrations to larger rivers or lakes before returning to freshwater streams to spawn. This review presents evidence that individual variation in migratory behaviour and physiology in salmonid fishes is controlled by developmental thresholds and that part of the variation in proximal traits activating the development of alternative migratory tactics is genetically based. We summarize evidence that alternative migratory tactics co‐exist within populations and that all individuals may potentially adopt any of the alternative phenotypes. Even though intra‐specific genetic divergence of migratory tactics is uncommon, it may occur if female competition for oviposition sites results in spawning segregation of alternative phenotypes. Because of their polygenic nature, alternative migratory tactics are considered as threshold traits. Threshold traits have two characteristics: an underlying 'liability' trait that varies in a continuous fashion, and a threshold value which is responsible for the discreetness observed in phenotypic distribution. We review evidence demonstrating that body size is an adequate proxy for the liability trait controlling the decision to migrate, but that the same phenotypic outcome (anadromy or residency) may be reached by different developmental pathways. The evidence suggesting a significant heritable component in the development of alternative migratory tactics is subsequently reviewed, leading us to conclude that alternative migratory tactics have considerable potential to respond to selection and evolve. We review what is known about the proximal physiological mechanisms mediating the translation of the continuous value of the liability trait into a discontinuous migratory tactic. We conclude by identifying several avenues for future research, including testing the frequency‐dependent selection hypothesis, establishing the relative importance of adaptive phenotypic plasticity in explaining some geographic gradients in migratory behaviour and identifying the physiological and genetic basis of the switching mechanisms responsible for alternative migratory tactics.
A PHYSICALLY -ADDRESSEDL4 K ERNEL

All current implementations of the L4 microkernel map thread control blocks (TCBs) into a linear array in virtual memory, a decision that was originally made almost entirely for the performance advantages it offers on the Intel 486 platform. The drawback of this design choice is that page faults generated within L4 complicate the kernel and in particular its verification by formal methods. An alternative exists however on architectures where physical addressing, or at least a loose equivalent in superpages, is available. On such architectures, TCBs may be addressed physically via indirection provided by an auxiliary lookup table. Addressing TCBs in this manners leads to a completely physically-addressed L4 kernel that offers advantages in simplicity, but has a non-obvious effect on the cache footprint of the performancecritical IPC path that warrants examination. This thesis endeavours to provide a thorough investigation into the performance trade-offs involved in making the L4Ka::Pistachio implementation of the L4 Version 4 API completely physically addressed. We stress architectural issues that effect the outcome of these trade-offs and explore various implementational design choices that aim to weaken the performance penalties a physically-addressed kernel may suffer. We conclude by running Linux on top of the L4 microkernel to obtain a concise set of benchmarks that prove, at least for the MIPS64 architecture, that the simplicity of a completely physically-addressed L4 kernel may be enjoyed without any notable performance degradation.
Quantitative magnetic resonance imaging evidence of synovial proliferation is associated with radiographic severity of knee osteoarthritis.

OBJECTIVE To evaluate the relationships between both quantitative and semiquantitative assessments of the degree of knee synovitis on 3T magnetic resonance imaging (MRI) and the severity of knee osteoarthritis (OA) on radiography. METHODS Fifty-eight patients with knee OA underwent nonfluoroscopic fixed-flexion knee radiography. In addition, dynamic contrast-enhanced 3T MRI of the knees was performed, before and after gadolinium administration, to quantify synovial membrane volume (SV) as a measure of synovial proliferation (expressed as the quantitative SV), and semiquantitative measures of synovitis were also applied using both contrast-enhanced and unenhanced images. Two radiologists scored the knee radiographs using the Osteoarthritis Research Society International atlas; interreader agreement was assessed using kappa statistics and concordance correlation coefficients. Multiple linear and logistic regression analyses were used to assess associations among variables, while controlling for the effects of age, body mass index, sex, and meniscal extrusion. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for measures of disease activity. RESULTS The Kellgren/Lawrence (K/L) grade of radiographic knee OA severity (β=0.78), the diseased compartment joint space width (dcJSW) (β=-0.22), and the diseased compartment joint space narrowing (dcJSN) score (β=0.53) were each significantly associated with the quantitative SV (P=0.0001, P=0.0003, and P=0.0001, respectively). Furthermore, the quantitative SV strongly correlated with the total volume of subchondral bone marrow lesions (BMLs) (β=0.22, P=0.0003). The K/L grade, dcJSW, and dcJSN score were each significantly associated with the semiquantitative Boston Leeds Osteoarthritis Knee Score (BLOKS) for the extent of infrapatellar synovitis (OR 9.05 [95% CI 1.94, 42.3] for K/L grade; OR 0.75 [95% CI 0.54, 1.03] for dcJSW; and OR 2.22 [95% CI 1.15, 4.31] for dcJSN score) and extent of joint effusion (OR 5.75 [95% CI 1.23, 26.8] for K/L grade; OR 0.70 [95% CI 0.50, 0.98] for dcJSW; and OR 1.96 [95% CI 1.02, 3.74] for dcJSN score). In addition, the semiquantitative synovitis grade on contrast-enhanced MRI was significantly associated with the K/L grade (β=0.036, P=0.0040) and dcJSN score (β=0.015, P=0.0266), and also significantly associated with the BLOKS synovitis score. CONCLUSION Synovitis is a characteristic feature of advancing knee OA and is significantly associated with the K/L grade, JSW, JSN score, and total volume of BMLs on radiographs. Furthermore, BLOKS scoring of synovitis on unenhanced MRI is associated with measurements of synovitis on contrast-enhanced MRI.
Species delimitation in native South American fire ants

The taxonomy of fire ants has been plagued by difficulties in recognizing species on the basis of morphological characters. We surveyed allozyme markers and sequences of the mtDNA COI gene in several closely related nominal species from two areas of sympatry in the native ranges to learn whether the morphology‐based delimitation of these species is supported by genetic data. We found that Solenopsis invicta and Solenopsis richteri, pest species whose distinctiveness has been debated, appear to be fully reproductively isolated at both study sites. This isolation contrasts with the extensive hybridization occurring between them in the USA, where both have been introduced. We also found strong genetic differentiation consistent with barriers to gene flow between Solenopsis quinquecuspis and the other two species. However, several lines of evidence suggest that nuclear and mitochondrial genes of S. invicta and S. richteri are introgressing into S. quinquecuspis. The latter apparently is a recently derived member of the clade that includes all three species, suggesting that there has been insufficient time for its full development of intrinsic isolating mechanisms. Finally, our discovery of genetically distinct populations within both S. invicta and S. richteri suggests the presence of previously unrecognized (cryptic) species. Their existence, together with the difficulties in developing diagnostic morphological characters for described species, imply that the group is actively radiating species and that morphological divergence generally does not keep pace with the development of reproductive isolation and neutral genetic divergence in this process.
Differences in subthreshold resonance of hippocampal pyramidal cells and interneurons: the role of h-current and passive membrane characteristics

The intrinsic properties of distinct types of neuron play important roles in cortical network dynamics. One crucial determinant of neuronal behaviour is the cell's response to rhythmic subthreshold input, characterised by the input impedance, which can be determined by measuring the amplitude and phase of the membrane potential response to sinusoidal currents as a function of input frequency. In this study, we determined the impedance profiles of anatomically identified neurons in the CA1 region of the rat hippocampus (pyramidal cells as well as interneurons located in the stratum oriens, including OLM cells, fast‐spiking perisomatic region‐targeting interneurons and cells with axonal arbour in strata oriens and radiatum). The basic features of the impedance profiles, as well as the passive membrane characteristics and the properties of the sag in the voltage response to negative current steps, were cell‐type specific. With the exception of fast‐spiking interneurons, all cell types showed subthreshold resonance, albeit with distinct features. The HCN channel blocker ZD7288 (10 μm) eliminated the resonance and changed the shape of the impedance curves, indicating the involvement of the hyperpolarisation‐activated cation current Ih. Whole‐cell voltage‐clamp recordings uncovered differences in the voltage‐dependent activation and kinetics of Ih between different cell types. Biophysical modelling demonstrated that the cell‐type specificity of the impedance profiles can be largely explained by the properties of Ih in combination with the passive membrane characteristics. We conclude that differences in Ih and passive membrane properties result in a cell‐type‐specific response to inputs at given frequencies, and may explain, at least in part, the differential involvement of distinct types of neuron in various network oscillations.
The Hippo Pathway Maintains the Equatorial Division Plane in the Ciliate Tetrahymena

The mechanisms governing organelle pattern formation in ciliates are still poorly understood. Jiang et al. investigate how the cell duplicates its. The mechanisms that govern pattern formation within the cell are poorly understood. Ciliates carry on their surface an elaborate pattern of cortical organelles that are arranged along the anteroposterior and circumferential axes by largely unknown mechanisms. Ciliates divide by tandem duplication: the cortex of the predivision cell is remodeled into two similarly sized and complete daughters. In the conditional cdaI-1 mutant of Tetrahymena thermophila, the division plane migrates from its initially correct equatorial position toward the cell’s anterior, resulting in unequal cell division, and defects in nuclear divisions and cytokinesis. We used comparative whole genome sequencing to identify the cause of cdaI-1 as a mutation in a Hippo/Mst kinase. CdaI is a cortical protein with a cell cycle-dependent, highly polarized localization. Early in cell division, CdaI marks the anterior half of the cell, and later concentrates at the posterior end of the emerging anterior daughter. Despite the strong association of CdaI with the new posterior cell end, the cdaI-1 mutation does not affect the patterning of the new posterior cortical organelles. We conclude that, in Tetrahymena, the Hippo pathway maintains an equatorial position of the fission zone, and, by this activity, specifies the relative dimensions of the anterior and posterior daughter cell.
Placement of Data in Multi-Zone Disk Drives

This paper describes a placement technique for the layout of files across the surface of a multizone magnetic disk drive to maximize its bandwidth. It argues for a file system that monitors the frequency of access to the files and modifies the placement of files in order to respond to an evolving pattern of file accesses. Such a file system is particularly useful for repositories whose primary functionality is to disseminate information, such as the World-Wide-Web along with thousands of ftp sites that render documents, graphic pictures, images, audio clips, and full-motion video available on the Internet. Employing software techniques to enhance the disk performance is important because its mechanical nature has limited its hardware performance improvements at 7 to 10 percent a year.
Anandamide Suppresses Proliferation and Cytokine Release from Primary Human T-Lymphocytes Mainly via CB2 Receptors

Background Anandamide (AEA) is an endogenous lipid mediator that exerts several effects in the brain as well as in peripheral tissues. These effects are mediated mainly by two types of cannabinoid receptors, named CB1R and CB2R, making AEA a prominent member of the “endocannabinoid” family. Also immune cells express CB1 and CB2 receptors, and possess the whole machinery responsible for endocannabinoid metabolism. Not surprisingly, evidence has been accumulated showing manifold roles of endocannabinoids in the modulation of the immune system. However, details of such a modulation have not yet been disclosed in primary human T-cells. Methodology/Significance In this investigation we used flow cytometry and ELISA tests, in order to show that AEA suppresses proliferation and release of cytokines like IL-2, TNF-α and INF-γ from activated human peripheral T-lymphocytes. However, AEA did not exert any cytotoxic effect on T-cells. The immunosuppression induced by AEA was mainly dependent on CB2R, since it could be mimicked by the CB2R selective agonist JWH-015, and could be blocked by the specific CB2R antagonist SR144528. Instead the selective CB1R agonist ACEA, or the selective CB1R antagonist SR141716, were ineffective. Furthermore, we demonstrated an unprecedented immunosuppressive effect of AEA on IL-17 production, a typical cytokine that is released from the unique CD4+ T-cell subset T-helper 17. Conclusions/Significance Overall, our study investigates for the first time the effects of the endocannabinoid AEA on primary human T-lymphocytes, demonstrating that it is a powerful modulator of immune cell functions. In particular, not only we clarify that CB2R mediates the immunosuppressive activity of AEA, but we are the first to describe such an immunosuppressive effect on the newly identified Th-17 cells. These findings might be of crucial importance for the rational design of new endocannabinoid-based immunotherapeutic approaches.