Miracle-dz/UniFAR-FTUs huggingface dataset:
Cumulative Effects of Several Nonenzymatic Mechanisms on the Resistance of Pseudomonas aeruginosa to Aminoglycosides

ABSTRACT Screening of a Tn5-Hg insertional library (12,000 clones) constructed in wild-type Pseudomonas aeruginosa strain PAO1 identified four genes (namely, galU, nuoG, mexZ, and rplY) whose disruption individually led to increased resistance to aminoglycosides (means of twofold). Inactivation of these genes was associated with (i) impaired outer membrane uptake, (ii) reduced active transport, (iii) increased MexXY-OprM-mediated active efflux, and (iv) alteration of target of aminoglycosides, respectively. In addition, suppression of the gene rplY, which codes for ribosomal protein L25, was found to result in both moderate upregulation of the efflux system MexXY-OprM and hypersusceptibility to β-lactam antibiotics. Construction of double, triple, and quadruple mutants demonstrated cumulative effects of the different mechanisms on aminoglycoside resistance, with MICs increasing from 16- to 64-fold in the quadruple mutant compared to the wild-type strain PAO1. Altogether, these results illustrate how P. aeruginosa may gradually develop high resistance to these antibiotics via intrinsic (i.e., nonenzymatic) mechanisms, as in cystic fibrosis patients.
Evolution of generative design systems for modular physical robots

Recent research has demonstrated the ability for automatic design of the morphology and control of real physical robots using techniques inspired by biological evolution. The main criticism of the evolutionary design approach, however, is that it is doubtful whether it will reach the high complexities necessary for practical engineering. Here we claim that for automatic design systems to scale in complexity the designs they produce must be made of re-used modules. Our approach is based on the use of a generative design grammar subject to an evolutionary process. Unlike a direct encoding of a design, a generative design specification can re-use components, giving it the ability to create more complex modules from simpler ones. Re-used modules are also valuable for improved efficiency in testing and construction. We describe a system for creating generative specifications capable of hierarchical modularity by combining Lindenmayer systems with evolutionary algorithms. Using this system we demonstrate for the first time a generative system for physical, modular, 2D locomoting robots and their controllers.
Implicit Theories of Creativity in Computer Science in the United States and China

To study implicit concepts of creativity in computer science in the United States and mainland China, we first asked 308 Chinese computer scientists for adjectives that would describe a creative computer scientist. Computer scientists and non-computer scientists from China (N = 1069) and the United States (N = 971) then rated how well those adjectives described creative computer scientists using a 5-point Likert Scale. Factor analysis revealed that the concept of a creative computer scientist had four dimensions: (1) smart/effective, (2) outgoing, (3) creative thinking and (4) unsociable. Differences in the implicit concepts across disciplines, ethnicity, gender, age, and working experience were analyzed. We discuss the implications of these findings for our understanding of the domain specificity of creativity.
THE SWIFT GAMMA-RAY BURST HOST GALAXY LEGACY SURVEY. I. SAMPLE SELECTION AND REDSHIFT DISTRIBUTION

We introduce the Swift Gamma-Ray Burst Host Galaxy Legacy Survey (“SHOALS”), a multi-observatory high-redshift galaxy survey targeting the largest unbiased sample of long-duration gamma-ray burst (GRB) hosts yet assembled (119 in total). We describe the motivations of the survey and the development of our selection criteria, including an assessment of the impact of various observability metrics on the success rate of afterglow-based redshift measurement. We briefly outline our host galaxy observational program, consisting of deep Spitzer/IRAC imaging of every field supplemented by similarly deep, multicolor optical/near-IR photometry, plus spectroscopy of events without preexisting redshifts. Our optimized selection cuts combined with host galaxy follow-up have so far enabled redshift measurements for 110 targets (92%) and placed upper limits on all but one of the remainder. About 20% of GRBs in the sample are heavily dust obscured, and at most 2% originate from z > 5.5 . > Using this sample, we estimate the redshift-dependent GRB rate density, showing it to peak at z ∼ 2.5 ? > and fall by at least an order of magnitude toward low (z = 0) redshift, while declining more gradually toward high ( z ∼ 7 ? > ) redshift. This behavior is consistent with a progenitor whose formation efficiency varies modestly over cosmic history. Our survey will permit the most detailed examination to date of the connection between the GRB host population and general star-forming galaxies, directly measure evolution in the host population over cosmic time and discern its causes, and provide new constraints on the fraction of cosmic star formation occurring in undetectable galaxies at all redshifts.
Differential Effects of Rifampin and Ketoconazole on the Blood and Liver Concentration of Atorvastatin in Wild-Type and Cyp3a and Oatp1a/b Knockout Mice

Atorvastatin is eliminated by CYP3A4 which follows carrier-mediated uptake into hepatocytes by OATP1B1, OATP1B3, and OATP2B1. Multiple clinical studies demonstrated that OATP inhibition by rifampin had a greater impact on atorvastatin systemic concentration than itraconazole-mediated CYP3A4 inhibition. If it is assumed that the blood and hepatocyte compartments are differentiated by the concentration gradient that is established by OATPs, and if the rate of uptake into the hepatocyte is rate-determining to the elimination of atorvastatin from the body, then it is hypothesized that blood concentrations may not necessarily reflect liver concentrations. In wild-type mice, rifampin had a greater effect on systemic exposure of atorvastatin than ketoconazole, as the blood area under the blood concentration-time curve increased 7- and 2-fold, respectively. In contrast, liver concentrations were affected more by ketoconazole than by rifampin, as liver levels increased 21- and 4-fold, respectively. Similarly, in Cyp3a knockout animals, 39-fold increases in liver concentrations were observed despite insignificant changes in the blood area under the blood concentration-time curve. Interestingly, blood and liver levels in Oatp1a/b knockout animals were similar to wild types, suggesting that Oatp1a/b knockout may be necessary but not sufficient to completely describe atorvastatin uptake in mice. Data presented in this work indicate that there is a substantial drug interaction when blocking atorvastatin metabolism, but the effects of this interaction are predominantly manifested in the liver and may not be captured when monitoring changes in the systemic circulation. Consequently, there may be a disconnect when trying to relate blood exposure to instances of hepatotoxicity because a pharmacokinetic-toxicity relationship may not be obvious from blood concentrations.
Aging-Induced Nrf2-ARE Pathway Disruption in the Subventricular Zone Drives Neurogenic Impairment in Parkinsonian Mice via PI3K-Wnt/β-Catenin Dysregulation

Aging and exposure to environmental toxins including MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) are strong risk factors for developing Parkinson's disease (PD), a common neurologic disorder characterized by selective degeneration of midbrain dopaminergic (DAergic) neurons and astrogliosis. Aging and PD impair the subventricular zone (SVZ), one of the most important brain regions for adult neurogenesis. Because inflammation and oxidative stress are the hallmarks of aging and PD, we investigated the nature, timing, and signaling mechanisms contributing to aging-induced SVZ stem/neuroprogenitor cell (NPC) inhibition in aging male mice and attempted to determine to what extent manipulation of these pathways produces a functional response in the outcome of MPTP-induced DAergic toxicity. We herein reveal an imbalance of Nrf2-driven antioxidant/anti-inflammatory genes, such as Heme oxygenase1 in the SVZ niche, starting by middle age, amplified upon neurotoxin treatment and associated with an exacerbated proinflammatory SVZ microenvironment converging to dysregulate the Wingless-type MMTV integration site (Wnt)/β-catenin signaling, a key regulatory pathway for adult NPCs. In vitro experiments using coculture paradigms uncovered aged microglial proinflammatory mediators as critical inhibitors of NPC proliferative potential. We also found that interruption of PI3K (phosphatidylinositol3-kinase)/Akt and the Wnt/Fzd/β-catenin signaling cascades, which switch glycogen synthase kinase 3β (GSK-3β) activation on and off, were causally related to the impairment of SVZ-NPCs. Moreover, a synergy between dysfunctional microglia of aging mice and MPTP exposure further inhibited astrocyte proneurogenic properties, including the expression of key Wnts components. Last, pharmacological activation/antagonism studies in vivo and in vitro suggest the potential that aged SVZ manipulation is associated with DAergic functional recovery.
The Sulfated Laminarin Triggers a Stress Transcriptome before Priming the SA- and ROS-Dependent Defenses during Grapevine's Induced Resistance against Plasmopara viticola

Grapevine (Vitis vinifera) is susceptible to many pathogens which cause significant losses to viticulture worldwide. Chemical control is available, but agro-ecological concerns have raised interest in alternative methods, especially in triggering plant immunity by elicitor treatments. The β-glucan laminarin (Lam) and its sulfated derivative (PS3) have been previously demonstrated to induce resistance in grapevine against downy mildew (Plasmopara viticola). However, if Lam elicits classical grapevine defenses such as oxidative burst, pathogenesis-related (PR)-proteins and phytoalexin production, PS3 triggered grapevine resistance via a poorly understood priming phenomenon. The aim of this study was to identify the molecular mechanisms of the PS3-induced resistance. For this purpose we studied i) the signaling events and transcriptome reprogramming triggered by PS3 treatment on uninfected grapevine, ii) grapevine immune responses primed by PS3 during P. viticola infection. Our results showed that i) PS3 was unable to elicit reactive oxygen species (ROS) production, cytosolic Ca2+ concentration variations, mitogen-activated protein kinase (MAPK) activation but triggered a long lasting plasma membrane depolarization in grapevine cells, ii) PS3 and Lam shared a common stress-responsive transcriptome profile that partly overlapped the salicylate- (SA) and jasmonate-(JA)-dependent ones. After P. viticola inoculation, PS3 specifically primed the SA- and ROS-dependent defense pathways leading to grapevine induced resistance against this biotroph. Interestingly pharmacological approaches suggested that the plasma membrane depolarization and the downstream ROS production are key events of the PS3-induced resistance.
Evaluation of the pulse pressure variation index as a predictor of fluid responsiveness during orthotopic liver transplantation.

BACKGROUND The pulse pressure variation (PPV) index has been shown to be a reliable predictor of fluid responsiveness (FR) in a variety of clinical settings. However, it has not been formally evaluated in the setting of orthotopic liver transplantation (OLT). METHODS Fifteen (n=15) patients undergoing OLT were enrolled in this study. All patients were monitored with a modified pulmonary artery catheter which measured the cardiac output on a semi-continuous basis. A fluid challenge (FC) with 350 ml of colloid was attempted during the following stages of surgery: hepatectomy (TH), anhepatic phase (TA), early post-reperfusion [(TE)--during the first 30 min], late post-reperfusion [(TL)--after hepatic artery anastomosis], and at the beginning of abdominal closure (TC). PPV and stroke volume index (SVI) were recorded at baseline and 5 min after the FC. Each individual FC which raised the SVI more than 10% from baseline was classified as responsive (R); otherwise, it was considered non-responsive (NR). RESULTS Forty-one FCs were performed, with 14 (34%) classified as responsive and 27 (66%) as non-responsive. The baseline PPV did not differ significantly between the R and NR groups, showing considerable overlap of its values throughout the procedure [R vs NR; TH: 20% (inter-quartile range 7-32) vs 7% (5-14); TA: 10% (7-14) vs 19% (12-21), and TE+TL: 7% (5-11) vs 9% (7-16)]. CONCLUSIONS Under the conditions of this study, the PPV index was not shown to be a reliable predictor of FR during OLT. Further studies are warranted to elucidate the role of this and other dynamic indexes in this specific setting.
Timber Beams Strengthened with GFRP Bars: Development and Applications

Repair and rehabilitation of infrastructure is becoming increasingly important for bridges due to material deterioration and limited capacity to accommodate current load levels. An experimental program was undertaken to study the flexural behavior of creosote-treated sawn Douglas fir timber beams strengthened with glass fiber-reinforced polymer (GFRP) bars. Twenty-two half-scale and four full-scale timber beams strengthened with GFRP were tested to failure. The percent reinforcement ratios were between 0.27 and 0.82%. Additional unreinforced timber beams were tested as control specimens. The results have shown that using the proposed experimental technique changed the failure mode from brittle tension to compression failure, and flexural strength increased by 18 to 46%. Research findings indicate the use of near-surface GFRP bars overcomes the effect of local defects in the timber and enhances the bending strength of the members. Based on the experimental results, an analytical model is proposed to predict the flexural capacity of both unreinforced and GFRP-reinforced timber beams. The article also reviews implementation of the proposed technique for strengthening a timber bridge near Winnipeg, Manitoba, Canada.
AID-Driven Deletion Causes Immunoglobulin Heavy Chain Locus Suicide Recombination in B Cells

Suicidal B cells In response to an infection, immunological B cells undergo a maturation process that results in the production of immunoglobulin (Ig) that is better able to bind and clear the invading pathogen. This occurs through somatic cell hypermutation and class switch recombination of the Ig gene and requires activation-induced deaminase (AID). Péron et al. (p. 931, published online 26 April) observed that the 3' cis-regulatory region of the heavy-chain locus is transcribed and undergoes AID-mediated mutation and recombination. The resulting deletion of the Ig heavy gene cluster generates B cells that are no longer able to express Ig on the cell surface. Because cell-surface Ig expression is essential for B cell survival, this process is termed “locus suicide recombination” (LSR) and may be important in shaping the dynamics of B effector cell differentiation and homeostasis. Recombination-induced deletion of the immunoglobulin heavy chain gene in activated B cells may influence B cell homeostasis. Remodeling of immunoglobulin genes by activation-induced deaminase (AID) is required for affinity maturation and class-switch recombination in mature B lymphocytes. In the immunoglobulin heavy chain locus, these processes are predominantly controlled by the 3′ cis-regulatory region. We now show that this region is transcribed and undergoes AID-mediated mutation and recombination around phylogenetically conserved switchlike DNA repeats. Such recombination, which we term locus suicide recombination, deletes the whole constant region gene cluster and thus stops expression of the immunoglobulin of the B cell surface, which is critical for B cell survival. The frequency of this event is approaching that of class switching and makes it a potential regulator of B cell homeostasis.
Restructuring for large databases: three levels of abstraction

The development of a powerful restructuring function involves two important components—the unambiguous specification of the restructuring operations and the realization of these operations in a software system. This paper is directed to the first component in the belief that a precise specification will provide a firm foundation for the development of restructuring algorithms and, subsequently, their implementation. The paper completely defines the semantics of the restructuring of tree structured databases. The delineation of the restructuring function is accomplished by formulating three different levels of abstraction, with each level of abstraction representing successively more detailed semantics of the function. At the first level of abstraction, the schema modification, three types are identified—naming, combining, and relating; these three types are further divided into eight schema operations. The second level of abstraction, the instance operations, constitutes the transformations on the data instances; they are divided into group operations such as replication, factoring, union, etc., and group relation operations such as collapsing, refinement, fusion, etc. The final level, the item value operations, includes the actual item operations, such as copy value, delete value, or create a null value.
How stress selects for reversible phenotypic plasticity

Stress occurring in periods shorter than life span strongly selects for reversible phenotypic plasticity, for maximum reliability of stress indicating cues and for minimal response delays. The selective advantage of genotypes that are able to produce adaptive reversible plastic phenotypes is calculated by using the concept of environmental tolerance. Analytic expressions are given for optimal values of mode and breadth of tolerance functions for stress induced and non‐induced phenotypes depending on (1) length of stress periods, (2) response delay for switching into the induced phenotype, (3) response delay for rebuilding the non‐induced phenotype, (4) intensity of stress, i.e. mean value of the stress inducing environment, (5) coefficient of variation of the stress environment and (6) completeness of information available to the stressed organism. Adaptively reversible phenotypic plastic traits will most probably affect fitness in a way that can be described by simultaneous reversible plasticity in mode and breadth of tolerance functions.
Microscopic Damage Mechanism of Nickel-Based Superalloy Inconel 738LC Under Creep-Fatigue Conditions

Creep-fatigue damage in Inconel 738LC was clarified by in-situ observation and a new creep-fatigue life prediction model was proposed based on the mechanism identified. Creep-fatigue tests on standard specimens show that the tensile hold creep-fatigue lives were reduced to 60 to 80 percent and those in the compressive hold condition were reduced to 20 to 40 percent of the fatigue life of the same total strain condition. In-situ creep-fatigue tests on miniature specimens show that grain boundary sliding could be observed under the compressive strain hold condition and under the tensile strain hold condition grain boundary cavity damage and grain boundary sliding were observed. These mechanisms are regarded as the main cause of the damage acceleration under the creep-fatigue loading conditions. Therefore, the new creep-fatigue life prediction model, which is based on the nonlinear damage accumulation method, employed two damage acceleration parameters d sl and d cr' which represent grain boundary sliding damage and grain boundary cavity damage, respectively, Creep-fatigue lives of the test results were well predicted by the proposed model.
Large Scale Multiple Kernel Learning

While classical kernel-based learning algorithms are based on a single kernel, in practice it is often desirable to use multiple kernels. Lanckriet et al. (2004) considered conic combinations of kernel matrices for classification, leading to a convex quadratically constrained quadratic program. We show that it can be rewritten as a semi-infinite linear program that can be efficiently solved by recycling the standard SVM implementations. Moreover, we generalize the formulation and our method to a larger class of problems, including regression and one-class classification. Experimental results show that the proposed algorithm works for hundred thousands of examples or hundreds of kernels to be combined, and helps for automatic model selection, improving the interpretability of the learning result. In a second part we discuss general speed up mechanism for SVMs, especially when used with sparse feature maps as appear for string kernels, allowing us to train a string kernel SVM on a 10 million real-world splice data set from computational biology. We integrated multiple kernel learning in our machine learning toolbox SHOGUN for which the source code is publicly available at http://www.fml. tuebingen.mpg. de/raetsch/projects/shogun .
Elaboration Likelihood in Knowledge Management: A Model and Experimental Test

Understanding knowledge transfer using computer-mediated context is becoming essential given that organizations are spread more and more globally. In this paper, we adopt elaboration likelihood theory to investigate knowledge transfer processes in a knowledge management system (KMS). We report the results of an exploratory experiment conducted to examine the impact of argument quality, source credibility and validation on knowledge usefulness of a document in a KMS. Our findings indicate that while validation of knowledge in KMS positively affects perceptions of knowledge usefulness, higher argument quality was associated with lower usefulness ratings. Surprisingly, source credibility has no effect on perceptions of knowledge usefulness. The implications of these results for both researchers and practitioners are discussed.
THE HEXATONIC SYSTEMS UNDER NEO-RIEMANNIAN THEORY: AN EXPLORATION OF THE MATHEMATICAL ANALYSIS OF MUSIC

Neo-Riemannian theory developed as the mathematical analysis of musical trends dating as far back as the late 19th century. Specifically, the musical trends at hand involved the use of unorthodox sets of pitches. These sets had the characteristic of retaining their triadic harmonies, but of sounding atonal. Neo-Riemannian theory not only allowed for the mathematical construction and description of these sets, some of which later were called the Hexatonic Systems, but also a means to explain how these systems were used. Involving the application of the PLR Operations, the analysis of the Hexatonic Systems is a primary component of neo-Riemannian theory. In this paper, I give a self-contained description of Rick Cohn’s Hexatonic Systems, as well as the group-theoretic structures at hand.