Detection of bearing failure in mechanical devices using neural networks

We present a novel time-domain method for the detection of faulty bearings that has direct applicability to monitoring the health of the turbo pumps on the Space Shuttle Main Engine. A feed-forward neural network was trained to detect modelled roller bearing faults on the basis of the periodicity of impact pulse trains. The network's performance was dependent upon the number of pulses in the network's input window and the signal-to-noise ratio of the input signal. To test the model's validity, we fit the model's parameters to an actual vibration signal generated by a faulty roller element bearing and applied the network trained on this model to detect faults in actual vibration data. When this network was tested on the actual vibration data, it correctly identified the vibration signal as a fault condition 76 percent of the time

Gene regulation by CcpA and catabolite repression explored by RNA-Seq in Streptococcus mutans

A bacterial transcriptome of the primary etiological agent of human dental caries, Streptococcus mutans, is described here using deep RNA sequencing. Differential expression profiles of the transcriptome in the context of carbohydrate source, and of the presence or absence of the catabolite control protein CcpA, revealed good agreement with previously-published DNA microarrays. In addition, RNA-seq considerably expanded the repertoire of DNA sequences that showed statistically-significant changes in expression as a function of the presence of CcpA and growth carbohydrate. Novel mRNAs and small RNAs were identified, some of which were differentially expressed in conditions tested in this study, suggesting that the function of the S. mutans CcpA protein and the influence of carbohydrate sources has a more substantial impact on gene regulation than previously appreciated. Likewise, the data reveal that the mechanisms underlying prioritization of carbohydrate utilization are more diverse than what is currently understood. Collectively, this study demonstrates the validity of RNA-seq as a potentially more-powerful alternative to DNA microarrays in studying gene regulation in S. mutans because of the capacity of this approach to yield a more precise landscape of transcriptomic changes in response to specific mutations and growth conditions

Genetic Analysis of the Functions and Interactions of Components of the LevQRST Signal Transduction Complex of Streptococcus mutans

Transcription of the genes for a fructan hydrolase (fruA) and a fructose/mannose sugar:phosphotransferase permease (levDEFG) in Streptococcus mutans is activated by a four-component regulatory system consisting of a histidine kinase (LevS), a response regulator (LevR) and two carbohydrate-binding proteins (LevQT). The expression of the fruA and levD operons was at baseline in a levQ mutant and substantially decreased in a levT null mutant, with lower expression with the cognate inducers fructose or mannose, but slightly higher expression in glucose or galactose. A strain expressing levQ with two point mutations (E170A/F292S) did not require inducers to activate gene expression and displayed altered levD expression when growing on various carbohydrates, including cellobiose. Linker-scanning (LS) mutagenesis was used to generate three libraries of mutants of levQ, levS and levT that displayed various levels of altered substrate specificity and of fruA/levD gene expression. The data support that LevQ and LevT are intimately involved in the sensing of carbohydrate signals, and that LevQ appears to be required for the integrity of the signal transduction complex, apparently by interacting with the sensor kinase LevS

Script development as a ‘wicked problem’

© 2018 Intellect Ltd Article. Both a process and a set of products, influenced by policy as well as people, and incorporating objective agendas at the same time as subjective experiences, script development is a core practice within the screen industry –yet one that is hard to pin down and, to some extent, define. From an academic research perspective, we might say that script development is a ‘wicked problem’ precisely because of these complex and often contradictory aspects. Following on from a recent Journal of Screenwriting special issue on script development (2017, vol. 8:3), and in particular an article therein dedicated to reviewing the literature and ‘defining the field’, an expanded team of researchers follow up on those ideas and insights. In this article, then, we attempt to theorize script development as a ‘wicked problem’ that spans a range of themes and disciplines. As a ‘wicked’ team of authors, our expertise encompasses screenwriting theory, screenwriting practice, film and television studies, cultural policy, ethnography, gender studies and comedy. By drawing on these critical domains and creative practices, we present a series of interconnected themes that we hope not only suggests the potential for script development as a rich and exciting scholarly pursuit, but that also inspires and encourages other researchers to join forces in an attempt to solve the script development ‘puzzle’

Phylogenomics and the dynamic genome evolution of the genus Streptococcus

The genus Streptococcus comprises important pathogens that have a severe impact on human health and are responsible for substantial economic losses to agriculture. Here, we utilize 46 Streptococcus genome sequences (44 species), including eight species sequenced here, to provide the first genomic level insight into the evolutionary history and genetic basis underlying the functional diversity of all major groups of this genus. Gene gain/loss analysis revealed a dynamic pattern of genome evolution characterized by an initial period of gene gain followed by a period of loss, as the major groups within the genus diversified. This was followed by a period of genome expansion associated with the origins of the present extant species. The pattern is concordant with an emerging view that genomes evolve through a dynamic process of expansion and streamlining. A large proportion of the pan-genome has experienced lateral gene transfer (LGT) with causative factors, such as relatedness and shared environment, operating over different evolutionary scales. Multiple gene ontology terms were significantly enriched for each group, and mapping terms onto the phylogeny showed that those corresponding to genes born on branches leading to the major groups represented approximately one-fifth of those enriched. Furthermore, despite the extensive LGT, several biochemical characteristics have been retained since group formation, suggesting genomic cohesiveness through time, and that these characteristics may be fundamental to each group. For example, proteolysis: mitis group; urea metabolism: salivarius group; carbohydrate metabolism: pyogenic group; and transcription regulation: bovis group

Identifying chemokines as therapeutic targets in renal disease: Lessons from antagonist studies and knockout mice

Chemokines, in concert with cytokines and adhesion molecules, play multiple roles in local and systemic immune responses. In the kidney, the temporal and spatial expression of chemokines correlates with local renal damage and accumulation of chemokine receptor-bearing leukocytes. Chemokines play important roles in leukocyte trafficking and blocking chemokines can effectively reduce renal leukocyte recruitment and subsequent renal damage. However, recent data indicate that blocking chemokine or chemokine receptor activity in renal disease may also exacerbate renal inflammation under certain conditions. An increasing amount of data indicates additional roles of chemokines in the regulation of innate and adaptive immune responses, which may adversively affect the outcome of interventional studies. This review summarizes available in vivo studies on the blockade of chemokines and chemokine receptors in kidney diseases, with a special focus on the therapeutic potential of anti-chemokine strategies, including potential side effects, in renal disease. Copyright (C) 2004 S. Karger AG, Basel

Attentional Processing in C57BL/6J Mice Exposed to Developmental Vitamin D Deficiency

Epidemiological evidence suggests that Developmental Vitamin D (DVD) deficiency is associated with an increased risk of schizophrenia. DVD deficiency in mice is associated with altered behaviour, however there has been no detailed investigation of cognitive behaviours in DVD-deficient mice. The aim of this study was to determine the effect of DVD deficiency on a range of cognitive tasks assessing attentional processing in C57BL/6J mice. DVD deficiency was established by feeding female C57BL/6J mice a vitamin D-deficient diet from four weeks of age. After six weeks on the diet, vitamin D-deficient and control females were mated with vitamin D-normal males and upon birth of the pups, all dams were returned to a diet containing vitamin D. The adult offspring were tested on a range of cognitive behavioural tests, including the five-choice serial reaction task (5C-SRT) and five-choice continuous performance test (5C-CPT), as well as latent inhibition using a fear conditioning paradigm. DVD deficiency was not associated with altered attentional performance on the 5C-SRT. In the 5C-CPT DVD-deficient male mice exhibited an impairment in inhibiting repetitive responses by making more perseverative responses, with no changes in premature or false alarm responding. DVD deficiency did not affect the acquisition or retention of cued fear conditioning, nor did it affect the expression of latent inhibition using a fear conditioning paradigm. DVD-deficient mice exhibited no major impairments in any of the cognitive domains tested. However, impairments in perseverative responding in DVD-deficient mice may indicate that these animals have specific alterations in systems governing compulsive or reward-seeking behaviour

Shocklets and Short Large Amplitude Magnetic Structures (SLAMS) in the high Mach foreshock of Venus

Shocklets and short large-amplitude magnetic structures (SLAMS) are steepened magnetic fluctuations commonly found in Earth's upstream foreshock. Here we present Venus Express observations from the 26th of February 2009 establishing their existence in the steady-state foreshock of Venus, building on a past study which found SLAMS during a substantial disturbance of the induced magnetosphere. The Venusian structures were comparable to those reported near Earth. The 2 Shocklets had magnetic compression ratios of 1.23 and 1.34 with linear polarization in the spacecraft frame. The 3 SLAMS had ratios between 3.22 and 4.03, two of which with elliptical polarization in the spacecraft frame. Statistical analysis suggests SLAMS coincide with unusually high solar wind Alfvén mach-number at Venus (12.5, this event). Thus, while we establish Shocklets and SLAMS can form in the stable Venusian foreshock, they may be rarer than at Earth. We estimate a lower limit of their occurrence rate of ≳14%

Treatment Discontinuation Patterns for Patients With Chronic Lymphocytic Leukemia in Real-World Settings: Results From a Multi-Center International Study

Introduction: This study assessed treatment discontinuation patterns and reasons among chronic lymphocytic leukemia (CLL) patients initiating first-line (1L) and second-line (2L) treatments in real-world settings. Materials and / Methods: Using deidentified electronic medical records from the CLL Collaborative Study of Real-World Evidence, premature treatment discontinuation was assessed among FCR, BR, BTKi-based, and BCL-2-based regimen cohorts. / Results: Of 1364 1L patients (initiated in 1997-2021), 190/13.9% received FCR (23.7% discontinued prematurely); 255/18.7% received BR (34.5% discontinued prematurely); 473/34.7% received BTKi-based regimens, of whom 28.1% discontinued prematurely; and 43/3.2% received venetoclax-based regimens, of whom 16.3% discontinued prematurely (venetoclax monotherapy: 7/0.5%, of whom 42.9% discontinued; VG/VR: 36/2.6%, of whom 11.1% discontinued). The most common reasons for treatment discontinuation were adverse events (FCR: 25/13.2%; BR: 36/14.1%; BTKi-based regimens: 75/15.9%) and disease progression (venetoclax-based: 3/7.0%). Of 626 2L patients, 20/3.2% received FCR (50.0% discontinued); 62/9.9% received BR (35.5% discontinued); 303/48.4% received BTKi-based regimens, of whom 38.0% discontinued; and 73/11.7% received venetoclax-based regimens, of whom 30.1% discontinued (venetoclax monotherapy: 27/4.3%, of whom 29.6% discontinued; VG/VR: 43/6.9%, of whom 27.9% discontinued). The most common reasons for treatment discontinuation were adverse events (FCR: 6/30.0%; BR: 11/17.7%; BTKi-based regimens: 60/19.8%; venetoclax-based: 6/8.2%). / Conclusion: The findings of this study highlight the continued need for tolerable therapies in CLL, with finite therapy offering a better tolerated option for patients who are newly diagnosed or relapsed/refractory to prior treatments

Identification of sortase A (SrtA) substrates in Streptococcus uberis: evidence for an additional hexapeptide (LPXXXD) sorting motif

Sortase (a transamidase) has been shown to be responsible for the covalent attachment of proteins to the bacterial cell wall. Anchoring is effected on secreted proteins containing a specific cell wall motif toward their C-terminus; that for sortase A (SrtA) in Gram-positive bacteria often incorporates the sequence LPXTG. Such surface proteins are often characterized as virulence determinants and play important roles during the establishment and persistence of infection. Intramammary infection with Streptococcus uberis is a common cause of bovine mastitis, which impacts on animal health and welfare and the economics of milk production. Comparison of stringently produced cell wall fractions from S. uberis and an isogenic mutant strain lacking SrtA permitted identification of 9 proteins likely to be covalently anchored at the cell surface. Analysis of these sequences implied the presence of two anchoring motifs for S. uberis, the classical LPXTG motif and an additional LPXXXD motif