Search

This paper reviews the state of the art in offshore wind farm operations and maintenance with a focus on decision support models for the scheduling of maintenance. Factors influential to maintenance planning are collected from the literature and their inclusion in state-of-the-art models is discussed. Methods for modeling and optimization are presented. The methods currently used and possible alternatives are discussed. The existing models are already able to aid the decision-making process. They can be improved by applying more advanced mathematical methods, including uncertainties in the input, regarding more of the influential factors, and by collecting, analyzing, and subsequently using more accurate data. [ABSTRACT FROM AUTHOR]

The aim of this literature review is to provide an overview of recent advances in our understanding of known pathogenicity factors implicated in ring rot disease caused by Clavibacter michiganensis sepedonicus (Cms). Several genetic determinants with possible functions in plant-pathogen interaction were identified. Functional analysis of genes involved in pathogenicity offered us some clues regarding the infectious process. Successful eradication of the ring rot disease relies on prevention by the exclusive use of certified, ring rot-free seed potatoes, sanitation and early detection. An important factor that contributed to the persistence of the ring rot disease in potato cultivation areas in northern Europe and North America is the occurrence of latent infections and limitation of detection technique. Early detection of the bacterium is a fundamental element of eradication program; however, screening tests do not provide the needed information about the potential pathogenicity or virulence of the detected bacteria. Recently developed molecular based detection protocols were demonstrated to be fast, sensitive and specific. Their use could improve the first line screening for ring rot in potato tubers. We anticipate that further genomic studies will allow the identification of pathogenicity or virulence markers useful in the advancement of new diagnostic tools as alternative strategies to the time-consuming pathogenicity tests. [ABSTRACT FROM AUTHOR]

Coccidiosis in poultry, caused by protozoan parasites of the genus Eimeria , is an intestinal disease with substantial economic impact. With the use of anticoccidial drugs under public and political pressure, and the comparatively higher cost of live-attenuated vaccines, an attractive complementary strategy for control is to breed chickens with increased resistance to Eimeria parasitism. Prior infection with Eimeria maxima leads to complete immunity against challenge with homologous strains, but only partial resistance to challenge with antigenically diverse heterologous strains. We investigate the genetic architecture of avian resistance to E. maxima primary infection and heterologous strain secondary challenge using White Leghorn populations of derived inbred lines, C.B12 and 15I, known to differ in susceptibility to the parasite. An intercross population was infected with E. maxima Houghton (H) strain, followed 3 weeks later by E. maxima Weybridge (W) strain challenge, while a backcross population received a single E. maxima W infection. The phenotypes measured were parasite replication (counting fecal oocyst output or qPCR for parasite numbers in intestinal tissue), intestinal lesion score (gross pathology, scale 0–4), and for the backcross only, serum interleukin-10 (IL-10) levels. Birds were genotyped using a high density genome-wide DNA array (600K, Affymetrix). Genome-wide association study located associations on chromosomes 1, 2, 3, and 5 following primary infection in the backcross population, and a suggestive association on chromosome 1 following heterologous E. maxima W challenge in the intercross population. This mapped several megabases away from the quantitative trait locus (QTL) linked to the backcross primary W strain infection, suggesting different underlying mechanisms for the primary- and heterologous secondary- responses. Underlying pathways for those genes located in the respective QTL for resistance to primary infection and protection against heterologous challenge were related mainly to immune response, with IL-10 signaling in the backcross primary infection being the most significant. Additionally, the identified markers associated with IL-10 levels exhibited significant additive genetic variance. We suggest this is a phenotype of interest to the outcome of challenge, being scalable in live birds and negating the requirement for single-bird cages, fecal oocyst counts, or slaughter for sampling (qPCR). [ABSTRACT FROM AUTHOR]

The immune landscape in brain metastasis is a very heterogeneous framework. Amongst a broad plethora of cells within the tumor microenvironment, the presence of activated microglia has been perfectly described. The innate role of microglial cells is to detect and eliminate any insults that may disturb the regular behavior of the brain. As part of its defensive role, it releases pro- and anti-inflammatory cytokines that aim to modulate the inflammatory scenario at the metastatic foci. However, the long term effects that these cells may exert on the metastatic progression is not clear. One of the biggest challenges in the field is to distinguish between brain resident microglial cells and infiltrated bone-marrow derived macrophages. Part of this issue is the fact that both cell types share similar phenotypes. Current studies are based on the modulation of the immune response against cancer cells (immunotherapy). However, most of current clinical trials and newly developed drugs focus on the adaptive immune response (e.g., immune blockade check-points). Additionally, the unique structure of the central nervous system with the presence of the blood-brain barrier have hindered a significant advance in novel therapies against brain metastasis. In this manuscript, we describe current advances in characterization of tumor-associated microglia and macrophages, the importance of microglia during the anti-cancerous response, and the future direction for the development of new strategies against this complex disease. [ABSTRACT FROM AUTHOR]

Background: Phototropism is the response a plant exhibits when it is faced with a directional blue light stimulus. Though a seemingly simple differential cell elongation response within a responding tissue that results in organ curvature, phototropism is regulated through a complex set of signal perception and transduction events that move from the plasma membrane to the nucleus. In nature phototropism is one of several plant responses that have evolved to optimize photosynthesis and growth.Objective: In the present work we will review the state of the field with respect to the molecules and mechanisms associated with phototropism in land plants.Methods: A systematic literature search was done to identify relevant advances in the field. Though we tried to focus on literature within the past decade (1998-present), we have discussed and cited older literature where appropriate because of context or its significant impact to the present field. Several previous review articles are also cited where appropriate and readers should seek those out.Results: A total of 199 articles are cited that fulfill the criteria listed above.Conclusions: Though important numerous and significant advances have been made in our understanding of the molecular, biochemical, cell biological and physiologic mechanisms underlying phototropism in land plants over the past decade, there are many remaining unanswered questions. The future is indeed bright for researchers in the field and we look forward to the next decade worth of discoveries. [ABSTRACT FROM AUTHOR]

Marker genes are widely used to differentiate and classify yeast at a species level. Diagnostic marker genes (DMGs) derived from a whole genome comparison allow the differentiation of strains of Saccharomyces cerevisiae according to their potential application. This approach, which has not been previously described, uses the software tool BIAst Diagnostic Gene Finder (BADGE). We compared the genome sequences of 25 brewing yeast strains to predict DMGs for the discrimination of Saccharomyces yeasts according to their brewing style. Two promising DMGs were chosen for PCR screening in order to test the presence of these genes in 83 yeast strains. A first PCR screening of 25 top‐fermenting S. cerevisiae strains, using the DMG‐specific primer pairs for wheat beer marker I (putative AMD2) and wheat beer marker II (GEX1), distinguished yeast strains of the wheat beer style from all other beer styles. The PCR screening of an extended set of 83 yeast strains displayed a more variable distribution of the selected DMGs to different potential applications. Furthermore, 60 out of 83 yeast strains were positive for at least one DMG. The diagnostic marker genes proved to be useful for the differentiation of wheat beer strains (100% positive identification for both genes) to German Alt‐Kölsch and ale yeasts (87.5% negative identification for both genes). © 2018 The Institute of Brewing & Distilling [ABSTRACT FROM AUTHOR]

Connective tissue growth factor (CTGF) and transforming growth factor (TGF-β2) have essential roles for structure, function, growth, and production of extracellular matrix during eye development. The current study aim was to examine the localization of CTGF and TGF-β2 by immunohistochemical labeling during eye development in four different habitat species of Egyptian birds i.e. chicken (Gallus gallus domesticus), duck(Cairina moschata), quail (Coturnix coturnix), and egret (Bubulcus ibis). Fertilized eggs were obtained to access pre-and post-hatching stages of developing eye. CTGF and TGF-β2 were detected in the inner non-pigmented epithelium layer of ciliary body during eye development of studied birds. Moreover, CTGF was well expressed in the developing sclera, but not expressed in the developing retina. On the contrary, expression of TGF-β2 was detected in the developing retina but was not detected in the developing sclera. The pattern of expression and distribution of CTGF and TGF-β2 in ciliary body, retina and sclera concluded the important cellular function of these growth factors during eye development of studied birds. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Chemistry is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Borrelia burgdorferi sensu lato (Bbsl), the causative agent of Lyme disease, establishes an initial infection in the host’s skin following a tick bite, and then disseminates to distant organs, leading to multisystem manifestations. Tick-to-vertebrate host transmission requires that Bbsl survives during blood feeding. Complement is an important innate host defense in blood and interstitial fluid. Bbsl produces a polymorphic surface protein, CspA, that binds to a complement regulator, Factor H (FH) to block complement activation in vitro. However, the role that CspA plays in the Bbsl enzootic cycle remains unclear. In this study, we demonstrated that different CspA variants promote spirochete binding to FH to inactivate complement and promote serum resistance in a host-specific manner. Utilizing a tick-to-mouse transmission model, we observed that a cspA-knockout B. burgdorferi is eliminated from nymphal ticks in the first 24 hours of feeding and is unable to be transmitted to naïve mice. Conversely, ectopically producing CspA derived from B. burgdorferi or B. afzelii, but not B. garinii in a cspA-knockout strain restored spirochete survival in fed nymphs and tick-to-mouse transmission. Furthermore, a CspA point mutant, CspA-L246D that was defective in FH-binding, failed to survive in fed nymphs and at the inoculation site or bloodstream in mice. We also allowed those spirochete-infected nymphs to feed on C3-/- mice that lacked functional complement. The cspA-knockout B. burgdorferi or this mutant strain complemented with cspA variants or cspA-L246D was found at similar levels as wild type B. burgdorferi in the fed nymphs and mouse tissues. These novel findings suggest that the FH-binding activity of CspA protects spirochetes from complement-mediated killing in fed nymphal ticks, which ultimately allows Bbsl transmission to mammalian hosts. [ABSTRACT FROM AUTHOR]

Arachis hypogaea L. geocarpy is a unique feature different from other legume plants. Flowering and fertilization occur above ground, while the following processes of pod formation and development proceed in the soil. The zygote divides only few times to develop into pre-embryo and then further embryo developmental process stops when the gynoecium is exposed to light condition or normal day/night period. In this study, eight phytochrome genes were identified in two wild peanuts (four in Arachis duranensis and four in Arachis ipaensis). Using RACE and homologous cloning, the full CDS of AhphyA, AhphyA-like, AhphyB and AhphyE were acquired in cultivated peanut. Protein structure analysis showed that the conservative coding domains of phytochromes from a number of other plant species were found in these proteins. The C-terminal of AhphyA, AhphyA-like and AhphyB could interact with phytochrome-interacting factor 3 in vitro. The expression patterns of these genes in various tissues were analyzed by qRT-PCR, and significant differences were observed. Interestingly, the expression levels of AhphyA-like changed significantly during gynophore growth and early pod development. Furthermore, protein accumulation patterns of AhphyA and AhphyB in gynophore were different during early pod development stages in that AhphyA and AhphyB proteins were not detected in S1 and S2 gynophores, while significant accumulation of AhphyA and AhphyB were detected in S3 gynophore. These results provided evidence that phytochromes mediated light signal transduction may play key roles in peanut geocarpy development. [ABSTRACT FROM AUTHOR]

We present structural information for oat phyA3 in the far-red-light-absorbing (Pfr) signaling state, to our knowledge the first three-dimensional (3D) information for a plant phytochrome as Pfr. Solid-state magic-angle spinning (MAS) NMR was used to detect interatomic contacts in the complete photosensory module [residues 1-595, including the NTE (N-terminal extension), PAS (Per/Arnt/Sim), GAF (cGMP phosphodiesterase/adenylyl cyclase/FhlA) and PHY (phytochrome-specific) domains but with the C-terminal PAS repeat and transmitter-like module deleted] auto-assembled in vitro with 13C- and 15N-labeled phycocyanobilin (PCB) chromophore. Thereafter, quantum mechanics/molecular mechanics (QM/MM) enabled us to refine 3D structural models constrained by the NMR data. We provide definitive atomic assignments for all carbon and nitrogen atoms of the chromophore, showing the Pfr chromophore geometry to be periplanar ZZEssa with the D-ring in a b-facial disposition incompatible with many earlier notions regarding photoconversion yet supporting circular dichroism (CD) data. The Y268 side chain is shifted radically relative to published Pfr crystal structures in order to accommodate the b-facial ring D. Our findings support a photoconversion sequence beginning with Pr photoactivation via an anticlockwise D-ring Za!Ea photoflip followed by significant shifts at the coupling of ring A to the protein, a B-ring propionate partner swap from R317 to R287, changes in the C-ring propionate hydrogen-bonding network, breakage of the D272-R552 salt bridge accompanied by sheet-to-helix refolding of the tongue region stabilized by Y326-D272-S554 hydrogen bonding, and binding of the NTE to the hydrophobic side of ring A. We discuss phyA photoconversion, including the possible roles of mesoscopic phase transitions and protonation dynamics in the chromophore pocket. We also discuss possible associations between structural changes and translocation and signaling processes within the cell. [ABSTRACT FROM AUTHOR]

IEA Wind Task 32 exists to identify and mitigate barriers to the adoption of lidar for wind energy applications. It leverages ongoing international research and development activities in academia and industry to investigate site assessment, power performance testing, controls and loads, and complex flows. Since its initiation in 2011, Task 32 has been responsible for several recommended practices and expert reports that have contributed to the adoption of ground-based, nacelle-based, and floating lidar by the wind industry. Future challenges include the development of lidar uncertainty models, best practices for data management, and developing community-based tools for data analysis, planning of lidar measurements and lidar configuration. This paper describes the barriers that Task 32 identified to the deployment of wind lidar in each of these application areas, and the steps that have been taken to confirm or mitigate the barriers. Task 32 will continue to be a meeting point for the international wind lidar community until at least 2020 and welcomes old and new participants. [ABSTRACT FROM AUTHOR]

Background: There is growing evidence linking low blood vitamin D concentration to numerous diseases in people and in dogs. Vitamin D influences cellular function by signaling through the vitamin D receptor (VDR). Little is known about which non‐skeletal tissues express the VDR or how inflammation influences its expression in the dog. Objectives: To define which non‐skeletal canine tissues express the VDR and to investigate expression in inflamed small intestine. Animals: Thirteen non‐skeletal tissues were collected prospectively from 6 control dogs. Thirty‐five dogs diagnosed with a chronic enteropathy (CE) and 24 control dogs were prospectively enrolled and duodenal biopsies were evaluated for VDR expression. Methods: Prospective; blinded assessment of canine intestinal VDR. Dogs with CE were included once other identifiable causes of intestinal disease were excluded. Age matched controls were included with no intestinal clinical signs. VDR expression was assessed immunohistochemically in all samples, using a Rat IgG VDR monoclonal antibody. Quantitative real‐time polymerase chain reaction (qPCR) was also used for duodenal biopsies. Results: VDR expression as assessed by immunohistochemistry (IHC) was highest in the kidney, duodenum, skin, ileum and spleen, and weak in the colon, heart, lymph node, liver, lung, and ovary. Gastric and testicular tissue did not express the VDR. There was no statistical difference in duodenal VDR expression between the 24 healthy dogs and 34 dogs with CE when quantified by either qPCR (P = 0.87) or IHC (P = 0.099). Conclusions and Clinical Importance: The lack of down regulation of VDR expression in inflamed intestine contrasts with previous studies in humans. Our findings support future studies to investigate whether vitamin D and its analogues can be used to modulate intestinal inflammation in the dog. [ABSTRACT FROM AUTHOR]

Plants utilize light as sole energy source. To maximize light capture, they are able to detect the light direction and orient themselves toward the light source. This phototropic response is mediated by the plant blue-light photoreceptors phototropin1 and phototropin2 (phot1 and phot2). Although fully differentiated plants also exhibit this response, it can be best observed in etiolated seedlings. Differences in light between the illuminated and shaded site of a seedling stem lead to changes in the auxin distribution, resulting in cell elongation on the shaded site. Since phototropism connects light perception, signaling, and auxin transport, it is of great interest to analyze this response with a fast and simple method. Moreover, pre-exposure to red light enhances the phototropic response via phytochrome A (phyA) and phyB action. Here we describe a method to analyze the phototropic response of Arabidopsis seedlings to blue light and the enhanced response with a red-light pretreatment. With numerous mutants available, its fast germination, and its small size, Arabidopsis is well suited for this analysis. Different genotypes can be simultaneously probed in less than a week., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Summary: Clavibacter michiganensis ssp. capsici is a Gram‐positive plant‐pathogenic bacterium causing bacterial canker disease in pepper. Virulence genes and mechanisms of C. michiganensis ssp. capsici in pepper have not yet been studied. To identify virulence genes of C. michiganensis ssp. capsici, comparative genome analyses with C. michiganensis ssp. capsici and its related C. michiganensis subspecies, and functional analysis of its putative virulence genes during infection were performed. The C. michiganensis ssp. capsici type strain PF008 carries one chromosome (3.056 Mb) and two plasmids (39 kb pCM1Cmc and 145 kb pCM2Cmc). The genome analyses showed that this bacterium lacks a chromosomal pathogenicity island and celA gene that are important for disease development by C. michiganensis ssp. michiganensis in tomato, but carries most putative virulence genes in both plasmids. Virulence of pCM1Cmc‐cured C. michiganensis ssp. capsici was greatly reduced compared with the wild‐type strain in pepper. The complementation analysis with pCM1Cmc‐located putative virulence genes showed that at least five genes, chpE, chpG, ppaA1, ppaB1 and pelA1, encoding serine proteases or pectate lyase contribute to disease development in pepper. In conclusion, C. michiganensis ssp. capsici has a unique genome structure, and its multiple plasmid‐borne genes play critical roles in virulence in pepper, either separately or together. [ABSTRACT FROM AUTHOR]

Streptomyces kanasensis ZX01 produces some antibiotics and a glycoprotein with antiviral activity. To further evaluate its biosynthetic potential, here we sequenced the 7,026,279 bp draft genome of S. kanasensis ZX01 and analyzed all identifiable secondary gene clusters for controlling natural products. More than 60 putative clusters were found in S. kanasensis ZX01, the majority of these biosynthetic loci are novel. In addition, the regulators for secondary metabolism in S. kanasensis ZX01 were abundant. The global regulator nsdA not only controls biosynthesis of some antibiotics, but also enhances production of glycoprotein GP-1 with antiviral activity. This study importantly reveals the powerful interplay between genomic analysis and studies of traditional natural product purification/production increasing. [ABSTRACT FROM AUTHOR]

The red/far-red light absorbing photoreceptors phytochromes regulate development and growth and thus play an essential role in optimizing adaptation of the sessile plants to the ever-changing environment. Our understanding of how absorption of a red/far-red photon by phytochromes initiates/modifies diverse physiological responses has been steadily improving. Research performed in the last 5 years has been especially productive and led to significant conceptual changes about the mode of action of these photoreceptors. In this review, we focus on the phytochrome B photoreceptor, the major phytochrome species active in light-grown plants. We discuss how its light-independent inactivation (termed dark/thermal reversion), post-translational modification, including ubiquitination, phosphorylation and sumoylation, as well as heterodimerization with other phytochrome species modify red light-controlled physiological responses. Finally, we discuss how photobiological properties of phytochrome B enable this photoreceptor to function also as a thermosensor. [ABSTRACT FROM AUTHOR]

Land plants possess the ability to sense and respond to far-red light (700-760 nm), which serves as an important environmental cue. Due to the nature of far-red light, it is not absorbed by chlorophyll and thus is enriched in canopy shade and will also penetrate deeper into soil than other visible wavelengths. Far-red light responses include regulation of seed germination, suppression of hypocotyl growth, induction of flowering and accumulation of anthocyanins, which depend on one member of the phytochrome photoreceptor family, phytochrome A (phyA). Here, we review the current understanding of the underlying molecular mechanisms of how plants sense far-red light through phyA and the physiological responses to this light quality. Light-activated phytochromes act on two primary pathways within the nucleus; suppression of the E3 ubiquitin ligase complex CUL4/DDB1COP1/SPA and inactivation of the PHYTOCHROME INTERACTING FACTOR (PIF) family of bHLH transcription factors. These pathways integrate with other signal transduction pathways, including phytohormones, for tissue and developmental stage specific responses. Unlike other phytochromes that mediate red-light responses, phyA is transported from the cytoplasm to the nucleus in far-red light by the shuttle proteins FAR-RED ELONGATED HYPOCOTYL 1 (FHY1) and FHY1-LIKE (FHL). However, additional mechanisms must exist that shift the action of phyA to far-red light; current hypotheses are discussed. [ABSTRACT FROM AUTHOR]

Checkpoint signaling requires two conserved phosphatidylinositol 3-kinase-related protein kinases (PIKKs): ATM and ATR. In budding yeast, Tel1 and Mec1 correspond to ATM and ATR, respectively. The Tel2-Tti1-Tti2 (TTT) complex connects to the Rvb1-Rvb2-Tah1-Pih1 (R2TP) complex for the protein stability of PIKKs; however, TTT-R2TP interaction only partially mediates ATM and ATR protein stabilization. How TTT controls protein stability of ATM and ATR remains to be precisely determined. Here we show that Asa1, like Tel2, plays a major role in stabilization of newly synthesized Mec1 and Tel1 proteins whereas Pih1 contributes to Mec1 and Tel1 stability at high temperatures. Although Asa1 and Pih1 both interact with Tel2, no Asa1-Pih1 interaction is detected. Pih1 is distributed in both the cytoplasm and nucleus wheres Asa1 localizes largely in the cytoplasm. Asa1 and Pih1 are required for proper DNA damage checkpoint signaling. Our findings provide a model in which two different Tel2 pathways promote protein stabilization of Mec1 and Tel1 in budding yeast. [ABSTRACT FROM AUTHOR]

Giant linear plasmids, which replicate independently of the chromosomes, widely exist in actinobacteria. Previous studies mostly focused on the replication and evolution of the linear plasmids or the secondary metabolite gene clusters and the resistance gene clusters therein. However, the relationships of the linear plasmids to the productivities of secondary metabolites have not been studied. In this work, we developed a method to eliminate the indigenous linear plasmid pSHJG1 in Streptomyces hygroscopicus var. jinggangensis, and validamycin A titer increased by 12.5% (from 19.16 ± 1.93 to 21.56 ± 2.25 g/L) in the high-yielding strain TL01 and 43.7% (from 4.67 ± 0.05 to 6.71 ± 0.21 g/L) in the wild-type strain 5008, whereas the cellular growth of the plasmid-cured mutant was reduced. Subsequently, the plasmid-cured mutant was complemented with three structure genes involved in cellular growth in pSHJG1 under the control of a strong PvalA promoter. Among them, the complementation of genes pSHJG1.069 and pSHJG1.072, encoding a putative hydrolase and putative P-loop ATPase, respectively, resulted in the restoration of cellular growth and validamycin A titer. Furthermore, the elimination of indigenous linear plasmid pHZ228 in the candicidin producer Streptomyces sp. FR008 also led to enhanced candicidin production and reduced cellular growth. Because of the wide distribution of indigenous linear plasmids in actinobacteria, the engineering strategy described here could be implemented in a variety of strains for the overproduction of various natural products. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most prevalent malignancies in women worldwide. Early-stage breast cancer is considered a curable disease; however, once distant metastasis occurs, the 5-year overall survival rate of patients becomes significantly reduced. There are four distinct metastatic patterns in breast cancer: bone, lung, liver and brain. Among these, breast cancer brain metastasis (BCBM) is the leading cause of death; it is highly associated with impaired quality of life and poor prognosis due to the limited permeability of the blood-brain barrier and consequent lack of effective treatments. Although the sequence of events in BCBM is universally accepted, the underlying mechanisms have not yet been fully elucidated. In this review, we outline progress surrounding the molecular mechanisms involved in BCBM as well as experimental methods and research models to better understand the process. We further discuss the challenges in the management of brain metastases, as well as providing an overview of current therapies and highlighting innovative research towards developing novel efficacious targeted therapies., (© 2021. The Author(s), under exclusive licence to Cancer Research UK.)

Different configurations of gearbox, generator and power converter exist for offshore wind turbines. This paper investigated the performance of four prominent drive train configurations over a range of sites distinguished by their distance to shore. Failure rate data from onshore and offshore wind turbine populations was used where available or systematically estimated where no data was available. This was inputted along with repair resource requirements to an offshore accessibility and operation and maintenance model to calculate availability and operation and maintenance costs for a baseline wind farm consisting of 100 turbines. The results predicted that turbines with a permanent magnet generator and a fully rated power converter will have a higher availability and lower operation and maintenance costs than turbines with doubly fed induction generators. This held true for all sites in this analysis. It was also predicted that in turbines with a permanent magnet generator, the direct drive configuration has the highest availability and lowest operation and maintenance costs followed by the turbines with two-stage and three-stage gearboxes. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Brain metastases are highly-evolved manifestations of breast cancer arising in a unique microenvironment, giving them exceptional adaptability in the face of new extrinsic pressures. The incidence is rising in line with population ageing, and use of newer therapies that stabilise metastatic disease burden with variable efficacy throughout the body. Historically, there has been a widely-held view that brain metastases do not respond to circulating therapeutics because the blood-brain-barrier (BBB) restricts their uptake. However, emerging data are beginning to paint a more complex picture where the brain acts as a sanctuary for dormant, subclinical proliferations that are initially protected by the BBB, but then exposed to dynamic selection pressures as tumours mature and vascular permeability increases. Here, we review key experimental approaches and landmark studies that have charted the genomic landscape of breast cancer brain metastases. These findings are contextualised with the factors impacting on clonal outgrowth in the brain: intrinsic breast tumour cell capabilities required for brain metastatic fitness, and the neural niche, which is initially hostile to invading cells but then engineered into a tumour-support vehicle by the successful minority. We also discuss how late detection, abnormal vascular perfusion and interstitial fluid dynamics underpin the recalcitrant clinical behaviour of brain metastases, and outline active clinical trials in the context of precision management. [ABSTRACT FROM AUTHOR]

Pathogenic animal trypanosomes affecting livestock have represented a major constraint to agricultural development in Africa for centuries, and their negative economic impact is increasing in South America and Asia. Chemotherapy and chemoprophylaxis represent the main means of control. However, research into new trypanocides has remained inadequate for decades, leading to a situation where the few compounds available are losing efficacy due to the emergence of drug-resistant parasites. In this review, we provide a comprehensive overview of the current options available for the treatment and prophylaxis of the animal trypanosomiases, with a special focus on the problem of resistance. The key issues surrounding the main economically important animal trypanosome species and the diseases they cause are also presented. As new investment becomes available to develop improved tools to control the animal trypanosomiases, we stress that efforts should be directed towards a better understanding of the biology of the relevant parasite species and strains, to identify new drug targets and interrogate resistance mechanisms. [ABSTRACT FROM AUTHOR]

Background: Obtaining accurate estimates of biological or enzymatic reaction rates is critical in understanding the design principles of a network and how biological processes can be experimentally manipulated on demand. In many cases experimental limitations mean that some enzymatic rates cannot be measured directly, requiring mathematical algorithms to estimate them. Here, we describe a methodology that calculates rates at which light-regulated proteins switch between conformational states. We focus our analysis on the phytochrome family of photoreceptors found in cyanobacteria, plants and many optogenetic tools. Phytochrome proteins change between active (PA) and inactive (PI) states at rates that are proportional to photoconversion cross-sections and influenced by light quality, light intensity, thermal reactions and dimerisation. This work presents a method that can accurately calculate these photoconversion cross-sections in the presence of multiple non-light regulated reactions. Results: Our approach to calculating the photoconversion cross-sections comprises three steps: i) calculate the thermal reversion reaction rate(s); ii) develop search spaces from which all possible sets of photoconversion cross-sections exist, and; iii) estimate extinction coefficients that describe our absorption spectra. We confirm that the presented approach yields accurate results through the use of simulated test cases. Our test cases were further expanded to more realistic scenarios where noise, multiple thermal reactions and dimerisation are considered. Finally, we present the photoconversion cross-sections of an Arabidopsis phyB N-terminal fragment commonly used in optogenetic tools. Conclusions: The calculation of photoconversion cross-sections has implications for both photoreceptor and synthetic biologists. Our method allows, for the first time, direct comparisons of photoconversion cross-sections and response speeds of photoreceptors in different cellular environments and synthetic tools. Due to the generality of our procedure, as shown by the application to multiple test cases, the photoconversion cross-sections and quantum yields of any photoreceptor might now, in principle, be obtained. [ABSTRACT FROM AUTHOR]

Different stent structures lead to different deformations of blood vessels, such as different cross-sectional shapes, which further influence the blood flow patterns. In this paper, six non-commercial stents with different link structures called I-, C-, S-, U-, N- and W-types were considered. Their influences on arteries with five different curvatures (i.e., 0, 15, 30, 45 and 60) were studied using finite element method. Four indices including the maximum plastic strain of stents, the rate of expansion, the maximum von Mises stress and the ellipticity of arteries, were compared for all cases. The results showed that the S-type or U-type stents, with larger plastic strain and lower von Mises stress on the arteries, provided the optimal outcome. As the link structures became complex, the arterial expansion increased monotonically, while the ellipticity of arteries showed a decreasing tendency in the vessel models. The present study could be useful for the commercial design and clinic selection of a stent with different link structures for different curved arteries. [ABSTRACT FROM AUTHOR]

The cathepsin family of lysosomal proteases is increasingly being recognized for their altered expression in cancer and role in facilitating tumor progression. The aspartyl protease cathepsin E is overexpressed in several cancers and has been investigated as a biomarker for pancreatic ductal adenocarcinoma (PDAC). Here we show that cathepsin E expression in mouse PDAC tumors is increased by more than 400-fold when compared to healthy pancreatic tissue. Cathepsin E accumulates over the course of disease progression and accounts for more than 3% of the tumor protein in mice with end-stage disease. Through immunoblot analysis we determined that only procathepsin E exists in mouse PDAC tumors and cell lines derived from these tumors. By decreasing the pH, this procathepsion E is converted to the mature form, resulting in an increase in proteolytic activity. Although active site inhibitors can bind procathepsin E, treatment of PDAC mice with the aspartyl protease inhibitor ritonavir did not decrease tumor burden. Lastly, we used multiplex substrate profiling by mass spectrometry to identify two synthetic peptides that are hydrolyzed by procathepsin E near neutral pH. This work represents a comprehensive analysis of procathepsin E in PDAC and could facilitate the development of improved biomarkers for disease detection. [ABSTRACT FROM AUTHOR]

Purpose: 'Big data' are accumulating in a multitude of domains and offer novel opportunities for research. The role of these resources in mental health investigations remains relatively unexplored, although a number of datasets are in use and supporting a range of projects. We sought to review big data resources and their use in mental health research to characterise applications to date and consider directions for innovation in future.Methods: A narrative review.Results: Clear disparities were evident in geographic regions covered and in the disorders and interventions receiving most attention.Discussion: We discuss the strengths and weaknesses of the use of different types of data and the challenges of big data in general. Current research output from big data is still predominantly determined by the information and resources available and there is a need to reverse the situation so that big data platforms are more driven by the needs of clinical services and service users. [ABSTRACT FROM AUTHOR]

The photoreceptor phytochrome A acts as a light-dependent molecular switch and regulates responses initiated by very low fluences of light ( VLFR) and high fluences ( HIR) of far-red light. PhyA is expressed ubiquitously, but how phyA signaling is orchestrated to regulate photomorphogenesis is poorly understood., To address this issue, we generated transgenic Arabidopsis thaliana phyA-201 mutant lines expressing the biologically active phyA- YFP photoreceptor in different tissues, and analyzed the expression of several reporter genes, including ProHY5: HY5- GFP and Pro35S: CFP- PIF1, and various FR- HIR-dependent physiological responses., We show that phyA action in one tissue is critical and sufficient to regulate flowering time and root growth; control of cotyledon and hypocotyl growth requires simultaneous phyA activity in different tissues; and changes detected in the expression of reporters are not restricted to phyA-containing cells., We conclude that FR- HIR-controlled morphogenesis in Arabidopsis is mediated partly by tissue-specific and partly by intercellular signaling initiated by phyA. Intercellular signaling is critical for many FR- HIR induced responses, yet it appears that phyA modulates the abundance and activity of key regulatory transcription factors in a tissue-autonomous fashion. [ABSTRACT FROM AUTHOR]

Phytochromes recognize light signals and control diverse developmental processes. In rice, all three phytochrome genes- OsphyA, OsphyB, and OsphyC-are involved in regulating flowering time. We investigated the role of OsPhyA by comparing the osphyA osphyB double mutant to an osphyB single mutant. Plants of the double mutant flowered later than the single under short days (SD) but bolted earlier under long days (LD). Under SD, this delayed-flowering phenotype was primarily due to the decreased expression of Oryza sativa GIGANTEA ( OsGI), which controls three flowering activators: Heading date 1 ( Hd1), OsMADS51, and Oryza sativa Indeterminate 1 ( OsId1). Under LD, although the expression of several repressors, e.g., Hd1, Oryza sativa CONSTANS- like 4 ( OsCOL4), and AP2 genes, was affected in the double mutant, that of Grain number, plant height and heading date 7 ( Ghd7) was the most significantly reduced. These results indicated that OsPhyA influences flowering time mainly by affecting the expression of OsGI under SD and Ghd7 under LD when phytochrome B is absent. We also demonstrated that far-red light delays flowering time via both OsPhyA and OsPhyB. [ABSTRACT FROM AUTHOR]

A simple modular approach is presented which has been directed towards the synthesis of potentially monoanionic NN'N", NN'C, and NN'P pincer-type ligands. These pincers incorporate an amide functionality derived from the skeletal structure of readily available 2-(2-aminophenyl)-4,5-dioxooxazoles. All of the pincers are synthesized in moderate yields (up to 74%) and are characterised by nuclear magnetic spectroscopy (NMR), elemental analyses, and infrared (IR) spectroscopy. X-ray crystallography is also performed on the chiral and achiral alkyl halide precursors and on an oxide derivative of a pincer with a NN'Patom donor set. A palladium derivative of one of the NN'N"-pincers is shown to be an active catalyst for the addition of an allyl group to various benzaldehydes using n-Bu3Sn(allyl) as allyl source. [ABSTRACT FROM AUTHOR]

Hypocotyl phototropism of etiolated Arabidopsis seedlings is primarily mediated by the blue-light receptor kinase phototropin 1 (phot1). Phot1-mediated curvature to continuous unilateral blue light irradiation (0.5µmolm-2 s-1) is enhanced by overhead pre-treatment with red light (20µmol m-2 s-1 for 15 min) through the action of phytochrome (phyA). Here, we show that pre-treatment with blue light is equally as effective in eliciting phototropic enhancement and is dependent on phyA. Although blue light pre-treatment was sufficient to activate early phot1 signaling events, phot1 autophosphorylation in vivo was not found to be saturated, as assessed by subsequently measuring phot1 kinase activity in vitro. However, enhancement effects by red and blue light pre-treatment were not observed at higher intensities of phototropic stimulation (10&3181;mol m-2 s-1). Phototropic enhancement by red and blue light pre-treatments to 0.5µmol m-2 s-1 unilateral blue light irradiation was also lacking in transgenic Arabidopsis where PHOT1 expression was restricted to the epidermis. Together, these findings indicate that phyA-mediated effects on phot1 signaling are restricted to low intensities of phototropic stimulation and originate from tissues other than the epidermis. [ABSTRACT FROM AUTHOR]

Respiratory diseases are the prime cause of death and disability worldwide. The majority of lung-based diseases are resistant to treatment. Hence, research on unique drugs/compounds with a more efficient and minimum side effect for treating lung diseases is urgent. Punica granatum L (pomegranate) fruit has been used in the prevention and treatment of various respiratory disorders in recent times. In vivo and in vitro studies have demonstrated that pomegranate fruit, as well as its juice, extract, peel powder, and oil, exert anti-proliferative, anti-oxidant, anti-microbial, anti-inflammatory, anti-cancer, and anti-tumorigenic properties by attenuating various respiratory conditions such as asthma, lung fibrosis, lung cancer, chronic obstructive pulmonary disease (COPD), and alveolar inflammation via modulating various signaling pathways. The current review summarizes the potential properties and medical benefits of pomegranate against different lung-based diseases, also highlighting its possible role in the lung fibrinolytic system. The available data suggest that pomegranate is effective in controlling the disease progressions and could be a potential therapeutic target benefiting human health status. Furthermore, this review also outlines the preclinical and clinical studies highlighting the role of pomegranate in lung diseases further evoking future studies to investigate the effect of intake of this anti-oxidant fruit in larger and well-defined human clinical trials. PRACTICAL APPLICATIONS: This review outlines the putative pharmacologic benefits of P. granatum L (pomegranate) in treating various chronic lung-based diseases such as lung cancer, COPD, ARDS, asthma, lung fibrosis, and cystic fibrosis. This review also highlights the possible inhibitory role of P. granatum L (pomegranate) in the lung fibrinolytic system triggering the fibrinolytic markers. This review summarizes the preclinical and clinical studies using in vitro, in vivo, and human models highlighting the potential role of P. granatum L (pomegranate) in lung diseases. This review evokes future research to investigate the effect of intake of pomegranate fruit in well-defined human clinical trials., (© 2021 Wiley Periodicals LLC.)